FOREWARD

The course in Obstetrics and Gynecology for

students in the 6th year of General Medical Studies,
studying through English, represents a virtually
complete translation of our lectures printed at the
University of Medicine Press in lasi, in 1993.
We lay stress on this point because the
present

course

in

English

includes

extensive

updated information so that the text should be

useful

for

all

the

students

interested

in

our

speciality, including those who intend to sit for

overseas examinations.
The basic bibliography:
1. Beck W.W. Jr. and ass.: Obstetrics and
Gynecology, Harwal Publishing, 1993.
2. Berek

J.

S.,

Adashi

E.Y.,

Hillard

P.A.

(editors):
Novak's

Gynecology,

12th

Edition,

Williams

SWilkins, 1996.
3.Birkhauser
Menopause.

H.,RozenbaumH.

European

(editors):

consensus

development

(editor):

Gynecologic

conference, 1996.
4. Coppleson

M.

Oncology-Fundamental

Principles

and

Clinical

Practice, Churchill Livingstone, 1992.

5. Cunningham

F.

G.

(editor);

Williams'

Obstetrics, 19th Edition, Appleton & Lange, 1993.

6. Gabbe S. G. (editor): Obstetrics, Normal

and Problem Pregnancies, Second Edition, Churchill

Livingstone, 1991.

7. Harris J. R., Heilman S., Henderson I. C,

Kinne D. W.: Breast Diseases.

8. Llewellyn-Jones

D.:

Fundamentals

of

Obstetrics and Gynecology, 5th Edition, Faber and

Faber, 1990.
9. Shingleton H.M., Fowler W.C., Jordan J.A.,

Dwayne

Lawrence

W.;

Gynecologic

Oncology.

Current Diagnosis and Treatment, W.B. Saunders

Company Ltd, 1996.
8. 10.

Thibault

CH.

(editor);

Reproduction

in

Mammals
and Man, Ellipses, 1993.
9.

The course is published in two volumes

{Obstetrics, Gynecology) to include the curricular

subjects established in our Department.
We are grateful for the assistance of our

10.

colleagues

Cornelia

Tomosoiu,

Associate

Professor, author of the chapters:

11. The diagnosis of pregnancy, Normal labor

and

delivery,

physiological

and

biochemical

processes, Conduct of normal labor and delivery,

The

physiology

isoimmunization,

of

the

Dystocia

contraction,

Dystocia

dysfunction.

Puerperal

puerperium,
due

to

Rh
pelvic

caused

by

uterine

infection,

Post

partum

hemorrhage, Venous complications in pregnancy

and

puerperium,

Mammary

complications

and

lolanda Blidaru, Associate Professor, author of the

chapters :
12. Antenatal care, Infections of the genital

tract,

Uterine

prolapse,

displacements

Endometriosis,

and

utero-vaginal

Menopause,

Male

infertility, Family planning and contraception.

13.

14.

prof.dr. Miha PRICOP

15.

CONTENTS

1. The sexual cells (gametes). Fecundation. Segmentation

and migration / 7
2. Implantation. Development of the egg after implantation /

17
3. Placentation. Placental functions (transport) / 22
4. Endocrine function of the placenta. Placental

immunological phenomena / 36
5- The membranes. The amniotic fluid. The umbilical

16.

cord / 47
6. Maternal physiologic changes that occur during

17.

pregnancy, labor, delivery and puerperium / 52 C 7. The diagnosis

of pregnancy / 68 (Z 8. The physiology of uterine activity. Normal
labor and delivery. Physiological and biochemical processes / 72 C
9. Conduct of normal labor and delivery / 78 C 10. The physiology
of the pueperium / 87
18. 11. Medical and surgical disorders in pregnancy / 91 Q

12. Rh factor isoimmunization/124

13.

Gestational trophoblastic disease /133

14.

Hydramnios (Polyhydramnios) /140

19.

15.

Premature spontaneous rupture of the

membranes
(PSRM)/145
16.

Twin pregnancy /149

17.

Abnormalities of the umbilical cord / 156

18.

Spontaneous abortion / 164

19.

Ectopic pregnancy / 173

18.

(2 20. Dystocia due to pelvic contraction / 182

19. 21. Dystocia caused by uterine dysfunction / 189

22. Hypertensive

disorders

in

pregnancy.

General

considerations. Etiology and pathophysiology / 193

23.

Preeclampsia. Eclampsia / 202

24. Chronic hypertension. Premature separation of the

normally implanted placenta / 216

25.

Preterm birth / 226

26.

Posterm (postdate) (prolonged) pregnancy / 234

27.

Placenta praevia / 240

28.

Rupture of the uterus / 247

29.

Fetal distress/253

30.

Intra-uterine death / 266

31.

Antenatal care / 269

32.

Puerperal infection / 278

20.

33. Post partum hemorrhage / 283

21.

C-34. Venous complications in pregnancy and

puerperium / 287
22.

C 35. Mammary complications and abnormalities of

lactation in puerperium / 290

SEXUAL CELLS (GAMETS).

FECUNDATION. SEGMENTATION AND
24.
MIGRATION
23.

1. THE

25.
26.

27.

1.1. THE

SEXUAL CELLS (GAMETES)

28.

The term ' 'gamete" refers to the mature genu cell which has a haploid
set of chromosomes capable of initiating, by its fusion with another gamete,
the forming of a new individual.
30.
The s p e r m a t o z o o n is the male sexual cell. It is formed in the
seminiferous tubule epithelium in the testis as a result of certain
transformations known under the name of spermatogenesis.
31.
The mature seminiferous
tubule consists of: fibromuscular wall;
32.
Sertoli cells, involved in steroid and protein synthesis, in the control of
the maturation and migration of germ cells and playing a role against
secondary immune reactions in the presence of germ cells presenting antigenic
molecules;
33. :=> germ cells in different stages.
34. Among tubules there are nutritive vessels surrounded by clusters of
interstitial Leydig cells (endocrine elements).
35.
The functions of the male gonad are controlled by the anterior lobe of
the pituitary gland. FSH governs spermatogenesis. LH stimulates the
endocrine secretion. On the level of the Leydig cells it helps the conversion of
the circulating cholesterol into pregnenolone.
36. Starting with this stage the steroidogenesis in the testis follows two
37.
ways:
38.
=> delta 4: pregnenolone - progesterone- 17-hydroxiprogesterone androstenedione;
39.
=> delta 5 (overdominant): dehydroepiandrosterone (DHEA)
-androstenediol - testosterone - dihydrotestosterone (the last step takes place in
the target organs under the action of alpha 5 - reductase).
29.

The main circulating androgen is testosteron other androgens being:

androstenedione, DHEA, alpha 5 dihydrotestosterone. Other steroids produced
by testis are : estradiol, 17 hydroxiprogesterone.
41.
As it seems testosterone is essential in initiating spermatogonia division
and achieving meiotic division of spermatocytes.
42. FSH creates proper conditions for spermatid maturation and
spermatozoon formation. FSH release is done under control in which there are
involved GnRH, steroid hormones, inhibin (a gonadal glycoprotein that
preferentially inhibits secretion of FSH), activin (gonadal protein FSH releasing).
43.
Spermatogenesis stages: - spermatogonia (2N)(46 XY); mitosis
-spermatocyte I (2N), meiotic division - spermatocyte II (23 X)+(23 Y)
-mitotic division - spermatids (23 X)+(23 Y)+(23 X)+(23 Y), metamorphosis
of spermatids into spermatozoa (4). The duration of human spermatogenesis is
74 days.Spermatozoa are produced continuosly.
44.
Spermatozoon morphology (ultramicroscopic
elements)
45.
The head contains the acrosome and the nucleus. The acrosome has
several hydrolytic enzymes such as hyaluronidase and acrosine that are
involved in fertilization. Its role in fertilization hasn't been clarified yet.
Hypothesis:
physical penetration;
recognition and attachement to the pellucida zone;
enzymatic release by exocytosis.
46.
The nucleus consists of chromatin (DNA and basic proteins) and is
highly resistent especially in creating the protection of the genome during its
passage through the female genital tract.
47. The connective piece is the highest segment of the tail (flagellum). Its
function is to mentain the connection and to coordinate the movements of the head
and tail (it is less involved in generating motility).
48.
The flagellum (tail) is a microtubular complex (a system of 9 peripheral
tubules and 2 central microtubules) surrounded by dense outer fibres. It is the
generator of motility. Flagellar movement results from the microtubular
sliding (something similar to the movement of the actin and myosin
filaments).
49. On the level of the seminiferous tubules the spermatozoa are
motionless. They will go along tubuli recti, rete testis, efferent ductule
epididimys.The fertilization capability is achieved in the epididimys and deferent
duct, while mobility takes place in the moment of the contact with seminal
secretions.
50. During the epididimys maturation important cell transformations take
place on the level of the spermatic cell membrane especially in the acrosome.
51.
Spermatozoa, maturated in the epididimys and reaching the vagina
cannot achieve fertilization. While they are in the female genital tract they
undergo some physiological transformations which make them able to take
40.

part in the act of conception. These modifications are known under the name
o f c a p a c i t a t i o n (at least partially these modifications consists of
losing the material on the surface of the acrosome and of exposing the
receptors to the specific interactions).
52.
The time required for the spermatozoa (millions) to pass from vagina
into the tube varies from 5 to 68 minutes. About 1000 spermatozoa reach the
oviduct and in the ampullary segment their number does not exceed several
hundreds in the period of time of 2 to 34 hours from the intercourse. The time
limit of their motility is 85 hours (the limit of the fertile capacity is not
known).
53.
The utero-tubal junction is a serious filter. The tubal epithelium has two
cell types: ciliated (active especially during the luteal phase of the menstrual
cycle) and secretory which produce a secretion that is associated with the
tubal fluid.
54. The content of the tubal fluid:
55.

proteins, K, CI, Ca, Na, Mg;

56.

amilase and hydrogenase lactate (they contribute to the

glucose and piruvate synthesis, an essential substratum for the cleavage and
early growth of the egg).
57.
glucose, a major energetic substratum for
spermatozoa. After capacitation, the contact with the ovular elements
(cumulus
58.
and corona radiata) is achieved and a final maturation known under the
name of" acrosome reaction
59.

The o v u m is the female sexual cell. O v o g e n e s i s takes place from the

level of germinal epithelium. A. In the embryonic - fetal life.
61.
Germinal epithelium, arranged in cords, segments itself into small cell
clusters named primordial follicle.made up of : ovogonia, centrally placed,
with a diameter of 20 micron, granulosa cells (follicular), arranged in one
layer, basal membrane (Slavjansky).
62. During the fetal life, the ovogonia divide by mitosis reaching the stage
of oocyte I. Up to the time of puberty the primordial follicle remains
60.

unchanged. The oocyte remains blocked in the prophase of the first

meiotic division.
64. B. At puberty, the ovary contains about 300,000 follicles. The process of
follicle maturation, foliculogenesis, lasting for about three months, starts with the
transformation of the primordial follicles into primary follicles made up of:
65.
0 oocyte, enlarged (30-60 micron);
66.
0 full layer of cuboidal granulosa cells;
67.
0 follicle-oocyte space turns into zona pellucida (fibre material placed
between the two membranes, oocyte and granulosa, microvili originating in
the two membranes, desmosomes);
68.
0 Slavjansky membrane. The
tertiary follicle (Call-Exner follicle):
oocyte I (diameter of 60-80 micron);
granulosa cell massif;
cavities with follicular fluid produced by the granulosa
69.
cells;..
70.

stromal cells differentiate arround the follicle in theca

interna (predominantly cellular) and theca externa (predominantly fibrilar).
71.
Antral follicle:
outer diameter up to 12 millimeter;
oocyte with diameter up to 90 micron;
enlarged zona pellucida;
the cell massif, containing the oocyte, protrudes into the follicular cavity
forming cumulus proliger;
the follicular cells surrounding the oocyte, radially disposed, form corona
radiata;
Call-Exner corps gather to form the follicular cavity, containing follicular
fluid, bordered by granulosa cells.
73. Cumulus and oocyte cells have morphological and metabolic relations.
On the level of the gap junctions a small molecule transfer takes place. These
intercellular communications have a great functional importance (in the process of
meiosis as well).
74. There is a correlation between meiosis and intraoocyte contents of
cAMP. cAMP is transferred to the oocyte on the level of the follicular cells. LH
interrupts oocyte-cumulus cell connections and anihilates the inhibitory effects of
cAMP (meiosis blocking).
63.

72.

75.
76.

77.

The mature follicle (De Graaf) is unique in each cycle alternatively for
every ovary:

78.

79. => the outer diameter is 15-20 millimeter;

the quantity of follicular fluid increases rapidly;

81.
=> the oocyte has a peripheral location, its diameter being about 100
micron;
82.
z3> granulosa cells,
without vessels; => Slavjansky membrane;
83. theca interna, the endocrine gland producing estrogens and having
84.
vessels;
85. => theca externa.
86.
Between the age of 15 and 50, on the average 13 ovulations take place a
year. Therefore only about 500 of 6 million follicles existing in the intrauterine
life reach maturation.
87. Follicle functions:
88. => oocyte protection;
89. => supplying the proper conditions for its maturation;
90. => hormonal control of the endometrium;
91. => oocyte release in the right moment;
92. => creation of corpus luteum structure;
93.
setting up the hormonal conditions for pregnancy until the fetoplacental metabolism is established.
94. The mature follicle has a dominant condition initiating inhibition over
the rest of the follicular apparatus to which is belongs as well as to the controlateral
ovary. The other follicles are blocked and undergo a process of atresia.
95. The three stages of folliculogenesis:
96.
=> recruitment, a phase involving about 15 follicles and
starts about 85 days before ovulation ; this recruitment follows endocrine criteria
(estrogen synthesis capacity, the level of the FSH receptors);
97. selection of a follicle from those recruited is done on the
basis of the following criteria: estrogen production (aromatization capacity);
granulosa cell content; the FSH receptors content; follicular fluid properties; blood
supply;
98. dominance manifests itself on the eighth day of the
menstrual cycle by the secretion of large quantities of 17 beta estradiol which
induces atresia of the other follicles and the peaks of FSH and LH release which
control ovulation.
80.

The endocrine functioa mf the vrmy

100.
There are two theories:
101.
A.
The theory of the two pathways
102.
Before ovulation, the nonhxeionei tissue follows the delta 5 pathway
(by pass of progesterone). The cholesterol is taken from LDL and is
99.

10

transformed into pregnenolone; the next stages are: 17 hydroxi

pregnenolone, DHEA, androstenedione, testosterone, estradiol.
103.
After ovulation and luteinization, delta 4 pathway is used (especially
on the level of granulosa) with the following steps: LDL, cholesterol,
progesterone, 17 hydroxi progesterone, androstendione, testosterone,
estradiol.
104.
B.
Two cell hypothesis
105.
cAMP, a second messenger, grows intracellular under the influence of
gonadotropins and mediates the protein synthesis required by steroidogenesis.
Ovarian estrogen synthesis needs LH and FSH activities. Granulosa contains a
system of aromatization stimulated by FSH (cellular functional synchronism of
granulosa and theca interna).
106.
E2 and FSH act together to prepare the follicle to answer to the LH
action. LH has a determinant role in achieving ovulation and corpus luteum
activity.Corpus luteum produces all categories of sexual hormones. Ovarian
stroma produces mostly androgens.
107.
There are three categories of endocrine control:
108.
1.
The classical endocrine system (the hormones are released
into
circulation being directed to the target tissue);
109.
2.
Paracrine control (local diffusion of hormones);
110.
3.
Autocrine control (hormone-like substances interacting
with
the
cell receptors, named growth factors, cibernines or regulins).
111.
We will present some potential factors controlling autocrine/
paracrine events in the ovary :
112.
> catecholamines (luteal stimulatory function);
113.
- EGF, FGF, IGF, PDGF (mitogen and growth factors);
114.
> prostaglandins and leukotrienes;
115. LH binding inhibitor;
116.
FSH binding
inhibitor; > luteinization
stimulator;
117.
> oocyte maturation inhibitor (blocks meiosis together
with cAMP); > oxytocin, arginin-vasopressin; - relaxin;
118.
->POMC derivates (ACTH, alpha MSH, beta lipotropin, beta
endorphyn);
119.
> steroids;
120.
-> P substance, VIP.
121.
A short time before ovulation the meiotic process restarts
resulting in oocyte II (23 chromosomes) and the first polar body which is released
immediately before ovulation.
122.
Ovulation is the process by which the female gamete is transferred from
the ovary into a place where it can be fertilized. Follicular rupture takes place

on the surface of the ovary by means of the follicular apex (asymmetric growth
of theca externa in the direction of the ovary surface) being accompanied by
mechanical phenomena (pellucida membrane rupture, the wall which separates
the follicular cavity from the peritoneal cavity, stigma formation), histological,
cytological, biochemical, nuclear and cytoplasmatic maturation.
123.
The ovulation leads to oocyte II release together with cells of cumulus
and granulosa and follicular fluid, elements which will be grasped by
fimbriated extremity of the fallopian tube.
124. Ovulation takes place within 40 to 60 hours from the E2 peak. This surge
occurs 24 hours before LH peak. Therefore, ovulation is placed 16-40 hours after LH
peak. The ovum can be fertilized 24 hours after ovulation. LH peak stimulates:
125.
:=> the continuation of meiosis (blocked in the diplotene
stage of prophase I);
126. => first polar
body release; => OMI
inhibition; luteinization; ovum
release.
127.
Granulosa and theca interna cells change into luteal cells to form corpus
luteum. The release of the second polar body (mitosis) takes place in the
moment of conception.
128.
During periovulatory period three essential events occur:
1. follicular rupture;
2. oocyte maturation;
3. corpus luteum formation.
129. 1. Several factors are involved in the local phenomena of follicular
130.
rupture:
131.

proteolytic enzymes (collagenase and plasmin);

132.

prostaglandins (PGE, PGF, PGI2); it is believed that

the synthesis of these compounds is stimulated by gonadotropins; PGE increases
capillary permeability, stimulates proteolytic activity, increases local smooth muscle
contractility (in the follicular wall) and facilitates rupture;
histamine works in the same conditions as PG;
bradykinine, vasoactive peptide, stimulates PG and LB4
133.
synthesis;
134.

renin-angiotensin-aldosterone system has been found

in the ovary; in the follicular fluid renin and All like activities were identified; All
has a role in pre-ovulatory growth of the follicle and in its transformation into corpus
luteum.
135.
Smooth muscle cells in theca externa are considered to have the
following functions :
136.
0 during ovulation facilitates ovulatory material expulsion;
137.
0 takes part in the corpus luteum formation and in the process of
138.
atresia;
12

139.
0 controls-the ovarian vascular tone.
2. Nuclear and cytoplasmic maturation of the oocyte is induced by LH peak.

In this process are also involved: EGF, follicular fluid steroids.

3. The transformation of the ruptured follicle into corpus luteum is essential
for a succesful reproductive phenomenon. Corpus luteum has the privilege of
progesterone synthesis. Vascular phenomena take place (granulosa invasion,
previously avascular).
140.
Cell luteinization is characterized by a growth in size of granulosa
cells and their differentiation into luteal cells which produce progesterone.
141.
142.
143.

144.
145.

1.2.

FECUNDATION

Fecundation (fertilization) is a process by which the spermatozoa

penetrates the mature ovum, nuclear and cytoplasmic element fusion resulting in a
diploid egg (zygote).
147.
In the acid vaginal medium spermatozon motility is accelerated.
Cervical mucus has the highest permeability. After several tens of minutes the
spermatozoa reach the outer segment of the tube.
148.
Three mechanisms are involved in the transfer of the cumulus
oophorus from the surface of the ovary to the fallopian tube:
149. a.the negative pressure caused by the contractions of the tubal
muscles;
150.
b.
the contractions of the tubal fimbrie;
151.
c.
the contact between fimbriated tubal extremity and the
cumulus.
146.

The tubal fimbrie being in a congestive condition can pick up the

ovum from ovarian surface and direct it by fimbria ovarica (Richard). The role of
fimbriated structures is of a great importance.
153.
The ovum is fertilized in the outer third of the tube. It is quite difficult to
state the moment of conception (as a rule it is shortly after the ovulation).
154.
The ovum is surrounded by granulosa cells. For the penetration to take
place it is necessary to exist some fibrinolisins produced by the tubal
epithelium. After sperm penetration through the cumulus oophorus the sperm
interaction with zona pellucida takes place. This physical and chemical
phenomenon is possible due to the interaction of a glycoprotein (fertilisin)
synthesied by the zona pellucida and to some enzymes existing on the
spermatozoon head.
155.
Acrosomal hialuronidase destroys hialuronic acid from the
external portion of zona pellucida. Enzymatic processes are associated with a
mechanical force of penetration.
152.

After penetrating zona pellucida, the spermatozoon head enters the

perivitelline space to attach itself to the vitellus where it will be gradually
incorporated.
157.
The flagellum disapears and the head is transformed into the male
pronucleus which will be placed in the middle of the cytoplasma.
156.

The penetrated oocyte releases the second polar body and its
nucleus becomes the female pronucleus. The two pronuclei form the first diploid eel!
(XX or XY + 44 autosomes) which is immediately followed by the first mitotic
division resulting in two blastomeres (two cell stage) about 30 hours after
fertilization.
158.

159.
160.
161.

162.

1.3. SEGMENTATION AND

MIGRATION

163.

164. Segmentation (cleavage) continues during the tubal migration -'iergoing

the four and eight cell stages. From this stage division becomes uniform and we
can see:
=> micromeres - clear, small cells, which multiply quickly
forming XL outer mass of cells (trophoblast);
165.

166.

=> macromeres - dark, large cells, forming an inner cell mass, the

embryo.
In this period the egg cells are grouped together forming a sphere
named morula (12-16 blastomeres) on the outskirts of which still exists a thin zona
pellucida.
168.
The next events are:
167.

169.

170. blastocyst cavity formation between the embryo and

trophoblastic
171.
cells having a fluid content; zona pellucida disappears;
172.
-> macromeres from the embryo button, placed at one end of the
egg;
174.
- the egg reaches the uterus (the transport lasts 3-4 days). The tubal
transport (migration), a result of the muscle contractility, is under the control
of several factors:
steroids (E2 and progesterone);
catecholamines (the tube has alpha and beta adrenergic receptors);
PG (PGF2alpha stimulates contractility, PGE2 inhibits it);
VIP with an inhibitory effect;
173.

14

 Y neuropeptide inhibits adrenergic action;

P substance with positive effect;
cAMP stimulating and cGMP inhibiting effects;
oxytocin stimulates tubal contractility;
muscular activity is supported by epithelial cilia.
175.

176.
177.

178.

2. IMPLANTATION. DEVELOPMENT
OF THE EGG AFTER IMPLANTATION
179.

180.

The second week

182.
In the uterine cavity the egg remains free for about three days.
From the fecundation to the implantation there are about seven days.
183.
The implantation of the egg represents the period of time in which it
attaches on the uterine wall establishing vascular connections which will form
the future placenta.
184.
Implantation takes place in four stages:
1. pre-contact stage (preimplantation) in which the egg is in the proximity
of the implantation site;
2. attachement or apposition stage: the blastocyst is in close contact with the
uterine epithelial cells;
3. nidation (endometrial invasion or the real implantation): the blastocyst
penetrates gradually into the endometrium which undergoes the decidual
transformation;
4. placentation: around the trophoblastic proliferations endometrial vascular
sinuses open creating a connection between endometrial vessels and trophoblastic
lacunae.
185.
l.In the preimplantation stage the two tissue categories
(endometrium and trophoblast ) are characterized by proliferation and differentiation
in order to produce some specialized epithelia for the function of transport. In this
phase the apical membranes of the two epithelia are not in contact. The blastocyst is
fed by grasping on the basis of the uterine secretions.
186.
The implantation begins when the two adjacent membranes adhere
(zona pellucida is lost on the sixth day and the attachement starts on the sixthseventh day from the time of ovulation).
187.
The implantation needs a perfect synchronization of the
modifications of the endometrium and blastocyst. There is an endocrine
181.

16

188. profile of the implantation in which the most important role is played by the

luteal secretion of E2 and progesterone. The blastocyst is able to produce these

hormones as well as PG and PAF.
189.
PAF (Platelet Activating Factor) is a lipid mediator synthesized
during preimplantation stage, and interferes in the following processes:
190.

platelet activation ;
191.

release of some biological active agents (PDGF, TGFbeta,

fibronectine) in cellular adhesivity, the growth of the trophoblast and its invasive
capacity;
192.

control of PG synthesis.
193.
The preimplantation process is also influenced by other biological
active substances : PP12, PP14, IGF, RLX, PRL.
194.
' In the period of preimplantation, the endometrium undergoes a
secretory transformation, an obligatory modification in view of nidation:
195.
0 a massif load with glycogen and its release into the glandular
196.
cavity;
197.
0 stromal oedema;
198.
0 increase of the vascular permeability, enlarged capillary
network and twisted arterioles;
199.
0 apical membrane modifications (proteins involved in cellular
adhesivity, gap junctions);
200.
0 stromal cells differentiate becoming decidual cells and having
endocrine and immunological roles.
201.
Before attachement, a rapid proliferation of trophoblast takes
place. The trophoblast cells change into cytotrophoblast (CT) and
syncytiotrophoblast (ST). ST results from CT and has a multinuclear
protoplasmatic mass shape placed at the outer side, capable to produce substances
which can erode maternal tissues (proteolitic enzymes). It is clear now that the CT is
the germinal cell and the ST, the secretory cells, are derived from the CT.
202.
2.
The attachement to the endometrial epithelium represents
the initial step of the implantation.
203.
3.
Nidation takes place in three ways:
204.

intrusive invasion during which the trophoblast invades the

uterine intercellular space without cellular lysis;
205.

displacement invasion by trophoblast phagocytosis of

uterine cells;
206.

fusion invasion, during which the ST fuses with the uterine

cells giving rise to a syncytium made of cytoplasmic material and trophoblastic
nuclei (probably, the human model).
The common element of the three ways is the onset of the apical
membrane attachement. At the end of the first week, the blastocyst is superficially
207.

17

implanted on the level of the uterine body towards the fundus (the implantation
abnormalities induce the ectopic pregnancy or placenta praevia).
208. The accomplishment of implantation takes place during the second week. The
differentiation of the two trophoblast components progresses: > CT, with mitogen
activity, induces the increase of ST mass; j> ST has no mitosis.
209. The endometrium changes and takes the name of decidua (due to its
temporary existence the decidual tissue has been named "caduca"). The decidua is
characterized by: stromal edema;
210.
=> chorion modifications;
211.
=> presence of decidual cells (large cells, up to 100 microns),
originating in the uterine mucosal chorion which multiplies beginning with the
implantation zone, involving the whole compact layer (the phenomenon of
decidualisation). The deepest part of the endometrium, spongy layer, where
the glands remain, will be the place of cleavage during the third stage of labor.
212.
During the second week the blastocyst undergoes the following
transformations: the cells of the embryonic button differentiate into two distinct
strata, the endoderm, the deep one, and the ectoderm, the outer one being in contact
with the trophoblast. These two folds form the embryonic
213.
disc.
214.
The space between the trophoblast and the embryonic disc
contains mesenchymal tissue (extra-embryonic mesenchym) where the cavity of the
extraembryonic coelom is formed.
215.
Between endoderm and ectoderm the amniotic cavity develops.
On the deep side of the endoblast Heuser membrane is formed which will delimit the
primitive yolk sac (exococlomic), a cavity which will be lined with endoblastic cells
and will become the lecytocel.
216.
Inside ST isolated spaces (lacunae) appear where maternal blood
accumulates from the capillaries and, also, eroded gland secretion. This
nutritive fluid (embryotroph) reaches the embryonic disc by diffusion.
217.
The opening of the uterine vessels into the ST lacunae represents
the onset of the utero-placental circulation (the 9 day).On the 10 th day, the egg is
completely integrated into the endometrium. The epithelium restores and the
implanted egg induces a small deformity into the uterine cavity. The lacunae fuse
forming a lacunar network, the future itervillous space.
At the end of the second week, due to the proliferation of CT inside ST,
the solid primitive villi develop (the 13th-14th days).

218.

219.
220.

The

v
third week
221.
At the beginning of this week gastrulation occurs, whose
essential element is the formation of mesoderm (by cellular migration from the
ectoderm). The embryo is trilaminar.

18

In the point where the caudal segment of the embryonic disc

fuses with the lecytocel allantois, endoblastic diverticle appears. The disc turns into
the tube and isolates itself from its adnexa remaining connected with them by the
future umbilical cord.
223.
From the I5lh day, the solid primitive villi are invaded by
mesenchymal cells changing them into secondary villi, which cover the whole
surface of the chorion. Angiogenesis having occurred in situ from the mesenchymal
cores, the resulting villi are termed tertiary. These vessels will make the liasion with
the embryo heart.
224. CT cells proliferate beyond ST forming the cytotrophoblastic shell at
225.
the boundary of the chorion with the endometrial tissue.
222.

226.

227. The fourth week

The exocoelom decreases being pushed away from the increasing

cavity which surrounds the embryo.The lecytocel divides into umbilical vesicle and
the primitive gut connected by the vitelline duct.
229.
The allantois advances into the embryo pedicle together with the
mesenchymal tissue which will be the origine of umbilical vessels. The latter will
unite with the vascular network already formed into the villi which represents the
future feto-placental circulation (the 21sr day).
228.

230.

The fourth to eighth weeks (The embryonic period) Each

of the three laminae will differentiate into tissues and organs: => ectoderm:
nervous system, epidermis, medulla of adrenal; => endoderm:
gastrointestinal tract, liver, pancreas, gonads, dermis; => mesoderm:
skeleton, muscles, connective tissue, cardiovascular
232.
and urogenital systems.
231.

233.

During the second month, the essential morphogenesis processes

are
produced. The exocoelom disappears as a result of the developing
amniotic cavity. Vitelline vesicle attaches to the placenta and will degenerate.
From the allantois will remain the umbilical vessels.
235.
During the eighth week miometrial invasion by the extravillous
trophoblast begins in the vicinity of the implantation zone. The CT invades the walls
of the spiral arterioles, the future utero-placental arteries. These regressive
modifications of the arterial wall consists of the incorporation of interstitial
(extravillous) CT in the artery and /or into the perivascular space. Failure of the
trophblast to invade the spiral arteries has been suggested to be the primary cause of
PIH.
234.

19

This physiological phenomenon (vascular wall degradation) takes

place*to create an adequate maternal blood supply required by a normal fetal
development.
237.
The newly created egg consists of:
> the fetus;
> the fetal adnexa: placenta, membranes, umbilical cord, amniotic
238.
fluid.
236.

20

239.

3. PLACENTATION. PLACENTAL
240.

FUNCTIONS
(TRANSPORT)
241.

242.

3.1. Placentation

243.

It is an essential process which takes place during the first four

months of pregnancy. Its accomplishment requires 3 conditions:
245.
> the presence of a good quality trophoblast;
246.
- the normal development of the utero-placental circulation;
247.
> a normal functioning fetal-placental circulation.
248.
Placenta represents the site where maternal-fetal exchanges take
place. As it has been pointed out, placenta is a fetal organ which develops at the
same time with the embryo.
249.
The human type of placentation is hemochorioendothelial (maternal
blood directly bathes the ST which in its turn are separated from fetal blood
by the wall of the fetal capillaries).
250.
The trophonblast, the outer stratum of the blastocyst, consists of
the above mentioned cellular types (ST and CT).
251.
The placental development has two stages : pre-Iacunar and
lacunar. The primitive villi appear in the 14l day, being radially disposed from the
egg periphery to the maternal tissues and in contact with the maternal blood, the
utero-placental circulation being induced.
252.
The next stages are secondary and tertiary villi formation (during
the third week). The trophoblastic lacunae unite to form a continous space, limited
by ST, the intervillous space. This space has as its roof a cellular mass in contact
with the embryo, chorionic plate, and as its floor, cellular stratum in contact with
decidua basalis (maternal side).
253.
The connection with the embryo heart is made by tertiary villi vessels
and allantois vessels (the 21st day). Most villi arboresce and end freely in the
intervillous space without reaching the decidua or may be fixed on the uterine
wall by means of cytotrophoblastic shell (anchoring villi).
244.

21

From the eighth week, decidua (caduca), according to the

topography, differentiates into:
255.
=> decidua basalis (the area corresponding to the implantation side)
which separates myometrium from trophoblast;
256.
=> decidua parietalis, existing in the rest of the uterine cavity;
257.
=> decidua capsularis, corresponds to the surface of the egg on
the opposite side, having implantation in view. It protrudes into the uterine cavity
and the growing egg will attach to the parietalis decidua at the end of the first
trimester.
258.
The villi in contact with the decidua capsularis cease to grow and
undergo almost complete degeneration becoming chorion laeve, beginning
with the second month.
259.
At the end of the second month, decidua capsularis unites with the
decidua parietalis (uterine cavity is completely closed). The chorion disposed
towards the decidua basalis will represent the fetal component of the placenta,
with arborescent villi, chorion frondosum.
260.
The maternal component of the placenta is formed from the
decidua basalis.The compact layer of the decidua basalis develops and is called the
basal or decidual plate.
261.
During this period there is also some regression of the
cytotrophoblastic'elements in the chorionic plate and the cytotrophoblastic
shell, but clumps of cells persist in the latter location to form the
cytotrophoblastic cell islands that are found embedded within the fibrinoid
layer of Nitabuch (a continous fibrin layer placed between cytotrophoblastic
shell and decidua basalis).
262.
Cytotrophoblastic cells continue to migrate from anchoring villi and
from the cytotrophoblastic shell into the decidua and myometrium to play a
key role in the development of the maternal blood supply to the placenta.
263.
Until near the end of the third month, the chorion laeve remains
separated from the amnion by the exocoelomic cavity. Thereafter, the amnion
and chorion are in intimate contact. In humans, the chorion laeve and amnion
form amniochorion (fetal membranes) which is an important site of transfer
and of metabolic activity.
264.
It is important to note that the chorion laeve does not extent over the
placental surface. The amnion is in direct contact with the adventitial surface
of the chorionic vessels and the chorionic plate on the fetal surface of the
placenta.
265.
From the chorionic plate there emerge about 15-30 villi trunk
grade L Each trunk divides into several branches parallel to the chorionic plate,
trunks grade II. These trunks produce 20-40 trunks grade III directed towards basal
plate having numerous ramifications. These villous arboiescenses are disposed in
such a way as to form a complex named placenton. Each placenton has a
corresponding intervillous space centrifugally perfused (named also cotyledon).
254.

22

The villous tree ends into terminal villi with diameters of 30-80
milimicrons which possess capillaries occupying half of the stroma. Mesenchymal
villi generate all types of villi and maintain their plasticity until the end of pregnancy.
266.

267.
268.
269.

270.

Placental - fetal circulation

271.

Fetal blood flows to the placenta through the two umbilical

arteries, which cany deoxygenated or venous-like blood. At the juncture of the
umbilical cord with the placenta, the umbilical arteries branch forming 16-24
chorionic arteries.
273.
In this zone there exists an 1:1 ratio of artery to vein. Immediately
before, or just after entering the chorionic plate, the two umbilical arteries are joined
by a transverse anastomosis, referred to as the HyrtI anastomosis.
274.
Chorionic branches give 60-70 arterial and venous ramifications which
pass through the chorionic plate and are called the truncal vessels. Each
truncal artery supplies one cotyledon. There is a decrease in smooth muscle of
the vessel wall and an increase in the caliber of the vessel as it penetrates
through the basal plate.
275.
The loss in smooth muscle continues as the truncal arteries branch into
the rami. The same is true of the vein walls. There is a capillary network in the
terminal divisions. In these segments, blood circulates slowly, a phenomenon
destined to increase feto-maternal exchanges. The blood, with a significantly
higher oxygen content, returns to the fetus from the placenta through the
single umbilical vein.
276.
In the fetal-placental blood flow regulation there are involved a
lot of factors : blood volume, coloid osmotic and hydrostatic pressures, hypoxemia,
cathecolamines, serotonin, oxytocin, arginin-vasopressin, A II, PG, endothelins
(peptides produced by the endothelium), ANP (atrial natriuretic peptide),
vasorelaxant and stimulator of water and natrium deprivation.
272.

277.

tero - Placental circulation characteristics

(Maternal - placental circulation particulars)

278.

The uterine artery through its branches (5 to 14) sends towards

uterus helicoidal collaterals which unite into an arcuate system. From the latter
emerge radial arteries which are directed towards the uterine cavity. In the vicinity of
the decidua there appear basal arteries involved in nutrition and spiral (coiled)
arteries, which before entering spongi layer display enlarged portions.
280.
At term, placenta is irrigated by about 120-150 spiral arteries.
The enlarged segment extends into the compact layer ending at the level of the basal
plate in the form of an ostium widely opened into the intervillous space.
281.
The spiral arteries deeply modify themselves and., after the
trophoblast invasion, have only a slight resemblance with the known vascular
structure. The trophoblast invasion of the utero-placental vasculature appears to
279.

23

occur in two stages. The decidual segments are structurally modified during the first
trimester and later in the second trimester, a second wave of endovascular
trophoblast begins to modify the myometrial segments of these vessels.
282.
The maternal blood flow enters the central area of the placenton
under the form of jets, being distributed towards the periphery. The relative failure in
oxygen at the perifery of the placenton is a stimulus for terminal villi formation.
283.
The adjustement of the placental blood flow to fetal growth is a
characteristic of normal pregnancy. Placenta is an organ without any
innervation. Maternal-placenta! circulation control is made by local and
umoral mechanisms:
284.
=^> the estrogens induce flow increase, while cathecolamines decrease
it;
285. PG act in a different way according to the extra or intra
myometrial segment (PG 12 vasodilator, TX vasoconstrictor), calcium channel
blockers are vasodilators, Mg vasodilator too, All is an important vasoconstrictor.
286.

Architectural study of the placenta The chorionic plate

(fetal surface)
287.
It is relatively flat and represents the support for chorionic and
villi vessels. It is limited by the insertion of the membranes and has two overlying
strata:
=> a gelly-like one, acellular, covered by amniotic epithelium,
containing branches of the umbilical vessels;
289.
=> a fibrous one in a continuum with villous stroma towards
intervillous space, being covered by ST and Langhans fibrinoid.
290.
The insertion of the umbilical cord on the chorionic plate is usually
central or paracentral (otitside it, the insertion is velamentous).
288.

291.

292.

The villous massif

293.

It develops together with the intervillous space. The mechanisms

of the villous development are numerous and the formation of the new villous trunks
is possible until the end of pregnancy.
295.
Recent researchers have reached the following conclusions :
296.
>
mesenchimal villi represent the starting point for the
growth and differentiation of all types of villi;
297.
>
the process of differentiation leads to the extension of the
villous
298.
tree and to its maturation.
299.
The terminal villi (functional placental units) growing, will form the
vasculosyncytial membranes (fetal capillar enlarged plus ST) which facilitates
closer relationships between the maternal and fetal circulation.
294.

300.
301.

The intervillous space

24

302.

It is the place of the maternal blood circulation, entirely lined with ST

and has fibrinoid deposits: Langhans fibrinoid on the chorionic plate and
Rohr fibrinoid on the basal plate.
304.
At the periphery, the intervillous space contains less villi and
more important deposits of fibrinoid. Such deposits can be seen even in the central
areas and represent up to a point normal aspects. They play a part in the processes
of" villous repair " and in the trophoblast functions.
305.
Deposits in excess have a pathological significance (chronic
villous inflammations, fibroid necrosis).
306.
The arterial blood reaches the intervillous space with a 70-80 mm
Hg pressure through about 120 utero-placental arteries enlarged when they penetrate
the basal plate. The opening is normally made in the center of the cotyledon. At the
periphery of the cotyledons into the basal plate, venous oriffices opened (8mm Hg
pressure). Inside the intervillous space the blood pressure is about 10mm Hg, while
inside villi the pressures are 48mm Hg (arterial), 24mm Hg (venous).
303.

The maternal blood flow is about 600-800ml / min.

Conclusion : The maternal blood entering through the basal plate
is driven by the head of maternal arterial pressure high up toward the chorionic plate
before lateral dispersion occurs. After bathing the chorionic villi, the blood drains
through venous orifices in the basal plate and enters the uterine veins. The spiral
arteries are generally perpendicular and the veins parallel to the uterine wall, an
arrangement that facilitates closure of the veins during a uterine contraction and
prevents squeezing of essential maternal blood from the intervillous space.
307.
308.

309.

310.

The basal plate (maternal surface)

311.

It corresponds to the maternal and fetal tissue junction and is

formed by the fusion of the chorion with decidua basalis. At term, one can see the
following structures of the basal plate:
313.
=> ST (lining the intervillous space);
314.
=> Rohr fibrinoid;
315.
=^> remnants of cytotrofoblastic shell;
316.
=> Nitabuch fibrinoid (which separates the maternal tissues from the
fetal ones);
317.
=> remnants of the decidua basalis.
318.
From the basal plate, originating in CT the intercotyledonary septae
emerge towards the intervillous space without touching the chorionic plate.
They divide that space into about 30 cotiledonary cavities each containing a
complete villous tree.
319.
Inside the basal plate, several categories of cells intermingle. Among
them we mention the macrophages which are considered to have several roles:
320.
local immunological protection;
321.
> intrauterine immune suppresion, probably by PGE 2
production; - enzymatic activity.
312.

25

At the periphery of the placenta the basal and chorionic plates

adhere closely. On this level a fibrinoid crown is produced forming the Winkler
obliterating ring.
322.

323.

324.

The macroscopic anatomy of the placenta

325.

Examined after delivery, placenta appears as a fleshy organ

having the form of a disc or an ellipsis with a diameter of 18-20cm, a central
thickness of 3-4cm and the peripheral one of 5-6mm.
327.
The normal weight at term is about 500-600g (1/6 of the fetus weight).
328.
The placenta has two surfaces: a fetal one, which is smooth, glossy,
lined with amnion through which we can see the great calibre superficial
vessels ; on this side the ombilical cord is inserted (80% centrally);
329. the maternal one, with a fleshy aspect due to the
cotyledons,
330.
separated by ditches.
331.
The placental edge corresponds to the caduca junction and
membrane insertion.
326.

332.

333.

The microscopic study of the chorionic villous

334.

The chorionic villous is the fundamental element of placenta. In the

second month, stroma consists of a lax connective tissue containing the
branches of umbilical vessels (one artery and one vein) having a rich capillary
network.
336. There are Hofbauer cells in stroma. These cells have a vacuolated cytoplasnia
and various granular inclusions. Their origin is not clarified (mesenchymal or from
hematopoietyc system). Hofbauer cell functions are: 0 endocrine or / and secretory; 0
control of the stromal content of water; 0 modeling of the stromal components; 0
transfer of intercellular information; 0 fetal nutrition; 0 phagocytosis; 0
immunologic. The villous wall (trophoblast) has two layers:
a superficial one (ST), an irregular protoplasmatic mass, containing nuclei
and various proliferative zones ;
a deeper one (CT) (Langhans stratum), polyedric large cells, well
delineated, arranged in one row, with a clear nucleus; CT function is to form ST.
337.
During the fifth month, the villous structure has the following
335.

16.

characteristics:
338.
-> stroma becomes denser;

26

- capillaries multiply;
Hofbauer cells decrease in number;
339.

> ST becomes thinner;

341. > CT disrupts in some areas, facilitating closer relationships between the
fetal vessels and the maternal blood. At term:
> thin villi;
> connective core much reduced;
capillaries with a rich blood content;
> ST thin and disrupted (vasculosyncytial membranes).
342.
Electron microscopic studies reveal a ST with a " brush border "
made of microvilli. On this level there are transport vesicles, lisosomes. The
microvillositary surface represents the interface between the maternal and the fetal
blood, being vitally involved in the absoiptive processess of nutrients, O: transfer,
immunological protection, hormonal secretion and release.
343.
The microvillous side has enzymes, receptors, small channels,
junctional elements. Deep into ST there are nuclei, mitochondria, ribosomes.
endoplasmic reticulum, secretory droplets and elements illustrating enzymatic
activity and intense metabolic processes.
344. ST and CT lie on a basal lamina which delimit them from the stromal core.
Between maternal and fetal circulations the following strctures interfere: ST;
345.
=> CT (frequently
absent); => basal lamina; ^>
stroma;
346.
=> capillary epithelium.
347.
In summary, as pregnancy progressess, the placental membrane
undergoes the following changes:
348.
> the CT ceases to form a continous layer after about 12
weeks;
349.
the relative amount of connective tissue in the core of the villi is
reduced;
350.
- the number and size of fetal capillaries increase;
351.
> some fetal capillaries fuse with the ST to form areas thought to be
important in the gaseous exchange.
352.
As the human placenta matures, the placental membrane may be
reduced anatomically to a thin covering of trophoblast, capillary wall and
trophoblastic and endothelial basement membranes separated by mere wisps of
connective tissue.
353.
The term barrier as applied to placental physiology should
therefore be replaced by the more accurate term, placental membrane.
Furthermore, :he number of layers is a poor index of the true approximation of the
fetal and maternal circulation.
340.

354.

3.2. PLACENTAL FUNCTIONS

355.

Placenta is the organ which makes the connections between the

maternal organism and fetus in the framework of the maternal - placental -fetal unit.
356.

27

357.

358. The transport function

359.

By facilitating the transfer between the maternal and fetal

circulations, placenta achieves an essential function in the fetal growth and
development.
361.
ST is the fetal tissue interface of the placental arm of the
transfcellulary transfer. Recently, the pathways of an extracellular transfer (channels
going through the trophoblast) have been revealed.
362.
The multiplication of villi and capillaries, the gradual decrease in
the villous wall thickness increases the possibility of diffusion. ST is a complex
structure having multiple functions and a great metabolic activity. Vasculosyncytial
membranes, areas where ST is thin, without nuclei, in contiguity with capillary
endothelium formed towards the 32th week.
363.
Placenta acquires a functional maturity only after the uteroplacental circulation comes into being. At the end of pregnancy, maternal circulation
has a flow of 600-800ml / min and creates a permanent structural and functional
adjustment of villi to hemodynamic conditions.
364.
The maternal circulation plays an active role in the formation of
placentons. The utero-placental arteriols open at the basis of the placental lobe and
the blood diffuses centrifugally at the periphery of the system an area where the flow
speed is reduced and terminal villi are more numerous.
360.

365.

366.
Modes of transfer across the placenta:
367. simple diffusion (O2, carbon dioxide, anesthetic gases, water,

most of the electrolytes) ;

368.
> facilitated transfer (glucose);
369. active transport (aminoacids, calcium); > receptor facilitated
endocytosis (immune gama globulin G, iron); - membrane disruption
(uncommon); -> restrictive diffusion (hypothetical transmembrane
channels). We will present briefly the transfer of some important elements.
370. Oxygen
371.

The mechanism of O2 transport is the simple diffusion. The O2

necessary to the uterus and its content at term is about 20ml / min of which
two thirds are trasferred to the fetus. This transfer may be influenced by
several factors:
373. the geometrical arrangement (multivillous flow):
374.
=> PO2 of uterine and umbilical venous blood;
375.
=> the rate of maternal blood flow through the intervillous space;
376.
=> the characteristics of fetal and maternal hemoglobin;
377.
=> the area available for exchange across the villous trophoblast
epithelium { villous area is about 12 square meter);
378.
=> the O? necessary of placenta.
372.

28

The fetus is endowed with a great capacity of maintaining the proper O2

necessary. HbF has a great affinity for O2 and the fetus has increased
possibilities to extract O2 in cases of hypoxemia. The chronic reductions in O2
supply are elements of IUGR physiopathology.
380.
The fetal hemoglobin O2 dissociation curve (Barcroft) is displaced to
the left, a fact which facilitates the intake and storage of O2. Fetal blood
accepts O2 with a lower PO2 in comparison with the maternal blood.
381.
The placental tissue requires a high rate of O2 necessity.
382.
In the circumstances of reduced O2 supply to the fetus, a great
part of the umbilical venous blood is diverted through ductus venosus (Arantius).
avoiding liver, to the heart and the upper part of the body. At the same time the
cathecolamines secretion increases facilitating vessel constriction. A preferential
tissue perfusion is achieved.
379.

383.
384.

385. Carbon dioxide

386.

CO2 transfer between mother and fetus has been studied less
extensively. The diffusion constant of CO2 is 20 times higher than that for 02.
The placenta is highly permeable for CO2, which traverses the chorionic villus
more rapidly than does O2.

387.

Fetal blood has a somewhat smaller affinity for CO? than does the blood
of the mother, thereby favoring the transfer of this gas from the fetus to the
mother.
389.
Although CO2 is present in the blood in the form of dissolved gas,
carbonic acid (the most important metabolite produced by the organism).
388.

bicarbonate ion, carbonate ion and carbaminohemoglobin, experimental

evidence indicates that only the dissolved gas diffuses across the placenta in
significant amonts.
391.
Transfer of CO2 is facilitated by the simultaneous uptake of O2
(Haldane effect). This fact protects the organism against acidification.
390.

392.

393. Water

transfer

394.

Water exchange across the placental membranes occurs rapidly.

In human pregnancy the rate rises progressively reaching a peak of 3.51 / h at 35
weeks, then falling to 1,51 / h towards term.
396.
Exchange of water is critical as any major physiologic insult to the
mother may be reflected in the fetal status. Thus severe dehydration or over
hydration (particularly with the use of salt-free solutions in labor) will have
major impact on fetal homeostasis and could lead to fatal consequences.
397.
Although experimental observations have demonstrated that
water crosses the placenta in response to an artificially imposed osmotic gradient, it
has not been possible to obtain direct evidence that this is the mechanism for the net
transfer of water to the fetus required for its growth.
395.

29

398.

399. Carbohydrate

transfer

400.

The major metabolic fuel for the fetus is glucose. The molecular
weight of glucose and its high polarity suggest that the diffusion rate across the
placenta would be rather slow and perhaps inadequate to meet fetal metabolic
requirements.
402.
In humans, the concentrations of glucose in maternal blood is
consistently higher than that in the fetal blood, which is compatible with a purely
diffusional process for glucose transport.
403.
However^ the D-glucose transport occurs much faster than for
molecules of comparable molecular weight and polarity which is not compatible
with a diffusional process.
404.
The transfer of D-glucose is accomplished by a carrier-mediated,
stereospecific, nonconcentrating process that can be saturated-facilitated diffusion.
405.
Transporter proteins for D-glucose have been isolated from the plasma
membrane of the microvilli of human trophoblasts.
406.
Maternal glucose is the principal supplier of energetic substratum
for the fetus. At term, the placental transfer is of 20mg / min ( about 30g / day ).
401.

A normal transfer of glucose represents an essential condition for

normal fetal growth.
408.
In the glucose transfer control there are, probably, involved : the
maternal and fetal insulin, GRH, glucocorticoids, progesterone, estrogens HCS
(HPL) and concentration gradients.
409.
Fructose is not used as a fetal fuel or as building material in significant
amounts, except perhaps during periods of fetal hypoglicemia.
407.

410.

411. A minoacid transfer

412.

All fetal proteins, with the exception of some immunoglobulins, are

synthesized from maternally derived aminoacids transferred across placenta
and present in the fetal plasma in larger amounts than in the maternal plasma.
414.
The placenta also concentrates a large number of aminoacids
intracellularly and the fetal uptake of aminoacids may depend to some extent
on this concentrating capacity.
415. The placental aminoacids transfer is of 3 categories: => simple
diffusion; => Na-dependent system; =^ Na-independent system. In the
IUGR, the supply is reduced by an abnormal placental transfer.
413.

416.

417. Proteins
418.

Generally, the transfer of larger proteins across the placenta is

very limited. There are important exceptions. A major one is immunoglobulin G (Ig
G). In humans, Ig G crosses the placenta in great amounts.
419.

30

420. Near term, Ig G is present in approximately the same concentrations in

cord and maternal sera. Ig A and Ig M are considerably lower in cord serum.
Although Ig A and Ig M of maternal origin are effectively excluded from the fetus, Ig
G crosses the placenta with considerable efficiency.
421.
Fc receptors are present on trophoblast (ST) and the transport of
Ig G is accomplished by way of these receptors through a process of endocytosis.
422.
Ig G transport from mother to fetus begins at about 16 weeks gestation
and increases as pregnancy proceeds (the bulk of Ig G is acquired by the fetus
during the last 4 weeks).
423.
The steps of receptor-mediated endocytosis:

31

424. binding of ligand to receptor ; the receptors aggregate on the cell

surface and collect in specialized membrane structures termed coated pits;

425.
> these coated pits, which contain the protein clathrin at their
cytosolic bases, are invaginated, pinch off, and enter the cell (the plasma membrane
segment that has been pinched off is called a coated vesicle);
426.
-> the coated vesicles shed their clathrin coats and fuse with one
another to form endosomes; the endosomes move deeper into the cytoplasm;
427.
- under the influence of their acidic environment the ligand is
separated from its receptor.
428.

429. Lipids
430.

431.

432. Neutral fat (triacylglycerols) does not cross the placenta but glycerol

do^s. The extent of transport of free fatty acids is not known. The LDL particles are
taken up by a process of endocytosis. Cholesterol is used in progesterone synthesis.
433. The concentration of arachidonic acid in fetal plasma is greater than in
maternal plasma (arachidonic acid is a component of membranes and an eicosanoid
precursor).
434.

435.

Vitamins and minerals

436.

437. The fetus needs vitamins and minerals' which are necessary as cofactors

or coenzymes for the various anabolic and catabolic pathways. The transfer of the fatsoluble vitamins are assumed to be similar to those for lipids.
438. The fat-soluble vitamins are transported in the maternal plasma as
lipoproteins complexes. The levels of these vitamins in the fetal blood are lower than
in the maternal blood.
439. The water-soluble vitamins are found in the fetal blood in levels higher
than those in maternal blood, indicating that transfer may be active.
440. Most of cations and anions are transported across the placenta with
relative ease. Ionized calcium levels are higher in fetal than in maternal blood. The
basal membrane of the ST has an ATP-dependent Ca++ transport system. This system
has a high affinity for calcium and as such is capable of interacting with calcium
found within the trophoblast cells.
441. The placental transfer of calcium is influenced by : metabolites of
vitamin D (1,25-dihydroxycholecalciferol), parathormone, prolactin, calcitonin.

32

442.

443. Iron (Fe++, bivalent) is transferred preferentially to the fetus by

a receptor-mediated endocytosis mechanism and achieves a higher

concentration there than in mother. In maternal plasma Fe++ is bound to
transferrin, which binds to receptors on the trophoblast.
444.
The net transfer of magnesium is against a concentration gradient, so it
is an active transport.
445.
Copper crosses placenta with relative ease. Zinc is transferred
apparently much more slowly.
446.
The concentrations of the phosphates are much higher in fetal than in
maternal plasma (phosphates are important in fetal nutrition).
447.
Certain toxic metals (mercury and lead) appear to cross the
placenta
448.
readily.
449.

450. Conclusion

The placenta is unique in its role separating the mother from the fetus
yet allowing a range of interactions to occur between the two separate
biological organisms while maintaining normal hormonal, nutritive
respiratory and excretory functions necessary to fetal growth.
452.
Ultimately, the fetus is essentially dependent on the nutrients that
are able to cross the placenta. The fetus depends on the exchange through the
placental membrane to dispose waste products it cannot yet handle.
453.
Items essential to fetal growth, aminoacids and some vitamins
and minerals are actively transported. Waste products such as creatinine and
bilirubin, which the fetus is too immature to handle, are actively returned to the
mother to be excreted.
451.

34

4. ENDOCRINE FUNCTION OF THE

PLACENTA. PLACENTAL IMMUNOLOGICAL
455.
PHENOMENA
454.

456.

457.

4.1. ENDOCRINE

FUNCTION OF THE PLACENTA

458.

The endocrine modifications characteristic to human pregnancy

are among the most remarkable ones in the physiology of mammals. At present, it is
known that the human placenta produces more than 30 hormones and possesses
receptors for almost all regulated factors. Placenta is the major endocrine organ
during pregnancy.
460.
Villous ST and CT are main sources in the hormone production.
The endocrine repertory of these structures differs. Th placental and fetal endocrine
processes cannot be evaluated separately, they should be included in the matemalplacental-fetal-unit.
461.
Placenta produces steroid hormones, protein hormones as well as
cytokines and growth factors.
459.

462.

463. Biosynthesis of steroid hormones

464.

From a hormonal point of view, the evolution of pregnancy can be

divided into two periods:
466.
=> the first, corresponding approximately to the first trimester, is
characterized by the presence of corpus luteum and trophoblast;
467.
=> the second, is the period in which in the hormonal balance the
differentiated fetal organs are involved especially the liver and fetal adrenal.
468.
An important requirement for the maintaining of pregnancy is that
the normal function of the corpus luteum, mainly the progesterone secretion, should
be extended until the placental steroids can sustain gestation by themselves.
469.
The increase in HCG provided by the blastocyst on the point to be
implanted, interrupts luteolytic phenomena, the activity of corpus luteum
-being amplified. The transfer of the luteal function to the placenta is
completely achieved on about the fiftieth day of pregnancy.
470.
In the middle and late periods of gestation, the complete
steroidogenesis occurs together with the fetal participation into the MPFU.
471. Estrogens
465.

472.

Placenta synthesises E starting from the precursors C19 steroids

(DHEA-S) having a fetal or maternal origin. Fetal adrenal produces daily about
75mg and supplies at term 90% of DHEA-S. The conversion of sulfated

473.

35

precursors in E, on the level of placenta, requires the action of 4 enzymatic

systems:
1. sulfatase is predominantly situated in ST ; it transforms the DHEA-S into
DHEA and 16-OH-DHEA-S into 16-OH-DHEA;
2. 3 beta-hydroxy steroid dehydrogenase is in fact an enzymatic complex (3
beta HSD - delta5,4 isomerase) which participates in the production of the
progesterone by transformation of pregnenolone and in the synthesis of
androstenedione (A4) from DHEA (A4 is transformed into estrone);
3. aromatase mediates:
474.
=> the conversion of A4 and T into E1 and E2; =^ the conversion of 16OH-A4 into E3 (estriol) ; (in the human pregnancy there are produced larger
quantities of E3 than E2);
475.
4.
17 beta hydroxysteroid oxydoreductase, an enzyme which
catalyses interconversion of El into E2 and T into A4.
476.
The trophoblast can synthesise the enzymes necessary to the hormonal
synthesis. Steroidogenesis depends on the exogen substratum, mainly on the
fetal adrenal.
477.
The most important biological effects of E: -> the control over the
synthesis and secretion of some proteins during the first trimester;
478. > the duct development in the mammary gland; -> the
cervical ripening;
479.
> influence over some factors involved in the physiology of the
normal labor:
myometrial gap junction stimulation;
positive effects in the synthesis of some receptors;
stimulation of the synthesis and release of PG;
stimulation of the synthesis of contractile proteins;
the same influence over the membrane permeability and on the
myometrial electric activity.
480.
E3 biosynthesis depends on the quality of MPFU. Due to the fact that
the precursors are in their majority of a fetal origin, it is considered that E3 is
significant in the development and the fetal well-being evaluation.
E3 represents 90% of the urinary estrogens. E3 excretion in maternal
urine in the last period of pregnancy is 10-14mg / day. Levels of 4mg / day or
lower indicate a severe pathological status or fetal death. E3 evaluation should
be made repeatedly. E3 can be evaluated in plasma by RIA.
482.
There is a test with DHEA-S which consists in quantifying the
degree of DHEA-S conversion, given to the mother intravenously, into urinary E in
24 hours. The rhythm of the response reflects the placental capacity of aromatization.
481.

483.

484.

36

Progesterone

485.

Placenta can transform cholesterol into pregnenolone and pregnenolone

into progesterone. The maternal cholesterol is the main precursor of these
steroids. It is extracted from LDL. The trophoblast has receptor sites for LDL.
In the cholesterol cleavage interferes cytochrome P450, cholesterol side chain
cleavage enzyme. In the pregnenolone transformation into progesterone acts
the 3 beta HSD / delta 5,4 isomerase system.
487.
In the last period of gestation, placenta produces daily 250-600mg
progesterone, ten times higher quantities than in the luteal phase of the cycle.
488. From synthesised P about 50% is transferred in the fetal side being used in the
mineral and glucocorticoids production. The remaining passes into the maternal side
where it is transformed into pregnanediol. The urinary pregnanediol has values of: =>
6mg / 24 hours at 6 weeks (values under 4mg are incompatible with the existence of a
functional corpus luteum); 12mg / 24 hours at 15 weeks; => 16mg / 24 hours at 20
weeks. The urinary pregnanediol reflects quite approximately the placental
production of P.
489.
The production of P depends, first of all, on the cholesterol
associated with LDL and on adequate blood flow.
490.
Estrogens increase P synthesis. Some growth factors and PG have
the same effects.
491.
P and E are the main steroid hormones produced by placenta,
essential hormones for several phenomena existing in initiation and maintaining of
pregnancy. It is believed that P is essential in maintaining pregnancy:
486.

> a local immune protection role against the graft rejection; -> a role
in the development of the placental tissue and in the increase of placental
vasculature;

492.

493.

inhibition of myometrial contractility.

494.
495.

Protein

hormones

Chorionic gonadotropin (HCG)

496.

It belongs to a group of glycoproteic hormones with similar

structures and functions (luteinizing hormone, follicle stimulating hormone, thyroid
stimulating hormone).
498.
The molecule consists of two subunits, alpha and beta. Beta
subunit is greatly responsible for determining the specificity of biological activity of
HCG.
497.

37

The main site of synthesis is ST. HCG was detected in the maternal
serum after ten days from the LH peak in the middle of the fertile cycle (a
period coinciding with the first contact between the trophoblast and the
maternal blood).
500.
Later on, the concentrations increase rapidly up to the eighth week.
Between the 8th and 12th weeks the levels remain stable and start to decrease
after the 18th week.
501.
Initially, HCG was determined in urine by biological methods,
beginning with the 45th day of gestation, hi the 5th-6n weeks, values higher than 1,500
i.u. / 1 indicate a normal pregnancy (in evolution). Under these limits we can speak
about an ectopic pregnancy or about an interruption of intrauterine pregnancy.
502.
Between 7th to 10th week the levels reach values toward 100,000
i.u. Higher values might indicate multiple gestation or hydatidiform mole. At present
measurements are made by immunological methods or by RIA.
503.
The dominant role of HCG is to stimulate the function of the
corpus luteum during the early pregnancy. Its role in the placental steroidogenesis
control hasn't been established.
499.

Clinical value of HCG determinations are linked to the early

pregnancy diagnosis and in monitoring the gestational trophoblastic disease.
505. Human placental lactogen (HPL)
506. (Chorionic somatomammotropin) (HCS)
504.

507.

-:'-v

It is a placental hormone diplaying a lactogenic activity. Its

primary structure resembles that of GH and PRL. ST is the main site of synthesis.
The placental secretion rate is considerably great, l-3g /day, the greatest of any known
hormone in humans.
509.
The concentrations in the maternal serum increase steadily until
Ih
the 34 week and then remain relatively constant. HPL interferes in the maternal
metabolisms of lipids and carbohydrates and by this in the fetal growth control. It has
proliferative effects in the mammary gland. Its role in lactogeriesis hasn't been
clarified.
510.
HPL values represent one of the best criteria to watch the
evolution of pregnancy in the third trimester. Low levels are currently associated with
pathological conditions as fetal impairement, IUGR, intrauterine death, indicating, by
repeated measurements, a chronic placental insufficiency. The best period to identify
IUGR by HPL is between 30-35 weeks (screening test).
508.

511.

38

512.

Hypothalamic-tike-releasing

hormones
513.

For each of the known hypothalamic-releasing or inhibiting

hormones described, namely GnRH, CRH, GHRH, TRH, there is an analogous
hormone produced in human placenta.
514.

515.

Gonadotropin- releasing hormone (GnRH)

517.
Its primary structure is identical with that of the hypothalamic
GnRH. CT is probably the site of synthesis (ST is the substratum of the action). The
highest placental concentrations are recorded in the interval 12-23 weeks (the same
for the serum ones).
518.
Activin (gonadal glycoprotein which stimulates pituitary release
of FSH, which is also synthesized by the placenta) amplifies GnRH release (an effect
balanced by the inhibin, another ovarian glycoprotein synthesized by placenta).
516.

The best studied function of GnRH is the physiological

stimulation of HGG production (it interferes also in the placental steroidogenesis and
in the PG production control).
519.

Corticotropin-releasing hormone (CRH)

521.
The maternal plasmatic concentrations reach the highest values during
delivery. It disappeares from maternal circulation a couple of hours after
delivery which is an argument supporting its placental origin.
522.
Another argument would be the reduced concentration present in
nonpregnant women. The synthesis site is not known (CT or ST).
523.
CRH is a potential stimulator in the pituitary release of POMC
derived peptides. CRH stimulates the production of PG and mediates its effects which
resulted in its being involved in the complex mechanism of labor initiation in
humans. In the same context it has been attributed the role in increasing the
myometrial sensitivity to the action of oxytocin.
520.

524.

Growth hormone- releasing hormone (GH)

526.
It was localized in ST. It can be detected in the maternal plasma
beginning with the middle of gestation, its levels increasing until term.
527.
It is considered that the placental GH has a major role in
controlling the maternal secretion of IGF-I and the placental transfer of glucose.
525.

528.

529.

peptides
530.

39

Proopiomelanocortin-derived

The structures of the pituitary and placental POMC derived peptides are
similar. The secretion is controlled by CRH.

531.

532.

533.

Beta-lipotrophin (Beta-LPH) and Beta-endorphin (Beta-

END)
534.
Beta-END is formed from Beta-LPH. The concentrations are higher in
the case of natural delivery in comparison with cesarean section.
535.
During labor, the increasing concentrations are obvious. This
aspect is a result of the stress state induced by labor and the large quantities of BetaEnd could realise the so called materna analgesia.
536.

Chorionic adrenocorticotropin (ACTH)

538.
In pregnancy there are three sources of ACTH : the pituitary
gland, placenta and fetus. Placental ACTH might stimulate steroidogenesis (E2 and
P).
537.

539.

Alpha Melanocyte-stimulating hormone

541.
Pregnancy is the only human physiological condition when MSH can be
detected in plasma. It has a synergetic action with ACTH and AH in increasing
aldosterone production and a trophic influence on fetal adrenal.
542. Neurohypophyseal peptides
543.
Oxytocin (OXT) Argininevasopressine ( A VP)
.
/-'.-''
.
.
~
544.
Villous ST has the capacity to synthesize and store OXT. Placenta also
synthesizes a cystine aminopeptidase (oxytocinase) which degrades OXT. OXT
possesses a stimulatory action on PG synthesis in the human reproductive
tissues.
545.
AVP has a similar structure with OXT. It stimulates the ACTH release in
the placenta.
540.

546.

547.

The polypeptide growth factors

548.

The growth factors are substances which induce proliferation and

differentiation. A great number of these factors have significant effects on the
placenta.

549.

550.

Epidermal growth factor (EGF)

552.
EGF is a polypeptide present in many fluids and tissues. There are
large quantities of EGF receptors in ST, a condition which supports the hypothesis of
their physiological actions on the placental level:
551.

40

> stimulation of HCG and HPL secretions;

> a positive effect on PG synthesis;
> improvement of placental protein phosphorylation (the
metabolic process of introducing a phosphate into an organic molecule).
553.
554.
555.

556.

Insulin
558.
As a matter of fact, it is not a growth factor but its potential
importance in the fetal- placental development and its close relation to IGF, motivate
its inclusion in the group.
559.
Placenta is an extremely rich source of insulin receptors. The
concentration of receptor increases with gestational age. The insulin receptors
appear to be located in the microvillous membrane of the ST as well as on the
microvillous brush border.
560. Insulin interferes in controlling some placental functions:
glucose transfer;
561. stimulation of 3 beta HSD
activity; => phosphorylation processes.
562.
By these functions its condition of a major factor of fetal growth
is motivated. Mitogenic influences are evident especially in the early stages of
pregnancy, while the metabolic ones are manifest in the second half of gestation.
557.

Insulin-like growth factors (IGF I and IGF II)

564.
They are structurally similar to insulin, have mitogenic properties and
the capacity to influence the condition of differentiating of the target cells by
stimulating mKNA production, synthesis and release of proteins.
565.
IGF-I was localized in ST. The maternal levels are the highest in
the third trimester. It interferes in the placental steroid synthesis, in the placental and
uterine growth and in the development of the mammary gland.
566.
IGF-II is an important stimulatory factor in the human
steroidogenetic tissue growth (fetal adrenal, placenta, ovary). It inhibits the aromatase
activity and stimulates 3 beta HSD and P450 functions.
563.

567.

R e I a x in
569.
It is a polypeptide with a structure similar to that of insulin and
close to that of IFG. It is produced by the coipus luteum but was also identified in
placenta, decidua and myometrium.
570.
The highest levels are recorded in the first trimester. The stimulus of
secretion is represented by HCG . RLX has the following activities:
571. is a major myometrial inhibitory substance (induces the uterine
muscle relaxation);
572.
=> has a role in producing softening and effacement of the uterine
573.
cervix;
568.

41

=> manifests qualities of a growth factor for the uterus and

574.

mammary gland;
=> favours membrane rupture by stimulating collagenase.

575.

576.

577.

The eicosanoids in the placental territory

578.

Eicosanoids are compounds derived from essential nonsaturated fat

acids the main precursor being arachidonic acid, transformed by the major
enzymatic pathways of cyclooxygenase and lipooxygenase.
580.
The metabolic products of AA, resulting from cyclooxygenase pathway
(PG and Tx) are important in controlling utero-placental and fetal
hemodynamic phenomena, in maintaining the tone of the ductus arteriosus and
the mechanisms of parturition.
581.
The placental synthesis of PG is stimulated by CRH. There is a
plasmatic inhibiting factor of PG synthesis during pregnancy. Placenta has an
important potential to destroy PG.
582.
Tx has vasoconstrictive properties manifest on the level of the human
placenta while PG 12 is a vasodilator. In preeclampsia, Tx quantities are higher
than PG 12 ones, and the blood flow diminishes.
583.
Leukotrines (compounds resulting from lipoxygenase pathway) interfere
in the implantation process and in the trophoblast invasion and in the uterine
contractility during labor.
579.

584.

585.

Utero-placental renin-angiotensin-aldosteron system

586.

RAAS is an important regulator of the arterial pressure. Placenta

takes part by a local RAAS in the physiology of pregnancy. From this level, prorenin
is released into the maternal circulation.
588.
Renin was identified in CT. Placenta synthesizes angiotensinogen
and contains the conversion enzyme.
589.
Pregnancy is characterized by a decrease of the response to vascular
activity of angiotensin II. All is a major stimulus for adrenocortical secretion of
aldosteron which together with antidiuretic hormone favors salt and water
retention during pregnancy.
590.
All is involved in controlling the local blood flow, in the contractility of
the uterine muscle and in inducing PG synthesis.
587.

591.
592.

4.2.

593.
594.

42

PLACENTAL IMMUNOLOGICAL PHENOMENA

From the moment the trophoblast is formed, until delivery,

trophoblast is the contact zone between the maternal tissues and embryo-fetal
structures.
596.
The trophoblast forms an interface with the maternal blood and
with the uterine cells/This interface exists on the level of all zones of possible
anatomical contact: placenta , chorioamnion, spiral arteries, basal plate, nonvillous
CT.
597.
The trophoblast membranes are not immunologically inert. There is an
allogeneic coexistence between the trophoblast and the maternal tissues
although the maternal organism induces immune responses towards trophoblast
antigens.
598.
The maternal immune system accepts the fetal allograft and helps
its development. In this way pregnancy is a spectacular immunological enigma.
599.
Many studies certify the activity of immunological supression
developed on the level of human decidua. The presence of the granular lymphocytes
in decidua during the early stages led to the hypothesis regarding the important role
in implantation and placentation.
600.
A great proportion of cells is held by the macrophages, involved
in the mechanisms of immunological supression.
601. Troph oblast antigens
595.

602.

They may be grouped into 3 categories: => major histocompatibility

complex antigens (MHC); => antigens with suspected functions (trophoblastlymphocyte cross-reactive antigens-TLX, transferrin, the major basic protein);
=^> antigens with unknown functions.
604.
MHC antigens are not expressed, probably, in the interval between
the eight cell stage and implantation (the embryo is protected by zona pellucida).
605.
HLA molecules (the genes controlling MHC antigens) were detected on
CT in the fifth week. MHC antigens cannot be found at the level of villous
trophoblast. They might be expressed on the nonvillous trophoblast.
606.
The explanation for the apparent immunologic privileged status of the
placenta is mostly related to the fact that all major class [1 histocompatibility
antigens are absent from trophoblastic tissue at all stages of gestation.
However, the type I MHC antigens are expressed and may in fact be beneficial
to the pregnancy.
607.
Transferrin and its receptor were identified on the level of
microvilli interface-maternal blood. The receptors are believed to have besides the
function of iron transfer an immunogenic one.
603.

43

The major basic protein was identified on nonvillous CT.

Probably it has a cytotoxic action to the limitation of an exuberant trophoblastic
invasion into the maternal tissue.
609.
TLX, antigens widely spread in the human tissues, were identified by
the trophoblast cells on the level of the placental bed. They might be involved
in the local matemal-fetal interactions.
610.
It is possible that the maternal immune responses to the fetal
antigens should be a normal phenomenon (in pregnancy) while the exagerated ones a
pathological condition (recurrent spontaneous abortion, gestational trophoblastic
disease, preeclampsia).
611.
One of the aspects of the immunological processes in pregnancy is
related to the presence of cytokines in the MPF unit. Cytokines represent a
large group of polypeptides which include interleukins, alpha and beta TNF
and interferons. These compounds are the chemical messengers of the cellular
interactions evident in the immune response and effectors in the immune
processes.
608.

44

The placenta may have an immunoregulatory role as

demonstrated by the release of factors that supress lymphocyte activation. Placenta
produces the following types of cytokines:
613.
=> colony stimulating factor (stimulates the clonal proliferation
and the capacity of phagocytosis and increases the defence against infections);
614.
=> interleukin 1 (immunoregulator protein which stimulates PG
E2 synthesis and induces cellular proliferation);
615.
=> interleukin 2 (interferes in cytotoxic reactions and in the
protection and survival of the embryo);
616.
=> TNF (is involved in limitating the inadequate trophoblast
invasion).
617.
The present knowledge considers cytokines to be a major
mediator in the immunological phenomena proper to pregnancy.
618.
In the endocrine control of the immune system in pregnancy there
interfere:
HGG, having possible immunosupressive qualities;
estrogens (by increasing the number of monocytes and granulocytes,
amplifying the activity of macrophages, stimulation of monocyte cellular colony
formation);
progesterone possesses antiinflammatory and immunosupressive
properties, facts which suggested that this hormone has a major role in preventing
lymphocyte activation on the level of the maternal-fetal interface.
612.

5. THE MEMBRANES. THE AMNIOTIC FLUID.

THE UMBILICAL CORD

5.1. THE MEMBRANES (chorion and amnion)

The chorioamniotic membranes form the geographic boundary for fetal

development in utero life. These membranes have anatomically different origins but
come from the same genetic pool as the fetus and, as such, must be considered fetal
tissues.

From earliest embryonic life the membranes play a critical role in fetal
development and protect the continuing pregnancy.
Growth of the chorion and amnion develops through gestation to
approximately 28 weeks. After that, mitotic activity is infrequently seen and
enlargement of the chorioamniotic sac takes place by stretching.
The chorioamniotic membranes arc not passive tissue barriers permeable to
fluids and solutes. Instead, they are dynamic and metabolically active and
contribute to the progression of the pregnancy in many ways.

The membranes are made up of two structures, from outside to inside,

chorion and amnion.
The chorion, placed between decidua and amnion, is a fibrous and transparent
structure. At the level of placenta, it becomes the chorionic plate. It adheres to
the decidua and can be easily separated from the amnion. Amniochorial
pouches may be formed between the two membranes.
On the level of the cervical internal orifice the chorion is in a direct
relationship with the mucus which obturates the cervical channel.
The chorion consists of a lax fibroblast layer and a reticular one. Its separation
from the amnion is made by a spongy stratum. The chorionic thickness is
about 0,2mm.
The amnion is a transparent, thin, extremely resistant membrane, which lines
the fetal place of the placenta and the umbilical cord. Its outer face is
connected with the chorion from which it can be easily detached.

The amnion consists of two layers:

 => the inner epithelial one, made up of several cellular strata,

with secretory properties (amnion cells) arranged on a basement layer;

=^ the outer one, made up of lax connective tissue, containing elastic
and nervous fibres, blood and lymphatic vessels.

The amnion epithelial cells take part actively in the maternal-fetal

transfers and, possibly, by the way of the intercellular channels.

After the 36th week they have the tendency to exfoliate.

The fetal membranes (chorion and amnion) and decidua represent deposits of
arachidonic acid (AA) esterified. AA is a critical precursor of PC A hypothesis
has been expressed according to which the enzymatic release of this acid from
the respective stocks could be an important step in initiating labor.
The A A release from glycerophosphoiipids is made under the influence of
phospholipase A 2. The role played by the fetal membranes in initiating
delivery can be also supported by clinical arguments : premature rupture of
membranes, chorioamniotitis, amnioinfusion with hypertone solutions or AA
can induce the onset of uterine contractions.

Phospholipase A 2, lisosomal enzyme, present in the membrane cell

lisosoms, during the whole course of pregnancy, increases its activity after having
affected the lisosomal membrane by trauma, gross modification of osmolality,
membrane rupture.
Besides the processess described (taking part in transfer, PG synthesis)
membranes are the site where the hormonal synthesis takes place. Membranes
create the condition for uterine closure, protecting the fetus against infections
which represent a risk after the rupture (of membranes).

5.2. THE

AMNIOTIC FLUID

The volume of the amniotic fluid can be quantified by means of ultrasounds

or by dilution methods: => 20ml at 7 weeks; => 300ml at 20 weeks;
1,000ml at 30 weeks (the highest volume, which decreases
gradually);
m> 600-1,000ml at term (between 1,000-2,000, a condition named
"liquid in excess4'; over 2,000ml, a pathological condition, named hydramnios; under
500ml, a pathological condition named oligoamnios.

It has an opalescent aspect, with small particles at term. Its

reaction is slightly alcalinc, pH 6,9 to 7,2.

Composition at the beginning of pregnancy it resembles the maternal

or fetal serum :
water, about 98%;

=> mineral elements 0.7% (natrium, chloride, potassium, calcium,

phosphorus);

47

=> organic elements 0.25% (glucose, urea, creatinine, lipids, estriol,

HPL, STH, bilirubin, immunoglobulins, alpha FP, PG).

Lecithin/sphingomyelin ratio is used in evaluating the lung maturation.

E 3 and HPL measurements help in controlling the fetal wellbeing. Bilirubin can indicate the liver maturation.

Alpha FP is a glycoprotein formed in the fetal liver ; the concentrations

in the amniotic fluid begin to decrease from the 14 Ul week : levels are increased in
the case of CNS malformations or in the intrauterine death.
Cytology : amniotic fluid contains: ->
desquamated fetal cells; -> lanugo;
> epithelial cells from fetal urinary system or from vaginal
epithelium;
- fragments of sebum, with a granular and whitish aspect.

The study of cells can supply elements to evaluate the fetal age, its sex
and the cariotype. Towards the term there appear umiucleated cells, sometimes in
clusters which colour in orange under blue Nile. They originate in the sebaceous
gland desquamation and they testify the fetai skin maturation. They are visible after
the 32nd week.
The origin of the amniotic fluid is triple: fetal, amniotic and maternal.
The fetal source is essential. At the beginning of gestation, this is a result of a
embryo-fetal extracellular fluid effusion. Later on it is the result of fetal
kidney excretion. At term, the fetus excrets 7nil/Kg/hour. To these there are
associated the lung and umbilical cord secretions.

The urinary system is, at least in the second part of pregnancy, the most
important site for amniotic fluid formation. The fetal kidney functions beginning
with the 9lh week (urine was detected in the fetal bladder in the 11 th week). At 40
weeks the urinary production is about 600ml/24 hours.

Amniotic source, result from the epithelium of amnion activity.

Placenta takes part in the amniotic fluid circulation by way of villous membranes
and the vasculature at the level of the chorionic plate.
The maternal origin is realised by diffusion on the level of the membranes.
Amniotic fliud resorption can be explained by two mechanisms: => fetal
deglutition: the swallowed amniotic fluid is absorbed at the level of the
intestine, reaches the fetal blood, crosses the placental barrier and through the
maternal circulation is eliminated by kidneys; by this process about 500ml/24
hours are excreted; at term the fetus swallows about 150ml/Kg/day;
resorption through amniotic epithelium is active for water and
carbohydrates.

In the first half of pregnancy, the forming fetal skin plays an important
part in the amniotic fluid circulation. After the 22 nd week, this participation
disappears, the skin becoming impermeable due to the epidermal keratinization.

The production-resorption relationships of the amniotic fluid creates a balance

which maintains the volume of this fluid relatively constant. Amniotic fluid is totally
renewed in 3 hours and water exchanges in this process involves 10-12 1/day. .

48

 The amniotic fluid functions

During pregnancy, amniotic fluid provides fetal hydration, water and

mineral element supply. It allows fetal growth, its movements, intrauterine
accomodation and its protection against temperature variations.
The fetus is protected against the external trauma and the umbilical cord
against compressions. The amniotic fluid has a protective role against
infections as the amniotic cavity is closed and the amnion is impermeable for
exogen germs, its antibacterial potential is provided by the content in Ig G and
lizozim.

The amniotic fluid has a protective role for the pregnant woman too by
diminishing the perception of the fetal movements.
During labor, the protection against infections and trauma continues. The
amniotic fluid is active in forming the water pouch.

5.3. THE UMBILICAL CORD

:

It is the fetal connective-vascular adnexa, covered in amnion, being the

link with the placenta. It derives from the vitelline duct (initially) and then forms
allantoid pedicle with its vessels.

The two allantoic arteries develop to form the umbilical arteries.

The allantoic veins fuse to generate the umbilical vein which supplies the
fetus with placental oxygenated blood.

The umbilical cord has a tubular, twisted form and a glossy whitish
colour. Its surface is irregular. Its average length is 50cm and its diameter 1.5cm. The
fetal insertion is on the level of the umbilicus. The other extremity is fixed on the
chorionic plate, more or less centrally.

Structure: a connective axis containing umbilical vessels, everything in

an amniotic cover (stratified epithelium); the connective tissue is mucoid, Wharton
jelly, and is crossed by a fibrilar network; in the central portion of the cord there is a
consistent connective tract which sends extentions forming compartments providing
cord resistance.
The umbilical vein contains oxygenated blood as well as arterial blood. It has
a large caliber. The arteries have a much smaller caliber and drive fetal blood
(poor in O2) to the placenta. They are wrapping the vein and have calibre
variations.
The cord also represents an area of secretion and absorption of amniotic fluid.

49

6. MATERNAL PHYSIOLOGIC CHANGES

THAT OCCUR DURING PREGNANCY, LABOR,
DELIVERY AND PUERPERIUM

Pregnancy may be considered to be a physiological condition occurring

on the basis of the integration of certain processes resulting in the development and
birth of a healthy child.
* The maternal homeostatic mechanisms function in new conditions, adjusting
themselves to the necessities recquired by embryo-fetal development. Adjustment
modifications can also be recorded during labor, delivery and pueperium.

The maternal adaptation takes place by systemic changes (circulatory

system, respiratory and urinary systems, gastrointestinal tract, endocrine system,
metabolisms) and local changes (uterus, ovaries, fallopian tubes, mammary gland).

SYSTEMIC CHANGES

A. Cardio - vascular system

During pregnancy and the puerperium there are remarkable changes involving

the heart and the circulation. Circulatory changes in the norma! pregnancy
occur as an anticipatory answer to the necessities of the fetal growth and as an
adjustment to the metabolical and nutritional processes of the fetus.
The total blood volume increases on the basis of the plasma volume and red
cell volume amplification. This is one of the major modifications.
The plasma volume increases from the 6th week until the 34-36th weeks when
it reaches the highest value. It remains constant until the term. The average
increase is 45% (1,200ml with primigrvida, 1,500ml with multigravida, up to
2,00ml with multifetal pregnancies).

50

After delivery, it decreases rapidly by 6OO-8OO111I. At 6-8 weeks it

comes back to the values of nonpregnancy.
In the hypervolemia mechanism several factors have been involved: =e>
steroid hormones characteristic to pregnancy;
decrease in the peripheral vascular tone; => individual factors. The red cell
volume increases less and more slowly (about 30%) and is achieved by an increased
production of erythropoietin. Erythropoietin is a glycoprotein produced by the
kidneys and its action is to stimulate the formation of red cells by increasing and
differentiating the precursor cells.

In the maternal serum, erythropoietin increases beginning with the 8 th

week reaching the highest value at 20 weeks, undergoing decrease in the last weeks.

The increase in the total blood volume may be interpreted as an

adaptive phenomenon :
> metabolical necessities;
-> fetus protection against the possibility of decrease in venous return
and the decrease in the cardiac output produced by the compression exerted by the
enlarged uterus;
-> as a compensatory mechanism to the blood loss at delivery. Other
blood modifications:
the number of red cells decreases (the increase in the red cell volume is
slow in comparison with that of the plasma volume);
hemoglobin decreases (10g% at 20 weeks ;1 lg% or less in the third
trimester signify anemia);
hematocrit decreases;
the number of the white blood cells increases (9,000/mm3 in the first
trimester, 10-1 l,000/mm3 in the second, l0.000/mm3 in the third);
erythropoiesis is increased;
Ca,Co,Zn,Mg,Cr are decreased;
decreased proteins, increased lipids;
carbohydrates decrease and glucosuria is relatively frequent;
hemostasis: a. primary: the number of platelets decreases slightly (not a
generally accepted point of view); unchanged adhesivity ;
b. secondary: increased fibrinogen, by amplification of synthesis, factors VII
(proconvertin), VIII (antihemophilic globulin), X (Stuart factor) increased, the
fibrinolytic activity of plasma decreased.

The increase of several coagulation factors and the decrease in the

fibrinolytic activity induces a low grade intravascular coagulation nonsignificant
under normal conditions. After delivery, fibrinogen and plasminogen decrease and
the fibrinolytic activity increases.
Anatomical heart modifications:

-> the heart takes a horizontal position and rotates somewhat on its long
axis (due to the fact that the diaphragm becomes progressively elevated);

51

-> myocardium undergoes hypertrophy and a degree of cardiomegaly

occurs.
Functional heart modifications

The cardiac output is the product of stroke volume and heart rate. The
increase in the cardiac output is one of the most significant. The onset of this
increase takes place in the I0,h week, reaches the highest value in the interval
between the 20-24th week and remains constant.

The increased values, in comparison with those in nonpregnancy, are

30-50% (higher in multifetal pregnancies). In explaning these modifications we
should take into account the ovarian and placental steroids. Initially, the increase is
made by stroke volume amplification and later on by the heart rate amplification.

An important and unique hemodynamic phenomenon consists in the

variability of the cardiac output related to the postural modifications. The enlarged
uterus (after having reached a certain volume) in a supine position compresses the
inferior vena cava which, in conditions of a poor paravertebral collateral circulation,
reduces the venous return to the heart and a hypotension by a decrease of cardiac
output occurs.

This is the supine hypotensive syndrome, manifest by dizziness,

lightheadedness, nausea and even syncope. Its frequency is between 0.5 to 11%. The
treatment consists in taking lateral recumbent position.

Vascular compression exerted by uterus may involve the aorta and its
branches.

The systolic pressure decreases by 5-10mm Hg and the diastolic one

by 10-15mm Hg. These decreases manifest in the first trimester, are evident in the
middle of pregnancy, and arterial pressure corns back to the normal values before
the term.

It is believed that the decreased arterial blood pressure, in normal

pregnancy, could be explained by the utero-placental circulation, which is a low
vascular resistance territory.

The vascular reactivity to angiotensin II is diminished (especially by an

increase in synthesis and/or in the vascular release of PG E2 or PG12).

Peripheral vascular resistance decreases. This decrease has the

highest values between the 14,h and 24th weeks, then a slow increase is recorded
without reaching the average values in nonpregnancy.
The decrease in PVR could be explained by a direct action of estrogens on
vessels resulting in a diminished response capacity to physiological pressure
stimuli. Progesterone favors venous relaxation and the increase of vascular
capacity with fluid retention.
Regional blood flows
The cardiac output, increased in pregnancy, is distributed mainly to the
functionally overloaded territories.
The utero-placental flow has an extremely important role in the egg
development. The decrease in the uterine vascular resistance leads to an
52

increase in the blood flow at this level in the first stages of the evolution of
pregnancy. The uterine flow increases from SOml/min in the 10 th week to the
500ml/min at term.
The placental fraction of the utero-piacental flow provides the maternal-fetal
exchanges in the intervillous space and the nutrition of the placental tissue.
The systemic modifications described above (total blood volume, cardiac
output, PVR) to which local factors (arterial flow, venous drainage, uterine
contractility) are added represent the maternal factors of the hemodynamic
control in the intervillous space.

The renal hemodynamics exhibit some of the most important

modifications in the physiology of pregnancy. Renal blood flow and glomerular
filtration increase favoring the oxygen supply and the amplification of some active
processes.
The increase of glomerular filtration contributes to the explanation of
glucosuria, aminoaciduria and to the increase of water-soluble vitamin
excretion.
The circulation on the level of the extremities increases as well as the one on
the level of skin and mammary gland.
The tissue demand of oxygen increases progressively and records a
maximum of 20 to 30% towards the term. This increase may be attributed to
the increased metabolical necessities manifest in the maternal and fetal sides,
to the increase of the heart effort and to hyperventilation.
Cardio-circulatory symptoms and signs in normal pregnancy:
-=> reduced tolerance to effort, fatigue and dispnea are relatively common
signs;
=> the pulse rate may increase after which diastolic decreases
may occur; => cardiac sounds:
I, increase in intensity;
II, tends to exhibit expiratory cleavage (after the 30th week);
III, can be perceived in protodiastola (90% of cases);
IV, contemporary to left atrium contraction, may be occasionally
perceived.

=> systolic murmurs are increased in frequency due to the increase of

circulatory speed and to the cardiac output augmentation;
electrocardiogram modifications: increase in left atrium and ventricle
dimensions, increase in left ventricular ejection time and increase in the fractional
shortening of the ventricular diameters.

Hemodynamics during labor, delivery and puerperium

During natural delivery, pain, emotional stress, uterine contractility lead

to increases of cardiac output (a uterine contraction induces a 30% cardiac output
increase), of arterial blood pressure and pulse rate.

53

During cesarean section, due to the fact that about 600ml blood from
the uterine wall enter suddenly into the circulation and due to a decrease in pressure
as a result of uterine evacuation, cardiac accidents can occur in cases with
cardiopathies. That is why cesarean operation is not recommended in cases having
cardiac problems.
In the puerperium, hemodynamic balance may be influenced by the loss of
blood resulting from the placental delivery. The cardiac output remains
increased for days and even weeks after delivery due to the uterine blood
drainage into the systemic circulation and by disappearance of the uterine
compression on inferior vena cava.

B. Respiratory system

Anatomical modifications:

=> lifting of diaphragm (the most important respiratory muscle);

=> the transverse diameter of the thoracic cage increases, the tone and
activity of the abdominal muscles decrease and breathing is more costal than
abdominal;
=> respiratory mucosa is hyperemic and edematous with hypersecretion.
Functional modifications:
the current volume increases, the residual one decreases;
the vital capacity may increase, decrease or may remain unchanged
(there are different points of view);
respiratory rate increases moderately;
the tidal volume increases as well as the alveolar ventilation (a
respiratory alcalosis takes place).
During labor:

-> there is an increase in: the respiratory rate, ventilation/minute,

alveolar ventilation, the current volume;
> hyperventilation, evident especially during uterine contraction, induces a
decrease in pC02 (maternal hypocapnca), maternal respiratory alkalosis and
fetal acidosis;

> the transport of 02 to the fetus decreases by about 25%

(administration of 02 during labor is a common practice).

C. Excretory system

Anatomical modifications:
kidney increases slightly in size during pregnancy;
urinary ways: pyelocalyceal and ureteral dilatation and decrease in peristalsis

occur (causes : ureteral compression on the level of pelvic brim produced by uterus
and the right iliac artery; muscular relaxation induced by progesterone); the effects
of these modifications are evident in the increased frequency of urinary infections
and asymptomatic bacteriuria. Functional modifications
The renal plasmatic flow and the glomerular filtration rate increase by 25%40% and 55% to 70% respectively. The plasma concentrations of creatinine
and urea decrease as a result.

The tubular functions are less modified.

54

 There are eliminations of glucose, aminoacids, uric acid. The natrium balance

is positive. The increase in glomerular filtration imposes an increased tubular

reabsorption for natrium. Natrium increase is in relation with the increase of
hydric volume.

RAAS is evidently stimulated during pregnancy:

- increased angiotensinogen synthesis (on the level of the liver, under
estrogen influence);
-> the renin plasma activity is increased and the result is an increase in All
production;
the pressor responsiveness to All is decreased; -> aldosterone production is
increased, a fact which contributes to the positive natrium balance;
> the increased of RAAS is manifest during labor, too ; its
participation in the mechanism of labor initiation was sugested.

During pregnancy, there is a triple functional RAAS : maternal, fetal

and utero-placental.

D. Gastrointestinal tract

=> appetite may be increased; modified food preferences;

hyperptyalism, especially during the day, accompanied or not by

nausea and vomiting, components of so-called "neuro-vegetative disorders";

=> gums may become hyperemic and softened; a focal highly vascular
swelling of the gums, the. so-called "epulis of pregnancy" develops occasionally but
typically regresses spontaneously after delivery;

=> heartburns (pyrosis) may occur after the second trimester related to
a gastroesophageal reflux;

=> the tone and motility of the stomach decrease; together with the
psychological component these modifications could explain nausea;

=> the gastric secretion is diminished (acidity and pepsine); increased

gastric mucous secretion may be related to the improvement in the ulcer disease in
pregnancy;

^>the motility of the small bowel is slower, tendency to constipation;

=> liver:

according to some opinions there is an increased hepatic

flow;

some of the laboratory tests commonly used to evaluate

hepatic function yield appreciable different results during normal pregnancy;
the enzymatic activity is not modified;
the functional disorders are minimal.
The gall bladder emptying time is increased and by this, pregnancy
predisposes to gall stone formation.

Pregnancy is the condition in which the energetic necessities and the

food intake increase. Under these conditions there is the problem of increased intake
or increased absorption. There may occur modifications of trasport types at the level
of intestinal epithelium.

55

 The pregnant woman's diet should not differ much from that of nonpregnant:

-> protein are important and can be supplemented

(1.5g/Kg);
carbohydrates 350-400g/day;
- more important mineral elements: Ca, Fe, P;

-> vitamine necessary increases (fresh food and vegetables). The

caloric rate will be 2.500 to 3.000 calories/day. hi the last trimester there should be
avoided : spices, tinned food, smoked meet, game, alcohol, tobacco.

E. Endocrine system Hypothalamus

and

pituitary gland

The pituitaiy gland enlarges in volume and weight, its vasculature is

intensified. There is a hyperplasia of anterior pituitary lactotrophs ; slight
modifications of the basophylic cells.

FSH and LH levels are low. The response to FSH-RH and LH-RH
stimuli are practically inexistent. Ovarian follicles undergo an early degeneration.
The ovulatory LH peak may occur if there is no breast feeding at about 6 weeks
after delivery.

The ACTH and MSH secretion increases, while the TSH ones remain
unchanged.
Oxytocin increases progressively during pregnancy. It is a nonapeptide
hormone synthesized in the hypothalamus (supraoptic and paraventricular
nuclei), stored and released in blood circulation in neurohypophisis. In
circulation it is bound to neurophysine, specific transport protein being under
estrogenic effects.
Oxytocin is the strongest endogenous uterotonic agent. Its participation in the
onset of labor represents one of the most important factors of this process.
The release of this hormone is discontinous. Its plasmatic levels do not
increase close to labor onset nor do those of oxytocinase, the enzyme which
decomposes oxytocin.
The uterine oxytocin receptors increase in number significantly just before the
initiation of labor. In the mechanism of labor, oxytocin stimulates myometrial
contractility also by activating local receptors and by supporting PO
production. Finally, oxytocin acts by increasing the intracellular calcium.

Thyroid gland

There are important changes in thyroidal economy during pregnancy

that are due to three modifications in the regulation of the thyroid hormones:

- first: pregnancy induces a marked increase in circulating levels of

the major thyroxine transport protein (thyroxine-binding globulin) in response to
high estrogen levels;

56

 > second: several thyroidal stimulatory factors of placental origin are

produced; the thyroid is under dual control of both thyrotropin and chorionic
gonadotropin during normal pregnancy;
> third: pregnancy is accompanied by a decreased availability of iodide for
the maternal thyroid. This is due to increased renal clearance and losses to the
feto-placental unit during late gestation and it results in a relative iodine
deficiency state.
The thyroid gland enlarges and synthesizes and secretes hormones actively
(thyroxine-T4-increased sharply between 6 and 9 weeks; the rise in total
triiodo thyronine-T3-is more pronounced up to 18 weeks).

Conflicting reports exist regarding the serum concentration of TSH.

Little if any transplacental passage of thyroid hormones T4 and T3 occur.
Therefore, fetal thyroid function appears to be independent of maternal
thyroid status. This protection of the fetus is likely to be the consequence of
placental inner ring thyroxine deiodination.

*.

..

-.

Adrenal gland

In normal pregnancy there is probably very little morphological change

in the maternal adrenal glands. There are, however, profound changes in secretion of
some of its cortical hormones:
=> in early pregnancy, the levels of circulating corticotropin (ACTH) are
reduced; as pregnancy progresses the levels of corticotropin rise;

=> there is a considerable increase in the serum concentration of

circulating Cortisol;

=> under the influence of estrogens, transcortin (cortisol-binding

globulin) levels rise and, together with Cortisol, produce a slight hypercorticism;

=> as early as 15 weeks of normal pregnancy, the maternal adrenal

secretes considerably increased amounts of aldosterone; the maternal plasma levels
of deoxycorticosterone are increased too; it is probable that the increased formation
of mineralocorticosteroids is important in the plasma volume expansion that
accompanies pregnancy.

Enlargement of the adrenal glands occurs progressively throughout the

prenatal period because of hyperplasia of the cortex.

Catecholamine metabolism appears unmodified.

METABOLIC CHANGES

Water metabolism

57

Generally, fluid equilibrium is under control of sodium retention or

excretion, a process in which arc involved: aldosterone. PG, AII, ANP and free
water retention or excretion dependent on ADH.

Increased water retention is a normal physiological alteration in

pregnancy. Most of the increase in weight during pregnancy (the average total
weight gain is 12.5 Kg) is attributable to the uterus and its contents (fetus, placenta,
amniotic fluid), the breasts and increases in blood volume and extravascular
extracellular fluid occur
A smaller fraction of the increased weight is the result of metabolic alterations
that produce an increase in cellular water and deposition of new fat and
protein (so-called maternal reserves).

Water retention manifests especially in the last 10 weeks (7-8 1 of

extracellular fluid).
Clearly demonstrable pitting edema of the ankles and legs is seen in a
substantial proportion of pregnant women, especially at the end of the day.
This accumulation of fluid is caused by an increase in venous pressure below
the level of the uterus as a consequence of partial occlusion of the vena cava
by the gravid uterus and by a decrease in interstitial colloid osmotic pressure.

Pathological retention of sodiun and water, with the development of

edema is commonly present in pregnancy induced hypertension.

Sodium retention is caused by increased glomerular filtration while

excretion remains unchanged in norma! pregnancy. ADH and progesterone are
involved due to their natriuretic action.

Although the normal pregnant woman has a very reduced sensitivity to

the hypertensive effects of All, the elevated levels in pregnancy lead to increased
aldosterone production and preservation of sodium homeostasis (a compensatory
activity directed against the natriuresis induced by progesterone and glomerular
filtration increase).

ANP has been reported to produce significant natriuresis and diuresis in

humans. The peptide induces an increase in renal blood flow and glomerular
filtration rate and decreased renin secretion.

However, the actual mechanism responsible for the natriuresis remains

unclear with evidence consistent for both hemodynamically induced natriuresis and
an inhibitory effect upon tubular sodium reabsorption (an All action).
Carbohydrate metabolism

Pregnancy is potentially diabetogenic. Diabetes mellitus may be aggravated

by pregnancy and clinical diabetes may appear in some women only during
pregnancy.

Normal pregnancy is characterized by mild fasting hypoglicemia,

postprandial hyperglicemia and hyperinsulinemia. In healthy pergnant women, the
fasting plasma glucose concentration falls somewhat, possibly due to increased
plasma levels of insulin.

The exact mechanism responsible for the beta cell hypertrophy,

hyperplasia and hypersecretion observed in pregnancy are not completely

58

understood, estrogen, progesterone and human placental lactogen are likely to be

involved.

Pregnancy is also characterized by a peripheral resistance to insulin.

The mechanism responsible for insulin tissue resistance is not completely
understood. Progesterone and estrogen may act to mediate this resistance. Plasma
levels of HPL increase with gestation and this protein hormone is characterized by
growth hormone-like action that may result in increased lipolysis and increased
liberation of free fatty acids. The increased concentration of circulating free fatty
acids may also facilitate increased tissue resistance to insulin.
The mechanisms cited ensure that a continuous supply of glucose is available
for transfer to the fetus.
There is insulinase activity in the human placenta. It seems unlikely, however,
that accelerated insulin degradation contributes appreciably to the
diabetogenic state induced by pregnancy, because the rate of degradation of
radiolabeled insulin in vivo does not appear to differ from pregnant to
nonpregnant women.

Fat metabolism

-. .

..

The concentrations of lipids and lipoproteins in plasma increase

appreciably during pregnancy. Plasma lipid levels increase continously throughout
gestation.
Plasma lipoprotein cholesterol levels change significantly. Low-density
Hpoprotein-cholesteroi levels reach a peak approximately in week 36. High-density
lipoprotein-cholesterol peak is at week 25, decreases until week 32 and remains
constant for the remainder of pregnancy. These modifications arc a consequence of
the hepatic effects of E2 and P.

HDL stimulates the release of HPL from placenta. Storage of fat occurs

primarily during midpregnancy. Later, as fetal nutritional demands increase

remarkably, fat storage decreases.

Protein metabolism

The products of conception as well as the uterus and maternal blood are

relatively rich in protein rather than in fat or carbohydrate. Nonetheless, their

protein content is rather small compared with the total maternal body protein.
At term, the fetus and placenta weigh about 4 Kg and contain approximately
500g of protein, or about one half of the total increase normally induced by
pregnancy. The remaining 500g of protein is added to the uterus as a
contractile protein, to the breasts, primarily in the glands, and to the maternal
blood in the form of hemoglobin and plasma proteins.

59

A positive nitrogen balance demonstrable early in gestation increases

progressively through the third trimester when fetal requirements are greatest.
Nitrogen acumulates during pregnancy far beyond the needs of the conceptus.
Good maternal protein nutrition plays a key role in providing for the normal
fetal growth and development and may be related to the actual condition of
the newborn. It is desirable that the majority of the protein be supplied from
animal sources.

LOCAL CHANGES

Uterus

In the nonpregnant woman, the uterus is an almost solid structure

which weighs 50-70g. At term, the uterine weight is 1,000 to l,200g.
Its capacity is of 6-8ml. By the end of pregnancy, the uterus has achieved a
500 to 1,000 times greater capacity than in the nonpregnant state (the total
volume of the content of the uterus at term averages is 5 I).

The uterus is 6 to 8cm high and increases in a direct relation with

amenorrhea duration until 32 to 34cm, or more, at term.
As an internal genital organ, the uterus is divided into a number of different
anatomic regions that serve crucial functions during gestation and parturition.
The dome of the uterus is the fundus which is superior to the ostia of the
fallopian tubes.

The greatest part of the uterus is called the body or corpus. The junction
between the cervix and the corpus is called the isthmus.

As the uterus increases in size (during pregnancy) it also undergoes

important modifications in shape. For the first few weeks, its original pear shape is
maintained, but as pregnancy advances, the corpus and fundus soon assume a more
globular form, becoming almost spherical by the third month. Subsequently, the
organ increases more rapidly in length than in width and assumes an ovoid shape.

The position of the gravid uterus changes as gestation advances. Early,

an exaggerated anteflexion is usual. Then, as the uterus rises from the pelvis,
varying degrees of dextrorotation develops because the rectosigmoid occupies a
relatively fixed position in the left posterior aspect of the pelvis.

Myometrium has two principal structural elements : muscular tissue

and connective tissue. During pregnancy, uterine enlargement involves stretching
and marked hypertrophy of existing muscle cells. The appearance of new muscle
cells is limited.

At the time of parturition, a single myometrial cell is about 500 microns

in length. The myometrial smooth muscle cell is surrounded by an irregular array of
collagen fibrils.

60

The force of contraction is transmitted from the contractile proteins of

the muscle cell to the surrounding connective tissue through the reticulum of
collagen.
Uterine musculature, during pregnancy, is arranged in three strata:

=> an external hood-like layer, which arches over the fundus and
extends into the various ligaments;

=> an internal layer consisting of sphincter-like fibers around the

orifices of the tubes and the internal os;

=> lying between these two, a dense network of muscle fibers

perforated in all directions by blood vessels ; the main portion of the uterine wall is
formed by this middle layer which consists of an interlacing network of muscle
fibers between which the blood vessels extend.

From the first trimester of pregnancy onward, the uterus undergoes

irregular contractions which are normally painless. In the second trimester, these
contractions may be detected by bimanual examination. These contractions are
named Braxton Hicks contractions, are infrequent but increase in frequency during
the last weeks. Braxton Hicks contractions appear unpredictably and sporadically,
and are usually nonrythmic.
The uterus receives its blood supply from two major vessels : the uterine and
ovarian arteries, hi the nonpregnant state, the uterine artery is most important,
but during pregnancy the vascular supply is derived from both uterine and
ovarian arteries.

After the 28th week, the isthmus starts its transformation in lower
uterine segment. The wall of the upper contractile portion of the uterus becomes
thicker during labor as the lower uterine segment which must undergo
circumferential dilation to permit passage of the presenting part, becomes thinned
out and about 10-11cm in length (the inferior limit is internal os of the cervix and
the superior one is the zone where the difference of musculature of the corpus is
evident).

Late in pregnancy and most particularly during labor, the lower uterine
segment becomes thinned out and its upper pole is more clearly demarcated from
the thick upper segment.
There are three principal structural components of the cervix : smooth muscle
(only 10%, while corpus has 50-60% muscular tissue), collagen and
connective tissue or extracellular matrix (ground substance).
The cervical ripening process principally involves changes that occur in
collagen, connective tissue and in its ground substance. Cervical ripening is
associated with two complementary changes:

=> collagen breakdown and rearrangement of the collagen fibers;

61

=> alterations in the relative amounts of the various

glycosaminoglycans.
PG E2 and PG F2 alpha applied directly to the cervix induce the maturationa!
changes of cervical ripening. Prostaglandin suppositories, placed
intravaginally, adjacent to the cervix are used clinically to effect cervical
softening and ripening to facilitate the induction of labor.

In the ripening of uterine cervix there are also involved: estrogens,

progesterone and relaxin. The role of human RLX in producing softening and
effacement of the uterine cervix is unknown. The topical administration of
pharmacological doses of a highly purified porcine RLX to the human cervix,
however, results in clinical softening and effacement as well as a more successful
rate of labor induction in treated versus nontreated women.

Ovary

Ovulation ceases during pregnancy and the maturation of new follicles

is suspended. Ordinarily, only a single corpus luteum of pregnancy can be found in
the ovaries of pregnant woman.

The corpus luteum of pregnancy most likely functions maximally

during the first 6 to 7 weeks of pregnancy and thereafter it contributes relatively
little to progesterone production. After this time in pregnancy, corpus luteum
removal (surgery) ordinarily does not cause abortion.

Fallopian tubes

The musculature of the fallopian tubes undergoes little hypertrophy

during pregnancy. The epithelium of the tubal mucosa is flattened compared with
that of the nonpregnant state. Decidual cells may develop in the stroma of the
endosalpinx, but a continous decidual membrane is not formed.

Pigmentation and cutaneous vascular changes

In many women, the midline of the abdominal skin becomes

markedly pigmented, assuming a brownish-black color to form the linea

nigra.

Occasionally, irregular brownish patches of varying size appear on the

face and neck, giving rise to chloasma gravidarum (mask of pregnancy), which,
usually, disappears after delivery.

Little is known of the nature of these pigmentary changes, although

melanocyte-stimulating hormone has been shown to be remarkably elevated from
the end of the second month of pregnancy until term. Estrogen and progesterone are
reported to have melanocyte-stimulating effects.

Angiomas, called vascular spiders, develop in about two thirds of white

women. The condition is often designated as nevus, angioma or telangiectasis.

62

Palmar erythema is encountered in pregnancy in about two thirds of

white women and one third of black women. The two conditions are frequently seen
together but are of no clinical significance.

During pregnancy, increased vascularity and hyperemia develop in the

skin and muscles of the perineum and vulva, and there is softening of the normally
abundant connective tissue of these structures.

The vagina becomes deeply congested and cyanotic (Chadwick's sign)

because of the greatly increased vascularity. Secretions present in the vaginal

vault have a highly acid pH (3.5 to 5.5) because of the increased glycogen
content of the vaginal epithelium.

Breasts
The breasts become enlarged and sensitive by the eighth week of pregnancy.

The primary areola deepens in color, and a more lightly pigmented secondary
areola develops at the periphery.

Sebaceous glands, located in the primary areola, undergo hypertrophy,

forming Montgomery's tubercles.
During pregnancy, there are striking changes in the breasts. In the early
weeks, the pregnant, woman often experiences tenderness and tingling. After
the second month, the breasts increase in size and become nodular as a result
of hypertrophy of the mammary alveoli.

Colostrum can be expressed from the nipples after about the tenth
week, but lactation is inhibited by the high estrogen-progesterone levels. Growth of
the mammary apparatus is a direct response to hormone stimulation (estrogen
stimulates proliferation of the ducts, progesterone causes proliferation of lobulealveolar tissue).

As the breasts enlarge, the vascular supply is increased, engorged veins

are frequently visible beneath the surface of the skin and striae may appear over the
outer aspects.

63

7. THE DIAGNOSIS OF PREGNANCY

7.1. FIRST TRIMESTER

History and clinical signs

=> Amenorrhea in a woman who has previously menstruated regulary

must be considered to be due to pregnancy. Although pregnancy is not the only
cause of amenorrhea which may occur of emotional stress, hormonal (imbalance) or
local uterine conditions, it is the commonest cause.

=> Nausea and vomiting occur in over 50 % of pregnant women,

usually between the 4-th and 9-th week after the lest menstrual period.

=> Bladder irritability: Frequency of micturition due to physiological

changes is common in the first trimester.

=> Breasts: abnormal heaviness and enlargement of the breasts with

associated symptoms of tension are common in early pregnancy. The nipple and
areola increase in size and become darker in color, with distended veins. In the
primary areola, Montgomery's tubercules become prominent.

Vulva and vagina: owing to the increased vascularity

occasioned by the intensified estrogen secretion, a dusky bluish discoloration may
be seen in the vulva extending up to the anterior vaginal wall and cervix ( speculum
examination ).

Uterus - bimanual examination: vagina and cervix appear softer

and more distensible. This symptoms are apparent from the 4-th week. The uterus
enlarges, anticipating the growth of the ovum and globus. Megar's sign is present:
this is the sensation experienced by the fingers in bimanual examinations. It is due
to the excessive softening of the lower segment. Measuring the symphisis- fundus
height it is found that the uterus grows-up with 4 cm per month ( 8-th week-4 cm,
12-th week-8 cm, 16-th week-12 cm).

Differential diagnosis is posiblc with: uterine myomata, ovarian cyst,

trophoblastic disease, bladder globus and amenorrhea which may occur because of
emotional stress, hormonal imbalance or local uterine conditions.

64

Laboratory tests for diagnosis of pregnancy are based on the fact that
there are releases into the circulation of large amounts of HCG in urine and plasma
(beta HCG).

~> biological tests performed on laboratory animals detect the amount

of HCG in urine.

> immunological tests: beta sub-unit HCG, which can be measured

by a sensitive monoclonal anti-HCG antibody test. The test can detect small
amounts of beta HCG 9 much more than in 0,81 in plasma uterine. These quantities
are found at the time of the missed period. The test can be made in a laboratory or
the women can purchase a home testing Kit.

The measurement of beta HCG enables pregnancy to be detected very

early;(2) ectopic gestation is excluded by two negative tests on successive days and
(3) trophoblastic disease follow-up to be performed.

=> ultrasound can be used for diagnosis earlier than 6-th week to:
estimate the size of amniotic sac;
visualise the fetus ( after 12-th week);
measure fetal-crown-rump (FCR) length;
determine the position of the placenta.

7.2.

SECOND TRIMESTER

Clinical signs: amenorrhea continues, over 16

weeks.The first fetal movements of the fetus will be felt by women and there is
enlargement of the abdominal wall.

Examination

Inspection of the breasts: increased vascularity sensation of heaviness,

the nipple and primary areola have become more pigmented, Montgomery's
tubercules (sebaceus glands) become prominent as raised pink-red nodules on the
areola. After 20 weeks the secondary areola has become prominent. Clear fluidcolostrum is secreted and can be pressed out.

The abdomen increases in size.

Pigmentation appears on the face (chloasma) and on the abdomen (linea

nigra). These changes are thought to be due to disposition of melanin. Melanocyte
stimulating hormone is elevated from early pregnancy.

The uterus becomes palpable. It is a globulous, contractile, painless,

soft mass.

The height of the fundus is determined with gentle pressure of the ulnar
bord of the hand and is marked (grow-up 4 cm per mouth, 20-th week-16 cm, 24
week -20 cm).

65

Deep palpation reveals the external ballottement signrone hand taps the
abdomen and sends the fetus across the uterine cavity. The other hand lying on the
uterus perceives the impulse.

Fetal heart sounds may be identified by* clinical examination from

about the 20-th week of pregnancy with an obstetrical stethoscope.
Normal fetal rate heart is 140 to 160 beats per minute.

Bimanual examination shows that the vagina and cervix are softer, the
uterus is enlarged and the vaginal (internal) ballottement is present (tap gently
upwards and hold finger against cervix. The fetus is displaced upwards. The fetus
sinks and a gentle tap is felt on the finger).

Differential diagnosis is possible with: uterine myomato, ovarian cyst

with abdominal developement.

Laboratory diagnosis includes biological and immunological tests and

ultrasound examination. Ultrasound examination may be used to:
confirm the gestational age;
establish the presence or absence of a multiple pregnancy;
identify some fetal malformations;
measure biparietal diameter;
observe the fetal heart movements;
determine the position of the placenta (insertion).

7.3. THIRD TRIMESTER

Clinical signs: amenorrhea over 29-th weeks, the presence of fetal movement

and the enlargement of the abdomen.

The breasts have the same specific changes as in the second trimester.

The abdomen increases in size. The abdominal skin develops striae

gravidarum and its midline becomes markedly pigmented, forming "linea nigra".

Gentle palpation (superficial) defines the pregnaht uterus.

A more accurate method is to measure the symphsis fundus height. The
patient lies on her back, with her legs straight and her bladder empty. The
height of the fundus is determined with gentle pressure exerted by the ulnar
border of the hand and is marked. The distance from the upper border of the
symphysis to the fundal mark is measured.
Deep palpation: the medical attendant turns and faces the patient's feet
and places his hands on the lower part of the uterus. With his fingers extended, he
gently presses downwards, and from side, attempting to recognize the presenting
pait.Usually it is the head,which is firm, large and rounded, and unless fixed in the
pelvis, can be ballotted from side to side between the fingers. If the presenting part
cannot be readily identified because it is fixed in the pelvis, the fingers are slipped
further downwards and inwards until they dip into the pelvic brim. If the patients

66

cannot relax her muscles, she should flex her legs slightly and the fingers should be
slipped in more deeply each time the patient forcibly breathes out.

Lateral palpation: the hands are now gently slipped along each side of
the uterus and gentle palpation is made of the corresponding sides of the uterus. So
the back is identified as an elongated firm mass on one side of the midline, and the
limbs as small irregular shapes in an area which is relatively empty when compared
to the other side of the uterus.
If there is doubt about the presentation of the fetus, ascultation of fetal heart
may solve the matter. In vertex presentation the fetal heart sounds are best
heard below the umbilicus.

Vaginal examination

During pregnancy, increased vascularity and hyperemia develop in the

skin and muscles of the perineum and vulva. The copious secretion and the
characteristic violet color of the vagina (Chadwick sign) similar to the cervical
changes during pregnancy, probably result chiefly from hyperemia.
The cervix is visualized employing a speculum; Bluish-red hyperemia of the
cervix is characteristic. The external cervical os is slit-like or round with
"mucous plug" in this area.

Before labor, the diagnosis of fetal presentation and position by vaginal

examination is often inconclusive, because the presenting part must be palpated
through a closed cervix and lower uterine segment.

Laboratory diagnosis

Ultrasonography performed during the third trimester should include

measurement or evaluation of the following structures: => the biparietal diameter;
=> the abdominal circumference; => the femur length;
=5 examination of the fetal thorax: demonstration of fetal heart motion and
breathing motion;

=^ evaluation of the amniotic fluid;

placental localization and development.

8. THE PHYSIOLOGY OF UTERINE ACTIVITY.

NORMAL LABOR AND DELIVERY.
PHYSIOLOGICAL AND BIOCHEMICAL
PROCESSES.

8. 1. THE PHYSIOLOGY OF UTERINE ACTIVITY

The myometrium is composed of interdigitating spiral fibres, derived from the

Mullerian ducts, which have joined together.

The middle spiral interdigitating layer is marked only in the uterine

portion and muscle content decreases toward the cervix so that muscle forms no
more than 10 per cent of the cervical tissue compared with over 90 per cent of
tlindal tissue.

67

Each muscle fibre is composed of bundles of fibrils which in turn are

composed of spindle-shaped cells, averaging 200 mm in length and 7 mm in
diameter.

Electron microscopy has shown that these cells are themselves made up
of smaller elements and they are the contractile elements of the uterus.

The contractile fibril is made up of interdigitating protein chains of

actin and myosin, surrounded by a membrane which alters in permeability.

Biochemistry of muscle activity. The interaction of myosin and actin is

essential to muscle contraction.

Myosin is made up of multiple light and heavy chain and is laid down
in thick myofilaments. The interaction of myosin and actin which causes activation
is effected by enzymatic phosphorylation of the light chain of myosin. The
phosphorylation is catalyzed by the enzyme kinase which is activated by Ca2+.

Ca2+ binds to calmodulin, a calcium m-binding regulatory protein,

which in turn binds to and activates myosin light chain kinase.

Agents that act on myometrial muscle cells to cause an increase in Ca 2+

promote contraction.

Conditions that cause a decrease in Ca2+ favor relaxation.

Relaxation is promoted by sequestration of Ca 2+ in the sarcoplasmic

reticulum, dephosphorylation of phosphorylated myosin by the action of
phosphatase and possibly phosphorylation (inactivation) of myosin light chain
kinase by CAMP dependent protein kinase.

Muscle fibre contraction. In the presence of oestrogen and probably

generated by prostaglandins an impulse alters the electric potential of the cell

membrane and permits the entry into the contractile fibril of sodium and
calcium ions, which start the energy-releasing cycle. This pulls the actin
fibrils into the spaces between the myosin fibrils.

Characteristics of myometrial contractions. Although the uterus is

composed of many fibres and fibrils, in practice it functions as a single muscular
organ and myometrial contractions can be measured by placing a thin polyethylene
catheter into the amniotic fluid and by attaching this to a recording apparatus to
determine the amniotic pressure. Since this is proportional to the tension in the
myometrium, it measures myometrial* activity.

1.-Uterine muscles are never completely relaxed and between

contractions a restingtone, ranging between 6 and 12 mm Hg is found.
2. - The contraction causes a risk in intra-uterine pressure, and this rise
is called the intensity or amplitude of contraction.
3.- The frequency of contractions is expressed as the number per unit
of time.
4. - Much of the research on uterine activity has been done in
Montevideo Units, the product of intensity and frequency over a 10 minute
period gives a measurement of uterine activity.

Recently, studies of uterine activity have been made using a

cardiotocograph linked to a computer. The computer measures the area under
68

contraction, above the base line. This is expressed in kilo-Pascals per 15 minute in
the print-out.

In normal uterine action the intensity and incremental stage of the

contraction is greater in the upper segment.

At the junction of the Fallopian tube and uterus, on each side there is a
"pacemaker", hi each woman one or other pacemaker is dominant and it is from here
that all contractile waves originate. The wave passes inwards and downwards from
the peacemaker, at a rate of 2 cm per second, to involve the entire organ in a
contraction. In normal uterine action, the intensity and increamental stage of the
contraction is greater in the upper segment as the muscle is thicker, and there is a
higher proportion of actomyosin to contract. In this way the contraction is coordinated, the maximal amount of contraction occurring in the final part of the
uterus, and the peak of the contraction occurring in all parts simultaneously.

In the second stage of labor, voluntary contraction of the diaphragm and

abdominal muscles, added to the uterine contraction, propels the baby

downwards, through the dilated vagina and overcomes the resistance of

perineal muscles to its advance.

Uterine activity continues unaltered after expulsion of the fetus and

leads to the expulsion of placenta.

8.2. NORMAL LABOR AND DELIVERY.

PHISIOLOGICAL AND BIOCHEMICAL PROCESSES

The mechanism by which human parturition is initiated spontaneously, either

at term or preterm, is not known.

It is not possible to determine when labor begins. At the end of

parturition the myometrium must be prepared for generating coordinated contraction
of sufficient force to cause cervical dilatation and fetal descent. For this to happen
the cervix must be softened and ripened.

The myometrial cells capacity to regulate cytoplasmic Ca 2+

concentration must be restored: myometrial cell responsitivity and intracellular
communicability must be reinstituted. Then labor can begin.

For a time immediately after delivery the myometrium must be held in

a state of persistent contraction and retraction. This causes compression and
thrombosis of the large uterine vessels limiting uterine bleeding and preventing fetal
postpartum hemorrhage.

Uterine phases of parturition The uterine parturitional process,

is divided into three functional

69

 states:

=> Phase 0: is the prelude to parturition;

=> Phase 1: is the interval of uterine getting ready for labor,

when functional changes in myometrium and cervix which are required for labor are
implemented (last days of pregnancy);
=> Phase 2: is the period of active labor: the uterine contractions that bring
about progressive cervical dilatation, fetal descent and delivery. This phase of
parturition is divided into the three stages of labor;
=> Phase 3: - parturient recovery takes place, which culminates
in uterine involution and restored fertility, the duration of Ph.3 is dependent on the
duration of breast feeding (because of lactation-induced anovulation and
amenorrhea).

The initiation of parturition is the transition from uterine phase 0 to

phase 1 of parturition.

70


In this case the terms "uterotropin" and "uterotonin" must be defined.
A.
- Uterotropin is an agent that prepares the uterus: the

myometrium
and cervix enable the synthesis of functional elements that prepare the uterine
tissues for labor (e.g. gap junctions and oxytocin receptors) and cervical
softening. Uterotropin can be produced in the myometrium by paracrine or
endocrine mechanisms.
B.
- Uterotonin is a uterine smooth muscle contractant, such as
oxytocin, prostaglandins and endothelin 1. Uterotonins act directly on
responsive myometrial smooth muscle cells, to cause myometrial cell
contraction.

Maternal factors
Oxytocin acts through a specific plasma membrane receptors to stimulate
phosphatidylinositol hydrolysis and thereby the formation of inosite
phosphates (IP).

The synthesis of oxytocin receptors may be inhibited by the action of

progesterone.

The number of these receptors in the myometrium is increased during

labor.

Prostaglandins

In strips of myometrial tissues obtained from the uterus of pregnant

women, PGE2 and PGF2 are relatively ineffective in promoting and increasing
myometrial cell Ca2+ and cause a contractile response. The uterotonic action of
administered PG may be mediated indirectly.

Huge amounts of these agents are required to induce abortion or labor

when administered intraamniotically.

Endothelin 1 acts to increase the frequency of contractions in

myometrial tissue strips. This action is mediated through an increase in Ca 2+ by the
release of Ca2 from intracellular stores influx of extracellular Ca 2+. Endothelin 1 is
less effective in myometrial muscle tissue of pregnant women.

Myometrial Cell Ca2+

One of the major means of regulating myometrial Ca 2+ is through the

plasma membrane and sarcoplasmic reticulum calcium pumps, wich are ATP-asedependerit Ca2+ - extrusion systems.

The plasma membrane Ca2+ pump extrudes Ca2+ from the cell into the
extracellular fluid.
The sarcoplasmic reticulum Ca2+ ATP- ase pump transports cytoplasmic Ca2+
to the sarcoplasmic reticulum wherein Ca + is sequestered.
Increases in Ca + can be effected by the mobilization of Ca" into the
cytoplasma from the extracellular fluid or from sequestered stores in the
sarcoplasmic reticulum.

71

Other means of maintaining myometrial cell Ca^':

=> calmoduline which is required for Ca2+ activation of myosin light

chain-kinase;

^ Ca2* binding proteins could be localized either in the cytoplasm or in

the sarcoplasmic reticulum of the miometrial cells;

=>the sex steroid hormones (oestrogne and progesterone) acting

directly or indirectly.

Myometrial cell contractile responsive during phase 1 may lead to an

increase in Ca"+ with sufficient magnitude to permit the commencement of uterine
contraction.

Rises in Ca~+ favor increased prostaglandin-formation by activating

Ca2+ - phospholipases that serve to mobilize arachidonic acid from storage forms (in
amnion tissue).

The stress and hypoxia stimulate the production of oxytocin and

endothelin 1.

Gap-Junction

Transcellular membrane channels consist of connexons. A connexon is a

hexametric assemblage of a specific connexin (the gap-junction protein). Connexons
are a conduit for the exchange of small molecules and ions between cells.

Thereby, communication is established between coupled cells for the

passage of current (electrical or ionic coupling) or metabolites (metabolite coupling).
The number and size of gap-junction between myometrial cells increase
before the onset of labor.
Estrogen promotes gap junction formation in the myometrium (by increasing
connexin 43 synthesis).

Progesterone inhibits gap-junction formation.

Progesterone and oxytocin. Synthesis and withdrawal One hypothesis

is that uterine quiescence is maintained during pregnancy by progesterone, secreted
by syncytiotrophoblast. It is believed that in humans "a progesterone block" of
uterine activity is counteracted by estrogen. Estrogen which causes myometrial
hyperplasia and hypertrophy in pregnancy is also thought to initiate the synthesis and
release of prostaglandins by decidual cells.

In the last 3 or 4 weeks of pregnancy a change in the ratio between free

(unbound) estriol and progesterone occurs. Estriol levels continue to rise while
progesterone levels either remain on plateau or fall slightly.
This leads to a raised oestrogen/progesteron ratio. Increased estrogen levels
are known to enhance the synthesis of PG in uterine tissue.

On a cellular level it has been demonstrated that progesterone is less

capable of binding receptors in myometrial cells in the last week of pregnancy.
These findings confirmed, support the belief that the progesterone block is less
efficient as the term approaches.

72

Role of the fetus in parturition

Many investigators have searched for a fetal signal that will lead to the
suspension of uterine phase 0. Unfortunately such a fetal signal has not been
discovered in human pregnancy.

In sheep the parturition signal seems to arise in the fetal brain

(experimental model).
The fetal brain inteiprets multiple signals representing sufficient organ
maturity and the fetal pituitary is called upon to be the messenger.

In late pregnancy the fetal pituitary produces ACTH and oxytocin.

These two hormones may be involved in the coordinated rhythmic uterine
contraction which characterizes labor.

Conclusion
The cause of the onset of labor in humans is still unknown although in recent
years more facts have been discovered and the process is better understood on
laboratory animals.

73

9. CONDUCT OF NORMAL LABOR

AND

DELIVERY

Labor is the process of birth. In response to uterine contractions the

cervix dilates, the birth canal is formed, and the baby descends through the pelvis.

Identification of labor

One of the most critical diagnosis in obstetrics is the accurate diagnosis

of labor. If labor is wrongly diagnosed, inappropriate interventions to augment labor
may be made. If labor is not diagnosed, the fetus may be damaged by complications.

The differential diagnosis between false and true labor can be made on
the basis of the following features.

Contractions of true labor:

=> contractions occur at regular intervals;

=> intervals gradually shorten;
=> intensity gradually increases;
=> discomfort is in the back and in the abdomen;
=> cervix dilates;
=> discomfort is not stopped by sedation.

Contractions of false labor:

74

contractions occur at irregular intervals:

> intervals remain long;
> intensity remains unchanged;
-> discomfort is chiefly in lower abdomen;
-> cervix does not dilate;
> discomfort is usually relieved by sedation.

 The general condition of mother and fetus should be ascertained accurately by

history and physical examination, including blood pressure, temperature and

pulse.

The frequency, duration and intensity of uterine contractions should be

documented.

The heart rate, presentation and size of the fetus should be determined
and documented on admission. The fetal heart rate should be checked, especially at
the end of a contraction and immediately thereafter, to identify pathological slowing
of the heart rate. Inquiries are made about the status of the fetal membranes and
whether there has been any vaginal bleeding.

Admittance vaginal examination

Most often, unless there has been bleeding in excess of bloody flow, a
vaginal examination under aseptic conditions is performed. Careful attention to the
following items is essential in order to obtain the greatest amount of information and
to minimize bacterial contamination from multiple examinations. A vaginal
examination must be properly performed, with appropriate preparation and care. The
number of vaginal examination during labor, however, do correlate with morbidity,
especially in cases of early membrane rupture.

1. Cervix. Softness, degree of effacement (length), extent of dilatation of

the cervix with respect to the presenting part and vagina are ascertained. The degree
of cervical effacement is usually expressed in terms of the length of the cervical
canal. When the length of the cervix is reduced by one half, it is 50% effaced. The
amount of cervical dilatation is ascertained by estimating the average diameter of the
cervical opening. The cervix is said to be fully dilated when the diameter measures
10 cm, because the presenting part of a term-size infant can usually pass through a
cervix that is widely dilated.
2. Detection of rupture membranes

Rupture of the membranes is significant for three reasons. First, if the

presenting part is not fixed in the pelvis, the possibility of prolapse of the umbilical
cord on cord compression is greatly increased. Second, labor is likely to occur soon
if the pregnancy is at or near term. Third, if delivery is delayed for 24 hours-or more
after membrane rupture, there is likelihood of serious intrauterine infection.

3.

Station. The degree of descent of the presenting part into the

birth
canal is identified. The level of the presenting part in the birth canal is
described in relationship to the ischial spines, which are halfway between the
pelvic inlet and the pelvic outlet. When the lowermost portion of the
presenting fetal part is at the level of the ischial spines, it is designated as
being at zero (o) station. In the past, the long axis of the birth canal above the
75

ischial spines was arbitrarily divided into thirds. That is, if the presenting part
is at the level of the pelvic inlet, it is at (-3) station, if it has descended one
third the distance from the pelvic inlet to the ischial spines, it is at (-2) station,
if it has reached a level two thirds the distance from the inlet to the spines, it is
at(-l) station.

The long axis of the birth canal between the level of the ischial spines
and the outlet of the pelvis has been similarity divided into thirds. If the level of the
presenting part in the birth canal is one third or two thirds the distance between the
ischial spines and the pelvic outlet, it is at (+1) or (+2) station, respectively. When
the presenting fetal part reaches the perineum, its station is (+3). Progressive cervical
dilatation with no change in the station of the presenting part, in a woman of low
parity, implies fetopelvic disproportion.

4.

Pelvic architecture. The diagonal conjugate, ischial spines,

pelvic
sidewalls and sacrum are reevaluated for adequacy.

MANA CEMENT OF FIRST ST A GE OF LABOR

The first stage of labor in a primigrvida lasts up to 12 hours and

sometimes longer and in a parous woman is usually 4 to 8 hours. In the first stage we
must pay attention to: care of the mother, care of the baby and progress in labor.

Care of the mother

Pulse rate, blood pressure and urinary output are measured
regularly. Analgesia is given as required.

The method chosen depends on the mother's preference, her reaction to

her contractions. There are different methods:
a. inhalation - Entonox is a 50/50 mixture of oxygen and nitrous oxide.
Self administration by inhalation through a mask attached to a cylinder;
b.narcotic drugs: Pethidine 100-200 mg; Morphine 10-20 mg.
Pentazocine (Fortral).

The first two may be combined with Promazine (Sparine) to reduce the

incidence of nausea. All three drugs depress fetal respiration and Naloxone
(Narcon Neonatal) should be used intravenously or intramuscularly if the baby
is affected.

c. continuous epidural anaesthesia

Bupivicaina 0,25% or 0,5% is instilled at 3-4 hours intervals through a
catheter inserted into the epidural space. This gives the patient complete
freedom from pain of labor.

Epidural anaesthesia should be administered by an experienced anaesthetist

and supervised by him throughout labor. Complications: mild hypotension; ->
sepsis; > bladder atony;
76

> total spinal block (if the substance is injected

into the cerebrospinal space).

Care of the baby

Assessment of the baby's condition in labor depends essentially on

observations of the fetal heart rate. The traditional method of recording the fetal
heart intermittently, between contraction by the Pinard stethoscope, suffers from the
grave drawback that the changes in the heart rate in association with uterine
contractions cannot be detected.
The presence of meconium in the liquor should always be noted. It is
postulated that fetal anoxia leads to vagus, stimulation of the fetal gut
resulting in the passage of meconium.

Fetal heart rate monitoring provides a continuous printed record of the

fetal heart rate and uterine contractions and also gives an immediate indication of the
FH through a ratemeter. a flashing light and an audible signal.

The F}IR may by recorded through an ultrasonic transmitter-receiver (a

transducer) or through the fetal EKG obtained with an electrode implanted in the
fetal scalp.

Uterine contractions are recorded by an external tocography a very

delicate pressure gauge or more accurately by an intrauterine catheter.

Interpretation of intrapartum FHR tracings l.The average baseline

rate should be between 120 to 160 beats, minute. Sustained tachycardia may be a
warning of fetal distress and prolonged or severe bradycardia is obvious.

2.
Baseline variability

The normal FHR fluctuates by 10 beats/min every 5 seconds-evidence

of fetal ability to react normally to the stress of labor.

Loss of this variability, especially in association with tachycardia,

indicates severe hypoxia ( this is sometimes referred to as "beat-to-beat variation").
3.
Response of FHR to uterine contractions

The uterine contractions act as a stress to the fetus, producing a

transient reduction in the oxygenated blood supply.
The normal FHR should be maintained with the contraction or it must present
only a slight deceleration of less, than; 40 beats/min. If it is greater than this,
and especially if there is a "lag phase" or late deceleration occurring after the
period of uterine contraction, a pathological degree of hypoxia may be present

Decelerations may be classified as:

a.Early where the lowest rate of the FHR coincides with the peak of
contractions. They may be normal in late labor, and should not be ignored if
persistent or severe;
b.
Late, where the lowest rate of the FHR follows the peak of
contractions. They are indicative of hypoxia;

77

 c.Variable, where the pattern and timing of deceleration varies with

contractions. These are thought to be due to cord compression. They should

not however be ignored if persistent or associated with other adverse features.

Fetal blood sampling

During the normal labor the mother develops a metabolic acidosis but
the pH is maintained at 7.38. In disftinctional labor the acidosis may be of such a
degree as to bring about an actual lowering of the pH. To obtain a sample of fetal
blood for pH estimation, a special tube is passed trough the cervix which must be
sufficiently dilated (micro ASTRUP).

The partogram - a graphic display of programs in labor, has become

widely used in many different situations.

Friedman conceived a graph of cervical dilatation and time (a

cervicogram) and applied it to the clinical management of labor.

Having been introduced initially to illustrate dilatation of the cervix and

to give warning of failure of normal progress, partograma is now used to illustrate all
the routine observations on mother and baby together with uterine action and drug
therapy.

MANAGEMENT OF SECOND STAGE OF LABOR

Identification- With full dilatation of the cervix which signifies the onset of

the second stage of labor, the woman typically begins to bear down, and with
descent of the presenting part she develops the urge to defecate. Uterine
contractions and the accompanying expulsive forces may last 1,1/2 minutes
and recur at a time after a myometrial resting phase of no more than a minute.

The medial duration of the second stage is 50 minutes in nulliparas and

20 minutes in multiparas, but it can be highly variable.
Feta\ heart rate- For the \ow-risk fetus, the heart rate shou\d be ascultated
during the second stage of labor at least every 15 minutes, whereas in those at
high risk, 5 minute intervals are recommended.

Maternal expulsive efforts - In most cases, bearing down is reflex and

spontaneous during second-stage labor but occasionally the woman does not employ
her expulsive forces to good advantage and coaching is desirable. Her legs should be
half- flexed so that she can push with them against the mattress. Instructions should
be to take a deep breath as soon as the next uterine contraction begins and with her
breath held, to exert downward pressure exactly as though she were straining at
stool. She should not be encouraged to "push" beyond the time of completion of
each uterine contraction.

Usually, bearing down efforts are rewarded by increasing bulging of the

perineum that is produced by further descent of the fetal head. The woman should be
informed of such progress for encouragement as this stage is very important.

78

During this period of active bearing down, the fetal heart rate ascultated
immediatly after the contraction is likely to be slow, but should recover to normal
range before the next expulsive effort.
As the head descends, the perineum begins to bulge and the overlying skin
becomes tense and glistening. Now the scalp of the fetus may be visible
through the vulvar opening.

Preparation for delivery. Actual delivery of the fetus can be

accomplished with the mother in a variety of positions. The most widely used and
often the most satisfactory one is the dorsal lithotomy position in order to increase
the diameter of the pelvic outlet. Preparation for actual delivery entails vulvar and
perineal scrubbing and usually covering with sterile drapes in such a way that only
the immediate area about the vulva is exposed.

Delivery of the head. With each contraction the perineum bulges

increasingly and the vulvovaginal opening becomes more dilated by the-fetal head,
gradually forming ah-ovoid and finally an almost circular opening. As the head
becomes increasingly visible, the vaginal outlet and vulva are stretched further until
they ultimately encircle the largest diameter of the baby's head. This encirclement of
the largest diameter of the fetal head by the vulvar ring is know as "crowning"

Ritgen maneuver By the time the head distends the vulva and perineum
(during a contraction) enough to open the vaginal introitus to a diameter of 5 cm or
more, a towel-draped, should be applied and a gloved hand should be used to exsert
forward pressure on the chin of the fetus through the perineum just in from of the
coccys. At the same time the other hand exserts pressure up against the occiput. It
allows the physician to control so that the head is delivered with its smallest
diameter. The head is delivered slowly with the base of the occiput rotating around
the lower margin of the symphysis pubis as a fulcrum; while the bregma (anterior
fontanel) brow, and face pass successively over the perineum.

Clearing the nasopharynx. To minimize the likelihood of aspiration of

amniotic fluid debris and blood that might occur once the thorax is delivered and the
infant can inspire, the face is quickly wiped and the-nares and mouth are aspirated.

Nuchal cord. Next, the finger should be passed to the neck of the fetus
to ascertain whether it is encircled by one or more coils of the umbilical cord. If a
coil of the umbilical cord is felt, it should be drawn down between the fingers and, if
loose enough, slipped over the infant's head. If it is applied too tightly to the neck to
be slipped over the head, it should be cut between two clamps and the infant
promptly delivered.

Delivery of shoulders. After its birth, the head falls posteriorly,

bringing the face almost into contact with the anus. The occiput promptly turns
toward one of the maternal thighs so that the head assumes a transverse position. The
movement of restitution (external rotation) indicates that the bisacromial diameter

79

(transverse diameter of the thorax) has rotated into the anteroposterior diameter of
the pelvis.

Most often the shoulders appear at the vulva just after external rotation
and are bom spontaneously! Occasionally a delay occurs and immediate extraction
may appear advisable. In this event, the sides of the head are grasped with the two
hands and gentle downward traction applied until the anterior shoulder appears
under the pubic arch. Then, by upward movement, the posterior shoulder is
delivered.
The rest of the body almost always follows the shoulders without difficulty,
but in case of prolonged delay, its birth may be hastened by moderate traction
of the head.

Immediately after delivery of the infant, there is usually a gush of

amniotic fluid, often tinged with blood but not grossly bloody.

Clamping the cord. The umbilical cord is cut between two clamps
placed 4,or 5 cm from the abdomen, and later an umbilical cord clamp is applied 2
or 3 cm from the fetal abdomen.

MANAGEMENT OF THIRD STAGE OF LABOR

Immediately after delivery of the infant, the height of the uterine fundus and

its consistency are ascertained. As long as the uterus remains firm and there is
no unusual bleeding, watchful waiting until the placenta is separated is the
usual practice. No massage is practised, the hand is simply rested, on the
fundus frequently to make certain that the organ does not become atonic and
filled with blood behind a separated placenta.

Signs of placental separation As the attempts to express the placenta

prior to its separation are futile and possibly dangerous, it is most important that the
following signs of placental separation should be recognized:(l) Tine uterus becomes
globular and as a rule firmer. This sign is the earliest to appear.(2) There is often a
sudden gush of blood. (3) The uterus rises in the abdomen because the placenta,
having separated, passes down into the lower uterine segment and vagina, where its
bulk pushes the uterus upward.(4) The umbilical cord protrudes farther out of the
vagina, indicating that the placenta has descended.These signs sometimes appear
within about a minute after delivery of the infant, usually within 5 minutes. When
the placenta has separated, it should be ascertained that the uterus is finnly
contracted. The mother may be asked to bear down, and the intraabdominal pressure
so produced may be adequate to expel the placenta. If these efforts fail or if
spontaneous expulsion is not possible because of anesthesia, and after ensuring that,

80

uterus is contracted firmly, pressure is exerted with the hand on the fundus to propel
the detached placenta into the vagina.

Delivery of the placenta Placental expression should never be forced before

placental separation lest the uterus is turned inside out. Inversion of the uterus
is one of the gravest complications associated with delivery. As pressure is
applied to the body of the uterus, the umbilical cord is kept slightly taut. The
uterus is lifted cephaled with the abdominal hand. This maneuver is repeated
until the placenta reaches the introitus. Traction on the umbilical cord must
not be used to pull the placenta out of the uterus. If the membranes start to
tear, they are grasped with a clamp and removed by gentle traction. The
maternal surface of the placenta should be examined carefully, to ihsure that
no placental fragments are in the uterus.
W*ff3&vvflf s b - r !1?f^:i
..fwhti j t -' ^l ^ \q ai:..i%fn. :/?si t 'h..*ffiffii

tftx$-HfiHfrzi* ; '>il^68*gnpH^ .V; tf&taaRft mU>mz tob*8

::-rftWJi'.; Oft:
''^'VlM^ QtlliMM l&smftU, fr'fl ?? QTfciib bail

:-

'

^i&d. him-.-tifi W ic-'ll 'U:-xc;!vf!i .

'

- .

2fjt 1$

r.v- l h e V.

f c ^qrnjoTq

>i tJygMB^st s&i stenosis ?8te^R?riW

ttufttw !uu'3ii Jri&ini 11 to

81

fhi ::

10.

THE PHYSIOLOGY OF THE PUERPERIUM

Puerperium is defined as the period of confinement during and just after

birth. Most specialists consider the first 6 weeks of postpartum to be the Puerperium.
During this time the reproductive tract returns anatomically to a normal nonpregnant
state, and in most women who are not breast feeding, ovulation is reestablished.
Classification:
1. Early Puerperium: 4 hours after childbirth
2. The veritable Puerperium: 10 days after childbirth
3. Late puerperium: 30 days after child birth.
L Early puerperium. The woman rests in the delivery room. Pulse and blood
pressure must be observed the form and consistence of the uterus as well. If
Pinard's globus is present it can be detected by inspection and palpation of the
uterus. It is firm and globulous due to contraction and retraction of the uterus.
Blood loss is about 250 ml.
2. The veritable puerperium
a)
Specific phenomena: > involution of the uterus;

-> the lochia;

lactation.
b)
Modifications of the organs and systems
Involution of the uterus, lmmediatly after placental expulsion, the fundus of
the contracted uterus is slightly below the umbilicus. The process by which the
uterus returns to nonpregnant state is known as "involution". Involution is
caused by the phenomenon of autolysis: enzymatic digestion of excess
cytoplasm and thrombosis, and hyaline degeneration of vessels. The
endometrium is regenerated by the 10-th day except at the placental site,
where it takes 6 weeks. The uterus reduces by about 1 to 1,5 cm/day. Fundal
height is measured each day. Failure of involution suggests retained placental
tissue.

82

 The lochia. Early in the puerperium, sloughing of decidual tissue results in a

vaginal discharge of variable quantity, this is termed lochia. Microscopically,

lochia consists of erythrocytes, shreds of decidua, epithelial cells and bacteria.

For the first few days after delivery, blood, which is termed the lochia is
sufficient to color it red, which is tenned "lochia rubra". After 3 or 4 days, lochia
becomes progressively paler, or "lochia serosa". After the 10-th day, because of an
admixture of leukocytes and a reduced fluid content, lochia assumes a white or
yellowish-white color, or "lochia alba". Foul-smelling lochia is suggestive of
infection, but such and odor is not diagnostic. The quantity of the lochia varies from
day to day and the total quantity is 1000 ml.

Lactation and breast feeding. During pregnancy the breasts develop.

This is a consequence of the increased circulating estrogen and p/ogesterone and is
probably influenced by HPL secreted by the syncytiotrophoblast. Estrogen leads to
an increase both in size and number of the duct system. Progesteron appears to
increase the number of alveolar cells. HPL stimulates the development of the cells
lining the acini or alveoli and probably initiates die changes in the cell structure
leading to the synthesis of casein, lactalbumin and lactoglobulin.

During pregnancy the breast secretes colostrum. It is a yellowish fluid,

containing a much greater quantity of proteins than normal milk, plus desquamated
endothelial cells. Its high gamma-globulin content may be a provision for the supply
of antibodies which the baby must acquire in the first month (protection against
disease).

Following child birth and placental expulsion the oestrogen levels fall
within 3 days, permitting prolactin to act on the alveoli to initiate lactation.

Neurohypophysis releases oxytocin by reflex suckling.

The oxytocin causes contraction of the myo-epithelial cells and ejection

of milk from the alveoli.

For the maintenance of lactation suckling is essential and it is also

necessary to have normal levels of ACTH, growth hormone, thyroid hormone and
insulin. Milk ejection or "letting down" is a reflex initiated especially by suckling,
which stimulates the neurohypophysis to liberate oxytocin. The major components
of milk are proteins, lactose, water and fat. All vitamins except vitamin, K are found
in the human milk, but in variable amounts.
Changes in the cervix and vagina. Immediatly after the third stage of labor, the
cervix and the lower uterine segment are thin, collapsed, flabby structures.
The outer margin of the cervix is usually lacerated, especially laterally-The
cervical opening contracts slowly for a few days immediately after labor. By
the end of the first week it has narrowed to a one-finger diameter. As the
cervical opening narrows, the cervix thickens and a canal is reformed.
Vagina and vaginal outlet Early in the puerperium, the vagina form a
capacious, smooth-walled passage that gradually diminishes in size but rarely

83

returns to nulliparous dimensions. The hymen is represented by several small

tags of tissue, which during cicatrization are converted into the myrtiform
caruncles characteristic to parous women.
Changes in the urinary tract

In the first few hours after delivery micturition may be difficult,

partially because of reflex suppresion of detrusor activity and sphincter spasm from
irritation of the levator and museles during delivery and partially due to oedema of
the bladder base which occurs in labor. During the first 1 or 2 days a marked diuresis
occurs, because of a fall in preogesterone content of the blood and the alteration of
cell metabolism to the non-pregnant state.

Blood. Rather marked leukocytosis occurs during and after labor, the
leukocyte count sometimes reaching 30000 per niL. The increase is predominantly
based on granulocytes. There is also a relative lymphopenia and an absolute
eosinopenia.

Normally, during the first few postpartum days, hemoglobin, hematocrit

and erythrocyte counts fluctuate moderately. By one week after delivery, the blood
volume has returned to almost its nonpregnant level.

Pregnancy induced changes in blood coagulation factors persist for

variable periods during the puerperium. Elevation of plasma fibrinogen is
maintained at least through the first week, and as a consequence, the elevated
sedimentation rate normally found during pregnancy remains high.

Bowel function: constipation has become much less of a problem in the

puerperium. Routine prescription of a stool softener is a common practice.
3. Late puerperium

Following vaginal delivery if there are no puerperal complications,

hospitalization is seldom warranted for more than 48 hours, excluding the day of
delivery. Before discharge, the woman should receive instruction concerning the
anticipated normal physiological changes of the puerperium,including changes in
lochia patterns, weight loss due to diuresis and when to expect milk let down.
She should also receive instructions concerning what to do if she
becomes febrile, has excessive vaginal bleeding, or develops leg pain, swelling or
tenderness.
Restoration of ovulation and menstruation

The more frequently the child suckles, the higer is the plasma prolactin
level and the longer ovulation is delayed. However, in a proportion of lacting
women, especially those who only partially breast-feed, ovulation may occur and
subsequently pregnancy without any menstrual period.
Ovulation is unusual among lactation women for about 20 weeks.

Menstruation may start earlier: 10% of breast-feeding women

menstruate by the 10-th week after childbirth, 40% by 20 weeks and 60% are
menstruating by 30 weeks.

84

.iflKjjfeq* la&cttriq

m: . / - i v i ?-:. 'W&vCf in

^rjf. iWddva&^vbxrt v^rstthmiOSQ ;iw* .

-i^

1" ^li&j^yffti :-y. -

i^S-Ubtffcffi

'

'

if

,[; /ad ^nmt:ynimi- eii^gofpi;; oi to ufti sruuhv boold wf]

.^iwibh jot ei^adf -giciaoi ft ^xiMm^^byotii & : ;^vr*pH--towr.^r

>3ftf.^Sl*l

-:

85

toicvofe>d* .Mr?

tT.vcif>o.- > bno;>i^:;- p - S&'dstf/wHrfl te [isaiclnififn

86

11. MEDICAL AND

SURGICAL DISORDERS
IN PREGNANCY

HEART DISEASE IN PREGNANCY

The major cardiocirculatory changes that occur .during normal

pregnancy include an increase in total blood volume and cardiac output and a
decrease in peripheral vascular resistance.

The added hemodynamic burden of pregnancy, labor and delivery can

aggravate symptoms and precipitate complications in woman with preexisting
cardiac disease.

Cardiovascular disease is one of the most important nonobstetric cause

of disability and death in pregnant women occurring in about 1% of all pregnant
women.

The influence of pregnancy on cardiovascular disorders In the past, almost

all were of rheumatic origin, but improvements in the treatment of rheumatic

fever have decreased the incidence of significant valvular lesions. As a
consequence, there has been a reduction in the total number of pregnancies
complicated by heart disease but the proportion caused by congenital
malformation has increased.

The American College of Obstetricians and Gynecologists has recently

(1992) classified women in three groups according to risks for death during
pregnancy:
- group 1 atrial septal defect
ventricular septal defect mortality 0-1% patent ductus arteriosus
mitral stenosis (class I and II)

- group 2 mitral stenosis (class III and IV)

aortic stenosis
aortic coarctation (without valvular involvement) mortality 5-15%

Fallot tetralogy (uncorrected)

artificial valve

- group 3 pulmonary hypertension

aortic coarctation with valvular involvement mortality 25-50% Marfan's

syndrome Eisenmenger s syndrome Mitral stenosis is the most common lesion

in young women with rheumatic heart disease. Most patients with mild to
moderate stenosis who are in sinus rhythm tolerate pregnancy well.

Those with moderate to severe disease are more likely to develop

complications such as pulmonary venous congestion or frank pulmonary edema,
right ventricular failure, pulmonary vascular hypertension, hemoptysis, atrial
fibrillation, systemic or pulmonary emboli and infective endocarditis.

However, sudden and unexpected deterioration can occasionally occur

during pregnancy with any degree of mitral stenosis.

The other common causes of pulmonary hypertension are:

^increased resistance to pulmonary blood flow at any of the several
sites in the pulmonary vascular bed (due to multiple pulmonary emboli, as primary
pulmonary vascular disease);
=> increased pulmonary blood flow as in left-to-right intra-orextracardiac shunts (Eisenmenger s syndrome);
=> increased resistance to pulmonary venous drainage (as in left
ventricular failure);
=> pulmonary parenchymal disorders (chronic fibrosis).

In patients with pulmonary hypertension the right ventricle tends to fail

early in pregnancy owing to the added hemodynamic load. Later in pregnancy, rapid
hemodynamic changes such as postural hypotension or a decrease in venous return
result in a sudden decrease in cardiac output with syncope. These patients are at
particularly high risk in the last trimester and during parturition.

Rhythm disturbances are common in pregnancy and most are well

tolerated in the absence of underlying heart disease unless the ventricular rate is over
200/min and the episodes are prolonged.

In patients with heart disease, especially those with mitral stenosis and
hypertrophic cardiomyopathy, tachycardia is poorly tolerated and can lead to rapid
decompensation. Cardiac arrhythmias may also be the first manifestation of serious
cardiac problems in patients in whom heart disease was not previously suspected.
Diagnosis and treatment of arrhythmias require the attention of a skilled internist or
cardiologist.

Even if patients with pulmonary hypertension appear to be at greatest

risk, most deaths are caused by heart failure. Alhough this can occur at any time, it is
most common when the maternal blood volume is at maximum. The normal heart
has no difficulty in increasing its output as the plasma volume expands, but if there
has been significant valvular damage the heart may be unable to respond to this and
other demands as well.

Failure can occur at the labor time when demands are greater than they
have been during pregnancy. Cardiac output reaches a maximum during labor and
delivery and then declines slightly during the first few hours after delivery. During
each contraction 250 to 300mi of blood is forced from the uterine into systemic
circulation.

Many of the physiological changes of normal pregnancy tend to make

the diagnosis of heart disease more difficult. Most cardiovascular diagnostic studies
are noninvasive and can be conducted quickly and efficiently in pregnant women.
Evaluation of the pregnant woman in whom heart disease is suspected should
include a careful medical history, complete physical examination and
noninvasive laboratory tests in order to establish a diagnosis and anticipate the
prognosis.

In patients with a previous diagnosis of heart disease, the physician

should ask for the following information: age at diagnosis, previous symptoms and
complications, previous diagnostic procedures, prior drug treatment etc.

In patients without an established diagnosis of heart disease, the

physician should inquire about a history of rheumatic fever and other illnesses that
may be related to heart disease.

There are some clinical indicators of heart disease during pregnancy:

=> symptoms: severe or progressive dyspnea, progressive orthopnea,

paroxysmal nocturnal dyspnea, hemoptysis, chest pain related to effort or emotion,
chronic cough;

=^> clinical findings: cyanosis, clubbing of fingers, persistent edema of

extremities, increased jugular venous pressure, systolic murmur of grade III or IV
intensity or palpable thrill, diastolic murmur, sustained arrhythmia, persistent split
second sound.
Certainly, clinical suspicion of heart disease warrants further investigation.
In most cases, conventional testing to include electrocardiography;
echocardiography and chest radiography will provide the necessary data. If
indicated, right-heart catheterization can be performed without X-ray
guidance.

The characteristic findings on physical examination, echocardiography

and electrocardiography are well described in standard texts. Careful assessment by
both the cardiologist and obstetrician should ensure that the patient's hemodynamic
status remains optimal during pregnancy.
There is no clinically applicable test for accurately measuring functional
capacity of the heart. A helpful clinical classification was first published in
1928 by the Heart Association and was revised for the eighth time in 1979.
Thus, the classification is no longer based only on clinical symptoms. Still, for
use in pregnancy, a functional classification is important.

The lesions are classified according to the functional grading of the

New York HeartAssociation as follows:

=> class 1 = patients with cardiac disease and no limitation of physical

activity; these patients do not have symptoms of cardiac insufficiency nor anginal
pain (uncompromised patients);
class II = slightly compromised: patients with cardiac disease and slight
limitation of physical activity; they are free from symptoms while at rest, but
ordinary activity is accompanied by undue fatigue, palpitation, dyspnea or anginal
pain;

=> class III = markedly compromised: patients with cardiac disease and
marked limitation of physical activity; less than ordinary activity causes discomfort
in the form of excessive fatigue, palpitation, dyspnea or anginal pain;

=> class IV = severely compromised: patients with cardiac disease and

inability to perform any physical activity without discomfort; symptoms of cardiac
insufficiency or of the anginal syndrome may develop even at rest and any activity
increases them.

Influence of cardiovascular disease on pregnancy In patients with limited

ability to increase cardiac output due to valvular or myocardial disease, the

added hemodynamic burden leads to -'symptoms early in pregnancy (often by
20 weeks) when blood volume has increased considerably. The increase in
blood flow to die uterus is limited resulting in increased incidence of
prematurity and low-birth-weight babies.

In women with cyanotic heart disease (Fallot tetralogy) the incidence of

spontaneous abortion may be as high as 60% and preterm delivery and fetal growth
retardation are common. There is a relation between chronic hypoxemia and the
polycytemia it causes with the outcome of pregnancy. When hypoxemia is intense
enough to stimulate a rise in hematocrit above 65%, pregnancy wastage is virtually
100%.
With satisfactory surgical correction prior to pregnancy maternal risks are
decreased dramatically and fetal environment is improved.

Since many drugs cross the placenta, their use during pregnancy has
potential for being teratogenic or directly harmful to the fetus (beta adrenergic
blocking agents, coumarin derivatives, phenytoin ete).

Operations to correct heart lesions are : seldom necessary during

pregnancy as it is indicated by the excellent results that can be obtained by medical
treatment alone. Whenever possible, the operation should be performed during the
first trimester (but, when necessary, it can be done later).
Although the experience in treating women with heart valve prostheses is
limited, it appears that they are resonable candidates for pregnancy but require
even more care than do other women with heart disease. Most of them must
be treated with antibiotics and mantained on heparin through pregnancy.
Warfarin (or Coumadin, an anticoagulant) crosses the placenta, is teratogenic
and should not be used during pregnancy.

Cardiovascular disease treatment during pregnancy

Women with serious heart disease probably should not become

pregnant. Maternal mortality varies directly with functional classification.
Therapeutic abortion is unnecessary in women with milder lesions and even in those
in classes III and IV if they can be provided proper care during the entire pregnancy.
Unfortunately, this is not always possible and if a patient cannot or do not follow
advice, the risk from continuing pregnancy may offer a serious threat to her lite.

If proper treatment cannot be administered, termination of pregnancy

and tubal sterilization are justifiable for the following patients .

> those who have decompensated previously,, particularly those who

have been in failure between pregnancies;
> those with atrial fibrillation;
- those in functional classes III and IV;
^> those over age 35 years with serious lesions;
those with pulmonary hypertension.

Management of classes I and IT

With rare exceptions, women in class I and most in class 11 go through

pregnancy without morbidity. Special attention should be directed toward both
prevention and early recognition of heart failure (almost 40% of class I patients
developed frank cardiac failure in a study made in 1981 by Sugrue and associates).

A specific routine that assures adequate rest should be outlined for each
woman. The pregnant woman should rest in bed for 10 hours each night and she
should lie down for half an hour after each meal. Light housework and walking
without climbing stairs are permitted. She should do no heavy work.

Items, rich
in
sodium
should
be
avoided.
Weight
gain
should
not
exceed 12 Kg.
?

Infections have proved to be an important factor in precipitating cardiac

failure. Each woman should receive instruction to avoid contact with persons who
have respiratory infections and to report at once any evidence of an infection.

Cigarette smoking is to be vigorously prohibited (because of its cardiac

effects as well as the propensity to cause upper respiratory infections). Alcohol use
is contraindicated for fetal reasons.

Illicit drug use may be particularly harmful as with the cardiovascular

effects of cocaine or amphetamines as well as the propensity for intravenous use of
any illegal substance to cause infective endocarditis.

The onset of congestive heart failure is often gradual. The first warning
sign of cardiac failure is likely to be persistent rales at the base of lungs frequently
accompanied by a cough.

A sudden diminution in the woman's ability to carry out her household

duties, increasing dyspnea on exertion, attacks of smothering with cough and
hemoptysis are other signals warning of serious heart failure as are progressive
edema and tachycardia.

-J.

' www

Management of class ill

Women in class HI cardiac disease present difficult problems that

demand expert medical care.The important question is whether pregnancy should be

undertaken. If women choose to become pregnant they must understand the risk and
cooperate fully with planned care.

Hospitalization and bed throughout pregnancy are recommended for

any woman in class 111 disease. Application of this basic principle, together with
good medical and obstetrical care reduced the maternal death rate to not much more
than that of the general obstetrical population.

Digitalis, sodium restriction and diuretics may be necessary for treating

congestive failure and atrial arrhythmias. Patients with chronic atrial .fibrilation
should be given heparin as an anticoagulant. Oral anticoagulants are contraindicated.

Anemia, intercurrent infection and thyrotoxicosis should be corrected.

Management of class IV
Treatment of women in class IV heart disease is essentially that of
cardiac failure in pregnancy, labor and the puerperium. Accordingly, treatment of
heart failure in pregnancy is primarily medical rather than obstetrical.

Surgical treatment

Occasionally, cardiac function in patients with valvular disease may

deteriorate and, when medical management fails, cardiac surgery may become
necessary. In patients with severe mitral stenosis, especially if manifested in
childhood, mitral valvotomy is often performed for relief of symptoms before
pregnancy.
Closed mitral commissurotomy can be performed any time during pregnancy
but is rarely necessary as a lifesaving procedure until cardiac output has
increased significantly in the late second or early third trimester.

In an occasional patient, mitral valve replacement may be necessary as

an emergency procedure during pregnancy. Recent reports indicate a low mortality
rate for both mother and fetus with cardiopulmonary bypass. However, open heart
surgery should be deferred until after the first trimester, if possible.

Care during labor, delivery and puerperium

Delivery should be accomplished vaginally unless there are obstetrical

indications for cesarean delivery. In spite of the physical effort inherent in labor and
vaginal delivery, less morbidity and mortality are associated with it.

Induction of labor for heart disease alone is contraindicated.

In some women with severe heart disease pulmonary artery catheterization
may be indicated for continuous hemodynamic monitoring. This may be
performed electively when labor begins or planned cesarean delivery is
performed.
During labor, the patient should be kept in a semirecumbent position.
The best index of the condition of the heart during labor is offered by pulse,
respiratory rates and blood pressure measurements. Pulse and respiration may
be checked between contraction at least four times every hour during the first
stage of labor and every 10 minutes during the second stage. Increases in the
pulse rate much above 100/miti or in the respiratory rate above 24,
particularly when associated with/dyspnea, suggest impending ventricular

failure. If there are any signs of begimiing decompensation, oxygen should be

administered and the patient should be given digitalis.

Pain, anxiety and muscular activity add to th burden on the heart and
the physician should try to eliminate them. This is best achieved with an epidural
anesthetic. If caudal or epidural anesthesia is not available the discomfort can be
relieved with morphine sulfate or meperidine.

In the presence of pulmonary edema, oxygen is .given by intermittent

positive-pressure, digitalis in the form of a rapidly glycoside intravenously and
furosemide (20 to 50mg) intravenously too.

Epidural analgesia is preferable when forceps or vacuum extraction are

used to shorten the second stage.

Many cardiologists and perinatologists recommend prophylactic

antibiotics in all cases of congenital or acquired heart disease to prevent subacute
bacterial endocarditis in uncomplicated vaginal deliveries.

If coincidental hemorrhage is manifest, careful blood replacement and

arrest of the hemorrhage are important.

Cesarean operation will be practised only in obstetrical indications.

Women who have shown little or no evidence of cardiac distress during

pregnancy, labor or delivery may still decompensate after delivery. Therefore it is
important that the same meticulous care provided during the antepartum and
intrapartum periods be continued into the puerperium. Postpartum hemorrhage,
anemia, infection and thromboembolism are much more serious complications in the
woman with heart disease.
If there was no evidence of cardiac compromise during labor, delivery and the
early puerperium, breast feeding is usually not contraindicated.

Reproduction in women with heart disease should usually be limited,

the size of family being determined by the functional capacity of the heart. The
patient should be instructed about a reliable contraceptive method before she leaves
the hospital. Tubal sterilization may be considered if the parents desire no more
children and if the operation can be performed with only slight risk.
Prognosis

The likelihood of a favorable outcome for the mother with heart disease
depends upon:> the functional capacity of the. heart;
> other complications that further increase the cardiac load;
> quality of medical care provided (psychological and socioeconmica! and
cultural factors also may assume great importance).

Cardiac failure is just as likely to develop during the last few weeks of
pregnancy or during labor and the puerperium. According to Sullivan &
Ramanathan( 198-5) maternal mortality is 0.4% in classes I and II, but McFaul and
coworkers (1988) encountered no maternal deaths in 445 such women. Maternal
mortality for classes III and IV has been reported to be 4 to 7%.
>
Most deaths are caused by heart failure. Although this can occur at any
time it is most common when the maternal blood volume is at a maximum.
>

>

DIABETES MELLITUS DURING PREGNANCY

Classification
The National Diabetes Data Group (1979) classifies diabetes in type 1
diabetes (often used synonymously with insulin-dependent diabetes) and type 2
which implies non-insulin dependent disease.
> Women whose pregnancies are complicated by diabetes can be separated into
those who were known to have diabetes before pregnancy and those with
gestational diabetes.
>
P. White classification (1978) was designed originally to prognosticate
pregnancy outcome, because infant survival decreased with increasing severity of
diabetes. The classification suggested by the American College of Obstetricians and
Gynecologists (1986) relates the duration of diabetes to the severity of end-organ
derangement, especially the eyes, kidneys, cardiovascular system.
>

Gestational diabetes

> Pregestational

diabetes

Pregestational diabetes

Diagnosis during pregnancy

>
High plasma glucose levels, glucosuria and ketoacidosis are elements of
diagnosis. Women with only minimal metabolic derangement may be difficult to
identify. In these cases diagnosis is based on: => strong familial history of diabetes;
=> large infants or unexplained fetal losses; => persistent glucosuria. Commercially
available diosticks may be used to identify glucosuria. The detection of glucosuria
during pregnancy warrants further investigation

> (even then, glucosuria most often reflects augmented glomerular filtration).
>

Effect of pregnancy on diabetes

>
During pregnancy, control of diabetes is usually made more difficult
due to a variety of complications. Nausea and vomiting may lead on the one hand to
hypoglycemic shock and on the other to insulin resistance if starvation is severe
enough to cause ketosis. The pregnant woman is more prone to develop metabolic
acidosis than when nonpregnant.
>
Infection during pregnancy commonly results in insulin resistance and
ketoacidosis unless it is recognized promptly and both infection and diabetes treated.
> The exertion of labor accompanied by the ingestion of little or no carbohydrate
may also result in troublesome hypoglycemia unless the amount of insulin
given is reduced accordingly, or glucose is provided by intrvenous infusion.
>
After delivery, the need of exogenous insulin most often decreases at a
rapid rate and to a considerable degree. Hypoglycemic shock occurs more often in
the immediate period following delivery than at any other time in pregnancy. This
can be prevented by appropriate reduction in insulin dosage and frequent chemical
observations.
> Effects of diabetes on pregnancy
>
Maternal effects of diabetes include the following :
The likelihood of preeclampsia-eclampsia is increased about four times. This
incidence is increased even in the absence of demonstrated preexisting
vascular or renal disease;
Some bacterial infections are more common in diabetic pregnancy;
Water balance is readily disturbed. Both fetal and maternal edema are common
complications. Hydramnios occurs in 5 to 50% of diabetic
> mothers;
> Excessive size of the infant (macrosomia) is so common a finding that
unrecognized maternal diabetes should be suspected in patients who deliver babies
weighing more than 4320g (9 pounds);
>
The rate of cesarean delivery is increased;
> Maternal mortality is increased because of the complications of diabetes
as well as an increased risk for hypertension, infection and operative delivery.
> Fetal and neonatal effects :
> 0 Stillbirth and neonatal death rates are increased even with mild maternal
diabetes. The risk of intrauterine fetal death rises sharply after the 36th week;
> 0 The incidence of preterm delivery in many cases induced because of
hypertension, is increased two to three times. Newborn infants of mothers with
diabetic vasculopathy may exhibit intrauterine growth retardation too;
>
0 Neonatal morbidity is common. In some instances, morbidity is direct
and results from birth injury as the consequence of fetal macrosomia. In other
instances it is indirect and takes the form of severe respiratory distress, acidosis,
hypoglicemia and hyperbilirubinemia;
>

> 0 Major congenital anomalies occur in 4% to 12% of infants and include:

anencephaly, spina bifida and hydrocephalus, cardiac anomalies (transposition

of the great vessels, atrial and ventricular septal defects), situs inversus, renal
anomalies. All of these malformations occur primarily as a result of the
influence of hyperglicemia on the developing embryo during the fifth to eighth
week after conception.
>

> Gestation

al diabetes Definition
> Gestational diabetes implies that this disorder is induced by pregnancy,
perhaps due to exaggerated physiological changes in glucose
>
metabolism. At the Third International WorkshopConference on Gestational Diabetes, held in Chicago in 1991, this disorder was
defined as carbohydrate intolerance of variable severity with onset or first
recognition during the current pregnancy (Williams Obstetrics 1911 ed.)
> This definition did not exclude the possibility that glucose intolerance may
have antedated pregnancy. Use of the diagnostic term "gestational diabetes"
was encouraged in order to communicate the need for . increased surveillance
and to convince women of the need for further testing in postpartum.
>
The most important perinatal concern in offsprings of
mothers with GD was excessive fetal growth which is observed two to three times
more often than expected.Importantly, more than half of women with GD
ultimately develop overt diabetes.
>
Screening
>
There is no international agreement as to the appropriate
and globally acceptable diagnostic criteria for GD. The American College of
Obstetricians and Gynecologists (1986) recommends screening only for women
considered to be at risk:
> age over 30;
> family history of diabetes;
> a prior macrosomic, malformed or stillborn infant;
> obesity, hypertension or glucosuria;
> hydramnios and repeated abortions.
> Women who have not been found to have glucose intolerance before the
th
24 week should be screened between the 24 and 28 th weeks. The screen consists
of a 50g oral glucose load given without regard to the time of the last meal or the
time of day. Venous plasma glucose is measured 1 hour later. A value greater than
140mg/dl is abnormal and dictates the performance of a standard glucose tolerance
test.
>
Adverse effects:
>
=> fetal anomalies are not increased;
>
=> class Al has not greater risk for fetal death;
>
class A2 has been associated with unexplained stillbirth similar to
pregnancies complicated by overt diabetes (F.D.Johnstone et al, 1990);

> => higher incidence of macrosomic fetuses. -

Management
> Pregnant women without persistent fasting hyperglycemia but with an
abnormal oral glucose tolerance test (class Al) are treated typically by diet alone.
An acceptable diet is that recommended by the American
> Diabetes Association in amounts that provide 30 to 35 kcal/ Kg of ideal body
weight each day.
>
Beta agonists given to forestall preterm labor will agravate GD. Many
patients with subclinical diabetes can be carried to term uneventfully and delivered
normally. Insulin should be added if the 2 hour blood glucose level cannot be kept
within normal range prescribed diabetic diet.
>

> Overt diabetes

Management before conception

>
It is generally believed that the increased frequency of severe
malformations is the consequence of poorly controlled diabetes both
preconceptionally as well as early in pregnancy. Women in whom periconceptional
glucose control was optimized had 4.9% fetal malformations compared with 9% in
the group who did not present for care until after organogenesis was complete.
>
Early pregnancy loss is also increased in poorly controlled diabetics.
> The newly released progestin implant system (Norplant) has minimal effects
on carbohydrate metabolism and may be ideal for contraception in diabetic
women. Progestin-only oral contraceptives-may be also utilized.
>
The risk of pelvic infection from an IUD is very likely increased in the
diabetic woman. In many of these women, barrier methods are also an excellent
choice for reversible contraception, followed by sterilization once it is certain that
the woman wants no more children.
>
Management during pregnancy
> The maternal glucose level should be kept as close to normal as possible. The
pregnancy should continue until the fetus is functionally mature, unless the
intrauterine environment is deteriorating.
> A precise knowledge of fetal age is important to a successful pregnancy
outcome (menstrual histoiy, measurements of uterine height, ultrasonic
examination).
>
In general, glucosuria is a signal to evaluate carefully the plasma
glucose levels.
> A highly motivated pregnant woman with relatively stable diabetes may have
to ingest in as many as five meals a day and take multiple forms of insulin two
or more times a day. Frequent measurements of plasma glucose, especially
before meals, and adjustment of insulin dosage and of diet on the basis of
these measurements, will help achieve the goal of avoiding both serious
hyperglicemia and hypoglicemia.
> Tolbutamide and other hypoglicemic agents are not used during pregnancy.
Because of increased hospitalization costs, routine antepartum
hospitalization for the overt diabetic woman is no longer commonly practised.
>

> Careful ophtalmological evaluation is integral to good prenatal care

(funduscopic examination). The blood pressure record, 24 hour urine protein

determination, creatinine clearance are requisite baseline studies of the
vascular system.
>
A diet containing 25 to 30 cal/Kg of ideal body weight with a lower
limit of 1,700 cal and a upper limit of 2,000 cal is prescribed (125g = 500 cal of
protein, remainder of the calories equally divided between fat and carbohydrates).
>
Regulation of insulin dosage is greatly enhanced by the use of glucose
reagent strips and a small reflectance meter either in the clinic or by the patient at
home.
> The threat to the fetus is greatly increased at any stage of pregnancy by neglect
or by development of any of the complications commonly associated with
maternal diabetes: ketoacidosis, hypertensive disorders, pyelonephritis or
polyhydramnios.
>
Techniques for monitoring fetal welfare and maturity:
>
ultrasound scanning: abnormalities in fetal growth, gross
anomalies, placental site, polyhydramnios;
>
maternal E3 determinations using either the 24 hours
estriol/creatinine ratio or the unconjugated plasma estriol;
> => nonstress test (fetal heart rate testing), contraction stress test (positive if
decelerations occur with contractions), biophysical profile (fetal heart rate,
fetal breathing, fetal body movement, fetal tone, amniotic fluid volume).
>
>

l-v

I*

Delivery
>
Ideally, delivery of the overtly diabetic woman should be accomplished
near term. More well-controlled, uncomplicated diabetic pregnancies can now
continue to term if all monitoring techniques indicate fetal well-being.
>
The lecithin/sphingomyelin ratio in amniotic fluid is measured at about
37 weeks and, if 2.0 or greater, delivery is effected during 38 th week. The presence of
phosphatidylglycerol is particularly useful in diabetic pregnancies.
>
Vaginal delivery is feasible if the diabetes is uncomplicated, the pelvis
is normal, size of infant is not excessive and if the cervix is favorable for induction.
A normal oxytocin challenge test provides a measure of assurance that vaginal
delivery is appropriate and safe. Electronic monitoring should be continued
throughout the labor. Cesarean section is indicated if: > the disease is severe; -
pregnancy complications exist; > induction is unsuccessful; .. > the progress in
labor is poor; > an excessive fetal size exist. Readjustment of insulin dosage is
required during labor, delivery and the period following delivery because insulin
requirement typically drop markedly after delivery.
> Management of the newborn patient:
>
=> since the incidence of hyaline membrane disease is increased, every
effort should be made to prevent or reduce respiratory distress;
>correction of acid-base abnormalities and maintenance of optimal
hydration, glucose levels and oxygenation are often critical matters;
> =^> treatment of hypocalcemia and hyperbilirubinemia.

>

URINARY TRACT

INFECTIONS Urinary tract changes during

pregnancy
> * dilatation of the renal calyces and pelvis-as the urteres, more

prominent on the right side and mediated by hormonal and mechanical factors, create
urinary stasis;
> * vesicoureteral reflux;
>
*
increases of renal plasma flow and glomerular
filtration. Infections of the urinary tract are the most common bacterial
> infections encountered during pregnancy. Although asymptomatic bacteriuria
is more common, symptomatic infection may involve the lower tract to cause
cystitis or it may involve the renal calyces, pelvis and parenchyma to cause
pyelonephritis.
>
Escherichia coli and Enterobacter species are the responsible organisms
in most acute infections but others may be present in women with chronic or
recurring infections.
>
Asymptomatic bacteriuria
> Asymptomatic (covert) bacteriuria refers to persistent actively multiplying
bacteria within the urinary tract without symptoms. A clean-voided specimen
containing more than 100,000 colonies/ml is considered evidence for
infection.
> The frequency during pregnancy varies from 2% to 10%. If asymptomatic

bacteriuria is not treated, about 25% of infected women subsequently develop

acute symptomatic infection during that pregnancy. It is advisable to screen all
obstetric patients for the presence of bacteria.
> Bacteriuria has been linked to an increased incidence of preterm births,
pregnancy-induced hypertension and anemia.
>
Women with asymptomatic bacteriuria may be given treatment with any
of several antimicrobial agents. The initial antibiotic selection should be empiric.
Based on the fact that the most common offending pathogen is E. coli, sulfonamides,
nitrofurantoin, ampicillin, cephalosporins could be selected. These antibiotics should
be safe for the mother and fetus with minimal side effects. A 10 to 14 day course of
one of these agents will effectively eradicate bacteriuria in about 70% of pregnant
patients.
> More recently, single-dose antimicrobial therapy for bacteriuria has been used
with success (Amoxicillin 3g dose alone or a 2g dose given with Probenecid
lg; Nitrofurantoin 200mg single dose; Sulfisoxazole 2g single dose;
Cephalexin 3g single dose etc).
>
Cystitis and urethritis
> Acute lower tract infections occur in 1 to 2% of women during pregnancy and
more often after delivery. The principal symptoms are frequency, dysuria and

suprapubic pain and tenderness. Many pus cells, red blood cells and bacteria
can be seen in the urine.
>
Although cystitis is usually uncomplicated it is presumed that the upper
urinary tract may become involved by ascending infection.
>
Bacterial cystitis responds readily to any of several regimens
(Ampicillin 500mg every 6 hours, Nitrofurantoin lOOmg once a day, Sulfisoxazole
lg, four times daily. Treatment should be continued for 10 days. Single-dose therapy
(as described for asymptomatic bacteriuria) has been shown effective.
>
Acute pyelonephritis
>
It is the most common serious medical complication of pregnancy
occuring in 1 to 2% of pregnant women. Acute upper urinary tract infections usually
develop late in the second trimester, early in the third or after delivery.
Approximately two thirds occur in women who have asymptomatic bacteriuria.
>
The usual symptoms are : chills, fever, flank pain, dysuria, nausea and
vomiting. The temperature may have high levels (40-41C). Palpation of the kidney
area produces severe pain and there may be tenderness along the course of the ureter
and over the bladder. The right kidney is most often involved, but the infection
frequently occurs bilaterally.
> The diagnosis is confirmed by examination of a catheterized specimen of urine
which will contain many pus cells and bacteria (E. coli, Klebsiella,
Enterobacter, Proteus). About 15% of women also have bacteriemia. The
white blood cell count may be as high as 20,000 to 30,000.
> The differential diagnosis can be difficult. The following conditions may be
suspected:
>
urinary tract infection; apendicitis, chorioamnionitis;
=> puerperal infection (the symptoms following delivery); => infarction of
a myoma; ^> metritis.
>
Undelivered patients are best treated in the hospital. Ampiciliin given
intravenously in doses of lg every 6 hours for from 48 to 72 hours, after which it can
be given orally. The medication should be continued for at least 14 days.
Antimicrobial resistance of E.coii to ampiciliin has often been encountered. For
these reasons, many prefer to give gentamicin or tobramycin along with ampiciliin or
a cephalosporin or extended spectrum penicillin. If there is no response, another
antibiotic, as determined by sensitivity studies, should be ordered.
>
Intravenous hydration to insure adequate urinary output is essential.
> Because changes in the urinary tract induced by pregnancy persist, reinfection
is possible. Recurrent infection is common and can be demonstrated in 30 to
40% of these women following completion of treatment for pyelonephritis.
>

>

Chronic pyelonephritis

At least half the women with chronic pyelonephritis have no history of

antecedent urinary tract infections. The pathogenesis of this disease is obscure, but it
is doubtful that it is simply from persistent bacterial infection.
> As in all chronic progressive renal diseases, the maternal and fetal prognosis
in a particular case depends on the extent of renal destruction. Women with
hypertension or renal insufficiency have a worse prognosis.
>

> When chronic pyelonephritis or any other chronic renal lesion is complicated

by bacteriuria during pregnancy, there is an associated risk of superimposed

pyelonephritis.
>

>

APPENDICITIS

>

Acute appendicitis occurs with the same frequency in pregnant as in

nonpregnant women, but the diagnosis is more difficult and delay in treatment is
hazardous. The difficulty in diagnosis and delay in operative intervention increase
with gestational age, as does maternal and fetal mortality.
>

Acute appendicitis in the last trimester may carry a poor prognosis and
it is worth emphasizing that in some series maternal mortality approaches 5%. The
enlarged uterus may obscure the appendix which tends to be displaced upward and
laterally in the direction of the right iliac crest and the flank, so that pain and
tenderness may not be prominent in the rigty lower quadrant.
> As the appendix is pushed progressively higher by the growing uterus,
containment of infection by the omentum becomes increasingly unlikely and
appendiceal rupture causes generalized peritonitis. Diffuse spreading
peritonitis is also favorized by the increased vascularity.
>

>

Effects on pregnancy outcome

> Abortion or premature labor may occur if the infection involves the uterine
serosa. Uterine contractions stimulated by the infection are frequently tetanic
and predispose to fetal hypoxia and intrauterine fetal death.
>
Diagnosis
>
Nausea and vomiting, epigastric pain localizing in the right side of the
abdomen and tenderness anywhere from McBurney's point to the right flank are
suggestive but the diagnosis is reputed to be more difficult because the clinical
picture tends to be masked by the symptoms and physical changes of pregnancy.
>

Some of the factors confusing the diagnosis are:

> nausea, vomiting and abdominal discomfort of early
pregnancy;
> => upward displacement of the appendix by the expanding uterus;
> Ground ligament spasm, physiologic leukocytosis and elevated sedimentation
rate.
>
During the first trimester, the pain localizes in the right lower quadrant;
at 6 months, the point of maximal thickness is above the iliac crest and at 8 months,
it rises to the level of the right costal margin.
> The temperature can be normal but is usually moderately elevated. More
particularly, an increased pulse rate is present One half of the patients will
have abdominal muscle spasm or guarding.
>
A single white blood count is of doubtful value in the questionable case
because a slight leukocytosis is physiologic during pregnancy. Serial studies at
hourly intervals that reveal an increase in both total count and in young
polymorphonuclear cells indicate the presence of an acute infectious process.
>

A urinanalysis is usually negative unless the inflamed appendix is

retroperitoneal and lying in close proximity to the right ureter. The differential
diagnosis includes:
>
=^> pyelonephritis or ureteral stone which present the greatest difficulty
(examination of a catheterized urine sample is indicated in every case and should be
repeated in an hour or two if the diagnosis is questionable);
> ^> cholecystitis, pancreatitis, intestinal obstruction;
> => ectopic pregnancy or torsion of an ovarian cyst;
> => abruptio placentae or uncomplicated premature labor; postpartum
endometritis.
>
Treatment
>
Persistent abdominal pain and tenderness are the most reproducible
findings. If appendicitis is suspected, then treatment, regardless of the stage of
gestation, is the immediate surgical exploration.
>
Even though diagnostic errors sometimes lead to the removal of a
normal appendix, it is better to operate unnecessarily than to postpone intervention
until generalized peritonitis has developed. In most reports, the diagnosis is verified
in about half of women who undergo surgical exploration (in the first trimester, 77%
of diagnoses are correct, in the latter two trimesters, only 57% of diagnoses are
confirmed).
> Technical difficulties are increased late in pregnancy because of the large
uterus and the position of the appendix. If leakage or perforation has occurred,
the peritoneal cavity should be lavaged with large quantities of warm saline
solution and large doses of broad-spectrum antibiotics should be administered
parenterally. The drainage is mandatory.
>
When indicated, cesarean operation will be performed before
appendectomy. In some cases, cesarean section could be followed by histerectomy.
> Maternal mortality is no higher in gravid than in nongravid patients if there is
no delay.
>

>

>

DISEASES OF THE LIVER

>

Viral hepatitis
> Hepatitis is the most common serious liver disease encountered in pregnant
woman. There are at least five distinct types of viral hepatitis. With all of these
forms of hepatitis, symptoms may precede jaundice by 1 to 2 weeks (nausea,
vomiting, headache and malaise).
>
Hepatitis A and pregnancy
>
In developed countries the effects of HA on pregnancy are not dramatic.
However, at least in some underprivileged populations, both perinatal and maternal
death are substantialy increased. Treatment consists of a well-balanced diet and
diminished activity. Women with less severe illness may be managed as outpatients.
>
There is no evidence that HA virus is teratogenic. Risk of transmission
to the fetus is negligible and to the newborn infant it is quite small. The risk of
preterm birth appears to be increased.
>

Hepatitis B and pregnancy

>
Viral hepatitis B, once referred to as serum hepatitis, is found
worldwide but is endemic in some regions, especially in Asia and Africa. HB
infection is a major cause of acute hepatitis as well as its serious sequelae, namely
chronic hepatitis, cirrhosis and hepatocellular carcinoma.
>
HB infections are found most often among intravenous drug abusers,
homosexuals, health care perssonnel and patients who have been treated often with
blood products. It is transmitted by infected blood or blood products and in saliva,
vaginal secretions and semen (it is a sexually transmitted disease).
>
The course of HB infection in the mother does not seem to be altered by
pregnancy. The likelihood of preterm delivery is increased.
> Transplacental viral transfer from the mother to the fetus is rare. Instead,
infection of the fetus or infant is by ingestion of infected material during
delivery or exposure subsequent to birth. Some infected infants are
asymptomatic but others develop fulminant disease and succomb. The
majority (85%) become chronic carriers who can infect others.
>
Mothers with hepatitis B surface antigen and e antigen are very likely to
transmit the disease to their infants, whereas those who are negative for e antigen but
positive for anti-Hbe antibody do not appear to transmit the infection.
>
Infection of the newborn whose mother chronically carries the virus can
usually be prevented by the administration of HB immune globulin very soon after
birth, followed promptly by HB vaccine.
> For these reasons HB serological screening for all prenatal patients is
recommended. If positive, and especially if e antigen is identified in the
mother, the offspring should be given HB immune globulin and recombinant
vaccine.
>
Hepatitis C and pregnancy
> HC virus is thought to be responsible for 80% of infections caused by
bloodborne non A, non B infections. Transmission of HC infection appears to
be identical to HB and thus it is more prevalent in intravenous drug abusers,
hemophiliacs and is sexually transmitted.
>

There is little published experience with the clinical course of HC

complicating pregnancy, but there is no reason to believe that it is different compared
with that in nonpregnant women. HC is transmitted vertically at birth. It seems
reasonable to administer immune globulin to the newborn of the mother who has
anti-C antibody, because it may prevent disease acquisition by the offspring.
>
Chronic active hepatitis
>
Chronic active hepatitis is a disorder of varying etiology that is
characterized by continuing hepatic necrosis, active inflammation and fibrosis that
may lead to cirrhosis and liver failure. Most cases are due to chronic infection with
either B or non A, non B hepatitis. Another cause is autoimmune chronic hepatitis.
>
Clinical characteristics of the disease are an insidious onset over weeks
to months with intermittent malaise, anorexia and low grade fever with recurrent or
persistent jaundice. Progression to citthosis is the rule.
>

The effect of pregnancy on chronic active hepatitis, as well as the

effects of the disease on pregnancy outcome, will depend on a large extent on the
intensity of the disease and whether there is portal hypertension or hepatic failure.
>
Pregnancy is uncommon when the disease is severe because anovulation
is common. Corticosteroids have increased both fertility and survival iji women with
autoimmune chronic hepatitis.
>
Fetal loss will be increased and preterm delivery will be common but
malformations are not increased. The long-term prognosis of these women is poor
and they should be counseled regarding abortion and sterilization. Intrahepatic
cholestasis of pregnancy Intrahepatic cholestasis of pregnancy has also been
referred as: => recurrent jaundice of pregnancy; => cholestatic hepatosis; => icterus
gravidarum. It is characterized clinically by pruritus, icterus or both. The major
histological lesion is intrahepatic cholestasis with centrilobular bile staining without
inflammatory cells or proliferation of mesenchymal cells. Pathogenesis
> The cause of cholestasis is unknown, but it appears to be stimulated in
susceptible persons by. high estrogen concentrations. Bile acids are cleared
incompletely by the liver and accumulate in plasma. Levels, typically, are
much greater than in normal pregnancy and total bile acids may be elevated 10
to 100-fold. These changes disappear after delivery but often recur in
subsequent pregnancies or when an oral contraceptive containing estrogen is
taken.
>
Most women with cholestasis develop pruritus in late pregnancy
although the syndrome occasionally occurs in the second trimester and even as early
as 8 weeks' gestation. Generalized pruritus is usually the presenting symptom but
there are no accompanying skin changes unless there are excoriations from
scratching. A minority of women develop jaundice within several days following
pruritus.
>
Effect of cholestasis on pregnancy
>
The majority of reported evidence indicates that adverse pregnancy
outcomes are increased in women with cholestatic jaundice ; stillbirths, neonatal
death, preterm delivery, postpartum hemorrhage, intrapartum fetal distress.
>
Management
> Pruritus associated with cholestasis is caused by elevated serum bile
salts and may be quite troublesome. Orally administered antihistamines may provide
some relief. Cholestyramine has been reported to be effective (20g daily). Prolonged
therapy may be beneficial. Absorption of fat-soluble vitamins, already impaired, is
worsened with cholestyramine. Thus, impaired coagulation as the consequence of
vitamin K deficiency may develop unless supplemental vitamin K is provided.
>
Some authors reported prompt relief of pruritus in women given
dexamethasone, 12mg daily, for 7 days.
>

>

'

.;

>
r
:

> ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)

>

The etiological agents of the immunodeficiency syndrome are human

immunodeficiency viruses, HIV-1 and HIV-2, which are RNA retroviruses capable of
inducing severe immunological dysfunction in T4 helper lymphocytes.
>
Transmission is similar to hepatitis B virus and sexual intercourse, especially
among male homosexuals,it is the major mode of transmission. It is also transmitted
by blood or blood-contamined products and infected mothers may infect their
infants. About 10% of infected individuals are women and more than half of those
are related to use of intravenous drugs or heterosexual relationship with intravenous
drug users. Pathogenesis
>
The common denominator of AIDS is profound immunosuppression,
principally of cell-mediated immunity, which gives rise to a variety of opportunistic
infections and neoplasms.
> Thymus-derived lymphocytes (T-lymphocytes), defined phenotypically by the
CD4 surface antigen, are the principal targets. After infection, in time the
number of T cells drops insidiously and progressively, resulting eventually in
profound immunosuppression.
>
Monocyte-macrophages may also be infected and microglial brain cell
infection may cause neuropsychiatrie abnormalities. Clinical manifestations.
Serological testing
>
The exact incubation period from infection to clinical disease is
unknown ; however, it is usually 2 to 3 months. The stimuli that cause further
progression from asymptomatic viremia to the immunodeficiency syndrome are
presently unclear, but the mean time is estimated to be about 10 years.
>
Some have less severe manifestations characterized by immune
dysfunction and generalized lymphadenopathy. When infection is associated with
symptoms of malaise, fatigue, weight loss and fever, then AIDS is diagnosed.
>
Enzyme-linked immunosorbent assays (ELISA) are used to determine
the presence of antibodies to HIV. Currently used tests have sensitivities and
specificities of 99% when repeatedly positive. The Centers for Disease Control
recommend that all positive tests be followed by additional testing of the same serum
sample using a Western blot test that identifies antibodies to specific viral proteins.
This technique is less sensitive and may have false-negative results. Work is in
progress to develop a test based on the polymerase chain reaction which amplifies
viral genes.
>
There is disagreement as to whom should be screened and more importantly
how positive results should be managed. Opinions currently vary as to the
advisability of routine prenatal HIV screening. The American College of
Obstetricians and Gynecologists (1992) recommends that screening be offered to all
women and encourages it if they are at risk. Maternal and fetus-infant infection
>
There is insuficient experience to ascertain the risk of fetal infection
from pregnant women with asymptomatic HIV infection or those with clinical
immunodeficiency syndromes. At least until fetal and maternal risks can be better
defined it is reasonable to advise that pregnancy, should be avoided in seropositive
women.
>

Precautions for antepartum, peripartum and pediatric care of infected

mothers and infants are similar to those for HB, with avoidance of exposure to blood
and baby fluids. Unfortunately, a large number of women with incubating infection
or who are asymptomatic but undiagnosed will pose a larger threat to medical
personnel.
>
Because trasplacental viral transfer is thought to be the major mode of
vertical transmission, at the present time there is no reason to think that cesarean
delivery will decrease the incidence of peripartum transmission.
>
Those who perform or assist in vaginal or cesarean deliveries should wear
gloves and gowns when handling the placenta or the infant until blood and amniotic
fluid have been 'removed from the infant's skin and should wear gloves during care
of the cord. Management
>
Counseling is mandatory for the HIV-positive woman early in
pregnancy, if possible. If she chooses to continue pregnancy, ongoing couseling for
psychological support is important. Testing for other sexually transmitted diseases as
well as tuberculosis, is done. Vaccination is given for HB. influenza and perhaps
pneumococcal infection.
> The American College of Obstetricians and Gynecologists recommends CD4
cell count determination during each trimester. If those are less 500/ml,
consideration is given to Zidovudine therapy. This drug is well tolerated in
pregnancy, without teratogenic effects when was given in early stages of
gestation.
> In nonpregnant patients, Zidovudine has been shown to slow down the
progression of AIDS in HIV positive patients whose CD4 counts have dropped
below 500/ml.
>

>

> TOXOPLASMOSIS
>

> Toxoplasma gondii is a protozoan which has a complex life cycle and three

forms (toxon, a Greek word, meaning arc shaped, is in relation with its
microscopic appearance). Trophozoite, a proliferative and invazive form can
persist intrcellularly and can invade all tissue of the body. In immune
competent humans, Toxoplasma infection. results in the development of
antibodies and cell-mediated immunity.
>
The incidence and prevalence of toxoplsmosis varies throughout the
world. Differences in diet, meat handling and animal husbandry practices account for
the differences in prevalence of the disease (toxoplasmosis is a zoonosis affecting
mammals, birds, the cat being the final host ; a pregnant woman may act as
incidental host).
> The incidence of congenital Toxoplasma infection has generally been
estimated to range from 0.6 to 6 per 1,000 live births.
Clinical aspects
> Toxoplasmosis in pregnancy is often but not invariably asymptomatic. When
clinical findings are present, there is lymphadenopathy and malaise without
fever. The posterior cervical nodes are most typically involved. The systemic
>

symptoms are similar to those of infectious mononucleosis. More severe

disease may involve the spleen, liver, myocardium, brain or lungs.
Chorioretinitis has been observed in 1% of adults with the acquired form of
disease.
>
Up to 60% of acutely infected women transmit the organism to their
offspring. There is no difference in the frequency of transmission of toxoplasmosis
whether the mothers were symptomatic or not.
> Effects on pregnancy
> The role of toxoplasmosis in the genesis of human first-trimester abortions is
minimal. The severely affected fetus may develop IUGR, nonimmune
hydrops, hydrocephalus or microcephalus. Apparently normal neonates may
develop problems later in life (neurologic and/or ophtalmologie sequelae).
>
Laboratory findings
> Accurate Toxoplasma serology is crucial in establishing the diagnosis of
maternal infection. Methodologies to detect Toxoplasma-specific Ig G and Ig
M include latex agglutination, ELISA (enzyme-linked immunosorbent assay)
and indirect FA tests.
>
Ig M appears as early as 1 to 2 weeks after an acute infection and
disappears after several weeks or months. The diagnosis of acute toxoplasmosis can
be excluded if lg G is present and ig M is absent. If Ig M is present, the infection is
probably recent.
> The diagnosis of fetal infection was established by detection of Toxoplasma
antigen or positive Toxoplasma cultures obtained from amniotic fluid, fetal
ascitic fluid, umbilical cord blood or placental or fetal tissue itself.
> Toxoplasma antigen has been detected in tissue culture by the recently
developed polymerase chain reaction. Other laboratory evidence suggestive of
Toxoplasma include fetal thrombocytopenia, eosinophilia and elevated hepatic
transaminases.
> The Sabin-Feldman dye test (1948) is the gold standard test to detect
Toxoplasma antibodies. This test turns positive 1 to 4 weeks after infection
and remains positive for many years.
> Ultrasonography may detect severely affected infants. Findings include IUGR,
nonimmune hydrops, hydrocephaly, cerebral calcifications and microcephaly.
>
Prevention
>
Several personal health measures can be employed to reduce the
likelihood of infection. Women should cook meat until it is well done. Myoglobin
converts to metmyoglobin at 65 C, accounting for the color of cooked meat. At this
temperature the cysts are no longer infectious.
> Hands, ustensils and kitchen surfaces should be thoroughly washed after
contact with raw meat.
>
Serologic screening has been suggested.
>
Management
>
The obstetrician is generally faced with these clinical situations:
* the pregnant woman who has a positive Toxoplasma titer on a TORCH
screen; the physician must determine what type of serologic method was used; if it is
an lg G method with a high false-positive rate, repeat Ig G; if an acute infection is
diagnosed, the patient must be counseled on the risk to the fetus;

* if the pregnant woman has a cat, she could acquire the infection from this

animal; patients with Ig G antibody and no IG M are immune; cats with

toxoplasmosis are asymptomatic;
* Toxoplasma screening can be performed, but most laboratories offering
screening are not reference laboratories;
* patients with symptoms suggesting acute toxoplasmosis must have serial
titers drawn ; appropriate tests should also be performed to rule oul other disorders,
such as mononucleosis and CMV infection, in the differential diagnosis;
* the patient who has given birth to a baby with clinical Toxoplasma
infections sensitive test for Ig M may be necessary.
>
Drug therapy
>
If the patient elects to continue her pregnancy in the face of a diagnosis
of acute toxoplasmosis, drug therapy should be initiated as soon as it is practical.
Medical therapy has been estimated to reduce the risk of damage from infection by
approximately 50%.
>
Spiramycin is an antibiotic that does not cross the placenta in significant
amounts, reduces the risk of transmission to the fetus in the face of an acute maternal
infection. It is recommended for use in acute maternal toxoplasmosis diagnosed
before the third trimester. Treatment is continued throughout the remainder of
pregnancy (500mg, six times daily, oral administration).
>
Pyrimethamine is an antimalarial drug, a folic acid antagonist, used to
treat proven fetal infection.Folinic acid (calcium leucovorin) can be given with
pyrimethamine to reduce its marrow toxicity. A recommended dose of
pyrimethamine has been 50 to 100 mg orally (first day), followed by a maintenance
dose of lmg/Kg every 3 to 4 days.
>
Sulfadiazine is also a folic acid antagonist (50 to 75mg/Kg of body
weight, followed "by 50 to lOOmg/day in four divided doses).
>
>
>

> NEOPLASTIC

DISEASES

>

Breast carcinoma Breast cancer is the most common malignancy of women

of all age groups. Thus, it is not surprising that breast cancer is encountered with
some frequency during pregnancy. Its exact incidence is not known, but has been
estimated to be about 1 in 3,000 to 10,000 pregnancies. Effects of pregnancy on
breast cancer
> A large number of breast cancers appear to be estrogen or progesterone
dependent. Theoretically at least, they should be more aggressive because of
the hyperestrogenemia and hyperprogesteronemia that characterize normal
pregnancy.
>
In reality, it appears that pregnancy does not exert much influence on
the cause of mammary cancer, thus therapeutic abortion does not improve its
prognosis.
> Although survival is stage-dependent, there may be serious delays in clinical
assessment, diagnostic procedures and treatment of pregnant women with
>

breast tumors. Hormonally induced physiological breast changes tend to

obscure breast masses and this is particularly evident during lactation when
there is lobular hyperplasia and galactostasis. This serves at least partially to
explain the more advanced stages of cancer at diagnosis, which consequently
have a worse prognosis.
>
Diagnosis and treatment
> The diagnostic approach in the pregnant woman with a breast tumor is not
different from that of a nonpregnant woman. Any suspicious breast mass
found during pregnancy should prompt an aggressive plan to determine the
cause, whether by mammography and fine-needle aspiration or by open
biopsy.
> The dense breast tissue of pregnancy makes mammography less
reliable.
> Using fine-needle aspiration it is possible to differentiate a cyst or galactocele
from solid tumors. Excisional biopsy should be done if cytological results are
negative but the mass persists.
Magnetic resonance imaging and ultrasonography are reasonable
alternatives to assess the liver involvement.
>
Surgical treatment should not be delayed because of pregnancy. In the
abscence of metastatic disease, a modified radical mastectomy or a total mastectomy
with axillary node dissection can be performed;
>
Radiotherapy is not recommended during pregnancy because
abdominal scatter is considerable even with shielding. Patients who are candidates
for wide local excision and axillary node clearing followed by radiation are most
often advised to terminate the pregnancy. While the potential for teratogenesis is
reduced later in pregnancy, radiation can affect fetal growth and may cany a risk for
future carcinogenesis.
> Prophylactic oophorectomy during pregnancy is not indicated.
> Patients who present with advanced breast carcinoma early in gestation
frequently elect a termination of pregnancy. Termination of pregnancy
facilitates the prompt administration of ^combination chemotherapy, which is
indicated in premenopausal women. Later in pregnancy, systemic
chemotherapy may be undertaken as the outcomes reported have generally
been good in leukemic patients treated with agents similar to those employed
for breast cancer.
>
Pregnancy following breast cancer
>
Recommendations for future pregnancies in women succesfully treated
for breast cancer are based on several factors, including consideration for recurrence.
It seems reasonable to advise a delay of 2 to 3 years which is the most critical
observation period for recurrence.
>
Athough there are studies which indicate that pregnancy does not
adversely affect survival, it does seem prudent that women without nodal disease
should wait a period of 2 to 3 years before contemplating pregnancy. The length of
observation should probably be extended to 5 years in patients with positive nodes.
>

As one-third of recurrences will develop in the first 3 years following

the primary procedure, this is a high-risk period during which contraception is
important. A full evaluation for metastatic disease should be undertaken prior to
pregnancy, including bone and liver scans, a chest X-ray, mammography of the
contralateral breast.
>

>

>

Cerv

ical neoplasia Frequency

>
It is the most common gynecologic malignancy found in pregnant
women. Incidence data for cervical neoplasia complicating pregnancy varies widely
and is based on collected series. According to N.F.Hacker and associates (1982) the
average incidence of carcinoma in situ during pregnancy is about 1.3/1,000 and for
invasive carcinoma it is about 1/2,200 pregnancies.
>
Intraepithelial neoplasia
> The effects of pregnancy and delivery on premaJignant and malignant
epithelial cervical lesions are not understood completely and disagreement
persists despite considerable interest displayed by numerous investigators.
> Unlike invasive cancer, carcinoma in situ of the cervix is often discovered
during the reproductive years. Therefore all pregnant patients should be
evaluated on their initial visit with cervical cytologic smears.
>
Evaluation of an abnormal cytological smear is the same as for
nonpregnant women with minor modifications. During pregnancy, endocervical
-curettage is omitted to avoid risks of hemorrhage and membrane rupture. Conization
is avoided because of an increased incidence of hemorrhage, abortion and preterm
labor. Other complications after a cone biopsy during pregnancy include infection,
stenosis and laceration during delivery.
> Cytological changes that are suggestive of moderate or severe dysplasia (CIN
II or CFN III) require biopsies to identify the responsible lesion. Women with
histologically confirmed intraepithelial neoplasia may be followed with
cytology and colposcopically directed biopsies, allowed to deliver vaginally
and given definitive treatment after delivery.
> Invasive carcinoma
>
Pregnancy coexisting with invasive cervical carcinoma complicates
both staging and treatment. Accurate identification of the extent of cancer is more
difficult during pregnancy because induration of the base of the broad ligaments,
which in nonpregnant women characterizes tumor spread beyond the cervix, may be
less prominent during pregnancy.
> The survival rate for invasive carcinoma has not been profoundly different for
pregnant and nonpregnant women within a given stage of disease. When
frankly invasive carcinoma is identified, most favor delivery by the abdominal
route.
> Treatment
> Once the diagnosis has been established, patients with carcinoma in situ and,
in some instances, microinvasive disease, may be followed to term without
further therapy. In patients continuing pregnancy, cytologic and colposcopic

examinations should be performed periodically to rule out progression of the

disease.
> Definitive therapy, using cryosurgery or laser, may be accomplished in the

postpartum period for patients with cervical intraepithelial neoplasia.

>
Invasive cancer demands relatively prompt therapy. In general, during
the first half of pregnancy, immediate treatment is advised, whereas during the later
half a reasonable option is to await fetal maturity.
> Preferred treatment for patients with stage lb and early stage 11a invasive
carcinoma is radical hysterectomy plus bilateral pelvic lymphadenectomy.
Surgical treatment allows ovarian conservation and vaginal function and
minimizes exposure at an early age to the adverse effects of radiation on the
intestinal and urinarv tracts.
>
Surgical dissection may be facilitated by softening of uterine supportive
structures. Before 20 weeks, hysterectomy is usually performed with the fetus in
utero.
> Radiotherapy is given for more extensive cancer. Spontaneous miscarriage
usually occurs during the course of external radiation therapy. Intracavitary
radiation is then accomplished with cesium or radium implants.
> Cesarean section is the preferred method of delivery and it is performed prior
to surgical treatment or radiation therapy when fetal pulmonary maturation is
documented (pulmonary maturation may occur at 32 to 34 weeks gestation,
particularly if corticosteroids have been administered).
> Prognosis
> The overall prognosis for all stages of cervical cancer during pregnancy is
probably similar to that for nonpregnant women.
>

Ovarian tumors in pregnancy

>
Ovarian neoplasms occur once in every 500 to 1,000 pregnancies. Their
existence may be unsuspected before the prenatal examination, at which time the
finding of an ovarian enlargement may present considerable diagnostic and
therapeutic difficulties.
>
Diagnosis
> The ovary containing the corpus luteum may be enlarged during the first
trimester but on reexamination at 2 or 3 week intervals it becomes
progressively smaller after the eighth to tenth week of pregnancy.
>
True ovarian neoplasms are usually larger than 5cm in diameter and do
not decrease in size on repeated examinations. Theca-lutein cysts and luteomas
develop during pregnancy in response to its specific hormonal status. They regress
following delivery and need no treatment unless they undergo torsion.
>

Discovery of an aclnexal mass is much easier if the first prenatal pelvic

examination is performed in the first trimester. As pregnancy advances, an ovarian
cyst is displaced by the enlarged uterus. If it is displaced laterally or is trapped iir the
cul de sac, it is still palpable by bimanual examination, but frequently the cyst is
carried upward above the uterus. In this case it is felt only by abdominal
>

examination. In most instances, the diagnosis can be made clinically and the
treatment is operative. Sonography may be helpful.
> The incidence of malignant ovarian neoplasm during pregnancy has been
reported to average 1 per 25.000 deliveries. This incidence is lower because of
the younger age of pregnant women. Most women who have ovarian cancer
are asymptomatic whether they are pregnant or not. At best, symptoms arc
notoriously vague and nonspecific, abdominal distension, gastrointestinal
discomfort may be attributed to pregnancy.
> Certainly, sonography is indicated for women in whom there is a
palpable adnexal mass and it is helpful to differentiate functional cystic masses from
solid or multisepted masses.
>
Complications and management
>
Torsion is the most common complication and may lead to rupture. The
symptoms are acute, with sudden onset of abdominal pain, vomiting and pyrexia.
Pelvic examination will reveal a tender cystic mass and the distinction from tubal
pregnancy may be possible.
>
Pressure symptoms may arise if the cyst becomes incarcerated in the
pelvis or it is of very large size. These will include dysuria. pain, abdominal
distension.
>
Suppuration is most likely in the puerperium as a result of trauma
sustained during delivery.
>
There is an increased tendency to spontaneous abortion if the cyst is
large. A cyst in the pelvis will obstruct labor, causing malpresentation or nonengagement of the head.
>
Immediate removal of the cyst is necessary, regardless of the stage of
pregnancy if symptoms of torsion or hemorrhage arise or if rapid growth of the mass
is detected.
>
If the neoplasm is diagnosed late in pregnancy and the birth canal is not
obstructed, vaginal delivery is preferable. Torsion of the elongated pedicle is
common as the uterine size decreases. If the cyst obstructs the pelvis, it or the uterus
may rupture during labor. Cesarean section and tumorectomy are preferable.
Malignant ovarian tumors confined apparently to one ovary require
complete surgical staging and this is recommended also in tumors of low malignant
potential (frozen section data).
>
Whereas in most advanced stages hysterectomy and bilateral
adnexectomy is indicated, in certain circumstances it can be justified to remove the
tumor and await fetal maturity.
> There does not appear to be an adverse influence of pregnancy on ovarian
cancer. Because of the relatively young age of the pregnant population, there is
a higher proportion of less-advanced tumors.
>

>

> Uterine fibromyomas

> The coexistence of uterine fibromyomas and pregnancy is relatively common.

Small tumors are of little consequence unless their location is submucous, in

which case the abortion rate is almost doubled.
>
AJthough tumors of any size may produce symptoms of pain or
pressure, surgical intervention is rarely necessary during pregnancy. Complications
are principally related to the size and location of the tumors, to degenerative changes
in the fibroid or to torsion of a pedunculated tumor.
>
Diagnosis
> The main problem in diagnosis is the recognition of the existence of
pregnancy in a fibroid uterus. This is particularly difficult when implantation
bleeding or threatened abortion complicates the early course. An accurate
menstrual history is an important early guide. Delayed or abnormal bleeding,
symptoms of early pregnancy, softening of the cervix or recent increase in size
of a fibroid uterus should suggest the possibility of pregnancy in every case. A
pregnancy test or sonography may be done.
>
Complications and management
>
Degenerative changes are likely to occur during pregnancy, the
hemorrhagic variety (red degeneration) being the most common. Pain, local
tenderness and slight elevation of temperature are the usual symptoms.
>
The process is ordinarily limited to the substance of the fibroid proper
and tends to subside spontaneously in a few days. Hence conservative treatment with
bed rest, local application of heat and mild analgesics will control the symptoms in
most instances.
>
Myomectomy is rarely necessary and is frequently followed by abortion
if the uterine wall is incised. Occasionally, a hysterectomy will be necessary to
control bleeding. An exception is a pedunculated subserous tumor, which may twist
and become necrotic as the uterus enlarges and rises out of the pelvis. If torsion
occurs, laparotomy is imperative before gangrenous changes and peritonitis develop.
This type of tumor can be usually removed without invading the myometrium.
> The major complications resulting from fibroids arise during labor and
delivery:
>
=> obstruction of the birth canal;
>
an increased incidence of dysfunctional labor; ^> fetal
malpositions: => faulty placental separation: => hemorrhage following
delivery.
>
Tumors blocking the inlet may make cesarean section necessary.
>
Those situated low in the anterior wall are usually pulled up out of the
pelvis as the lower uterine segment lengthens. If the tumor is placed posteriorly in
the hollow of the sacrum, elevation may be prevented by the promontory of the
sacrum.
>
Vaginal examination should be performed early in labor before deciding
on the route of delivery. If the birth canal is not obstructed and the fetal position does
not preclude vaginal delivery, a trial of labor should be eiven.

> Occasionally, the presence of fibroids alters uterine contractility and induces

dysfunctional labor or hemorrhage following delivery.

>
In rare instances, the placenta is attached over a submucous or deep
intramural fibroid which may interfere with the normal process of separation and
expulsion.
>
If cesarean section is necessary because of pelvic obstruction or
abnormal labor, hysterectomy may or may not be indicated, but generally
myomectomy should not be done because of hemorrhage.
> The blood supply to uterine myomas may be reduced suddenly, during the
puerperium,. Red degeneration is more common in this period. Laparotomy is
indicated if symptoms of degeneration develop and persist during the stage of
uterine involution.

>

12. Rh

FACTOR ISOIMMUNIZATION

>

Definition: Rh isoimmunization is caused by maternal antibody

production in response to exposure to fetal red blood cell antigens of the Rh group,
including Cc, Dd and Ee (the Rh alleles).
> The antibody response may potentially destroy fetal red blood cells, causing
anemia, and result in "erytroblastosis fetalis". All of the Rh alleles on the
surface of the red blood cells stimulate an IgG antibody response in the
mother.
> The initial exposure to a foreign antigen results in the production of maternal
IgM.
> The subsequent exposure (anamnestic response) results in the production of
maternal IgG.
>
Only IgG is capable of placental transfer to the fetus because of its
small size.
> Previous episodes of possible sensitization:
> 1.
Previous pregnancy:
=> spontaneous abortion;
> =^ ectopic pregnancy;
>
cesarean birth; => obstetrical
manoeuvre; ^preeclampsia and eclampsia;
=> manual placental removal.
> 2.
Previous transfusions with Rh positive blood.
> During labor and delivery, a much larger transfusion of fetal blood may occur,
and this is more likely to provoke antibody production. Should the woman
become pregnant again, the circulating antibodies would persist, might pass
through placenta, and cause haemolysis of fetal erythrocytes.
> The chance of a(Rh-) mother bearing a (Rh+) child is 75%, but even so, she
has only a 15% chance of being sensitized at the time of delivery of the first
child.
>

115

Once the mother is sensitized only small infusions of fetal erythrocytes

arc needed to stimulate antibody production.
> The first baby is almost never aftcctcd.
>
The second babv has a 15% chance of being affected, but the risk of the
fetus developing hemolytic disease increases with each subsequent pregnancy.
>
Immunology of Rh factor disease All humans can be divided into two
groups by determining whether or not their erythrocytes contain an antigen, found in
the erythrocytes of Rhesus monkeys.
>
Studies have shown that the proportion of the population with the (actor
Rh (Rh-*-") and without the factor Rli (Rh-) varies from region to region.
>

116

>
>

{PRIVATI7} j!

>

> I

USA. UK. Romania

Asia

99%

5
%

>

117

>

The Rh factor is a complex antigen consisting of three pairs of alleles

occupying a specific locus on a chromosome, but only one of the pairs -named D, is
likely to cause iso-immunisation.
> Thus if a (Rh-) individual receives a transfusion of (Rlv) blood, the
immunologically competent cells, in the body, become sensitized to the Rh \) ntg.
provided the amount is sufficiently large.
>
Following a subsequent exposure to the antigen, the cells are stimulated
to produce specific anli D antibodies, which combine with antigen sites on the
erythrocytes, and lead to their destruction.
> The Rh antigen are quite different from the ABO antigens found in humans,
but as they are carried on the erythrocyte plasma membranes act in a .similar
way causing agglutination of the erythrocytes and subsequent haemolysis,
provided complement is present.
>
Since the genotype of the fetus is derived from maternal and paternal
genes it is possible for a woman to have a fetus with a different ABO and Rh group.
>
If the fetus has a different ABO group from that of the mother and fetal
cells cross the placenta into the maternal circulation, normal immunological
processes take place, so that the cells are coated with antibodies and are distroyed in
the reticuloendothelial system. The antibodies formed are of a large size (a macroimmunoglobulin IgM) and are unable to pass through the placenta to affect the fetus.
>
The situation with Rh atg is different:
>
=> if a mother who is (Rh-) has a baby which is (Rh+), and
>
=> if sufficient fetal cells from that baby enter the maternal circulation,
antibody production is stimulated.
> The anti-D antibodies include both the IgM and IgG and the later are
sufficient to pass through the placenta and enter the fetal circulation, where
they immediately fix onto the antigen sites on the surface of fetal erythrocytes
(red cells).
> The antigen-antibody complex causes lysis of the erythrocytes. Clinically
this is fetal hemolytic disease.
>

>

> CONDUCT OF PREGNANCY

>

> The history and physical examination can help to predict the seventy of Rh

hemolytic disease. A detailed history should include the following information:

> The maternal blood type and antibody screen
>
If the mother is (Rh-) the blood type of the father of her baby must be
determined:
> a. If both mother and lather are Rh- there is no need to obtain further
antibody screen;
> b.If the (Rh-) mother has an (Rh+) partner and has a positive antibody
screen, then the antibody should be identified.

118

The blood of all (Rh-) women should be tested beginning with the 20th
week of pregnancy at an interval of 4 weeks from then on. If the iso-agglutinins are
found in a titre 1/8 1/16 1/32 by indirect Coombs method in any test, further
assesement should be made by amniocentasis (as the degree of haemolysis of fetal
erythrocytes does -not correlate with the maternal antibody titre).
>
The indirect test Coombs is used to detect and measure antibody in the
mother's serum. Antibody in the serum will coat the cells and agglutination will
occur when the Coombs reagent is added. By using dilutions of the mother's serum a
measure of the amount of antibody titre is obtained.
> The level of bilirubin in the amniotic fluid, correlates fairly well with amount
of erythrocyte distruction and hence with the degree of fetal anemia.
>
The quantity of bilirubin in the amniotic fluid can be estimated by
spectrophotometry.
>

> SPECTROPHOTOMETRY is used to measure the optical density reading

at 450 nm wave length.

>
The basis for amniocentesis in determining the severity of fetal
haemolysis, depends on what is known about fetal excretion of bilirubin (if it is
possible the position of the placenta should be determined using ultrasounds).
> Bilirubin circulates bound to albumin serum. Most of this is excreted into
the maternal circulation via the placenta, but a small quantity is filtered
into the amniotic fluid through the mucosa of the upper respiratory tract.
>
The fetal liver is unable to deal with this unconjugated bilirubin, it
has a limited capacity to conjugate it with glicuromic acid.
>
The conjugated bilirubin is water-soluble and is excreted by the
fetal kidneys into the amniotic fluid. The level of bilirubin in the amniotic sac.
correlates fairly well with the amount of erythrocytes destruction and hence
with the degree of fetal anemia.
>
The quantity of bilirubin in the liquor amnii can be estimated by
spectrophotometry.
>
In the absence of bilirubin the absorbtion spectra of amniotic fluid
for the range 360 to 630 nm in a spectrophotometry is expressed as a relatively
straight line.
>
[f albumin bound bilirubin is present in the fluid, increased
absorbtion is found at a wavelength of 450 nm and this appears as a
characteristic peak.
>
The measurement of the height of the peak above the "normal"
optical density at 450 rim gives a fairly close indication of the amount of
bilirubin present and of the severity of the hemolityc process.
>
If the patient develops antibodies during pregnancy (a titre more
than 1/8-1/16), amniocentesis should be performed to 28 weeks. The bilirubin
concentration is an indirect measure of fetal reel blood cell hemolysis and
anemia.
>
The bilirubin peak is entered on a chart divided by LILEY.

119

If the level lives in the high zone the baby will certainly be
severely affected and may die in utero.
>
If the pregnancy has 32 to 34 weeks labor should be induced.
>
Before that date intra-uterine fetal transfusion offers 35% salvage
rate (unless the fetus is hydropic).
>
If the peak lies in the mid zone a further amniocentesis is
performed 2 to 3 weeks later and the height of the peak is noted (treatment
being planned on this result).
>

> The objective is to maintain the pregnancy at least to the 32-nd week,

when delivery may be indicated.

> If the peak lies in the low-zone, a further tap is made at the 34 th week. If
the tap shows that the peak is now in the mid-zone, treatment is for that
condition, but if the peak remains in the low zone, pregnancy may
continue to ^8 weeks or to term.
>

> INTRAUTERINE TRANSFUSION

1. Intraperitoneal transfusion is guided by ultrasound. Following maternal

sedation and analgesia a needle is inserted through the maternal abdomen

and uterine wall into the amniotic fluid and finally into the fetal
abdomen. Packed red blood cells deposited into the fetal peritoneal
cavity, are absorbed by the lymphatic system and enter the fetal vascular
system.
2. Intravascular transfusion
> Techniquerafter locating the fetal position and the site of the cord
insertion by ultrasound, the patient is given a narcotic and an antibiotic.
A needle is advanced through the maternal abdomen wall, entering the
umbilical vein lumen. The needle stylet is removed and a pretransfusion
fetal hematocrit is obtained. Packed red cells are inserted through the
needle and another sample of blood is aspirated to check the final fetal
hematocrit. (0-) negative packed red blood cells are needed, but
compatible with mother and fetus (and of course negative for hepatitis,
cytomegalo virus and human immunideficiency virus. HIV).
Complications:
> => fetal death can occur: for nonhydropic fetus rate is 0-2%;
>
in hydropic fetus rate is 10-15%;
> bradycardia occurs in 8% of cases: =>
bleeding from the puncture site can occur;
> chorioamniotitis occurs in 0.5% of cases;
> preterm rupture of membranes occurs in 0.5% of cases; ^> premature
labor;
> laceration of fetal organs.
> 3.
Induction if labor can be considered in certain situations. The
decision is made on the amniotic fluid findings. Fetal maturity is
120

documented
by two elements:
- the Us ratio greater than 2 and,
- the presence of phosphatidylglyccrol.
>
At the time of the first fetal transfusion many perinatologists
administer corticosteroids to mature the fetal lung, in anticipation of an
eventual premature delivery.
>
When the patients are multiparous induction of labor by
amniotomy is the usual method.
> 4. Cesarean section has a limited frequency and should be considered if
oxilocyn fails to induce labor. Cesarean section is indicated if there are
anemic fetuses.
> They rarely tolerate active labor, because the oxygen carrying capacity of
their blood cells is low.
>

> HEMOLITIC DISEASE OF THE NEWBORN

>

The effect of the transplacental passage of isoagglutinins depends

upon the amount of immunoglobulin and the duration of its action. The infant
responds to the haemolisis by hyperplasia of its erythropoetie tissues, the bone
marrow becomes hyperactive and later the spleen and liver enlarge and begin
erythropoetie activity. The clinical appearance of hemolitic disease depends on
the balance of these two factors, and three grades of severity are found:
> 1.Hemolitic anemia of the newborn
> The hemoglobin level is reduced from the normal 18g% but is more than
l4g%, Jaundice is usually absent, or slight at birth, but may develop
during the 2-nd week of life, when further hemolysis occurs.
> The prognosis is good provided that haemoglobine concentration and
serum bilirubin levels are kept at resonabie levels.
> 2.Icterus gravis neonatorum
>
The baby is anemic - hemoglobin concentration 10 to 14g% and
jaundice ussualy appears soon after birth. The liver and spleen are enlarged and
the serum bilirubin level exceeds 210 mmol/litrc or ! 0 nig% in the first 24
hours.
> 3.Hydrops fetalis (total body edema)
>
In this condition the haemolitic process has outstripped the
capacity of the erythrocyte-producing organs to correct the anaemia and inlrauterine death from anaemia heart failure is common, "fhe fetus is grossly
edematous with ascites, pleural effusion and hepato-splenomegaly.
> The placenta in cases of babies affected by hemolitic disease is usually
enlarged, edematous and friable and disruption is common during
delivery with possible retention of a cotyledon.
>

121

On histological study the villi are found greatly enlarged with increased
density of collagen tissue. The fetal vessels are not enlarged but. because of the
hemolysis, contain a few erythrocytes and consequently appear larger. The
cytotrophoblast is increased in amount when compared with a normal placenta at a
comparable period of gestation.
>
4. Kernicterus is a condition which arises in any form of neo natal
jaundice, when the unconjugated bilirubin level rises above 340 mmol litre.
>
Bilirubin enters the fetal brain tissue causing necrosis of neurons
especially in the basal ganglia.
>
The infant becomes lethargic and refuses to suck. Convulsions, rolling
of eyes and head retraction develop. Death may occur. If the infant survives
permanent mental and physical disabilities develop.
>

>

> INVESTIGATION OF THE INFANT AT BIRTH

>

> 1.

Blood is taken for hemoglobin concentration. ABO and Rh

grouping;
2. A Coombs test is performed and a serum bilirubin estimation mad;
3. Reticulocyte count and bilirubin levels musx x zszt~~ > 4. Assessment of these investigations indxaoss --erer r ."-ir.ge
transfusion is needed.
>
Treatment
>
Deliver) of the bab> followed r> ss^srncrTr rf JS arifeai and exchange
transfusion is necessary :r the ndora ^Hrmar rf
> sensitised patients.
>
The timing of intervention in other ^se^ jrxzis :~
the patient's history;
amniocentesis results:
ultrasound surveillance.
>
After birth the cord blood is examined:
> a. the direct test Coombs is used to detect an affeciec irtafe m nr.;
Cells from cord blood are suspended with the reagent and if wttc tafe is
> affected (has maternal antibody attached) agglutination will ocac
> b. blood grouping and Rh typing;
> c. hemoglobin estimation:
> d. serum bilirubin.
Mild degrees of anemia (not below 12g% may not require treatment
and mild degrees of jaundice may respond lu phototherapy.
>
Exchange transfusion is given to all (Rh+) and Coombs direct
positive affected babies:
> a. when the cord Hb is 14,8 mrnol or less;
> b. when the cord bilirubin level is 105,5 mmol/1 (5mg%) or more, at
>

122

> birth;
> The exchange transfusion is carried out within 16 hours of birth. The

blood for exchange-transfusion should be (Rh-), but of the same ABO

group, as that of the baby. Fresh blood should be obtained if possible, as
stored blood becoms increasingly acid and can produce a fetal acidosis.
> Exchange transfusion is made into the umbilical vein and blood is
exchanged until a total of 80 to 100 ml per 0,5 kg body-weight has been
exchanged.
> The exchange transfusion is stopped at any time if the baby's condition
deteriorates.
>
Dangers of exchange transfusion
>
Without premature induction of labor and exchange transfusion of
the affected baby the perinatal mortality would be not less than 25%. With
exchange transfusion the mortality falls to less than 10%. The more severity
affected the baby, the earlier it is the transfusion needed.
>

> THE PREVENTION OF RHESUS ISO-IMMUNIZA TION

>

> About 98% of cases of Rh immunization can be prevented by giving

every unsensitized (Rh-) woman who gives birth to a (Rh+) baby an

injection of Rh anti-D gamma globulin within 72 hours of birth.
>
A similar injection should be given to unsensitized (Rh-) women
> after:

=> an abortion needing curettage;

=> an amniocentesis;
>
=> birth with obstetrical maneuvre (manual placental removal,
external version).
> The Rh anti D IgG either occupies D-antigen binding sites on the fetal
erythrocytes, which prevents them from expressing their antigenicity or
blocks maternal lymphocytes on the fetal cells.
>

The injections are of no value to women already sensitized.

>
Ami D lgG is prepared from plasma uf human donors, who have to be
subjected to regular plasmapheresis and who require periodic injection ol (Rh+) red
cells to maintain a higher titrc of antibodies in their plasma.
>
All (Rh-) unsen>iti/.ed women who give birth to a (RJr -.i bab\ arc given
an injection of 250 ma (2ml) of Rh-anti D igG within 72 hours of biiih.
>
As the amount of transplacental hacmorrage is unknown, an indirect
Coombs test is made 24 hours after die injection.
>
if the Coombs test is negative (indicating no circulating anti-L) igCi) a
Kleihauer test is made on the mother's blood. 1 'he test permits lo estimate the
number of fetal cells in her blood.
>

123

If a transplacental hemorrhage is present (more than 5 ml of fetal blood

are discovered) an additional injection of anti D gammaglobulin is given, so that the
dose is 20 mg per ml of red cells.
>

124

>

13. GESTATIONAL TROPHOBLASTIC DISEASE

>

Definition
The term of gestational trophoblastic disease refers to a complex
pathological pattern including four entities :
* hydatidiform mole (molar pregnancy)(benign mole) characterized by
trophoblastic proliferation and edema of villous stroma;
* chorioadenoma destruens or invasive mole with an invasive capability
of myometrium and peritoneum, vaginal vault and the adjacent parametrium
sometimes exhibiting metastasis;
* choriocarcinoma, malignant tumor made up exclusively of the
trophoblast (absence of a villous pattern), a unique tumor, present only in humans;
* placenta] site trophoblastic tumor; very rarely, a trophoblastic luinor
arises from the placental implantation site following either a norma! term
pregnancy or abortion; this tumor is characterized histologically by predominantly
cytotrophoblastic cells; gonadotropin levels may be normal to elevated; bleeding
is the main presenting symptom ; treatment consists in hysterectomy because this
tumor is unresponding to chemotherapy.
>
This disease originates in the fetal chorion, the benign mole
representing the beginning and the choriocarcinoma, with a high degree of
malignancy, the end.
>
The term of gestational trophoblastic disease is justified by the
absence of certain clear-cut limits among the four forms due to various biological
conditions and intermediary situations. Choriocarcinoma will be presented in the
chapter of the uterine corpus tumors.
>
Incidence
>
In Europe and North America the mole frequency is 1/2,000-1/3,000
pregnancies and the carcinoma one is 1/15,000 pregnancies. In South-East Asia,
West Africa and Mexico the mole incidence is 1/120-1/240 pregnancies and
choriocarcinoma 1/500 to 1/1,000 pregnancies.
>
>

125

Risk factors
Risk factors related to the disease incidence are:
>
=>age: incidence seems to be higher at the two extremes of the active
genital period; according to sonic authors, the disease would be more frequent
after the age of 40;
> parity: there are two opinions which consider multiparity to be a risk factor
mainly the fact that choriocarcinoma incidence is higher with the first
pregnancy;
>
=> ethnicity: studies earned out in polyracial socits (Hawaii.
Singapore, China) have shown ethnic differences in the incidence of hydatidiform
mole;
>
=^ consanguinity;
>
blood type: the malignant form seems to be more frequent in
> group A;
> => protein deficient
diet; => viral infections;
>
=> the presence of the ovarian theca-lutein cysts.
>
The presence or absence of an embryo or fetus has been used to
classify moles into: complete hydatidiform mole and partial hydatidiform mole.
>
Pathogenesis
>
There are three main hypothesis:
* placental vascular deficiency;
* genetic hypothesis;
* immunological theory. Genetic
hypothesis
>
Cytogenetic studies of complete molar pregnancies have identified
the chromosomal composition most often, but not always, to be 46/XX, with the
chromosomes completely of paternal origin. This phenomenon is referred to as
androgenesis. Typically, the ovum has been fertilized by a haploid sperm, which
then duplicates its own chromosomes after meiosis and thus the chromosomes are
homozygous. Infrequently, the chromosomal pattern in a complete mole may be
46'XY, that is heterozygous.
>
The risk of trophoblastic minors developing from a complete mole is
approximately 20%.
>
The majority of complete moles are diploid (most partial moles are
triploid).
>
>

>

When the hydatidiform changes are focal and less advanced and
maybe a fetus or at least an amniotic sac is seen, the condition has been classified
as a partial hydatidiform mole. The karyotype is typically triploid (69/XXX,
69/XXY, 69/XYY) with one maternal but usually two parental haploid
complements. The risk of choriocarcinoma arising from a partial hydatidiform
mole is low.
>

126

Immunological hypothesis
>
The antigenic relationships among the normal placenta, the complete
mole and the choricarcinoma haven not been clarified. The normal trophoblast has
a high proliferative capacity simulating some morphological criteria of
malignancy, invading maternal decidua. having the capability to be carried into
the pulmonary circulation.
>
The complete mole can be invasive, metastatic and in some cases it
may turn into choriocarcinoma.
>
The total mole is immunogenetic having the capacity to induce
immunization paternaly derived by MHC antigens. Normally, these antigens set
up a umoral and cellular immune response which has the effect of rejecting the
foreign tissues.
>
The maternal sensitivity to the paternal HLA antigens seems to be an
important element in the mole immunology.
>
Samples of mole tissue are present in these antigens on the level of
the stromal cells. The maternal reactivity would take place by means of the
contact of these cells, HLA positive, with the circulation on the level of villous
trophoblastic ruptures.
>
The development and progress of the trophoblastic tumors with the
negative prognosis can be facilitated by the host-tumor hystocompatibility.
>
Besides HLA antigens, the molar tissue exhibits some other antigens
as well. The TLX system is polymorphic and the paternal TLX antigens,
expressed by the trophoblast, can induce a strong maternal immune response.
>
In normal pregnancy, the maternal side produces TLX antibodies
which serve as blocking antigens to protect the fetal allograft.
> The choriocarcinoma prognosis is related to the degree of leukocyte
infiltration on the level of the tumor site. Lymphocytes and macrophages
are . involved in these reactions. Cytokynes, produced by lymphocytes and
macrophages, have cytotoxic activity for a variety of tumoral cell lines and
it is believed that they would play a role in the antitumoral defence.
>

> Complete hydatidiform mole (benign mole)(noninvasive

mole)
> Pathology
> Placenta
> Macroscopical aspects
> The total mass of the mole is about 200cc. The mole consists of clear

vesicles, with diameters ranging from a few milimeters to several

centimeters. They are spherical, connected by thin filaments giving it
the appeal ance of grapes. The content of vesicles is clear or opaque
fluid.
> Microscopical aspects
>
The histological structure is characterized by:
1. Proliferation of the trophoblastic epithelium;
2. Hydropic degeneration and swelling of the villous stroma;
127

3. Absence of blood vessels in the swollen villi. Uterus

In about 70% of cases uterine size clearly exceeds that expected from
the duration of gestation. Consistency is of a particular softness. Ovaries
>
In about 50% of cases, according to their sensitivity to chorionic
gonadotropins, uni or bilateral ovarian theca lutein cysts appear having a
volume that can reach diameters of 25 to 30cm. These cysts have a watery
content which is characterized by large quantities of chorionic
gonadotropins.
> Aspects of the molar biology
>
The molar tissue produces very large quantities of HCG,
glycoprotein made up of the alpha and beta subunits. The presence of free
alpha or beta subunits in serum, urine or tumoral extracts represents an
indication of an increased malignancy.
>
A population of beta HCG fragments has been identified being
called "beta core molecules". The presence of these molecules, in the
absence of HCG in urine or serum may be the only marker of persistent
molar tissue. This fragment was used as a marker in nontrophoblastic
malignancies (cervical cancer, endometrial cancer and ovarian malignant
tumors) with 75% reliability.
>
The HPL secretion is normal or decreased, the placental thyreotrop
factor is decreased, estrogens are decreased too. Clinical diagnosis
>
The molar symptoms before expulsion:
>
=> uterine bleeding is the most common sign (90%) as an initial,
early or delayed symptom; bleeding is less abundent, irregular, occurring
even al rest, progressively increasing, up to severe hemorrhage: it may be
accompanied by characteristic vesicles discharge;
>
=> intermittent abdominal and pelvic pain with variable
intensity ;
> => general phenomena: nausea, vomiting, headache, edema,
proteinuria, arterial hypertension; because PIH is rarely seen before 24
weeks, preeclampsia that develops before this time should at least
suggest hydatidiform mole.
> On examining with speculum, the presence of blood and possible
vesicles in the vagina can be found. Bimanual examination reveals : the
increase in uterine size which can vary from one day to the other
depending on the formation and evacuation of blood collections
(uterus being like an accordeon) ; very soft consistency of corpus and
cervix which may be closed or open ; the presence of ovarian cysts.
> Laboratory tests
> Sonography excludes the presence of fetus (absence of fetal heart
sounds, absence of ovular structures) and gives a typical image of the
mole justified by the numerous reflections against vesicle walls
("snow flake image"); sonography has a 96% reliability.
>
The urinary or serum HCG dosage: a maximum normal secretion
of HCG, established by urinary measurements, is 100.000 to 400,000 IU/24
hours (the 60 th -80 t day); in molar pregnancy the level is 1-2 milion IU;
>

128

serum measurement is more accurate, faster, without diurnal variations;

sometimes, it is necessary to perforin repeated HCG measurements; I [PL
levels are decreased; the HPL/HCG ratio is considered to have an important
diagnostic value.
>
Other tests : abdominal X-ray, pelvic arteriography,
hysterography, placental scintigraphy.
> Differential diagnosis
>
The increased uterine size can be distinguished from multiple
fetuses, unique, macrosomic fetus, hydramnios, uterine myomas. The
uterine bleeding may be differentiated from the same symptom present in
spontaneous abortion, noncomplicated ectopic pregnancy, decidual
endometritis, uterine fibroids, cancer of the uterine corpus, endometriosis.
> Spontaneous expulsion of a mole usually occurs in the third or fourth
month and can be associated with an important bleeding which can
lead to vascular failure and hemorrhagic shock.
> Management
>
It should be planned into two periods:
> A.
> B.
> A.

Before and during mole expulsion

After expulsion
The uterus should be evacuated as soon as possible after the
diagnosis is made. The technique does not influence the further malignant
potential. Evacuation methods : standard D&C (carefully curetting the
uterine wall with a large, sharp curette); suction curettage ; hysterotomy (in
the presence of severe bleeding) ; hysterectomy may be performed in cases
of multigravida or obstetrically old women.
>
Ancillary treatment : correcting anemia, oxytocin infusion,
prophylactic chemotherapy (although some advocate prophylactic chemotherapy,
there is no evidence that such therapy improves the long term prognosis). When it
is performed, there is frequently used methotrexate, folic acid antagonist that
interferes with normal metabolism, orally given (I0-30mg/day, for 5 days, four
cures at 7-14 day intervals).
> B.
The prognosis is good in 80 to 95% of cases:
the general condition improves;
hemorrhage disappears completely in 7 to 10 days;
uterine involution takes place in one to two weeks;
the ovarian cysts involution is slower;
HCG levels get to normal in a month;
> patients with increased HCG levels for 5 to 8 weeks after the
evacuation of the mole develop in 25 to 50% cases an invasive mole or
choriocarcinoma.
> The follow-up of the cases after evacuation is achieved by: 0 weekly
dosage of HCG (diagnosis of remission can be made after 3 succesive
dosage with normal results): 0 pelvic examination;
> 0 chest X-ray (the lung is the most frequent site for metastasis);
129

> 0 oral contraception (estrogen-progestin contraceptives have been

used commonly to prevent a subsequent pregnancy and to suppress pituitary

luteinizing hormone that cross-reacts with some tests for chorionic gonadotropin).
>

> Invasive mole (Chorioadenoma destruens) Definition

Invasive mole is similar to hydatidiform mole, from which it arises,

but its malignant potentials are much greater. It invades the myometrium, in some
instances penetrating the uterine wall completely and extending into the broad
ligament or the peritoneal cavity. In half or more of all cases, invasive mole
metastasizes through the peripheral circulation to distant sites, most
characteristically the lung. Pathologic findings
>
The histologic partem is similar to that of hydatidiform mole in that
the villous architecture is maintained, even in metastatic implants. The most
important differences are the excessive trophoblastic proliferation and
invasiveness.
>
The degree of anaplasia is variable. In some cases the metastatic
tissue looks completely benign and in others the cells are anaplastic. The
preservation of the villous pattern serves to differentiate invasive mole from
choriocarcinoma, which is so anaplastic that villi cannot form.
> Clinical course and diagnosis
>
Bleeding may continue after the evacuation of a mole if the lesion is
relatively superficial. There may be no blood loss if the trophoblast lies deep in
the myometrium. The first evidence of the disorder may be coughing or
hemoptysis from metastatic lung lesions.
>
Invasive mole or choriocarcinoma can be suspected if the
gonadotropin titers fail to regress or continue to rise after evacuation of a
hydatidiform mole. When this occurs, repeat curettage is indicated, but it may not
be conclusive. If the lesion is superficial, a diagnosis may be possible. If the
lesion lies deep in the muscle, the curette will not reach it.
>
A chest X-ray film will reveal metastatic lesions if they are present.
>
The potential for persistent disease or metastatic spread from
invasive mole is greater than that from benign mole but less than that from
choriocarcinoma.
> Treatment
>
It is identical to that for choriocarcinoma (chemotherapy, using drugs
like methotrexate, actinomycin D, etoposide, cyclophosphamide) or hysterectomy.
>

130

>

14. HYDRAMNIOS (POLYHYDRAMNIOS)

>

Definition
More than 2.000ml of amniotic fluid is considered an abnormal
condition. 1.000 to 2.000ml amniotic fluid is considered "excessive" and is
without pathological signification. In rare instances, the uterus contains an
enormus quantity of fluid, with reports of as much as 15L (normally, amniotic
fluid volume increases to about 1L).
>
Minor to moderate degrees of hydramnios. 2 to 3L. are rather
common, but the more marked grades are not. Because of the difficulty of
complete collection and measurement of amniotic fluid, the diagnosis is usually
based on clinical impression or, more recently, on sonographic estimation.
>
Classification
>
In most instances, the increase in amniotic fluid is gradual, develops
later in pregnancy and is called chronic hydramnios. Acute hydramnios tends to
develop earlier in pregnancy than does the chronic form, often as early as-16 to 20
weeks, and it may rapidly expand the hypertonic uterus to enormous size.
>
Incidence
>
The frequency of the diagnosis varies appreciably with different
observers from 1 in about 60 deliveries to 1 in 750. Acute hydramnios represents
about 5% of all cases with hydramnios.
>
>

>

> Ch ronic hydramn

ios Etiology
It is
unknown in about 40% of
cases. Ovular causes
>
Amniotic fluid volume is controlled in a number of ways. Although
the major source of amniotic fluid in hydramnios has most often been assumed to
be the amniotic epithelium, no histological changes in amnion or chemical
changes in amniotic fluid have been found.
>

> Significant

hydramnios is frequently associated with fetal

malformations, especially of the central nervous system and the
gastrointestinal tract. The hydramnios is present when swallowing is
inhibited as. for exemple, in cases of esophageal atresia.
>
In cases of anencephaly and spina bifida, increased transudation
of fluid from the exposed meninges into the amniotic cavity may be an
etiological factor. Another possible explanation in anencephaly is excessive
urination caused by lack of antidiuretic hormone.
>
In hydramnios associated with monozygotic twin pregnancy, the
hypothesis has been advanced that one fetus uzurps the greater part of the
circulation common to both twins and develops cardiac hypertrophy which
in turn results in increased urine output.
> The normal fetal lungs have the potential for the exchange of
relatively large volume of fluid as the consequence of inspiration.
Hypoplastic lungs may compromise this pathway for removal of
amniotic fluid.
>
The enlarged placenta may contribute to increased amniotic fluid.
Prolactin may have a role in the control of its volume. Maternal causes
>
Hydramnios that rather commonly develops with maternal
diabetes during the third trimester remains unexplained and fetal urine
formation is apparently normal.
> Maternal conditions associated with hydramnios are the more severe
forms of heart disease, preeclampsia, severe anemia, Toxoplasma or
CLMV infections.
> Syphilis, a classical etiology, acts by placental, umbilical cord and
fetal liver modifications (placenta may be large and edematous,
necrotizing funisitis is a characteristic lesion of the umbilical cord,
hepatosplenomcgalv may be present).
>
The pathophysiology of hydrops fetalis induced by Rh hemolytic
disease remains obscure. Theories of its causation include heart failure from
profound anemia, capillary leakage caused by hypoxia from severe anemia,
portal and umbilical venous hypertension from hepatic parenchymal
disruption by extramedullar}- hematopoiesis and decreased colloid osmotic
pressure from hypoprotcincmia caused by liver dysfunction.
> Clinical diagnosis
>
Major symptoms accompanying chronic hydramnios arise from
purely mechanical causes and result principally from pressure exerted
within and around the ovcrdistended uterus upon adjacent organs. The onset
is placed after 28 th week.

>

The accumulation of fluid lakes place gradually and the woman may
tolerate the excessive abdominal distension with relatively little discomfort. The
symptoms are : dyspnea, fatigue, abdominal and lumbar pain, indigestion, edema
is common in the lower extremities, the vulva and the abdominal wall, varicose
veins and hemorrhoids.
>
The uterus is bigger than expected.
>
Identification of the fetus and fetal parts is difficult.
>
Ballottemcnt of the fetus is easy (abdominal and vaginal).
>
Uterine tone is moderately increased.
> The fetal heart is difficult to hear.
>
Laboratory tests
>
Sonography
>
Large amounts of amniotic fluid can nearly always be readily
demonstrated as an abnormally large echo-free space between the fetus and the
uterine wall or placenta.
>
The differentiation among hydramnios. ascites and a large ovarian
cyst can usually be made without difficulty by ultrasonic evaluation. At times, a
fetal abnormality such as anencephly or other neural tube defects or a
gastrointestinal tract anomaly may be seen.
>
Radiography
>
A large radiolucent area around the fetal skeleton suggests
hydramnios, although a soft tissue mass (such as a sacrococcygeal tumor) may
appear the same. Most often, anenccphaly and other gross skeletal defects are
easily diagnosed.
>
Amniography. using contrast material, may help identify excess of
amniotic fluid, soft tissue tumors projecting from the fetus and the presence or
absence of fetal swallowing (etiological diagnosis).
>
Other tests which can be recommended; alpha FP evaluation, antiRh
antibodies, BW reaction. Toxoplasma detection, glucosemia. Differential
diagnosis: => multiple pregnancy;
>
macrosomal singleton; => ovarian
cyst with abdominal location; => ascites;
>
a full
bladder. Prognosis
Maternal
>
The hazards imposed on the mother by chronic hydramnios are
significant but, usually, not life-threatening. The most frequent maternal
complications are placental abruptio, uterine dysfunction and postpartum
hemorrhage.
>
Extensive premature separation of the placenta sometimes
follows escape of massive quantities of amniotic fluid because of the
decrease in the area of the emptying uterus beneath the placenta.
> Fetal
>

133

The incidence of fetal malformations is 15 to 20%. Perinatal

mortality is increased further by preterm delivery, in 20% of cases due to the
premature spontaneous rupture of the membranes.
>
Erythroblastosis, difficulties encountered by infants of diabetic
mothers, prolapse of the umbilical cord when the membranes rupture occurs
and placental abruption as the uterus rapidly decreases in size, add still
further to bad outcomes.
> Treatment
>
Minor degrees of hydramnios rarely require treatment. Even
moderate degrees with some discomfort can be usually managed without
intervention until labor ensues or imtil membranes rupture spontaneously.
>
If there is dyspnea or abdominal pain or if ambulation is difficult
hospitalization becomes necessary. Bed rest with sedation may make the
situation endurable, but it has rarely any effect on fluid.
>
Diuretics and water and salt restriction are likewise ineffective
and potentially dangerous.
>
Amniocentesis (paracentesis) is indicated to relieve maternal
distress and to that end it is transiently successful. About 500ml is
withdrawn. The maneuvre may be repeted in 2-3 days.
>
Amniotomy (the rupture of the membranes through the cervix)
has the disadvantages of the possibility of cord prolapse and especially of
placental abruption. Very slow removal of the fluid by amniocentesis helps
to obviate these dangers.
>
Several investigators have described the use of the PG-synthase
inhibitor Indomethacin to treat hydramnios. The most likely mechanism for
the efficacy of Indomethacin is decreased fetal urine production. The major
concern for the use of Indomehtacin is the potential for closure of the fetal
ductus arteriosus (premature ductal closure may induce cardiopulmonary
sequelae).
> During labor and delivery, uterine dysfunction and hemorrhage must
be treated. The newborn will be carefully investigated especially to
detect malformations.
>

Acute hydramnios It is always induced by a severe fetal

abnormality, frequently monozygotic twin pregnancy or anencephaly.
> Acute hydramnios lends to develop earlier in pregnancy than does the
chronic form, often as early as 16 to 20 weeks, and it may rapidly
expand the hypertonic uterus to enormous size.
>
Pain is likely to become intense and dyspnea so severe that the
woman is unable to lie flat. As a rule, acute hydramnios leads lo labor before
28 weeks, or the symptoms become so severe that intervention is mandatory.
>
Abortion and premature labor arc common complications. Fetal
mortality is almost 100%.
>
Differential diagnosis;
>

134

complicated ovarian
cyst; => abruptio placentae; =>
hydatidiform mole; ^> ascites.
> Sonography and radiography are
indicated. Treatment
> Amniotomy becomes necessary because the symptoms are severe.
Rupture of the membranes should be carried out under aseptic
conditions and an attempt should be made to drain the fluid slowly.
Free or rapid flow may encourage prolapse of the cord or a fetal part
and sudden reduction in size of the uterus may cause placental
separation.
>

135

15. PREMATURE SPONTANEOUS RUPTURE

>

OF THE MEMBRANES (PSRM)

>
>

Definition
>
PSRM has been applied most commonly to spontaneous rupture
of the membranes at any time before the onset of labor irrespective of the
duration of gestation. PSRM is an important obstetrical problem because it
can induce or favour intruterine infection (maternal and fetal), preterm
labor, cord prolapse, abnormal presentations.
>
PSRM occurs in approximately 10% of all pregnancies.
> Etiology
>
The etiology of PSRM is unknown. The fetal membranes are
made up of a thin layer of amnion and a thicker outer layer of chorion that is
directly opposed to maternal decidual tissue.
> The amount of physical stress tolerated by the membranes decreases
as pregnancy progresses. Membranes supported by a closed cervix
require much greater pressures to rupture than do membranes covering
an open area.
>
Most studies suggest that local delects within the membranes
may-predispose to rupture. Some explanations include changes in collagen
content in membranes that rupture prematurely compared with gestational
age-mf.tched control membranes. The interaction, of a variety of proteases
and proteolytic enzymes affects membrane elasticity and may also
contribute to PSRM.
>
A number of investigators have associated increased rates of
isolation of specific genital tract pathogens with the presence of P SRM
(T.vaginalis, C.trachomatis, N.gonorrhoeae, beta-hemolytic streptococci).
>
There are diseases and disorders associated with PSRM:
>
a. maternal associated conditions:
multiple previous pregnancies;
cervical incompetency:
urinary tract infections;
>

136

 sexually transmitted diseases;

familial history of PSRM;
nutritional deficit, cigarette smoking, heavy work, b. fetal associated

disorders;

0 twin pregnancy; 0
abnormal presentations; 0
hydramnios; 0 placenta praevia.
Diagnosis

Symptoms are the key to diagnosis. The patient usually reports a

sudden gush of fluid or continued leakage. Occasionally, patients will report
a persistent trickle suggesting a small tear or perforation of the membranes.
Additional symptoms that may be useful:

=> color and consistency of the fluid:

=> the presence of flecks of
vernix; reduced size of the uterus;

=> increased prominence of the fetus to palpation.

A most important step is examination with a sterile speculum:

> pH is tested with nitrazinc paper (amniotic fluid has a pH of

7.0-7,25);

> cervical secretions should be collected for culture;

> fern test (air-dry a drop of the fluid on a slide and examine
for arborization);

> determination of the L/S ratio, phosphatidylglycerol (after

34th week); Nile blue sulfate staining of fetal cells in the
suspected amniotic fluid; determine the cervical aspect (degree
of effacement and dilatation); > check for cord prolapse.
A careful physical examination should be done to search signs of
infection (fever, tachycardia).

Laboratory tests in amnionitis: maternal leukocytosis (more than

16.000). amniotic fluid C-reactive protein measurements, aerobic or
anaerobic culture.

Ultrasound examination is indicated to estimate the fetal size.

A firm diagnosis of rupture of the membranes is not always easy

to make unless amniotic fluid is seen or felt escaping from the cervical os by
the examiner. Although several diagnostic tests for the detection of ruptured
membranes have been recommended, none is completely reliable (perhaps
the most widely employed procedure involves testing the acidity or
alkalinity of the vaginal fluid).

Differential diagnosis:
==> urinary
incontinence; => vaginitis;
=> amnio-choriai pouch rupture;
=> decidual
endometritis. Prognosis
Maternal risks
137

Intrauterine infection is a potentially serious complication to the

mother. Intrauterine infection, defined as the presence of a positive amniotic
fluid culture regardless of the presence or absence of clinical evidence of
infection, occurs on average in 28% of women with PSRM. Amnionitis may
be more common at 23 to 31 weeks gestation than at 32 to 34 weeks
(J.Kitzmiller, 1984).

Fetal and neonatal risks

Infection is a major potential complication for the fetus and

neonate as well for the mother. The same vaginal organisms that lead to
maternal infection can result in congenital pneumonia, sepsis or meningitis.

The range of neonatal sepsis in cases of PSRM. with or without

clinical amnionitis, has ranged from 2 to 19% and the range of neonatal
deaths caused by infection from 1 to 7%.

There is a higher risk of frank or occult cord prolapse,

particularly when fetal membranes are ruptured prior to 26 weeks gestation.

The most important risk from PSRM is preterm birth.

Because of the central role of gestational age in determining the

relative risks inherent in the different approaches, it is crucial :o asses
gestational age accurately.

Treatment

Differences of opinion bordering on controversy exist regarding

details of management of PSRM. One group believes that nonintervention
may be more beneficial for both preterm and term fetuses than attempts to
deliver.

A second group holds that delivery should be induced within a

reasonable interval (usually no more than 8-12 hours) if gestational age is
greater than 33 weeks or if the fetus is mature according to physiologic
maturity tests. Both groups agree on the desirability of delivery when there
is PSRM and amnionitis.

If intervention is selected, the following recommendations have been

helpful:

=> gestational age over 36 weeks, fetal weight over 2,500g.

whenever the latent period exceeds 8-12 hours, induction by means of
oxytocin infusion is indicated to minimize the risk of infection;
=^> gestational age 34-36 weeks: induction is indicated: some may
prefer to wait 24-48 hours in the expectation of accelerated lung
surfactant production:

=> estimated gestational age 26-34 weeks, fetal weight 5002.OOOg: if there is evidence of lung maturation or chorioamnionitis
(bacteria in amniotic fluid), labor should be induced: if the L/S is in the
immature range and there is no evidence of amnionitis, the patient should be
maintained at bed rest; corticosteroid drugs (for lung maturation) may be
beneficial;

138

 gestational age under 26 weeks, there is very little chance of fetal

salvage and considerable maternal risk.

Cesarean section is often necessary if labor does not progress or if
fetal distress is recognized. Cesarean operation is also appropiate if
breech or another abnormal presentation is diagnosed or if any other
abnormality such as prolapsed cord is detected.
Induction of uterine contractility is realised with an intravenous
infusion of 5% dextrose to which lml (10U) of oxytocin is added
(1,000ml dextrose +- 10U oxvtocin = lOmU'each ml of solution).
The dosage necessary to stimulate contractions may be as low as
0.5mU/min (the constant infusion pump is set to deliver this dosage).

Contraindications to induction:

=> abnormal fetal presentations;

=> obvious feto-pelvic disproportion;

=> uterine scars.

Uterine contractions can also be initiated by the intrvenous.

intraamniotic, vaginal or extraovular administration of PG F2 or F2 alpha,
They also seem to be particularly effective in ripening the cervix before
induction.

139

16. TWIN PREGNANCY

Definition
It is a condition in which inside uterine cavity two fetuses develop at
the same time. It is a recessive, atavic phenomenon, a high-risk pregnancy. The
presence of two fetuses in the uterine cavity influences their growth and delivery.
Having this in view we have to consider four categories of factors:

^ the early and excessive distension of the uterus can induce an

inappropriate uterine contractility (having as its effect abortion or preterm labor):

=> sharing the intracavitary space and placental nutrition results in

IUGR, abnormal fetal presentation, velamentous insertion of the cord and
placenta praevia;

=> fetal malformations due to imperfect divisions;

=> dystocic elements: pathological presentations. PSRM, cord

prolapse, characteristic dystocia.

Classification
1, monozygotic twinning (single ovum) (identical twins) (15%) as a
result of a single fertilized ovum, that subsequently divides into two similar
structures, each with the potential for developing into a separate individual:
2. dizygotic twinning (double ovum) (fraternal twins) (85%) as a
result of two separate ova fertilization which takes place simultaneously.

Frequency

The frequency of monozygotic twinning is relatively constant

worlwide at approximately one set per 250 births and is largerly independent of
race, age. parity, ovulation induction.

The incidence of dizygotic twinning is influenced remarkably by

maternal age, parity, race, heredity, fertility drugs.

140

Etiology
It hasn't been completely clarified. The following factors are
involved:

> age and parity: the number of monozygotic pregnancies

increases slightly with age (parity has no role); the number of dizygotic
pregnancies increases slightly with parity (age has no role);

=> race: the frequency related to this factor is 1/100 pregnancies

among white women, 1/80 pregnancies for black women (in Nigeria, in a rural
community, once in every 20 births), in Japan, 1/155 births;
=> poor nutrition induces a low frequency of dizygotic pregnancies:
heredity: the genotype of the mother is much more important than that of
the father; a genetically explained predisposition and an individual
characteristic illustrated by the capacity to produce elevated levels of FSH
which induce multiple follicular maturation and polyovulation;

=> geographical areas: this type of pregnancy is more frequent with

women living in northern teritories;

=^> season: it is more frequent in summer ;

=> induction of ovulation by use of gonadotropins (FSH-t-HCG) or

of clomiphene enhances remarkably the likelihood of multiple ovulations;
ovulation induction likely increases both dizygotic and monozygotic twinning:

=3* in vitro fertilization: twinning is more common in pregnancies that

result from in vitro fertilization. Pathogeny

In dizygotic twinning there exist two independent eggs (two ova,

maturated and fertilized during a single ovulatory cycle). Pregnancies are always
dichorionic and diamniotic, without vascular communications between fetuses.

In monozygotic pregnancy, splitting of the zygote during the first 14

days after fertilization takes place:

-> in the first 72 hours (blastomeres stage), the dichorionicdiamniotic monozygotic twin pregnancy results (25%);

> during the 4t!,-8th day (embryonic button), monochorionic*

diamniotic pregnancy results (70%);

-> during the 8* -14th day (embryonic plate), monochorionicmonoamniotic pregnancy results (5%).

In monochorionic-diamniotic pregnancies there occur circulatory

anastomoses in about 90% of the cases and in monochorionic-monoamniotic
pregnancies the frequency of malformations is increased.

Morphology of the ovular

141

elements Dizygotic pregnancy is

characterized by:
eggs distinctly separated (dichorionic-diamniotic);
absence of circulatory anastomoses;
normal volume of amniotic fluid:
fetuses without phenotypic or genotypic identity;
identical or different sex. Monozygotic twinning
is characterized by: 0 a unique egg;

0 a unique placenta, with vascular anastomoses;

0 a unique or double amniotic sacs:

0 phenotypic and genotypic identity;

0 twin-twin transfusion syndrome;

0 hydramnios;

0 malformations.

About 90% of the monochorionic placentas exhibit vascular

communications between the two fetal circulations, most frequently the
anastomoses being isolated artery to artery or combinations of artery to
artery and artery to vein communications.

The determinant physiopathological element is the artery to vein

component on the capillary level (the blood passes from artery to vein, out
of one fetus into the other). The effects of the third circulation are evident
especially after the 4 fh month when the placental vasculature reaches final
shape.

There can be distinguished 3 variants of vascular relationships:

=> hemodynamic equilibrium:

marked asymmetry: its frequency is 15 to 30%; the

perfused fetus presents hypervolemia, heart failure, acute hydramnios and
the hypoperfused fetus has hypoxemia and oligoamnios (twin-twin
transfusion syndrome);

slight asymmetry: evident by slow transfusion which gives

the tranfused fetus the following characteristics: higher weight,
polycytemia. hyperbilirubinemia, hepatosplenomegaly, edema with or
without hydramnios.
Other pathological evidence pseudocharacteristic to gemellality: ->
prematurity: respiratory distress, acidosis, hypoglicemia,
hypocalcemia, hyperbilirubinemia;

> IUGR (hypotrophy), more important in monozygotic

pregnancies, due to nutritional deficiency, mechanical compressions, PIH;

congenital malformations: 3 to 7 times more frequent than in

singleton : they may be minor or severe (acardia, conjoined twins, vertebral
anomalies, renal esophageal, intestinal defects). Clinical diagnosis

It is unfortunate that the diagnosis of twins has frequently not

been made until late in pregnancy often as late as the time of labor.
Increasingly widespread use of prenatal ultrasound imaging has greatly
changed the incidence of overlooked twin gestations.
The history can provide information about familial antecedents of
twins, of the mother or in the father family, recent administration of
either domlphene or pituitary gonadotropin, placental hyperactivity
symptoms (ptialism, nausea and vomiting, heartburns, drowsiness).

In the third trimester, one can note excessive fatigue,

exaggerated increase in weight and abdominal distension, dyspnea, edema
(to inferior extremities, suprapubic and vulvar), varices.

142

Inspecting the abdomen one can see a discrepancy between

gestational age, determined from menstrual data, and that from uterine size,
glossy skin, striae and evident colateral circulation.

On palpation, the same increased volume is found, elevated tone,

sometimes hydramnios. Three fetal poles can be detected of which two are
similar. In 45% both fetuses have a cephalic presentation, in 35% the first
fetus has a cephalic presentation and the second a breech presentation, 10%
both fetuses have a breech presentation, in 6% the first fetus has a cephalic
presentation and the second a shoulder presentation, in 4% the first has a
breech presentation and the second a shoulder one.

One can hear fetal heart sounds in two different sites with a
maximum of intensity separated by a zone of silence. The frequences of the
two rates may be equal or different.

Bimanual examination can reveal the following aspects: a fetal

pole, smaller than expected in relation with uterine size ; sometimes, in
hypogastrum the fetal poles can't be detected: uterine cervix may be effaced
and the membranes are under tension.
Laboratory tests

Sonography provides
information concerning : ~ the number of
fetuses;

> type of placentation (an aspe'et related to

morbidity); fetal size and possible anomalies;
-> guidance to perform some maneuvres : amniocentesis, villous
sampling, selective reduction of multiple fetuses (performed in the first
trimester by intraembryonic instillation of CINa 5% solute, 3ml).

Biochemical tests: chorionic gonadotropin, estriol, placental lactogen,

alpha FP may have higher levels.

Differential diagnosis may be made with :

macrosomic singleton;
hydramnios;
hydatidiform mole (in the first months);
pregnancy associated with large ovarian cysts or uterine myomas.

Prognosis

In general, the degree of maternal physiological change is greater with

multiple fetuses than with a single fetus: the increase in blood volume; - =>
increased iron and folate requirements and a greater prevalence of maternal
anemia;

. => the increase of cardiac output;

=> the uterus and its contents may achieve a volume of 1OL or more and
weigh in excess of more than 20 pounds:

=> acute hydramnios may develop;

pregnancy-induced and pregnancy-aggravated hypertension are much
more likely to develop in pregnancies with multiple fetuses;

=> renal function can be reduced significantly if the uterus is large

enough to compress the ureters;

143

 => abortion and placenta praevia are more likely with twins than with

single fetus;
-=> maternal risk is somewhat increased because of the relativelv high
incidence of post partum hemorrhage which is more common after delivery
of a twin gestation.

The perinatal mortality, 10 to 15%. is considerably higher than that

for single birth. The principal causes of death are the complications of prematurity,
infection, prolapsed cord, hypoxia during delivery, malformations, transfusion
syndrome, IUGR.

The mortality for monozygotic twins is two to three times that for
dizygotic.

The mortality for the second twin is higher than that for the first
because it may assume an abnormal presentation, making vaginal delivery
difficult.

Prevention of preterm delivery

Several techniques have been applied in attempts to prolong

multifetal gestations. These include:
bed rest, especially through hospitalization;

prophylactic administration of beta mimetic drugs;

prophylactic cervical cerclage;

prevention of respiratory distress syndrome.

Bed rest is beneficial to twin fetuses presumably by enhancing

uterine perfusion and perhaps by reducing the physical forces that might act
deleteriously on the cervix to hasten effacement and dilatation. Routine
hospitalization is not beneficial.

Women with twins are managed as outpatients with frequent prenatal

visits and prompt hospitalization for complications.

There are controversies concerning benefits for prophylactic beta

mimetic therapy in reduction the frequency of threatened preterm labor.

No significant reduction in preterm delivery or perinatal deaths has

been demonstrated from prophylactic cervical cerclage. Since this surgical
procedure may be associated with sequelae it is recommended that cerclage be
limited to women with either a strong history or objectively documented cervical
incompetence.

Another concept related to early detection of preterm labor involves

ambulatory home monitoring of uterine contractions with a mobile
tocodynamometer.

Management of labor and delivery

Twin pregnancy has little effect on the length of labor, but

dysfunctional labor occurs more often than with single pregnancies.

The labor and delivery should be managed by an obstetrician who is

experienced in the delivery of twins and who is capable of performing the
operative maneuvers required for the delivery of both fetuses.

Cesarean section seems to be the delivery method of choice when the

presenting twin is in a nonvertex position (other than cephalic). Other major

144

0
0
0
0

indications are hypotonic uterine dysfunction, fetal distress, prolapsed cord,

prematurity, placenta praevia, hypertension induced or aggravated by pregnancy.

Vaginal delivery may be selected for the delivery of mature infants

when both are in vertex (cephalic) presentation. When the first fetus presents as a
breech, major problems arc most likely to develop if:
the fetus is unusually large and the aftercoming head taxes the
capacity of the birth canal;

=> the fetus is quite small so that the extremities and trunk are
delivered through a cervix inadequately effaced and dilated for the head to escape
easily;

=> the umbilical cord prolapses.

When these problems are anticipated or identified, cesarean delivery

will often be the better way to effect delivery.

The presenting part of the second infant should be identified soon

after the first is delivered so that plans can be made for its delivery. As a general
rule the membranes should be ruptured artificially after which the vertex or breech
usually descends into the upper pelvis.

If the second infant is lying transversely, an experienced obstetrician

can usually deliver it by bringing the legs through the cervix and extracting it as a
breech (internal podalic version and extraction).

The interval between delivery of the first and second twins is

commonly cited to be safest if at less than 30 minutes. There are situations in
which expeditious delivery of the second twin is desirable shortly after the first,
but this is not always the case.

Operative intervention is more likely in twin pregnancy because of

increased obstetric problems such as maipresentation. prolapsed cord and fetal
distress. If separation of the placenta is delayed or bleeding is brisk, extract the
placenta manually after the final delivery.

Postpartum hemorrhage is common in multiple pregnancy. Uterine

hypotony is often accompanied by excessive loss of blood owing to inability of
the overdistended uterus to contract well and remain contracted after delivery.

Because of this, venous access with a large-bore cannula is

mandatory. Hypotony should be treated promptly with oxytocin by rapid
intravenous infusion and massage of the fundus. If the uterus remains relaxed
despite these measures, manual exploration to search for an injury or retained
placental tissue should be performed promptly.

Hysterectomy may be indicated if all other methods have failed to

control bleeding.

145

A. Abnormalities of development

17. ABNORMALITIES OF THE UMBILICAL

CORD

The umbilical cord is the life line of fetal development. During the
course of gestation, there is increasing blood How through the cord to support the
developing fetus. By term it is approximately 300 to 350cc/inin and represents
almost 40% of the fetal cardiac output.

The vessels contained in the cord (two arteries and one vein) are
characterized by spiraling or twisting. The spiraling may occur in a clockwise or
anticlockwise direction. It is believed that the spiraling serves to attenuate
"snarling" which occurs in all hollow cylinders subject to torsion.

The extracellular matrix, which is a specialized connective tissue,

consists of Wharton jelly. The funis is covered by amnion and is placed in the
space created by generalized flexion of fetus body. All these elements are
important in protecting the umbilical cord against compressions.

The aspects of the umbilical cord pathology, revealed especially

during labor and delivery, can be classified in two categories:
A.
Abnormalities of development:
=> abnormalities of cord insertion:
marginal insertion;
velamentous insertion. =^>
abnormalities in cord length; =>
tumors of umbilical cord: =>
vascular anomalies;
B.
Accidental pathology:
-> loops;
knots; >
prolapse;
-thrombosis; ->
ruptures.

146

Abnormal
ities of cord
insertion

The umbilical cord is usually, but not always, inserted at or near

the center of the fetal surface of the placenta.

Marginal insertion

Insertion of the cord at the placental margin is sometimes

referred to as a battledore placenta and occurs in 2% to 15% of gestations.
Marginal insertion has been associated with a higher frequency of preterm
labor, although this concept is not universally held.

No other clinical problems have been apparent. However, some

authors consider that marginal insertion may be associated with IUGR, even
with intrauterine death. The site of insertion can be identified
ultrasonograph! cally.

Velamcntous insertion

Of considerable practical importance is velamcntous insertion of

the cord, because the umbilical vessels separate in the membranes at a
distance from the placental margin, which they reach surrounded onl\ b\ a
fold of amnio].. This mode of insertion is noted in a little more than 1% of
singleton deliveries but much more frequently with twins, and il is almost
the rule with triplets.

The origin of this fact is related to the initial location of the

abdominal pedicle and an excentrie development of primal} vascularizalionthc future placental site on the decidua basal is.

When with velamcntous insertion, some of the fetal vessels in

the membranes cross the region of the internal os and occupy a position
ahead of the presenting part of the fetus, the condition is termed vasa
praevia.
At times, the careful examiner will be able to palpate a tubular fetal
vessel in the membranes overlying the presenting part. Compression
of the vessels between the examining linger and the presenting part is
likely to induce changes in the fetal heart rate. The vessels may be
visualized directly, or they may be seen on ultrasonic examination.

With vasa praevia. there is considerable potential danger to the

fetus, for rupture of fetal vessel, causing exsanguination (Bcnkiser
syndrome).

Blood can be ascertained to be of fetal origin by demonstrating

resistance of hemoglobin to denaturation with alkali.

Some authors found no association with obstetrical outcome

and. more particularly, with the birth weight in relation to umbilical cord

147

insertion site, others, however, noted an increased incidence of IUGR and

preterm birth with velamentous insertion.

Cesarean operation is indicated when the diagnosis is made and

fetus is maturated. During labor, when conditions to perform the section are
not existent, delivery must be rapidely finished by forceps or by breech
extraction.

Abnormalities in cord length

Umbilical cord length varies appreciably, with the mean length

being about 55cm. Indirect evidence suggests that the length of cord at term
is determined by the amount of amniotic fluid and fetal activity present in
the first and second trimesters.
1. Cord absence (achordia) is an extremely rare situation. 2.Excessively
short umbilical cord (cord length less than 35cm) can induce :

=> abnormal
presentations; => fetal
heart rate injuries: =>
abruptio placentae;

=> rupture (with hemorrhage, which can cause fetal

death);

=> anomalies of parturition. 3. Excessive length (cord length more

than 70cm) favors complications as : vascular occlusion by thrombi, true
knots, cord prolapse through the cervix, loops of the cord.

Tumors

Tumors of the umbilical cord are extremely rare.

Angiomyxomas are the most common and arc thought to be extensions of
chorioangiomas of the placenta.

Other even rarer tumors have been described, including

teratomas and hemangiomas.Although strictly not tumors, hematomas are a
serious complication and are associated with postmaturity, fatty
degeneration of the vessels, infection and calcification of the vascular walls.
Antenatal ultrasound diagnosis has been reported.

Vascular anomalies Absence of one umbilical arterv

(Single Umbilical Artery)

(SUA)

The absence of one umbilical artery characterized 0.85% of all

cords in singletons and 5% of the cords of at least one twin. About 30% of
all infants with one umbilical arterv missinu had associated congenital
anomalies.

According to E.M.Bryan and H.G.Kohler (1975) infants with

SUA had an 18% incidence of major malformations. 34% were growthretarded, 17% delivered preterm.

148

ITie incidence is increased considerably in newborns of women

with diabetes, a condition associated with a threefold increase in anomalous
fetuses. Two-vessel cords are more frequently identified in fetuses aborted
spontaneously.

The comparatively high perinatal mortality associated with

SUA. 13% to 58%, is related to those infants with concomitant anomalies,
although deaths from prematurity-related complications are also significant.

Increased incidence of SUA was found in whiles more than in blacks. 1

Diagnosis of the SUA can readily be made at the lime of

delivery by examination of the gross specimen. Care should be taken to look
for this conditions in infants of diabetic mothers, twin gestations,
particularly the smaller twin, and in cases of velamentous insertion of the
umbilical cord,

Antenatal diagnosis of the SUA can be made ultrasonografically.

This is of importance because of the association between 1UGR and SUA.

B. Accidental pathology

It includes eventualities which lead to umbilical vessels

compression and fetal distress.
Loops of the cord The cord frequently becomes coiled around portions
of the fetus, usually the neck. Loops are favourized by excessive
length of the cord and by hvdramnios.

The incidence of the umbilical cord around the neck range from
one loop in 21% to three loops in 0.2%.
Typically, as labor progresses and the presentation descends the birth
canal, contractions compress the cord vessels, which cause fetal heart
rate deceleration.

During the management of normal delivery, after the head is

delivered, the finger should be passed to the neck of the fetus to ascertain
whether it is encircled by one or more coils of the umbilical cord. If a coil of
umbilical cord i>> felt, it should be drawn down between the fingers and. if
loose enough, slipped over the infant's head. If it is applied too tightly to the
neck to be .slipped over the head, it should be cut between two clamps and
the infant promptly delivered.

Fetal distress induced by tight umbilical cord loop is an

indication for cesarean section.

Umbilical cord knots

True knots must be distinguished from false knots that may be

varicosities in the cord or localized accumulations of Wharton's jelly. False
knots have no clinical significance.

149

True knots, which result from active fetal movements, can be

found in 1 . 1 % of births. True knots can be unique or multiple.

Unless tension develops in a true knot, the pregnancy usually

remains unaffected. Fetal distress appears during delivery, an 8% to 1 1%
perinatal mortality has been reported.

Umbilical cord prolapse Umbilical cord prolapse is defined as

descent of the umbilical cord into the lower uterine segment, where it may
lie adjacent to the presenting part (occult cord prolapse) or below the
presenting part (overt cord prolapse).

Funic presentation is characterized by prolapse of the umbilical

cord below the level of the presenting part before rupture of the membranes
occurs (procubitus). when the cord can be easily palpated through the
membranes if the cervix is opened.

Overt cord prolapse is associated with rupture of the membranes

and displacement of the cord into the vagina, often through the introitus.

Pathophysiology

Prolapse of the umbilical cord to a level at or below the

presenting part exposes the cord to intermittent compression between the
presenting part and the pelvic inlet, cervix or vaginal canal. Compression of
the cord compromises fetal circulation and. depending upon the duration
and intensity of compression, may lead to fetal hypoxia, brain damage and
death.

In overt cord prolapse, exposure of the cord to air causes

irritation and cooling of the cord, resulting in further vasospasm of the coixt
vessels.

Whether occult or overt, umbilical cord prolapse is associated

with significant rates of perinatal morbidity and mortality due to
intermittent compression of blood flow and resultant fetal hypoxia.
Perinatal mortality rates associated with all cases of overt umbilical
cord prolapse approach 20%. Prematurity, itself a contributor to incidence of cord
prolapse, accounts for a considerable portion of this perinatal loss.

Etiology

Any obstetric condition that predisposes to poor application of the

fetal presenting part to the cervix may result in prolapse of the umbilical cord.
Ovular factors:
prematurity;
abnormal presentations (breech, brow, face, transverse);
multiple gestation;
placenta pracvia;
hydramnios;
premature rupture of the membranes, occuring before engagement;

150

 excessive length of the cord.

Maternal factors: 0
multiparity; 0 pelvic tumors; 0
abnormal birth canal.

A special etiologic condition consists in artificial rupture of membranes

with an unengaged presentation. Clinical findings

Overt cord prolapse may be diagnosed simpiy by visualizing the cord

protruding from the introitus (second or third degree of prolapse), by speculum
examination or by palpating loops of cord in the vaginal canal (first degree
prolapse).

The diagnosis of funic presentation is also made by speculum and

bimanual examinations. Occult prolapse is rarely palpated during pelvic
examination. This condition may be inferred only if fetal heart rate changes
(variable decelerations) associated with intermittent compression of the cord are
detected during monitoring.

The fetus in good condition whose well-being is jeopardized by

umbilical cord compression may exhibit violent activity readily apparent to the
patient and the obstetrician.

Variable fetal heart rate decelerations will occur during uterine

contractions, with prompt return of the heart rate to normal as each contraction
subsides. If compression is complete and prolonged it induces the development of
hypoxia, metabolic acidosis and, finally, death.

Prevention

Patients at risk for umbilical cord prolapse should be treated as highrisk patients. Cases with malpresentations or poorly applied cephalic presentations
should be considered for ultrasonographic examination at the onset of labor to
determine fetal lie and cord position within the uterine cavity.

Because most prolapses occur during labor as the cevix dilates,

patients at risk for cord prolapse should be continously monitored to detect
abnormalities of the fetal heart rate.

Artificial rupture of membranes should be avoided until the

presenting part is well applied to the cervix.

At time of spontaneous membrane rupture a prompt, careful pelvic

examination should be performed to rule out cord prolapse.

Management
A.
Overt cord prolapse

The diagnosis of overt cord prolapse demands immediate action to

preserve the life of the fetus. A rapid pelvic examination should be performed to
determine cervical effacement and dilatation, station of the presenting part, the
strength and frequency of pulsations within the cord vessels, an eventual prolapse
of a fetal segment associated with ;he cord prolapse (compound presentation).

151

If the fetus is viable and conditions to perform cesarean section are

carried out, operation is mandatory. Abdominal delivery should be accomplished
as rapidly as possible through a midline abdominal incision and a pediatric team
should be standing by for immediate resuscitation of the newborn.
B.
Occult cord prolapse

If cord compression patterns (variable decelerations) of the fetal heart

rate are recognized during labor, an immediate pelvic examination is performed to
rule but overt cord prolapse.

If occult cord prolapse is suspected, the patient should be placed in

the lateral Sims or Trendelenburg position in an attempt to alleviate cord
compression.

If the fetal heart rate returns to normal, labor may be allowed to

continue, provided no further fetal insult occurs. Oxygen should be continously
monitored electronically.

If the cord compression persists or recurs to the point of fetal danger,

a rapid cesarean section should be accomplished.

152

C. Funic presentation

The patient at term with funic presentation should be delivered by an

expeditiously performed cesarean section prior to membrane rupture.

If the fetus is premature, the patient should be hospitalized at bed rest

in an attempt to reposition the cord within the uterine cavity. Serial
ultrasonographic examinations should be performed to ascertain cord position,
presentation and gestational age.

The umbilical cord prolapse represents an obstetrical emergency.

Cesarean section is the preferred route of delivery in most cases. Vaginal delivery
is the route of choice for an immature or dead fetus.

Neonatal prognosis

Fetal morbidity and mortality rates are high and the prognosis depends
upon the degree and duration of umbilical cord compression occurring before the
diagnosis is made and neonatal resuscitation begun. If the diagnosis is made early
and the duration of complete cord occlusion is less than 5 minutes, the prognosis
is good. If complete cord occlusion has occurred for longer than 5 minutes, fetal
damage or death may be inevitable. Thrombosis

Thrombosis of the umbilical cord can be favored by velamentous insertion,

loops or infection. It is a rare form of cord pathology but can induce acute fetal
distress even death in utero. Ruptures

A short cord can result in its rupture with tractions. It is a very rare
condition.

153

18. SPONTANEOUS

ABORTION

Definition
Abortion is the termination of pregnancy by any means before the
fetus is sufficiently developed to survive. When abortion occurs spontaneously,
the term miscarriage has been applied by laypersons. In the USA, this definition is
confined to the termination of pregnancy before 20 weeks gestation based upon
the date of the first day of the LMP. Another commonly used definition is the
delivery of product of conception that weighs less than 500g.

In some European countries, including Romania, this definition is

confined to the interruption of pregnancy before 28 weeks gestation or less than
l.OOOg.

Frequency

Spontaneous abortion is the most common complication of

pregnancy. Approximately 15% to 20% of clinically recognized pregnancies are
aborted spontaneously.

Classification

Abortion can be unique (isolated) or recurrent. The most generally

accepted definition of recurrent spontaneous abortion refers to three or more
consecutive spontaneous abortions.

Abortions that occur during the first 12 weeks are early abortions.
Late abortions are those that occur during the second trimester of pregnancy.

More than 80% abortions occur in the first 12 weeks of pregnancy,

and the rate decreases rapidly thereafter.

About 40% of implanted fertilized eggs terminate spontaneously and

most are not recognized clinically.

As an abortion progresses, it advances through a series of fairly

characteristic stages that can usually be recognized clinically. These are classified
as : threatened, inevitable (or in evolution), incomplete, missed and complete
abortion.

154

Etiology
The exact mechanisms responsible for abortion are not always
apparent but in early months of pregnancy, spontaneous expulsion of the ovum is
nearly always preceded by death of the embryo or the fetus.

For this reason, etiological considerations of early abortion involve

ascertaining whenever possible the cause of fetal death.

In the subsequent months, the fetus frequently does not die in utero
before expulsion and other explanations must be invoked.
Mechanisms responsible for abortion can be grouped in
6 categories: 1.- mechanical factors; 2.- infections; 3.- genetic
factors; 4.- endocrine factors; 5.- immunological
mechanisms; 6.- maternal systemic conditions.

1. Mechanical causes induce an abnormal uterine contractility and

expulsion of a live product of conception. Mechanical factors are of two types:
a.
ovular (multiple pregnancy, hydramnios);
b.
uterine defects:

0 congenital anomalies that distort or reduce the size of

uterine cavity;
0 uterine malposition, especially with retroversion (the
growing uterus cannot escape from the pelvis because of this abnormal position);
0 uterine tumors, particularly submucous or intramural
myomas may be associated with abortion by distorting the uterine cavity and by
reducing the area in which normal placental implantation and growth can take
place;
0 intrauterine adhesions: synechiae (Asherman syndrome) are
most frequently the result of curettage for an infected or missed abortion or post
partum curettage; it is caused by destruction of large areas of endometrium which
results in amenorrhea and recurrent abortions believed to be due to insufficient
endometrium to support implantation; the diagnosis can be made by
hysterosalpingogram or by hysteroscopy;
0 incompetent cervix (anatomic or functional incompetence of
the uterine cervix) is characterized by painless dilatation of the cervix in the
second trimester with prolapse and ballooning of membranes into the vagina
followed by rupture of membranes and expulsion of an immature fetus; numerous
methods have been described in the nonpregnant woman to make the diagnosis:
hysterography, pull-through techniques of inflated Foley catheter balloons and
acceptance without resistance at the internal os of specifically sized cervical
dilators; although the cause of cervical incompetence is obscure, previous trauma
to the cervix, especially in the course of dilatation and curettage, conization,
cauterization or amputation appear to be a factor in many cases; in other instances,
abnormal cervical development plays a role; cervical dilatation characteristic of
this condition seldom becomes prominent before the 16th week, because before
that time the products of conception are not sufficiently large to efface and dilate

155

the cervix except when there are uterine contractions; incompetence of the cervix
is relatively rare.
2. Infections are accepted causes of late fetal wastage and logically
may be responsible for early fetal loss as well. Microorganisms associated
with spontaneous abortion include variola, malaria, CMV, Toxoplasma,
Mycoplasma
hominis,
Chlamidia
trachomatis,
Salmonella
typhi,
Ureaplasma urealyticum.

Transplacental infection occurs with each of these microorganisms

and sporadic losses could plausibly be caused by any.
3. Genetic factors

The most common morphological finding in early spontaneous

abortions is an abnormality of development of the zygote, embryo, early fetus or
the placenta. Abnormal fetal development, especially in the first trimester, may be
classified into that with an abnormal number of chromosomes (aneuploidy) or
development with a normal chromosomal component (euploidy).
Aneuploid abortion

Chromosomal abnormalities are common among embryos and early

fetuses that are aborted spontaneously and account for much or most of early
pregnancy wastage. At least 50% of clinically recognized pregnancy losses result
from a chromosomal abnormality.

Autosomal trisomy is the most frequently identified chromosomal

anomaly associated with first trimester abortions. Monosomy X (45/X) is the next
most common chromosomal abnormality and is compatible with live-bom females
(Turner syndrome). Triploidy is often associated with hydropic placental
degeneration. Incomplete hydatidiform moles may have fetal development that is
triploid or trisomic for chromosome 16.
Chromosomal structural abnormalities are common causes of
abortion and have been identified only since the development of banding
techniques (translocations and inversions).
Euploid abortion

Chromosomal ly normal abortuses are usually lost later in pregnancy.

The reasons for euploid abortions (with an incidence dramatically increased after a
maternal age of 35 years) are generally unknown, but the following are
possibilities:

^> a genetic abnormality such as an isolated mutation or polygenic

factors;

=> various maternal factors;

=> eventualy some paternal factors (chromosome translocation in

sperm).

Known to be responsible for most sporadic abortions, numerical

chromosomal abnormalities (aneuploidy) may also be responsible for recurrent
fetal losses. The recurrent abnormality is usually trisomy.

4. Endocrine factors

Disturbances in the secretions of reproductive hormones are

undoubtedly responsible for some abortions, but, probably, are less important than

156

they have been considered to be. Reduced hormone secretion may be a result of
abnormal trophoblastic secretion.

If the ovum is fertilized, HCG from the trophoblast stimulates the

corpus luteum to continue to produce estrogen and progesterone. If the secretion
of progesterone by the corpus luteum is inadequate, the endometrium may be so
poorly prepared for nidation and for support of the fertilized egg that early
abortion may result.

Progesterone secreted by the corpus luteum is necessary to support

the endometrium until the trophoblast produces sufficient progesterone to
maintain pregnancy, an event occuring around 7 menstrual weeks (5 weeks after
conception). The term luteal phase deficiency (LPD) is used to describe the
endometrium manifesting an inadequate progesterone effect. LPD is believed by
many to be a common cause of recurrent pregnancy loss (35%).

Combined deficiency of estrogen and progesterone is the most

common cause among the endocrine factors. Other forms of endocrine
disturbances are : isolated estrogen insufficiency, isolated progesterone
insufficiency and hyperandrogenism.

Abortions caused by associated insufficiencies occur in the 5 th week

to 9th week interval (45%), 10th-14* week interval (35%) and 15th-18th week (15%).

5.Immunological factors
Autoimmune mechanisms

Autoimmune mechanisms are those by which a cellular or humoral

response is directed against a specific site within the host. Antiphospholipid
antibodies, including the lupus anticoagulant and anticardiolipin antibodies, are
examples of autoimmune disease that can cause recurrent abortion.

These antibodies are directed against platelets and vascular

endothelium and cause vascular damage, thrombosis, placental destruction,
abortion and fetal morbidity and death.

Antiphospholipid antibodies are IgG and lgM immunoglobulins.

Because these antibodies are directed against glycerophospholipids, all of the
phospholipid-dependent clotting tests are prolonged. The diagnosis is then
confirmed if there is an abnormal tissue thromboplastin-inhibition test, platelet
neutralization test or dilute Russel viper venom time.

The diagnosis of the anticardiolipin antibody requires a high titer of

the specific IgG or lgM antibody.

Abortions are more likely in women with antiphospholipid

antibodies.
Alloimmune mechanisms

The human embryo is an allogenic transplant that is tolerated by the

mother for reasons that are incompletely understood. However, several
immunological mechanisms are reported to prevent fetal rejection. These
mechanisms include:
I - histocompatibility factors;
II - circulating blocking factors;
III - local supressor factors;
IV - maternal or antipatemal antileukocytotoxic antibodies.

157

I.
There is strong circumstantial evidence that maternal-fetal
histoincompatibility is essential to successful human pregnancy and that if
mother and fetus are ''too compatible" reproduction failure develops. In
some cases of recurrent abortion, there is an increased sharing of maternal
and paternal HLA sites.

II. Maternal blocking antibodies to paternal antigens appear to be

essential to the maintenance of normal pregnancy. Failure to synthesize
blocking antibodies that protect the fetus from her own antibodies directed
against paternal antigens shared by the fetus might result in abortion.

III. Local suppressor factors are most essential to normal

pregnancy
and their absence may be involved in the mechanism of recurrent abortion.
Suppressor T cells are lymphocytes that produce soluble factors that
suppress immune responses. These are present in decidua of normal
pregnancies but absent in some abortions.

IV. Maternal antipaternal antileukocytotoxic antibodies increase in

early pregnancy and then decrease near term. Some authors noted that it maybe
the failure of the mother to develop these antibodies that results in recurrent
abortion.
6. Maternal systemic conditions

Maternal factors cause spontaneous abortion more frequently in the

second trimester. Representative problems are as follows:
^> endocrine disorders (hyper or hypothyroidism, diabetes
mellitus); => cardiovascular-renal hypertensive disorders; => protein and
vitamin undernutrition;

=> blood group incompatibility due to ABO, Rli or other less

common factor systems;

=> toxic factors such as anticoagulants, lead piosoning, cocaine

abuse, excessive alcohol consumption, cigarette smoking, folic acid antagonists
etc;

=> psychic or emotional causes, advanced maternal age, poor socioeconomic status.
Clinical stage and treatment
Threatened abortion

At some time during early pregnancy, usually after having missed

one or two periods, the patient becomes aware of bleeding, which is slight and
usually consists of the spotting of bright blood or of dark brown discharge. She
may also experience some slight cramping pain.

The symptoms may subside within a day or two, but in about half the
cases both the cramps and the amount of bleeding increase. The eventual outcome
is uncertain and pregnancy may continue, uneventfully.
No change is observed in the cervix during this stage. Usually, bleeding
begins first and cramping abdominal pain follows a few hours to several
days later. Differential diagnosis: ectopic pregnancy; => dysfunctional
uterine bleeding; => uterine fibromyomas; hydatidiform mole;

158

benign lesions of the cervix or invasive cancer.

Inevitable abortion

The term "inevitable" implies that the changes are reversible and that
any attempt to maintain pregnancy is useless. Pain and bleeding with an open
cervix indicate impending abortion and the expulsion of the uterine contents is
imminent.

In the first two months, elimination of the products of conception

takes place in a single time, whereas during the second trimester, abortion takes
place in two times: rupture of the membranes and fetal expulsion followed by
incomplete expulsion of the placenta.
Incomplete abortion

In the majority of spontaneous abortions varying amounts of

placental tissue may remain within the uterus either attached to the wall or lying
free in the cavity. With abortions that are more advanced, bleeding is often profuse
and occasionally may be massive to the point of producing profound
hypovolemia. Vessels in the denuded segment of the placental site, deprived of the
constriction provided by myometrial contractions, bleed profusely.

Severe or persistent hemorrhage during or following abortion may be

life-threatening. Obviously, the more advanced the gestation, the greater the
likelihood of excessive blood loss.

Sepsis develops in cases with criminal or self- induced abortion but

may also occur in women who are sexually active immediately following
abortion.
Missed abortion

A missed abortion is defined as retention of dead products of

conception in utero for several weeks. More information when we will present
"fetal death and delayed delivery".
Complete abortion

A complete abortion is one in which the uterus empties itself

completely of the fetus and its membranes, the placenta and the decidual lining.
This occurs only during the first 6 weeks.

Treatment

As the management of each of the various uterine stages and types of

abortion is different, an accurate evaluation must be made before treatment can be
planned.

A properly performed pelvic examination does not adversely

influence the course of the abortion and it is necessary to establish the presence of
pregnancy, to eliminate tubal pregnancy or other pathological condition as a cause
of symptoms and to determine how far the abortive process may have advanced.

The examination should include gentle visual and digital examination

of the cervix and bimanual palpation of the uterus and of the adnexa.

159

The degree of cervical effacement and dilation can be determined by

palpation. As pathogenic organisms may be carried directly to the placental site,
gloves, instruments and materials used in examination must be sterile.

Benign lesions of the cervix such as polyps and cervicitis as well as

invasive cancer may be a source of bright red bleeding. Such lesions can be
detected by visual examination of the cervix.

Ultrasonic scanning may be helpful in determining the probable

outcome of bleeding during early pregnancy. With an intact, normal-appearing sac
containing a normal embryo or fetus, the prognosis is favorable. If the sac is
broken or empty, there is no chance of a normal pregnancy, and the uterus should
be emptied promptly.

The patient with threatened abortion may be kept at home, but, in

general, if the symptoms are more severe, she should hospitalized. These cases
have been treated with progesterone intramuscularly or with a wide variety of
synthetic progestational agents orally or intramuscularly.

Recommended treatment of LPD consists of exogenous progesterone

25mg twice daily, beginning with the basal body temperature elevation and
continuing at least 6 to 8 weeks. Other forms of treatment: HCG and clomiphene
citrate.

As the diagnosis of inevitable abortion implies that irreversible

progress toward uterine evacuation has already taken place, treatment should be
directed toward reducing blood loss and pain. In the event of profuse bleeding, it
is preferable to empty the uterus surgically as soon as a moderate amount of
cervical dilation has occurred or earlier.

Placental tissue remaining in the uterus after an incomplete abortion

should be removed because it often becomes infected and, in addition, may be
responsible for continued and excessive bleeding. The uterus should be evacuated
(with suction technique or surgical procedure) unless there is evidence of
endomyometritis or parametritis.

When infection is present, the operation should be delayed, unless excessive

blood loss cannot be controlled, while antibiotics are being administered.

Among the etiologic factors responsible for repeated abortion can be

noted congenital and acquired structural defects in the uterus, chromosomal
abnormalities, immunologic deficiencies.

The treatment of cervical incompetence is surgical, consisting of

reinforcement of the weak cervix by some type of pursestring. It is best performed
after the first trimester but before cervical dilatation of 2 to 3cm is reached.
Bleeding, uterine contractions or ruptured membranes are contraindications to
surgery.

Cerclage should be delayed until after 14 weeks'gestation so that

early abortions due to other factors will be completed. The simple procedure
recommended by Mc Donald (1963) is less traumatic with reduced blood loss
160

(suture of number 2 monofilament placed in the cervix very near the level of
internal os as to encircle the os).

The recommended treatment of Asherman syndrome is lysis of the

adhesions via hysteroscopy and placement of an PUD to prevent recurrence of
synechiae. Continuous high-dose estrogen therapy is also recommended by some
for 60 to 90 days.

Successful pregnancies have been achieved in high percentage of

women with lupus erythematosus using low-dose aspirin to inhibit thromboxane
production by damaged platelets and endothelium. Heparin is given to inhibit
thrombosis and corticosteroids to supress antiphospholipid antibodies as well as to
inhibit their action on target antigens. Potential efficacy of immunotherapy is
highly controversial.

The obstetrician faced with a couple experiencing spontaneous

abortion has several obligations:

=> inform them of the frequency of fetal wastage and its etiology, at
least 50% cytogenetic;

indicate recurrence risk;

=> determine the necessity of a formal evaluation for repetitive

abortions.

161

19. ECTOPIC PREGNANCY

Definition

Ectopic pregnancy (extrauterine pregnancy) (heterotopic pregnancy)

(eccyesis) is one in which a fertilized ovum implants in an area other than the
corpus uteri cavity. The term i'extrauterine" is inadequate because this would not
apply to the occasional comual and cervical pregnancies that are not in fact
outside of the uterus.
Frequency

The incidence is about 1% pregnancies (1 in 80-200 pregnancies)

and over 75% are diagnosed before the 12 n week of gestation. There has been a
marked increase in both the absolute number and rate of ectopic pregnancies in
the United States, Eastern Europe, Scandinavia and Great Britain. Although the
reasons for this increase are multiple, some likely causes include:

=> increased prevalence of sexually transmitted tubal infection;

=> popularity of contraception that prevents intrauterine but not

ectopic pregnancies;

=> insuccessful tubal sterilizations and previous pelvic surgery

(salpingotomy, tuboplasty);

=> induced abortions followed by infection;

==> better and earlier diagnostic techniques;

=^> assisted reproductive techniques.

Classification and specific incidence

Ectopic pregnancy may be classified as follows :

-* tubal: isthmic (25%), ampullary (55%), fimbrial (17%), interstitial

(2%);

> uterine: cornual, cervical (rare);

> intraligamentous (rare);
- ovarian (0.5%);

162

- abdominal (0.1%): primary, secondary;

-^heterotopic (combined with intrauterine pregnancy) (1/17,000-

1/30,000).
Etiology

A.
Mechanical factors that prevent or retard passage of the
fertilized ovum into the uterine cavity include the following:
1. Salpingitis causes agglutination of the folds of the tubal mucosa with
narrowing of the lumen or formation of blind pockets. Reduced ciliation of the
tubal mucosa due to infection may also contribute to tubal implantation of the
zygote.
2. Peritubal adhesions caused by postabortal or puerperal infection,
appendicitis or endometriosis may induce kinking of the tube and narrowing of
the lumen.
3. Previous ectopic pregnancy (after one, the risk of another is 7 to
15%).
4. Previous operations on the tube.
5. Multiple previous induced abortions (increase in the incidence of
salpingitis).
6. Tumors that distort the tube (uterine myomas, ovarian cysts).
7. Developmental abnormalities of the tube (diverticula, hypoplasia,
accesory ostia).
B.
Functional factors that delay passage of the fertilized ovum
into
the uterine cavity include the following:
1. Altered motility may follow changes in serum levels of estrogens and
progesterone, change in the number and affinity of adrenergic receptors in uterine
and tubal smooth muscle, use of progestin - only oral contraceptives, cigarette
smoking.
2. Transmigration of the fertilized ovum, a condition in which an ovum
produced in one ovary enters the opposite fallopian tube. The corpus luteum is in
the ovary opposite the involved tube. With external migration the ovum is
presumably fertilized in the cul de sac, where it begins to develop before it is
picked up by the fallopian tube.

With internal migration the fertilized ovum enters the uterine cavity
but by some means crosses and enters the opposite fallopian tube. In either case
the delay in entering the tube permits the ovum to develop to a point at which it
can implant.
3. Menstrual reflux has been suggested as a cause, however, there is
little supporting evidence for this.

C.

Ectopic endometrial elements (endometriosis in fallopian

tubes)
may enhance tubal implantation.
D.
Assisted reproduction. Several forms of assisted reproduction
have been reported to increase the incidence of ectopic pregnancy.

163

Tubal pregnancy has been reported to be increased following:

ovulation induction, gamete intrafallopian transfer (GIFT), in vitro fertilization.

Heterotopic tubal pregnancy is increased after IVR embryo transfer

and ovulation induction.

Cervical pregnancy and abdominal pregnancy may be increased after

IVF, GIFT and ovum transfer.
E.
Failed contraception increases the incidence of ectopic
pregnancies (tubal fulguration, fistula following total or subtotal
hysterectomy).
Pathologic anatomy

One important aspect of ectopic pregnancy is the lack of resistance or

response of tissues into which the developing ovum is abnormally implanted.
Implantation is beneath the endosalpinx in the connective tissue next to the serosa.
There may be little or no decidual reaction and minimal defense against
permeating trophoblast.

The trophoblast invades the blood vessels to cause local hemorrhage.

A hematoma in the subserosal space enlarges as pregnancy progresses, with
bleeding out of the distal end of the tube but not out of the tubal lumen. In tubal
pregnancy, distension and thinnes of the tube predispose to rupture.

The uterus undergoes some of the changes associated with normal

early pregnancy, including softening of the cervix and isthmus and an increase in
size.

The degree to which the endometrium is converted to decidua is

variable. The finding of uterine decidua without trophoblast suggests ectopic
pregnancy but it is not an absolute indication (endometrial changes-epithelial cells
enlarged, hypertrophic, hyperchromatic, lobular nuclei, vacuolated cytoplasmhave been collectively referred to as the Arias-Stella reaction). These cellular
changes are not specific for ectopic pregnancy and may also occur with
intrauterine gestations.

External bleeding, which is seen commonly in cases of tubal

pregnancy, is uterine in origin and associated with degeneration and sloughing of
the uterine decidua.

A common termination of tubal pregnancy is separation of the

conceptus from the implantation site and extrusion through the fimbriated end of
the oviduct. Tubal abortion is common in ampullary tubal pregnancy, whereas
rupture of the tube is the usual outcome with isthmic pregnancy.

Some bleeding usually persists as long as the zygote remains in the

oviduct. If the fimbriated extremity is occluded, the fallopian tube may gradually
become distended by blood forming a hematosalpinx.

Often there is gradual disintegration of the tubal wall followed by

slow leakage of blood into the tubal lumen, the peritoneal cavity, or both. Signs of
active hemorrhage are absent, and even mild symtoms may subside, but gradually
the trickling blood collects in the pelvis, more or less walled off by adhesions, and
a pelvic hematocele results.

164

The invading, expanding products of conception may rupture the

oviduct at any of several sites. The immediate cause of rupture may be trauma
(bimanual examination) although in most cases rupture occurs spontaneously. The
woman commonly shows signs of collapse from intraperitoneal hemorrhage and
hypovolemia.

If an early conceptus is expelled essentially undamaged into the

peritoneal cavity, it may reimplant giving rise to an abdominal pregnancy.

When the original implantation of the zygote is toward the

mesosalpinx, rupture may occur at the portion of the tube not immediately
covered by peritoneum and the contents of the gestational sac may be extruded
into a space formed between the folds of the broad ligament (broad ligament
pregnancy).

Implantation of the fertilized ovum within the segment of tube that

penetrates the uterine wall results in an interstitial pregnancy (cornual
pregnancy)(3% of all tubal pregnancies). The hemorrhage may rapidly prove fatal
because the implantation site is located between the ovarian and uterine arteries.

Cervical implantations occur only once in 15,000 to 16,000

pregnancies. The cervix is enlarged, friable and profuse bleeding occurs.

With ovarian pregnancy the ovum is fertilized before it is extruded

into the peritoneal cavity and the trophoblast develops within the ovary itself.

Many tubal pregnancies, probably more than become clinically

obvious, undergo spontaneous regression. Either the ovum dies at an early stage,
or it implants so close to the tubal ostium that it is soon extruded.

Clinical and laboratory features of tubal pregnancy

Clinical manifestations of a tubal pregnancy are diverse and depend
on whether rupture has occured. Even though symptoms and signs of ectopic
pregnancy often range from indefinite to bizarre, more women are seeking
medical care before the classical clinical picture develops.

The physician must make every reasonable effort to diagnose the

ectopic pregnancy before dangerous events occur, but the task may not be simple.
Signs and symptoms
Amenorrhea

A history of amenorrhea is not obtained in a quarter or more of cases.

The absence of a missed menstrual period does not exclude tubal pregnancy. It is
very important that the character of the last menstrual period be elicited in detail
with respect to time of onset, duration and amount of bleeding.

Bleeding

Its usually scanty, dark brown, and may be intermittent or

continuous. Pain

May be anywhere in the abdomen or may be absent prior to rupture.

Exquisite tenderness on abdominal palpation and vaginal examination, especially
on motion of the cervix, is demonstrable in over three fourths of women with
ruptured or rupturing tubal pregnancies.

If the patient experiences extremely sharp sudden pain, particularly

with a syncopal episode, tubal rupture should be feared. Suprascapular pain
signifies phrenic nerve irritation by the resultant hemoperitoneum.

165

Elements revealed by bimanual examination

In about 25% of cases, the uterus grows to nearly the same size as it
would with an intrauterine pregnancy. The uterus may be pushed to one side by an
ectopic mass.

Pelvic mass is palpable in about 20% of patients and varies in size,

consistency and position. Such masses are often soft and elastic. It is almost
always either lateral or posterior to the uterus. Pain often precludes identification
of the mass by palpation. Bulging of the cul-de-sac can usually be detected by
vaginal or rectal examination if a pelvic hematoma has formed or if the cul-de-sac
is distended with fluid blood.

Early responses to moderate hemorrhage may range from no change

in pulse and blood pressure to a slight rise in blood pressure or a vasovagal
response with bradycardia and hypotension.

Acute tubal rupture may induce falling of blood pressure,

hemoglobin and hematocrit and classic symptoms of hemorrhagic shock with
weakness, thirst, profuse perspiration, "air hunger" and oliguria. Complications of
acute tubal rupture may be life-threatening.

Fever is slight or absent except in the rare patient with a secondary

infected pelvic hematocele.

Orthostatic changes in pulse rate and blood pressure are dependent

on the amount of bleeding and represent a very important part of the exam.

The diagnosis of an unruptured tubal pregnancy is not too difficult to

be made when classic symptoms (pain, bleeding, tender adnexal mass) are
present. Unfortunately, symptoms are often atypical and pelvic findings may be
misleading.
Laboratory tests

Chorionic gonadotropin (HCG) is secreted by the ST 7 to 8 days after

fertilization. Serum RIA for beta-HCG is the most precise method. Because of
sensitivity of this assay, a pregnancy may be confirmed before there are
pathological changes in the fallopian tube.

A single positive pregnancy test does not exclude an ectopic

pregnancy. Because of this, several different methods utilizing serial quantitative
serum beta-HCG values, alone or in combination with sonography, have been
developed to establish the diagnosis of an ectopic pregnancy.

Sonography, particularly with the endovaginal probe, is very helpful

in making the diagnosis of tubal pregnancy. A direct diagnosis can be made if a
typical gestational sac is identified outside the uterus.

A characteristic and normally situated gestational sac within the

uterine cavity virtually excludes ectopic pregnancy, except in rare instances of
combined tubal-intrauterine pregnancies.

Use of vaginal sonography alone can result in the correct diagnosis of

ectopic pregnancy in more than 90% of cases. The combination of a positive
pregnancy test without ultrasonic evidence of an intrauterine pregnancy 6 weeks
or more after the onset of the LMP is very suggestive of tubal pregnancy.

166

Heinoperitoneum can be detected by needle culdocentesis. Needle is

inserted through the posterior vaginal fornix into the cul-de-sac. If dark or bright
red nonclotting blood flows freely through the needle, the presence of
intraperitoneal bleeding is confirmed. The hematocrit of the aspirate is usually
above 15%. If nonclotting blood is aspirated one may proceed directly to
laparotomy.

Differentiation between threatened or incomplete abortion of an

intrauterine pregnancy and a tubal pregnancy may be accomplished in many
instances by curettage.The identification of decidua alone in uterine curettings
strongly implies ectopic pregnancy. Decidua alone may also be found following
complete abortion. The Arias-Stella endometrial reaction is also not diagnostic of
an ectopic pregnancy.

Fiber-optic laparoscopy provides a means of visual diagnosis of

pelvic disease, including ectopic pregnancy. Advantages of diagnostic laparoscopy
include:

-> a definitive diagnosis;

-> a concurrent route to remove the ectopic mass using operative

laparoscopy;

> a direct route to inject chemotherapic agents into the ectopic

mass.
Differential diagnosis
Threatened or incomplete abortion

The period of amenorrhea preceding the onset of symptoms is

usually longer, the amount of vaginal bleeding is greater, the pain is more severe
than in early ectopic pregnancy and is in the midline and crampy in nature. No
adnexal mass and tenderness are present.

Adnexitis

With either adnexitis or ectopic pregnancy, the bleeding may be

irregular, prolonged and more painful than usual. The pain, tenderness and
palpable tubal enlargement are usually bilateral with salpingitis. The temperature
is ordinarly elevated and leukocytosis is much greater than with ectopic
pregnancy. The pregnancy test is negative.

Appendicitis

There is usually a history of digestive disturbances, no amenorrhea or

abnormal bleeding, no adnexal mass. The pregnancy test is negative.

Twisted ovarian cyst (see benign ovarian tumors).

Rupture of a corpus luteum or follicular cyst

Intraperitoneal bleeding from an ovarian cyst may be difficult to distinguish

from a ruptured tubal pregnancy. Most often, the diagnosis is made only at the
time of exploratory laparotomy. Treatment

The usual treatment of tubal pregnancy is surgical. If the case has

been diagnosed early, it is often possible to preserve the tube (salpingostomy).
This technique is used to remove a small pregnancy that is usually less than 2cm
in length and located in the distal one third of the fallopian tube.

Segmental resection and anastomosis is recommended for an

unruptured pregnancy in the isthmic portion of the tube.

167

Conversely, if there has been delay in making the diagnosis, the tube
may be so damaged that it cannot be salvaged and must be removed
(salpingectomy).

If the patient's condition is stable and the operator is . an

accomplished laparoscopic surgeon, ectopic pregnancy may be treated by
operative laparoscopy.

The patient with ruptured tubal pregnancy and massive

intraperitoneal hemorrhage must be operated on as soon as she can be transported
to the hospital. Type-specific blood must be administered while the patient is
being prepared.

Medical management uses METHOTREXATE. In general, the

following principles apply : success is greatest if the gestation is less than 6 weeks
and the tubal mass is not more than 3.5 cm in diameter.

Chemotherapy is contraindicated in symptomatic women. Therapy can be

systemic or with ultrasound-guided injection of the gestational sac, eliminating
the need for a major surgical procedure. Abdominal pregnancy

The incidence is 1 in 10,000 live births to 1 in 25,000 births. Almost

all cases of abdominal pregnancy follow early rupture or abortion of a tubal
pregnancy into the peritoneal cavity.

Fetal viability in an abdominal pregnancy is exceedingly precarious

and the great majority succumb.

Abdominal pregnancy may be suspected in relation to bizarre

pregnancy symptoms, a pregnancy complicated by unusual gastrointestinal
symptoms, fetal movements that are very marked or painful, easy palpation of the
fetal parts and movement.

A strong suspicion of abdominal pregnancy may be confirmed by Xray with a probe or radiopaque material in the uterus. The fetus then is shown
clearly to lie outside the uterine cavity.

Ultrasonic findings most often do not allow an unequivocal diagnosis

to be made. However, in some suspected cases, these findings may be diagnostic.
Magnetic resonance imaging appears to be the most accurate and specific
technique.

Surgery for abdominal pregnancy may precipitate massive

hemorrhage related to the lack of constriction of hypertrophied opened blood
vessels after placental separation.

Surgery is indicated as soon as the diagnosis has been established. If

the placenta is left in situ, to prevent the hemorrhage, its involution may be
monitored using ultrasound.

The maternal mortality rate is about 10%. Only about 20% of fetuses
survive.
Cervical pregnancy

The incidence is about 1 in 16-18,000 pregnancies.

In a typical case, the endocervix is eroded by trophoblast and the

pregnancy proceeds to develop in the fibrous cervical wall. The duration of the

168

pregnancy is dependent upon the site of embryo implantation. The higher it is

implanted in the cervical canal, the greater it is its capacity to grow and bleed.

Specific clinical diagnostic criteria arc:

^> uterine bleeding without cramping, after a period of amenorrhea;

=> softened cervix, disproportionally enlarged to a size equal to or

larger than the corpus;
complete confinement and firm attachement of the products of
conception to the endocervix.

=> a large, dark, highly vascularized cervix with bleeding or

extrusion of dark tissue through the external os will be noted.

Immediate surgery is indicated as soon as the diagnosis is suspected.

Hemorrhage may be massive and, sometimes, fatal.

Curettage of the endocervix and endometrium may stop the bleeding.

Packing of the endometrial cavity, dilated cervical canal and vagina

with gauze for counterpressure may control bleeding.

If tissue damage or necrosis is great, hysterectomy will be necessary.

Because of the risks of uncontrolled hemorrhage, nonsurgical methods utilizing
methotrexate and other drug treatments have been developed.

169

20. DYSTOCIA DUE TO PELVIC CONTRACTION

Definition; Abnormalities of the size and shape of the pelvis.

The size of the "normal" female pelvic brim varies from race to race,
and is influenced by the special status of the woman within that race.

Within each race, women who have had good nutrition prenatally
and during infancy and childhood, are more likely to have normal pelvis than
women from the deprived sections of the community.

Genetic influences also play a part and big parents tend to have big
children with big pelvis, although this is not always so.

The shape of the female pelvis is subject to many influences, which

operate during infancy and puberty, before the bony ring of the pelvis is fully
ossified.

In the past, poor socio-economic conditions, shortage of calcium and

proteins in the diet, and lack of sunshine produced rickets, with the increased
malleability of die bones due to the disease, gross distortion of the pelvic cavity
results.

The incidence of disproportion and contracted pelvis varies, being

influenced by selection of cases for hospital care.

In most hospitals in Western European countries 1 to 2 % of cases

fall into this category whilst in Asia and Australia the incidence is less than 0,5%
of all admissions.
The ideal obstetric pelvis

Because of the many variations in the "normal 1', the ideal obstetric
pelvis is an abstraction, rather than a reality, but this notion has importance as
abnonnalities in pelvic shape and size are judged referring to it.

The description is summarized as follows: the brim should be round

or slightly oval transversely, with no undue projection of the sacra! promontory.
The measurements of the brim should be as follows:

=> antero-posterior diameter = 12 cm;

=> widest transverse diameter = 13 cm;

=> mid transverse diameter = 12,5 cm;

170

=> obstetrical conjugate = 10,5 cm.

The cavity should be shallow with straight side walls from which the
ischial spines do not project unduly. The distance between the ischial spines
should measure at least 10,5 cm.

The pelvis arch of the outlet should be rounded and subpubic angle 85.
The intertuberous diameter should measure 10 cm. Classification
A.
Dimensional classification

According to antero-posterior diameter (obstetrical conjugate

-promonto retropubian):

=> less than 7 cm - the contraction of the pelvis is of second degree;

=> when the diameter is 7-9,1 cm the contraction is of first degree;

=> when the diameter is 9-10,5 cm the degree is on limit of normal

and pathologic. In this cases the vaginal delivery is possible.
B.
Morphological classification
Narrow pelvis => all dimensions are smaller than normal.
Ring - shaped pelvis => the sacrum is flat

Flat pelvis antero-posterior with the anteo-posterior diameter smaller

than normal;
=> transversal - with the transversal diameter smaller than
normal.

Assimetric pelvis.
C.
Ethiological classification

Abnormalities of bone development

a)
Defects of nutrition:

Minor defects triangular brim (android)

flat brim (platypelloid) Major
defects 0 rachitic

0 osteomalacic
b)
Deseases or injuries:
1.
Spinal:
kyphosis;
scoliosis;
spondylolisthesis;
2.
Pelvic:
* tumors;

fractures; A
caries.
3.
Limbs:
poliomyelitis in childhood;

V congenital dislocation of the hip.

4.
Congenital malformations:
ONaegele's pelvis;
0 Robert's pelvis;

0 high assimilation pelvis.

In a young child suffering from rickets, the weight of the upper

body presses down through the spine on to the softened pelvic bones. The sacral
promontory is pushed forwards and downwards, whilst the sacrum itself pivots
backwards. At the same time the ligaments of the back draw the spinous process
medially so that the ilia flare outward, as do the ischial tuberosites. In extreme
cases the softened acetabulae may be forced inwards. The main alteration in
pelvic shape is a marked reduction of the anteroposterior measurement of the
brim, with some irregular widening of the cavity.

171

Osteomalacia, due to an acquired deficiency of calcium encountered

in adult life causes the same deformities as rickets, but this is rare.
1.
Spinal diseases

Kyphosis of the lower dorsal or lumbar region which started in

childhood, may alter shape of the brim of the pelvis, as the weight of the body
pushes the upper part of the sacrum backward and the lower part forward. The
side walls of the pelvis converge forming a funnel.

In scoliosis the altered pressure distribution on the soft bones, may

cause bay on each side of the sacral promontory, so that the shape of the brim is
asymmetrical.

Spondylolisthesis, which means slipping forward of the fifth lumbar

vertebra so that it projects beyond the sacral promontory, is rare.
2.
Pelvic deseases

Osteomata may develop or an injury may lead to excessive bone

formation over the side of the fracture. If the patients are examined vaginally at
the first visit these abnormalities will be detected.
3.
Limb desease

Poliomyelitis in childhood, or congenital dislocation of the hip, may

cause pelvic deformity. The child puts most of its weight on the stronger leg, and
on this side the pelvis is pressed in with flattening of the brim on the same side.

4.

Congenital malformations

Naegele's pelvis and Robert's pelvis are due to the defective

development of one or both sacral lateral masses, so that the sacrum ftises with
the ilium on one or both sides. The high assimilation pelvis occurs when the fifth
lumbar vertebra is fused to the sacrum, thus increasing the inclination of the
pelvic brim. This hinders engagement of the fetal head.
Clinical diagnosis The history of the patient must reveal if she

had or has:
- rickets, kyphosis, scoliosis, poliomyelitis, congenital dislocation of the

hip, fractures.

If all patients are examined at the first visit these abnormalities will
be detected.
Clinical examination

Height of less than 150 cm may indicate pelvic contraction.

The patient's appearance and gait may also indicate the possibility of
pelvic abnormality.

Pelvic examination at the first visit will enable the obstetrician to

determine if bony tumors, or other space occupying lesions are present (a fracture
of the bones of the pelvis).

The most important sign in a primigravid is non-engagement of the

fetal head in the pelvis by the 37-th week of pregnancy. Whilst the cause may not
be pelvic contraction, this must be excluded first.

In the case of patients who are less than 150 cm tall, or who have a
history of previous difficulty in labor or who are primigrvida and are found to

172

have a fetus with an "unengaged" head, a careful pelvic assessement is

mandatory.

Pelvimetry

The questions the obstetrician should ask when performing a pelvic

examination are:
1. - Can the sacral promontory be reached?
2. - Is the sacrum flat or curved?
3. - Are the side walls of the pelvic convergent?
4. - Are the ischial spines prominent?
5. - What is the shape of the pubic arch?

In most cases the pelvis assessement will indicate whether or not

fetal head will engage in the pelvis. When any doubt exists, particularly if the
fetus presents by the breech, a radiological pelvimetry should be arranged.

Ecography

Sonographic measurements: the fetal biparietal diameter and head

circumference can be measured precisely by ultrasonic means.

Fetal pelvis index: Morgan and co-workers (1986) attempted to

develop a standardized method for comparing fetal size with the maternal pelvis.
They measured fetal head and abdominal circumference using ultrasound.

Maternal pelvic inlet and midpelvic circumferences were measured

using x-ray pelvimetry.

They computed a fetal pelvic index number based upon differences

in the pelvis and fetal circumferences.

The prognosis for delivery

1.
Dangers to the mother

Uterine damage: the association of an abnormal uterine action with

disproportion frequently leads to prolonged labor with an increased risk of
intrauterine infection.

Moreover, if the degree of the pelvic contraction or the size of the

fetus were miscalculated, labor may become obstructed. If this happens, two
patterns of uterine activity result: in the primigravida uterine inertia occurs; but in
the multigravida the uterus continues to contract more and more forcibly until
uterine rupture threatens to appeal-. A patient who reaches this stage has been
grossly neglected.

Damage to the bladder

If the fit of the head into the pelvis is tight, once full dilatation of the
cervix has occurred, marked pressure is exerted on the bladder base, which is
pressed between the head and the posterior surface of the symphysis pubis.

If the forceps, is used the bladder could be damaged directly. In

either cases a vesicovaginal fistula will result.

Vaginal and cervical damage

Vaginal delivery in cases of contracted pelvis requires experience

and attempts to deliver before full cervical dilatation or with undue force in the
second stage. The result are cervical or vaginal lacerations.
2.
- Dangers to the fetus - The prognosis for the child

Until the membranes rupture the fetus is at little risk, after this time
increasing danger is present. Moulding of the head may be marked. If a forceps
delivery is attempted the compression may be sufficient to cause intracranial
damage.
173

Intrauterine infection may occur with prolonged labor and may

infect the baby. Stress asphyxia due to excessive uterine contraction, which
causes interference with the placental circulation may be a factor in the etiology
of cerebral palsy.

The prognosis for the child depends on the degree of pelvic contraction and
the duration of the labor. The skill of the obstetrician should operate delivery after
careful analysis of the case. Treatment

There are two methods of treatment:

1. elective cesarean section at tenn and
2. trial or labor.
1. Elective cesarean section at term

If the antero-posterior diameter of the pelvic brim is less than 7 cm

and the baby of averange size, elective cesarean section is probably unavoidable.

If the degree of pelvic contraction is less marked but some other

obstetrical complications are present ( such as postmaturity or pregnancy induced
hypertension) which are known to increase the risk to fetus, or if the patient has a
history of a long period of infertility, or if caesarean sections have been
performed because of a contracted pelvis, another caesarean section is probably
unvoidable. 2. Trial of labor

Once labor is established, the character and frecquency of the uterine

contractions are recorded regularly if the contractions are inco-ordinate or
infrequent, then you try to stimulate with an oxytocin infusion. The time of the
membranes rupture and the character of the liqor amnii are noted. The vaginal
examination must be done to determine:

0 the station of the fetal head;

0 the dilatation of the cervix;

0 if a prolaps cord exists.

The findings are recorded on a partogram and are assessed at

intervals so that analysis of the progress of the trial is made.

Each case must be considered individually because the personality of the

patients and of the doctor will often influence the outcome. Durations of the trial

The trial should be abandoned:

if no increase in cervical dilatation occurs over a period of 4 hours
despite coordinated, well sustained contractions;
if after rupture of the membranes the cervix fails to dilate whithin 2
hours;
if the uterine contractions do not improve in quality and frequency
over 4 hours period;
if after full dilatation of the cervix the head does not engage within
1 hour;
if there is any deterioration in the general condition of the mother or
signs of fetal distress.

An indication of the value of trial labor can be gauged from hospital

statistic:
about 50% delivery spontaneously;
30% require forceps to complete the delivery;

174

 20% the trial is abandoned and delivery effected by cesarean section.

Fetal caused dystocia

Dystocia may result from a fault in: =>

the presentation of the fetus;
=> the position of the presenting part;
the size of the fetus;

gross congenital malformation of the fetus.

1. The presentation of the fetus - The mechanism of labor in the various
abnormal presentation has been discussed. Exceptions occur when the fetus
is big and particularly if the baby presents by the face (in the mentoposterior position) or by the shoulder.
2. Position of the presenting part - This factor cannot be dissociated from
that of presentation but is of the greatest significance in face and vertex
presentation.

If the vertex fails to flex during descend and retains a "military

attitude" a greater area of the head fills the narrow straight of the pelvis and
rotation may fail to occur, the head becoming arrested.

Similary, the occipito-posterior position of die head may be

associated with prolonged labor.
3.
The size of the fetus

The larger the baby, the greater is the chance of dystocia. It is almost
impossible to define in absolute terms what constitutes an excessively large baby
but dystocia in a normal sized pelvis is unusual if the baby weight is less than
3500g.

Etiology is obscure:
> some women habitually produce large babies; diabetics mothers
are liable to have excessively large babies (the biggest recorded weighted
11kg);

> excessive eating in pregnancy;

-> postmaturity may be complicated by an exccesively large baby.

4.
Thas an gross congenital malformation of the fetus. Hydrocefaly The
incidence of about 1 in 1000 deliveries. The malformation is often
associated
with a meningocele or a spina bifida. Gross enlargement of the head should
be diagnosed clinically in pregnancy and confirmed by ultrasound or
radiology.

Although treatment is possible for cases of minor hydrocephaly, in

80% of infants the distended ventricles have caused severe cortical damage and
the prognosis is bad.

If diagnosed in pregnancy and the fetus presents as a vertex, labor

should be induced by amniotomy at the 37-th week and fluid withdrawn from the
skull by perforating through one of the gaping sutures (if the spina bifida is also
present).

175

 21.

DYSTOCIA CAUSED BY UTERINE

DYSFUNCTION

The normal contractile wave which is propagated over the entire

uterus in labor is characterized by a triple descending gradient of activity:
1. the intensity of the contraction is stronger in the upper muscular part
of the uterus than in the lower part;
1. the duration of the contraction is longer in the upper part of the
uterus;
3.
the propagation of the wave is downwards towards the cervix
from
the pacemakers.

The peak of the contraction occurs in all parts of the uterus

simultaneously.

These components cause fundal dominance and the progressive dilatation

of the cervix. Classification: => hypoactive states; => hyperactive states; =>
incoordinate states.
Hypo-active
states The etiology is
unclear:

=> the uterine dysfiinction seems predominantly a disease of

primigravidae;

=> in some cases a minor degree of cephalopelvic disproportion is

present;

=> the poor application of the fetal head to the uterine cervix;

^psychological factors - since the emotions are known to affect

hypothalamic activity it may be considered that the releasing factor requires to
liberate oxytocin when the posterior pituitary gland is inhibited;
excessive sedation or the institution of the epidural nerve block too early in
labor;

176

=> overdistention of the litems as with twins and with hydramnios;

=> multiparity.
Clinically
This pattern of abnormal uterine activity presents:
- the resting tone usually lowered;
- the intensity of the contraction reduced;
- the frequency of the contractions normal or reduced, so that they occur at
long intervals.

Clinically the patient is not distressed by the contraction, and any

pain which is felt is abdominal, with little or no backache. The pain is of shorter
duration than the palpable contraction. This pattern of uterine activity must be
recorded in the partogram. Fetal heart rate is normal.

Vaginal examination should be performed to:

-> determine the dilatation of the cervix (this doesn't progress

because of inefficient uterine action) and the presence or absence of
cephalopelvic disproportion:

> establish the level of the biparietal diameter in relation to the

ischial spine (the position of the fetal head and the degree of its "engagement" in
the pelvis).

Management of the hypoactive states

If the hypoactive state is identified, treatment is to rupture the

membranes and to set up an oxytocin infusion.

Amniotomy - artificial rupture of the membranes - appear lo release

a local secretion of endogenous prostaglandins.

Conditions for amniotomy:

=> absence of cephalo-pelvic disproportion;

=> the dilatation of the cervix bigger than 4 cm;

=> vertex presentation.

The procedure is carried out by an aseptic technique. The color and
quantity of the liquid removed should be noted. The absence of the
umbilical cord pathology should be checked (prolapse of the cord). The
operation may be done blindly by passing the instrument along the fingers
or by direct vision using a speculum.

Oxytocin

Synthetic oxytocin, by continuous intravenous infusion, is

commonly used after amniotomy to stimulate uterine contraction.

It must be administered with great care by the doctor, who should be

present all the time (oxytocin may cause fetal hypoxia or uterine rupture). It is
necessaiy to adjust the dosage to the individual patient's response.

The best method of administration is by an infusion pump and drop

counter. The dose is 1 U oxytocin or syntocin in 100 ml Hartman's solution or in
glucose solution 5% beginning with 10 drops per minute. This is increased every
15 min. until normal contractions are established.

177

If the rate of cervical dilatation does not occur in spite of the oxytocin
infusion, the case should be reviewed and cesarean section considered.
Hyperactive states

The aetiology:

=> cephalo-pelvic
disproportion; r> fetal malposition;

==> the cervix too rigid to dilate (cervical fibrosis); =>

tumors: uterine myomas;

=> the missuse of oxytocin, particularly when this is given

intramuscularly. Clinically

In this pattern of abnormal uterine activity:

the resting tone is increased; -> the intensity
of the contraction is greater; > the frequency of
the contraction is greater.

Clinically the patient is distressed and complains constantly of

backache which increases during each contraction. The peak of the contraction is
extremely painful. The patient has often a desire to "bear-down" during the
contraction, although examination shows the cervix to be thick and not to have
reached nil] dilatation.
The fetal head is frequently not well applied to cervix.

The FHR is affected (bradycardia, arythmia).

The danger to the mother is in the first delivery when laceration of

the cervix, vagina or perineum may occur.

A greater danger exists for the baby which may become anoxic in
utero, due to the intense and frequent contractions, causing a hypertonic state.

The fetus may suffer intracranial hemorrage during its rapid descent
through the birth canal.

The management of the hyperactive states

If a hyperactive uterine state is diagnosed in a woman who does not

have epidural analgesia, either an epidural is established, or the patient is sedated
with an intravenous infusion of pethidine (300 mg), together with diazepam 10
mg, in 5 % glucose.

If no cervical dilatation has occurred after 2 to 4 hours, labor is

terminated by cesarean section.

Incoordinate states Hyperactive lower uterine segment is

the most common type of uterine dysfunction, which often occurs in association
with minor degrees of disproportion or malposition of the fetal head. In this
pattern the normal triple descending gradient does not occur, and flindal
dominance is lost. The abnormal contractile wave starts in the lower uterine
segment and passes upwards, towards the fundus.

The cervix fails to dilate despite strong uterine activity.

178

The fetal head is frequently not well applied to the cervix. ^> In
colicky uterus: various paits of the uterus contract independently. The
contraction may be most intense in the lower segment or in the fundal area.
Constriction ring dystocia is rarely encountered. An annular spasm
occurs in the myometrium, usualy at the junction of the upper and lower uterine
segments, but occasionally at the level of the internal os.

The ring tends to form around the neck of the fetus and thus prevents
its descent. The uterus above the ring continues to contract.
The diagnosis is rarely made in the first stage of labor. In the second stage
failure of the fetal head to descend during a contraction may make the
obstetrician suspect this condition.
Because no other drug has any effect on the construction ring treatment is
to anesthesize the patient deeply, before attempting delivery,.

Cervical dystocia

Clinically, in spite of strong co-ordinated uterine constriction, the

cervix fails to dilate, .becoming stretched. Labor tends to be prolonged and the
patient complains severe backache.

Cervical dystocia is rare and its physiopathology unclear.

Treatment is to make small (2 cm) incisions in the cervix at the 10 o'clock
position, or to deliver the baby by forceps or by cesarean section.

179

22. HYPERTENSIVE DISORDERS IN

PREGNANCY GENERAL
CONSIDERATIONS. ETIOLOGY AND
PATHOPHYSIOLOGY

22.1. GENERAL CONSIDERATIONS

Pregnancy can induce hypertension in normotensive women or

aggravate already existing hypertension. Generalized edema, proteinuria or both
may also accompany pregnancy-induced or aggravated hypertension. If
hypertension is untreated, convulsions may develop.

Hypertensive disorders complicating pregnancy are common and

form one of the deadly triad, along with hemorrhage and infection, that results in
a large number of maternal deaths.
In 1986, The American College of Obstetricians and Gynecologists
published updated definitions and a newer classification. Unfortunately, no
classification is adequate if etiology is unknown. Therefore, because of the
confusion that has arisen from these classifications, we use the modified
classification of The American College of Obstetricians and Gynecologists:

Pregnancy-induced hypertension: hypertension that develops as a

consequence of pregnancy and regress postpartum.
1. hypertension without proteinuria or pathological edema;
2. preeclampsia-with proteinuria and/or pathological edema:

a.
mild;
b.severe.
3.
eclampsia-proteinuria and/or pathological edema along with
convulsions.
Pregnancy-aggravated hypertension: underlying hypertension
worsened by pregnancy:
1. superimposed preeclampsia;
2. superimposed eclampsia.

Coincidental hypertension: chronic underlaying hypertension that

antecedes pregnancy or persists postpartum.

Traditionally, our obstetrical schoool includes abruptio placentae in

this chapter of pathology. The primary cause of placental abruption is unknown,
but, by far, the most commonly associated condition is either pregnancy induced
or chronic hypertension.
So, pregnancy induced hypertension (PIH) is diveded into three categories:

180

 =>

hypertension alone; =>

preeclampsia (PE); =>
eclampsia.

The diagnosis of PIH is made when blood pressure is 140/90mm Hg

or greater. Increases in systolic and diastolic blood pressure can either be normal
physiological changes or signs of developing pathology.

The diagnosis of PE has traditionally required the identification of

PIH plus proteinuria or generalized edema. Proteinuria is an important sign of PE
(300mg or more of urinary protein/24 hours). This element is present when the
glomerular lesion considered to be characteristic of PE is evident.

The combination of proteinuria and hypertension during pregnancy

markedly increases the risk of perinatal mortality and morbidity.
Eclampsia is diagnosed by convulsions precipitated by pregnancy induced
or aggravated hypertension.

Chronic hypertensive disorders, regardless of their cause, predispose

to development of superimposed PE or eclampsia. The diagnosis of coincidental
or chronic underlying hypertension is suggested by the following:
1.
hypertension (140/90mm Hg or greater) antecedent to
pregnancy;
2. hypertension (140/90mm Hg or greater) detected before the 20 lh
week of pregnancy (unless there is gestational trophoblastic disease);
3.
persistent hypertension long after delivery.
There are many causes of hypertension that may be encountered during
pregnancy :
A.
hypertensive diseases : essential familial hypertension:

=> renovascular hypertension;

=^> coarctation of the aorta; => primary
aldosteronism; => pheochromocytoma.

B.

renal and urinary tract disease:

~> glomerulonephritis (acute or chronic);

-> nephrotic syndrome:

> chronic renal

insufficiency:

-> pyelonephritis;
> lupus erythematosus;
-> polycystic kidney disease:
-> diabetic nephropathy.
Dangers specific to pregnancy complicated by chronic hypertension include
the risk of pregnancy-aggravated hypertension which may de\e!op in as
many as 20% of these women. Additionally, the risk of abruptio placentae

181

is increased substantively. The fetus is at increased risk for growth

retardation and intrauterine death.

Preexisting chronic hypertension worsens in some women, typically after

24 weeks' gestation. Such pregnancy-aggravated hypertension may be
accompanied by proteinuria or pathological edema. The condition is then termed
superimposed preeclampsia. Often, the onset of superimposed PE occurs earlier in
pregnancy than pure PE and it tends to be quite severe and accompanied in many
cases by fetal growth retardation. Incidence of PI H

PIH more often affects nulliparous women. Older women, who

accrue an increasing incidence of chronic hypertension with advancing age. are at
greater risk of pregnancy-aggravated hypertension.

The incidence of PE is commonly cited to be about 5%. although

remarkable variations are reported. The frequency varies among different
hospitals, regions and countries.
The incidence is influenced by parity. It is related to racial and thus to
genetic predisposition. Environmental factors may also have a role.
Sociocconomically advantaged women have a lesser incidence of PE.

Nearly 20% of nuiliparas have hypertension compared with an

incidence of 7% in multiparas. The incidence is significantly increased in patients
with twin prcgnancies.The tendency for PE-eclampsia is inherited. An appropiate
genetic marker has not been identified.

In general, eclampsia is preventable and has become less common in

developed countries.

Any satisfactory theory must account for the observation that

pregnancy induced or aggravated hypertension is very much more likely to
develop in the woman who:

~> is exposed to chorionic villi for the first time:

=> is exposed to a superabundance of chorionic villi as with twins or

hydatidilbrm mole:

=> has preexisting vascular disease;

is genetically predisposed to hypertension developing during
pregnancy.
22.2 ETIOLOGY AND PATHOPHYSIOLOGY

The etiology of PE is unknown. Many theories have been suggested, some

are still under consideration:

1- abnormal trophoblast invasion;
2- coagulation abnormalities;
3- vascular endothelial damage:
4- changes in prostanoids ;
5- cardiovascular maladaptation;
6- immunologic phenomena; 1genetic predisposition ;
182

8- dietary deficiencies or excesses.

Vasospasm is basic to the pathophysiology of PE-eclampsia.

1. The human placenta receives its blood supply from numerous

uteroplacental arteries that are developed by the action of migratory interstitial
trophoblast into the walls of the spiral arteries, transforming the uteroplacental
arterial bed into a low resistance, low pressure, high flow system.
In a normal pregnancy, these trophoblast-induced vascular changes extend
ail the way from the intervillous space to the origin of the spiral arteries, in
the imier one third of the myometrium. It is suggested that these vascular
changes are effected in two stages and result in the conversion of spiral
arteries into distended, tortuous and funnel-shaped vessels that
communicate through multiple openings into the intervillous space
In contrast, pregnancies complicated by PIH demonstrate inadequate
maternal vascular response to placentation. In these pregnancies, the
vascular changes described are usually restricted only to the decidual
segments of the uteroplacental arteries. Hence, the myometrial segments of
the spiral arteries are left with their musculoelastic architecture, thereby
rendering them responsive to hormonal influences.
These pathologic changes may have the effect of curtailing the increased
blood supply required by the fetoplacental blood flow seen in most cases of
PE.

2.3. PE is associated with vasospasm, activation of the coagulation system

and abnormal hemostasis. There are an endothelial injury, increased platelet

activation with platelet consumption in the microvasculature and excessive
clotting activity.
A. A. Saleh and coworkers (1987) evaluated the hemostatic system
before and after delivery in cases with PE and found that PE was associated with:

^> high fibronectin (reflected endothelial injury);

=> low antithrombin III (reflected clotting);

=> low alfa 2-antiplasmin (reflected fibrinolysis).

They concluded: "vascular endothelial injury plays a central role in

the hemostatic changes associated with PE".

Elevated fibronectin was found in patients prior to the development

of PE. Fibronectin might be useful for diagnosing superimposed PE in women
with chronic hypertension.

The vasospasm in PE may result from potent vasoconstrictors

released at sites of endothelial cell injury. Endothelins are potent
vasoconstrictors. Endothelin-1 is the only endothelin produced by human
endothelium. Higher levels have been reported in preeclamptic women.

183

Endothelium-derived relaxing factor (EDRF) is a potent

vasodilator whose absence or decreased concentration might also play a role in
the etiology of PIH. Currently, endothelin-1 and EDRF are being studied actively
in both normal and hypertensive pregnancies. As yet, their exact roles in the
etiology of PIH, if any, remain to be established. The very nature of their
production, their sites of action and their apparent opposite effects are suggestive
being not etiological factors, they may still have important potential as therapeutic
agents.

Antithrombin III is a plasma proteinase inhibitor and is a major

plasma inhibitor of thrombin. The level of plasma antithrombin III activity
remains unaltered during normal pregnancy but is reduced in patients with PE.

The following hematological abnormalities may develop in some

women who present pregnancy-induced or pregnancy-aggravated hypertension:

=> thrombocytopenia (at times may become so severe as to be life

threatening);

=> the level of some plasma clotting factors may be decreased;

=> erythrocytes may be so traumatized that they display bizarre shapes and
undergo rapid hemolysis.
Hematological changes consistent with intravascular coagulation may
complicate PE and especially eclampsia.

4. The

exact mechanism by which prostaglandins or related

substances mediate vascular reactivity during pregnancy is unknown, but
some findings have possibly elucidated the mechanisms involved. Increased
concentrations of vasodilating PG during normal pregnancy was reported.

In general, the data suggest that the production of both prostacyclin

(PG I 2) and thromboxane A 2 (Tx A 2) is increased during pregnancy, with the
balance in favor of PG I 2.

Reproductive tissues produce large amonts of both prostanoids and

production increases in both maternal and fcto-placental tissues. Prostacyclin is
produced by the vascular endothelium as well as in the renal cortex. It is a potent
vasodilator and inhibitor of platelet aggregation.
Tx A 2 is produced by the platelets and trophoblast. It is a potent
vasoconstrictor and platelet aggregator. Hence, these eicosanoids have
opposite effects and play a major role in regulation of vascular tone and
vascular blood flow.

An imbalance in prostanoid production or catabolism has been

suggested as responsible for the pathophysiologic changes in PH. However, the
role of PG in the etiolouv of PE remains unclear. There is aareement in the
literature that in PE placental production of PG 1 2 is reduced while that of Tx A 2
is increased leading to an increased Tx A 2/PG I 2 ratio. This aspect, however,
may be an effect rather than a cause of PE.

184

5. Hemodynamic changes accompanying severe PE and eclampsia

have been studied by a number of investigators. Five general observations

can be made:

=> myocardial contractility is rarely impaired prior to therapy and

ventricular function is usually within the normal to hyperdynamic range;

=^> afterload is elevated in absence of therapeutic interventions;

=> cardiac output predictably varies inversely with vascular

resistance and as blood pressure and afterload increase, cardiac output falls;

=x> medications that reduce peripheral vascular resistance, such as

hydralazine, increase cardiac output;

=> ventricular preload is usually norma! or even low in severe PE in

the absence of volume expansion.

Hemoconcentration in women with eclampsia was emphsized.

The virtual absence of an expanded blood volume is likely to be the
consequence of generalized vasoconstriction, often made worse by
increased vascular permeability (too little fluid intravascularly and too
much extra vascularly).
Atrial natriuretic peptide is released upon atrial wall stretching from blood

volume expansion. It is vasoactive and also likely to promotes sodium and

water excretion by inhibiting aldosterone, renin activity and angiotensin II.
This peptide is increased in normal pregnancy.

The ANP is increased substantively in women with PE. With volume

expansion, there is an augmented release of the compound in preeclamptic
compared with normotensive pregnant women. Increases in ANP, following
volume expansion, result in comparable increases in cardiac output and decreases
in peripheral vascular insistence in both normotensive and preeclamptic women.

During normal pregnancy, renal blood flow and glomerular filtration

rate are increased appreciably. With development of PIH, renal perfusion and
glomerular filtration are reduced. Plasma uric acid concentration is tipically
elevated, especially in women with more severe disease.

As with other glomerulopathy (probably induced by immunological

mechanisms) there is increased permeability to most large-molecular-weight
proteins. Abnormal albumin excretion is accompanied by other proteins, such as
hemoglobin, globulins and transferrin.
Changes identifiable by light and electron microscopy are commonly found
in the kidney:

=> glomeruli are enlarged (by about 20%);

capillary loops are variably dilated and contracted; endothelial cells are
swollen and accompanied by subendothelial deposits of protein material
(fibrinogen derivative): these changes are called glomerular capillary
endothcliosis.
The renal changes identified by electron microscopy have been advanced as
being pathognomonic of PE. Renal tubular lesions are common in women
185

with eclampsia. Acute renal failure from tubular necrosis may develop.
Although this is more common in neglected cases, it is invariably induced
by hemorrhage, usually associated with delivery, for which adequate blood
replacement is not given.

More than 50% of patients with hypertension and acute renal failure
had aiso a placental abruption and more than 85% had postpartum hemorrhages
(B.M.Sibai et al 1990).

With severe PE, there are at times alterations in tests of hepatic

function and integrity. Liver involvement in PE-eclampsia is serious and is
frequently accompanied by evidence of other organ involvement, especially the
kidney and brain, along with hemolysis and thrombocytopenia.
There are reports which have described the syndrome of hemolysis,

elevated liver enzymes and low platelets in severe PE (HELLP syndrome).

Thrombocytopenia is the most consistent finding. Hemolysis is certified by
abnormal peripheral blood smear, increased lactic-dehydrogenase and
elevated enzymes by increased serum glutamic oxaloacetic transaminase
(SGOT) and increased lactic dehydrogenase.
Hepatic rupture is a dramatic complication of PE. It carries a maternal
mortality of 70%.

M.L.Mc.Call (1953) reported that cerebral blood flow, oxygen

consumption and vascular resistance were not altered in women with PE,
eclampsia or essential hypertension. However, the possibility of focal cerebral
hypoperfusion or hyperperfusion could not be excluded.
The most common findings (on cranial computed tomography scanning)
are hypodense cortical areas which corresponded to petechial hemorrhage
and infarction sites. It seems reasonable that the brain, like the liver and
kidney may be more involved in some women than in others, and the extent
of ischemic and petechial subcortical lesions influences the incidence of
eclampsia.

Visual disturbances are common with severe PE. Some women with
varying degrees of amaurosis are found to have radiographic evidence of
extensive occipital lobe hypodensities. This is likely to be an exaggeration of the
lesions described above. Retinal detachment may also cause altered vision.
Coma usually follows sudden and severe blood pressure elevations. It is
likely that this phenomenon represents an inability to autoregulate cerebral
blood flow with severe acute hypertension. The result is generalized
cerebral edema.
Another cause of coma is intracranial hemorrhage from a ruptured
intracerebral vessel, an arteriovenous malformation or a berry aneurysm.
These lesions have a much poorer prognosis than coma from cerebral
edema.

186

 Compromised placental perfusion from vasospasm is almost certainly a

major culprit in the genesis of increased perinatal morbidity and mortality

associated with PIH or PAH.

Using electron microscopical studies of arteries taken from the uteroplacental implantation site, F.De Wolf and co-workers (1975) reported that early
preeclamptic changes included endothelial damage, insudation of plasma
constituents into vessel walls, proliferation of myointimal cells and medial
necrosis. Most investigators are now in accord that there is a lesion, but they do
not agree on its precise nature and on its specificity.
6.The possibility that immunological as well as endocrine and genetic

mechanisms are involved in the genesis of PE is intriguing. The risk of PIH

is appreciably enhanced in circumstances where formation of blocking
antibodies to antigenic sites on the placenta might be impaired, such as
during immunosuppressive therapy to protect a renal transplant, where
effective immunization by a previous pregnancy is lacking, as in first
pregnancies or where the number of antigenic sites provided by the
placenta is unusually great compared with the amount of antibody as with
multiple fetuses.
There are studies which reported no association of human lymphocyte
antigens (HLA) A and B with PE. Other authors note, however, a higher
incidence of recurrent hypertension in pregnancy in women with HLA DR
4 phenotypes, an observation consistent with an increased incidence of
chronic hypertension and not PE.

Despite appealing theories that hypertension in pregnancy may be

associated with an immunological disorder convincing proof of clinical
significance is lacking.
7. Concerning genetic hypothesis there is a single-gene involvement, but

multifactorial inheritance cannot be excluded.

7. Dietary deficiencies have been suspected as a cause of PE. This

hypothesis lacks supportive data:

o as pregnancy "depletes'* a woman nutritionally, PE should be more

common in multiparous compared to nulliparas, but it is not;

=> various types of dietary supplementation do not decrease the

frequency of hypertension;

=> the incidence of PE is not related to the level of dietary protein.

After midpregnancy, dietary supplementation with 2g of elemental

calcium per day significantly reduced the incidence of hypertension. The apparent
effectiveness of supplemental calcium may be explained by an overriding of
impaired absorption or defective renal handling of calcium. Other possibilities
exist, however, including changes in vasodilation and vascular reactivity mediated
by increased prostacyclin or nitric oxide production.
187

The blood pressure lowering effect of calcium was also thought to be

mediated by alterations in plasma renin activity and parathyroid hormone. In
addition, calcium supplementation during pregnancy was shown to reduce All
vascular sensitivity in such cases.

188

23. PREECLAMPSIA. ECLAMPSIA

23.1. PREECLAMPSIA Clinical

aspects of PE
The pregnant woman is usually unaware of the two most important
signs of PE (hypertension and proteinuria). By the time, symptoms such as
headache, visual disturbances or epigastric pain develop, the disorder is almost
always severe. Hence, the importance of prenatal care in the early detection and
management of PE is obvious.

Blood pressure
The basic derangement in PE is arteriolar vasospasm and the most
dependable warning sign is an increase in blood pressure. Diastolic pressure is
probably a more reliable prognostic sign than the systolic one, and any diastolic
pressure of 90mm Hg or more that persists is abnormal.

The diagnosis of PE and determination of the severity of the disease

process are generally based on maternal blood pressure measurements. Several
factors may influence measurement of the blood pressure by means of a
sphygmomanometer:

accuracy of the equipment used;

duration of rest period before recording; posture
of patient.
It is recommended that all blood pressure values be recorded with the
woman in a sitting position (ambulatory patient) or in a semireclining
position (hospitalized patient). The right arm should be consistently in a
roughly horizontal position at heart level.

For diastolic blood pressure measurements muffling sound should be

used for diagnosis (there are two phases : muffling and disappearance sounds).

It is important to emphasize that the presence of other symptoms is

more reliable than the absolute level of blood pressure in establishing the
diagnosis of PE.

189

Weight gain
A sudden increase in weight may precede the development of PE,
and indeed, excessive weight gain in some women is the first sign. A weight
increase of about 1 pound/week is normal, but when weight gain exceeds more
than 2 pounds in any given week, or 6 pounds in a month, developing PE should
be suspected.

The suddeness of excessive weight gain is characteristic of PE rather

than an increase distributed throughout gestation. Such a weight gain is due
almost entirely to abnormal fluid retention.

Proteinuria
The degree of proteinuria varies greatly in PE, not only from case to
case but also in the same woman from hour to hour. The variability is suggestive
of a functional vasospasm rather than an organic cause.

In early PE. proteinuria may be minimal or entirely lacking, but in

most severe forms it is usually demonstrable. Proteinuria almost always develops
later than hypertension and usually later than excessive weight gain.

Headache
Headache is unusual in milder cases but is increasingly frequent in
the more severe disease. It is often frontal but may be occipital, and is resistant to
relief from ordinary analgesics. A severe headache almost invariably precedes the
first eclamptic convulsion.

Epigastric pain
Epigastric pain or right upper quadrant pain is often a symptom of
severe PE and may be indicative of imminent convulsions. It is probably due to
stretching of the hepatic capsule, possibly by edema and hemorrhage.

Laboratory findings

The hemoglobin and hematocrit may be elevated due to

hemoconcentration or, in more severe cases, there may be anemia secondary to
hemolysis.

Trombocytopenia is often present.

Fibrin split products and decreased coagulation factors may be

detected.

Uric acid is usually elevated above 6mg/dl.

Serum creatinine is most often normal (0,6-0,8mg/dl) but may be

elevated in severe PE.
Although hepatic abnormalities occur in about 10% of patients, the
bilirubin is usually below 5mg/dl and the SGOT below 500 IU. Alkaline
phosphatase may increase 2 to 3 times. Lactate dehydrogenase may be quite
high (because of hemolysis).

Blood glucose and electrolytes are nonnal.

Urinalysis reveals proteinuria and occasional hyaline casts.

190

Fetal status is assessed by serial ultrasound and weekly nonstress and

oxytocin challenge tests. Amniocentesis to determine the lecithin/sphingomyelin
ratio is not frequently used in PE, since early delivery is usually for maternal
indications, but may be useful as the fetus approaches maturity.

Corticosteroids may be used to accelerate fetal lung maturity in

patients with PE and delivery must occur in the next 2-7 days.

With rapidly worsening PE, fetal monitoring should be continuous

because of the risk of abruptio placentae and placental insufficiency.

Prophylaxis and early treatment

As women are usually asymptomatic and seldom notice the signs of

incipient PE. its early detection demands careful observation at appropiate
intervals, especially in women known to be predisposed to PE. Major
predisposing factors are:

multiparity; => familial history

of PE-eclampsia; => multiple fetuses;

diabetes mellitus; =>

chronic vascular disease; =>
renal disease; => fetal hydrops.
A review of the world literature reveals that more than 100 clinical,
biophysical and biochemical tests have been recommended to predict or
identify the patient at risk for the future development of the disease.

The value of MEAN ARTERIAL PRESSURE (MAP) in the second

trimester in predicting PE was investigated by L.C.Chesley and B.M.Sibai. The
sensitivity of the test ranged from 0 to 99%. The MAP is determined as:

MAP = systolic BP+(2 x diastolic BP) / 3 and average is > 8590mmHg.

The roll-over test may be useful in predicting gravidas at risk of developing
PE. Blood pressures are recorded between 28 and 32 weeks, after
stabilization, first in the lateral recumbent position and then in the supine
position. In the study, a rise in diastolic pressure of more than 20mm Hg
occurred on assuming the supine position in 93% of normotensive women
who later developed PIH.

Other clinical tests to predict PE are : isometric exercise test,

angiotensin II infusion test at 26-30 weeks, Doppler velocimetry of uterine and
umbilical vessels at 18-26 weeks are not sufficiently reliable for use as a
screening tests in clinical practice.

Rapid weight gain any time during the latter half of pregnancy, or an
upward trend in diastolic blood pressure is worrisome. Every woman should be
examined at least weekly during the last month of pregnancy and every 2 weeks
during the previous 2 months.

At these visits, weight and blood pressure measurements are made.

Furthermore, all women should be advised to report immediately any symptoms
or signs of PH. such as headache, visual disturbances and puffiness of hands or
face. The reporting of any such symptoms calls for an immediate examination to
confirm or exclude PE.

191

Although diuretics have been alleged to prevent PE, proof of their

efficacy is tenuos. Diuretics reduce renal and uteroplacental perfusion.

It was reported that A II-sensitive women at high risk for developing

PIH could be rendered refractory to A II in most cases by a 1-week course of daily
low-dose aspirin therapy (80mg/day). Such therapy significantly decreases
thromboxane synthesis, likely by blocking the cyclooxygenase pathway of
arachidonic acid conversion. Low-dose aspirin may be effective in some, but not
all women, in preventing the development of PIH and IUGR.

There are a variety of specific thromboxane inhibitors now available

that spare PG I 2 while blocking thromboxane. Hopefully, within the next decade
obstetricians will have the means to prevent PIH.

Treatment of PE
Objectives of treatment
Basic management objectives for any pregnancy complicated by PIH are: 3>
termination of pregnancy with the least possible trauma to mother and
fetus;
=> birth of an infant who subsequently thrives;
=> complete restoration of health to the mother.

The most important information that the obstetrician has for

succesful management of pregnancy is precise knowledge of the age of the fetus.

Hospitalization is considered for women with PIH if there is a

sustained elevation in systolic blood pressure to or above 140mm Hg or a
sustained diastolic pressure to or above 90mm Hg. With hospitalization, a
systematic study should be instituted that includes the following:

-> a history and general physical examination followed by daily

searches for development of signs and symptoms such as headache, visual
disturbances, epigastric pain and rapid weight gain:

> admittance weight and every day thereafter;

> admittance analysis for proteinuria and every other days thereafter;
blood pressure readings every 4 hours, except between midnight and
morning, unless the midnight pressure has increased;

> measurements of plasma creatinine, hematocrit, platelets and

serum liver enzymes (the frequency to be determined by the severity of
hypertension);

> frequent evaluation of fetal size and amniotic fluid volume by clinical
examination or by sonography. Mild PE

Bed rest, or at least reduced physical activity, throughout much of the

day is beneficial. Ample, but not excessive, protein and calories should be
included in the diet, without salt restriction.

Phcnobarbital or other sedatives or tranquilizers can be

recommended. Diuretics and antihypertensive drugs are not prescribed.

Spontaneous diuresis ensues within the firsl 48 hours of

hospitalization in the majority of cases. The diuresis is usually accompanied by a
decrease in weight and improvement in maternal blood pressure.

192

The antepartum use of antihypertensive drugs for mild PE remote

from term is highly controversial.

Labetalol is a nonselective beta-blocker with some alpha 1-blocking

effects. Recent clinical studies suggest that this drug is ideal for managing PE
remote from term. Patients oiven labetalol exhibited significant reductions in
severe hypertension, proteinuria and platelet consumption. There were no adverse
side effects.

If the patients with mild PE becomes nonnotensive in the absence of

significant proteinuria, outpatient observation may be considered in a selected
group of patients (early stages of the disease, immature fetus, absence of evidence
of fetal jeopardy, good socioeconomic and cultural status etc).

Severe PE

Occasionally, fulminant or neglected PE is encountered, with blood

pressure recordings in excess of 160/110mm Hg, edema and proteinuria.
Headache, visual disturbances or epigastric pain are indicative that
convulsions are iminent. Oliguria is another ominous sign.

In these cases, the ultimate goals of therapy must always be safety of

the mother first and then consideration for optimum perinatal outcome. The
decision for immediate delivery versus expectant management is usually
dependent on one or more of the following:
severity of the disease process;
fetal gestational age;
maternal condition:
Bishop score.

Since the only cure for severe PE is delivery, there is universal

agreement to deliver all patients if the disease develops beyond 34 weeks
gestation, or if there is evidence of fetal lung maturity and/or fetal jeopardy prior
to that time. In this situation, appropriate management should include parenteral
medication to prevent convulsions, control of maternal blood pressure within a
safe range, and then induction of labor to initiate delivery.
There is disagreement about the best way to manage cases who have severe
disease before 34 weeks gestation. Some institutions consider delivery the
definitive therapy for all cases, regardless of gestational age. Others
recommend prolonging pregnancy in all patients remote from term until
development of fetal lung maturity, fetal or maternal jeopardy or gestational
age of 36 weeks or greater.
The maintenance or promotion of urinary output is desirable in treating
severe PE. It is essential that the patient not be overloaded with fluid that
she cannot excrete. Reduction of vasospasm may be helpful, but diuretics
are usually contraindicated because they are ineffective in stimulating urine
output.

Magnesium sulfate can be given intramuscularly as a 50% solution

or intravenously in a 20% or 25% solution as an anticonvulsivant therapy. When
given intravenously, an initial dose of 4 to 6g is administered during a period of 4
to 5 minutes. The maintenance dosage is about lg/hour using an infusion pump.

193

Calcium gluconate, which counteracts the effect of magnesium promptly

(overdosage of magnesium induces loss of pattelar reflex, respiratory depression,
cardiac arrest) should be kept at the bedside where it will be readily available if
needed. Magnesium is excreted in the urine, consequently, an adequate urinary
output is essential. If the urine volume decreases below 30ml/hour, the dosage of
magnesium sulfate must be reduced.
Until the blood pressure is greatly elevated, hypotensive drugs are
ordinarily unnecessary in the treatment of severe PE because the magnesium
sulfate usually depress the blood pressure to a reasonably safe level. If the systolic
blood pressure is rising rapidly or is over 160 to 180mm Hg or if the diastolic
pressure is higher than 110mm Hg. a definite effort should be made to control it.
Hydralazine (Apresoline), 10 to 20mg diluted to 20ml and slowly given
intravenously, will often lower the blood pressure and maintain it at a safe level
for several hours.

When given by mouth (100-200mg/24 hours) the drug has much less
effect.

In severe hypertensive crisis, nitroprusside or nitroglycerin can be

used. Sodium nitroprusside is an extremely rapid acting agent that acts on both
arterial and venous smooth muscle. Central monitoring with a pulmonary artery
catheter is essential for the safe use of this agent.
The decisive cure for PE-eclampsia is termination of pregnancy at a
carefully chosen time. In most women with severe PE any response to
medical treatment is temporary and the progression of the disease cannot be
halted. Delivery after a preliminary period, when attempts are made to
stabilize the process, is the only way to prevent eclampsia with its increased
maternal and perinatal mortality.

Labor should be induced by intravenous oxytocin. In severe cases

this is often successful, even when the cervix is judged unfavorable for induction.

Whenever it appears that labor induction almost certainly will not

succeed, or attempts at induction of labor are not fruitful, cesarean delivery is
indicated for the more severe cases
After delivery, there is usually rapid improvement, although at times
hypertension may worsen transiently. Typically, but not always, PIH
dissipates spontaneously during the first 2 weeks postpartum. Hypertension
persisting at this time usually signifies chronic vascular disease.
Pregnancies complicated by severe PE are usually associated with high
perinatal mortality and morbidity rates. This increase in perinatal risk is
mainly related to extreme prematurity, IUGR, abruptio placentae, fetal
distress.

Severe PE is a major cause of maternal mortality and morbidity.

Complicated or mismanaged cases are responsible for most deaths. Maternal
complications in PE could be: abruptio placentae, disseminated intravascular
coagulation, HELLP syndrome, acute renal failure, pulmonary edema, cerebral
hemorrhage, ruptured liver.
23.2. ECLAMPSIA

194

Eclampsia is the occurrence of convulsions or coma unrelated to

other cerebral conditions, with signs and symptoms of PE.
The pathophysiologic events leading to convulsions remain unknown.
There is a functional derangement of multiple organ systems, such as the
central nervous, cardiovascular, hematologic, renal, hepatic systems. These
dysfunctions are:

cardiovascular: generalized vasospasm, increased peripheral

vascular resistance, increased left ventricular stroke work index, decreased central
venous pressure, decreased pulmonary wedge pressure;

=> central nervous system : cerebral edema and/or hemorrhage;

=> hematologic: decreased plasma volume, increased blood

viscosity, hemoconcentration, coagulopathy;

=> renal: decreased glomerular filtration rate, decreased renal plasma

flow, decreased uric acid clearance;

hepatic: periportal necrosis, hepatocellular damage, subcapsular

hematoma.

Almost without exception, PE precedes the onset of eclamptic

convulsions. Isolated cases are occasionally cited of an eclamptic convulsion
occurring without warning in women who were apparently in good health.

Eclampsia usually begins as a gradual process, starting with rapid

weight gain and ending with the onset of generalized convulsions or coma. Coma
without convulsions has also been called eclampsia. Convulsions caused by
cerebral involvement in PIH are but one manifestation of severe PE. However,
due to its associated high mortality, eclampsia is regarded with particular concern.
Frequency and classification

Eclampsia represents about 1% of all PIH cases. Depending on

whether convulsions appear before, during or after labor, eclampsia is designated
as antepartum, intrapartum or postpartum.
Eclampsia is most common in the last trimester and becomes increasingly
more frequent as term approaches. Nearly all cases of postpartum
eclampsia develop within 24 hours of delivery but atypical cases are seen
up to 10 days postpartum. About 3% first develop seizure more than 48
hours postpartum (Miles et al, 1990). Another atypical form is eclampsia
which may occur before 20 weeks gestation.

Diagnosis

Women in whom eclampsia develops exhibit a wide spectrum of

signs and symptoms ranging from extremely high blood pressure, proteinuria,
generalized edema to minimal blood pressure elevation, absence of proteinuria or
edema and normal reflexes.

Hypertension is the hallmark of eclampsia and excess weight gain

and'or edema is not necessary for the diagnosis.

In about 20% of cases, hypertension may be "relative", signified by

any rise in blood pressure that is 30mm Hg systolic or 15mm Hg diastolic above
the first trimester blood pressure reading. Headache, visual disturbances and right

195

upper quadrant/epigastric pain are the most common premonitory symptoms

before convulsions.
Eclampsia is primarily a disease of the young primigravida, but its
incidence is also increased in women more than 35 years of age.

Eclamptic convulsions are a life-threatening emergency and require

proper care in order to minimize morbidity and mortality.

The eclamptic seizure has four stages:

1.
Premonitory stage (8-10 seconds)
Initially, the patient's face becomes distorted and there is protrusion of the
eyes. This is followed by a congested facial expression. Foam often exudes
from the mouth. The woman usually bites her tongue unless it is protected.
2.
Tonic convulsions stage (20-30 seconds)
The entire body becomes rigid in a generalized muscular contraction.
Respirations are absent. The face is distorted, the eyes protrude, the arms
are flexed, the hands are clenched and the legs are inverted.
All muscles are in a state of tonic contraction. Cyanosis is intense, due to
fixation of the chest and diapfiragm.
3.
Clonic stage (40-60 seconds)

Suddenly, the jaws begin to open and close violently and soon after,
the eyelids as well. The other facial muscles and then all muscles alternately
contract and relax in rapid succession.
The breathing is stertorous. The muscular movements are so forceful that
the woman may throw herself out of her bed and almost invariably, unless
protected, her tongue is bitten by the violent action of the jaws.

The face is congested and the conjunctivae are injected. Gradually,

the muscular movements become smaller and less frequent and finally the woman
lie motionless.
The first convulsion is usually the forerunner of others, which may vary in

number from 1 or 2 in mild cases to even 100 or more in untreated severe

cases. In rare instances, convulsions follow one another so rapidly that the
woman appears to be in a prolonged, almost continuous convulsion.
Observing the development of an eclamptic convulsion is frightening.

4. Period of coma
The duration of coma after convulsions is variable. When the convulsions
are infrequent, the woman usually recovers some degree of consciousness
after each attack. As the woman arouses, a semiconscious combative state
may ensue. In very severe cases, the coma persists from one convulsion to
another and death may result before she awakens.

Respirations after an eclamptic convulsion are usually increased in

rate and may be stertorous. The rate may reach 50 or more per minute.

A temperature of 38C or more is a very grave sign because the fever

is probably a consequence of a central nervous hemorrhage.

Proteinuria is almost always present and occasionally anuria

develops. Hemoglobinuria is common.
196

Cerebral blood flow is autoregulated within a wide range of blood

pressure. Loss of autoregulation has been suggested as the first step in acute
hypertensive encephalopathy, leading to abnormally high cerebral perfusion.
Local edema formation, petechial hemorrhages, patchy vessel wall necrosis are
lesions characteristic to acute hypertensive encephalopathy.

CT scan evaluation in patients with eclampsia was performed.

Magnetic resonance imaging appears superior to other processes for

defining intracranial anatomy and pathophysiology.

Abnormal electroencephalogram findings have been reported in

eclampsia and these abnormalities are directly related to the severity of maternal
hypertension.

A significant number of patients have thrombocytopenia.

Liver function test results are abnormal in many cases (LDH

elevated, alkaline phosphatase and SGOT increased).

Pulmonary edema, which is a grave prognostic sign, may follow

eclamptic convulsions. There are at least two sources:

-> aspiration pneumonitis, which may follow inhalation of gastric

contents if simultaneous vomiting accompanies convulsions;

-> cardiac failure, as a result of a combination of severe hypertension

and vigorous intravenous fluid administration.
Ill some women, sudder. death occurs synchronously with a convulsion or
follows shortly thereafter, as a result of a massive cerebral hemorrhage.
This complication is more likely in older women with underlying chronic
hypertension.
Blindness may follow a seizure having at least two causes: => varying
degrees of retinal detachment; occipital lobe ischemia or infarction. The
prognosis for return of normal vision is good and usually complete within a
week.

Differential diagnosis

Generally, eclampsia is much more likely to be diagnosed too

frequently rather than overlooked because epilepsy, encephalitis, meningitis,
cerebral tumor, ruptured cerebral aneurysm, even hysteria during late pregnancy
and the puerperium may simulate eclampsia.
Until other causes are excluded, all pregnant women with convulsions
should be considered to be eclamptics.

Treatment Treatment of

eclampsia consists of:

control of convulsions;
correction of hypoxia and acidosis;
blood pressure control;
delivery after control of convulsion.

197

 As management of the eclamptic patient requires the availability of

neonatal and obstetric intensive care units and personnel with special
expertise, cases must be managed in high specialized units.
Before transfer, toward these units, blood pressure should be stabilized and
convulsions controlled. An accepted regimen is 4g intravenous magnesium
sulfate as a loading dose, with a simultaneous intramuscular dose of lOg.
Such patients should be sent in an ambulance with medical personnel in
attendance for proper management in case of subsequent convulsions.

Treatment of convulsions

The patient is placed in a dimly lighted, quiet room with an attendant

constantly present. A padded tongue blade should be inserted between the patients
teeth to prevent biting of the tongue. The patient must be placed on her left side
and then suction the foam and secretion from her mouth and trachea must be
made.
Because hypoxia is always associated with hemoconcentration, the

administration of oxygen is a valuable aid therapy. Oxygenation can be

improved by performing endotracheal intubation whenever pulmonary
edema is diagnosed, when respirations are labored or when there is a
suggestion of cyanosis.
An indwelling catheter is inserted into the bladder and hourly urine outputs
are recorded. The ordinary diuretic preparations are completely-valueless
because the anuria is a result of decreased glomerular filtration and most
diuretics act at a tubular level.

Because the decrease in glomerular filtration is at least in part a

result of glomerular arteriolar spasm, the most important part of the treatment is to
decrease peripheral spasm.

-Magnesium sulfate is used to arrest and prevent convulsions due to

eclampsia without producing generalized central nervous system depression in
either the mother or the fetus. MgS04 is not given to treat hypertension. The drug
most likely exerts a rather specific anticonvulsivant action on the cerebral cortex.
Typically, the patient stops convulsing after the initial administration of MgSO.4
and within an hour or two regains consciousness sufficiently to be oriented as to
place and time.

MgS04 dosage schedule :

=> 4g as a 20% solution intravenously at a rate not to exceed

lg/min;
=> lOg of 50% solution, one half (5g) injected deeply in the
upper outer quadrant of both buttocks (promptly after intravenous administration);
=> if convulsions persist, after 15 minutes, up to 2g more
intravenously as a 20% solution at a rate not to exceed lg/min;
=> every 4 hours thereafter, 5g of a 50% solution injected
deeply in the upper outer quadrant of alternate buttocks, only after assuring that:

> the patellar reflex is present;

-> respirations are not depressed;

-> urine output in the previous 4 hours exceed 100ml.

198

Magnesium sulfate is discontinued 24 hours after delivery.

Eclamptic convulsions are almost always prevented by plasma magnesium
levels maintained at 4 to 7mEq/L. Loss of the patellar reflex begins with
plasma levels of 8 to lOmEq/L. Respiratory arrest occurs at levels of
12mEq/L or more.

Calcium gluconate, lg administered slowly intravenously and oxygen,

usually suffice for treatment of respiratory depression. If respiratory arrest

occurs, prompt tracheal intubation and ventilation are lifesaving.

When there is renal insufficiency, plasma magnesium levels must be

checked periodically.

Convulsions that continue despite adequate MgS04 therapy can often

be controlled by the intravenous administration of DIAZEPAM (Valium) lmg, or
Amobarbital sodium (AMYTAL), 300mg. These drugs should not be necessary
often and should be used with caution as they are powerful cerebral depressants.

It is not necessary to lower the blood pressure to a normal level. In

some patients even a moderate fall in blood pressure will reduce the renal output
of urine and compromise placental perfusion.
If the diastolic pressure remains above lOOmg Hg an antihypertensive
agent should be administered. HYDRALAZINE is given intravenously in
5 to lOmg doses at 15 to 20 minutes intervals until a satisfactory response is
achieved.
The tendency to give a larger initial dose of Hydralazine when the blood
pressure is higher must be avoided.

Other antihypertensive agents: DIAZOXIDE (this therapy is

accompanied by many adverse side effects), NITROGLYCERIN, PRAZOSIN,
LABETALOL, NIFEDIPINE. Labetalol lowers blood pressure more rapidly and
associated tachycardia is minimal. Hydralazine lowers mean arterial pressure to
safe levels more effectively.

Lactate Ringer solution containing 5% dextrose at the rate of 60ml

to no more than 125ml/hour is routinely administered. Infusion of large fluid
volumes could and does enhance the maldistribution of extracellular fluid and
thereby appreciably increases the risk of pulmonary and cerebral edema.
Delivery
Delivery is the treatment for eclampsia. FHR and intensity of uterine
contractions should be closely monitored. Once convulsions have been
controlled, induction of labor with oxytocin is initiated.
If labor is not well established and in the absence of fetal malpresentation
or fetal distress, oxytocin may be used to induce labor in all patients beyond
32 weeks gestation. The same approach is used in patients with a
gestational age below 32 weeks if the cervix is favorable for induction.

Vaginal delivery is preferred if there are no contraindications.

Cesarean section is to be considered only for those in whom there is a
contraindication to vaginal delivery or for those in whom labor cannot be
induced.

199

Our view, that the extension of cesarean section indications to the

cases with PIH not responding to medical treatment, is a reliable choice. In the
last decades, it was the policy of our clinic to include hypertensive disorders
complicating pregnancy among the indications of cesarean section.

Prevention of eclampsia

Eclampsia is generally considered a preventable complication of

pregnancy especially by appropriate prenatal care. F.P.Zuspan (1978) stresses that
when eclampsia does occur, it is because of failure to diagnose PE, lack of
surveillance of women at risk of development of PE-eclampsia and inadequate
treatment once PE develops.

However, approximately 30 to 40% cannot be prevented despite

adherence to present standards of prenatal care.

Prognosis

The prognosis of eclampsia is always serious. This is one of the most

dangerous conditions that can afflict a pregnant woman and her fetus.

In women in whom the onset of eclampsia occurs before 28 weeks

the risk of maternal death is increased. The prognosis is more reserved in
multigravid women. This is probably attributable to the higher incidence of
chronic hypertension and underlying renal disease in this category of patients
rather than to any effect of eclampsia per se. The incidence of pulmonary edema
and renal failure is much higher in multigravid women.

The maternal mortality for properly treated eclampsia should be less

than 5%.

The main risks to the fetus of the eclamptic woman are abruptio
placenta, prematurity, RJGR and hypoxic episodes during the convulsions. The
perinatal mortality is 20% to 25%.

200

24. CHRONIC HYPERTENSION. PREMATURE

SEPARATION OF THE NORMALLY IMPLANTED
PLACENTA

24.1. CHRONIC HYPERTENSION

Pregnancies complicated by chronic hypertension are associated with

increased perinatal mortality and morbidity. These women are at increased

risk for the development of superimposed PE and abruptio placentae.
The reported incidence of superimposed PE ranges from 10 to 15%,
depending on the degree of hypertension at the onset of pregnancy.

Diagnosis
If the patient has a history of hypertension either between pregnancies or
repeatedly during pregnancy, it is likely that the 'present episode is a
chronic vascular disease. The blood pressure elevation is usually present
before the twentieth week of pregnancy and there may be other evidences
of chronicity of the condition such as organic changes in the retinal vessels.
If the elevation in blood pressure is not accompanied by edema (abnormal
weight gain) and proteinuria, a diagnosis of essential hypertension is likely
to be made.
Patients with severe hypertension should be quickly and completely
evaluated when first seen. The examination should include:
=> general physical examination;
frequent blood pressure recordings;

=> eye examination for evidence of retinitis;

=> renal function studies as fluid intake and urine output measurements,
creatinine and uric acid clearances, quantitative protein determinations; => blood
urea nitrogen determination; => cardiac evaluation.
A baseline is thus established to repeat examinations during pregnancy and
a decision can be made as to whether pregnancy should continue.

201

Some of the women may have had previous intrauterine fetal deaths.
Tests for fetal well-being and continuing growth (indicating adequate placental
function) are:
periodic sonographic measurement of various fetal diameters (to
determine if they are increasing);

-> nonstress test, contraction stress, periodic fetal activity.

Effect ofpregnancy on hypertension In about a third of all pregnant women

with essential hypertension PE is superimposed on the chronic condition.

The incidence of both fetal and maternal death is increased.

Effect of hypertension on pregnancy

The infant almost always weighs less than do those born after normal

pregnancies of the same duration. The cause of the growth retardation is

altered placental function by multiple small infarcts as a result of
hemorrhage into the decidua from maternal arterioles supplying the
intervillous space. Fetus may even die in utero.

A patient who begins pregnancy with a systolic blood pressure higher

than 200mm Hg and a corresponding rise in diastolic pressure has no more than a
50% chance of delivering a normal baby.
About half of all cases of severe premature separation of the placenta
(abruptio placentae) occur in women with vascular disease. This is
associated with a high fetal mortality and an increased maternal mortality.

Of all women with vascular disease, 30 to 40% will develop signs

characteristic of PE during pregnancy. The complication usually appears late in
the second trimester and is associated with a high fetal and maternal mortality.
The blood pressure may rise to alarming heights in a few days and renal function
deteriorates rapidly.

Renal cortical necrosis is sometimes encountered in women with

hypertension and premature placental separation.

Intracranial hemorrhage is a more common cause of death in

chronic hypertensive disease than in PE because the vessels may have undergone
an organic degenerative change and because the arterial blood pressure is usually
much higher.
Prenatal care
Pregnancy is dangerous and interruption should be
recommended if: the systolic blood pressure is higher than 180 to
200mm Hg or the
diastolic pressure is 110mm Hg or more and remains elevated after a period
of bed rest;
there are degenerative changes in the retinal arterioles;
the patient has had a previous cerebral hemorrhage or PE during
previous pregnancies;
the renal function is reduced.
If the pregnancy is allowed to continue, the patient is informed of her
condition and advised of the probabilities.
202

Patients with chronic hypertension should be examined at least every

2 weeks and often more frequently. They should rest every morning and afternoon
and spend at least 10 hours in bed each night.

Any prenatal patient with hypertension should be admitted to the

hospital at once if:

0 the blood pressure rises;

0 protein appears in the urine;

0 weight gain is abnormal or edema develops;

0 symptoms appear.
Many drugs are currently avai'able for treating chronic hypertension in
pregnancy. The drugs used most often are adrenoceptor blocking agents,
thiazide diuretics and hydralazine.

Methyldopa is considered the agent most frequently used to treat

hypertension during pregnancy (it acts by stimulation of central alpha 2
receptors). Oral dosage is : initial loading dose of lg, followed by a maintenance
dose of 1 to 2g/day given in four divided doses.

Clonidine is a potent alpha 2 adrenoreceptor central stimulant,

considered to be safe and as effective as Methyldopa.

Prazosin is a selective alpha 2-postsynaptic blocker. The usual dose is

Img twice daily.

Beta-blockers use in pregnancy has been associated with neonatal

bradycardia, hypoglicemia, TUGR, altered adaptation to perinatal asphyxia and
neonatal respiratory depression. .
Propranolol is the most commonly used beta-blocker in pregnancy. The
usual dose is 40 to 240mg/day, frequently combined with a diuretic and/or
vasodilator. Some authors reported that Atenolol was safe when used during
pregnancy.

Labetalol is a nonselective beta-blocker with some alpha 1 blocking

effects. The dose of labetalol ranges from 300 to 1,200mg/day. Side effects are
minimal. The blood pressure control is better with labetalol.
There are few reports describing the use of calcium channel blockers alone
or in combination with other drugs during pregnancy.

The angiotensin-converting enzyme inhibitors (Captopril,

Enalapril, Lisinopril) are not recommended in pregnancy.
There is considerable controversy regarding the benefits and risks of
diuretics for treatment of chronic hypertension during pregnancy.

Hydralazine is considered by some authors the drug of choice for

treating severe chronic hypertension during pregnancy. The usual oral dose is
10mg given four times daily, but this can be increased to 75mg given four times
daily, for a maximum dose of 300mg.

Termination of pregnancy

If the patient develops superimposed PE that cannot be controlled

with medical treatment, the pregnancy must be terminated even though the infant
is not yet viable (induction of labor or cesarean section).

21S

If the blood pressure remains stable or falls slightly and if PE does

not develop, the prognosis is reasonably good (induction of labor as soon as fetal
maturity is present).

Hydralazine may be given if the blood pressure is unusually high or

rises during labor. Nitroglycerin or nitroprusside can be used for acute
hypertensive crisis.

The maternal mortality is increased ten to twenty times over that of

the normal patient and the fetal loss is as high as 30 to 40%.

The principal causes of deaths are : abruptio placentae, eclampsia,

cerebral hemorrhage, renal cortical necrosis, postpartum collapse.

24.2. PREMATURE SEPARATION OF

THE NORMALLY IMPLANTED PLACENTA

Definition and nomenclature The separation of the placenta from its site of

implantation before the delivery of the fetus has been variously called:
=^ premature separation of the normally implanted placenta;
=^ placental abruption;
=> abruptio placentae;
=^> utero-placental apoplexy;

=> accidental hemorrhage. The term premature separation of the

normally implanted placenta (PSNIP) is most descriptive because it
differentiates the placenta that separates prematurely but is implanted over this
segment (that is placenta praevia).
It is cumbersome, however, and hence the shorter term abruptio
placentae (placental abruption) has been employed. The Latin abruptio
placentae, which means "rending asunder of the placenta" denotes a sudden
accident, a clinical characteristic in most cases of this complication.
The term abruptio placentae means "a carrying away of the
placenta" and is not used extensively.
The term frequently employed in Great Britain is accidental
hemorrhage in the sense of an event that takes place without expectation.
In the more severe forms of placental abruption, widespread
extravasation of blood into the uterine musculature and beneath the uterine
serosa is found. This phenomenon of uteroplacental apoplexy, first described by
Couvelaire early in this century, is now frequently called Couvelaire uterus.
Such effusions of blood are also occasionally seen beneath the tubal serosa, in
the connective tissue of the broad ligaments, as well as free in the peritoneal
cavity. These aspects can only be demonstrated conclusively at laparotomy.

Frequency

The frequency will vary because criteria employed for diagnosis

differ. The intensity of the abruption will often vary depending on how quickly the
woman seeks and receives care following the onset of * symptoms.
The reported frequency varies but averages about 1 in 150 deliveries.

204

 As stillbirths from other causes have decreased appreciably

(American studies) those from abruptio placentae have become especially

prominent (10 to 15%).
Even if the infant survives, there may be adverse sequelae
(significant neurological deficits within the first year of life). Maternal mortality
is uncommon but morbidity is frequent and may be severe.

Etiology
The primary cause of placental abruption is unknown but there are
several associated conditions. By far, the most commonly associated condition
is either pregnancy-induced or chronic hypertension. This is the reason why we
have placed the disease here.
Hypertension is often associated with PSNIP, the reported incidence
varying from about 11% to about 65%. Elevated blood pressure is more likely to
be present in women with complete placental separation than in those with
minor degrees.
Studies have suggested an increased incidence of abruption in
patients with advanced parity or age, maternal smoking, poor nutrition,
cocaine use and chorioamnionitis.
In the past, folic acid deficiency, a short umbilical cord and the supine
hypotensive syndrome had been suggested as etiologies for placental
abruption. Further evidence has shown, however, that these factors are
unlikely causes of placental abruption.

External maternal trauma is an uncommon but important cause.

Uterine myoma, especially if located behind the placental implantation site,
predisposes to abruption.

The risk of recurrent abruption in a subsequent pregnancy is very

high (10%), probably because the factors causing the initial separation are still
present. Submucous fibroids and uterine anomalies are the most common
recurring causes.

Pathology

Placental abruption is initiated by hemorrhage into the decidua

basalis. The decidua then splits, leaving a thin layer adherent to the myometrium.
Consequently, the process in its earlest stages consists of the development of a
decidual hematoma that leads to separation, compression and the ultimate
destruction of the placenta adjacent to it. In its early stage, there may be no
clinical symptoms (the condition is discovered only upon examination of the
freshly delivered organ).

In some instances, a decidual spiral artery ruptures to cause a

retroplacental hematoma, as it expands, dirupts more vessels to separate more
placenta. The area of separation rapidly becomes more extensive and reaches the
margin of the placenta. The escaping blood may dissect the membranes from the
uterine wall and eventually appear externally, or may be completely retained
within the uterus.

21S

Blood is also lost through hemorrhage into the uterine wall, through
extrauterine hematoma formation and through bleeding beneath serosal surfaces
and membranes if a clotting defect develops.

The clotting is caused by activation of the normal coagulation

mechanisms. Thromboplastin from abnormal subplacental decidua, the disrupted
placenta and serum in the subplacental clot enters the bloodstream through the
open vessels at the placental site and initiates an exaggerated intravascular
clotting process.

Fibrinogen is converted to fibrin, which may occlude small vessels

throughout the body producing local tissue anoxia. As more thromboplastin is
introduced into the circulation, more fibrinogen and consumable clotting factors
are used and become seriously depleted. The blood then becomes incoagulable
and abnormal bleeding is evident.

Because the coagulation defect is a consumption coagulopathy or

disseminated intravascular coagulation, factors other than fibrinogen are involved.
Factors V, VIII, XIII and platelets are consumed. A fibrinolytic process that
disintegrates the fibrin emboli is initiated. As a consequence, fibrin degradation
products form. They inhibit platelet aggregation and have a direct antithrombin
effect that interferes with fibrin conversion and the production of normal fibrin
threads in the clot.

Patients with severe abruptio placentae may develop oligo-anuria

because of acute tubular necrosis or bilateral renal cortical necrosis. Those with
tubular necrosis will recover if the damage is not too extensive, but they may need
renal dialysis. Most patients with cortical necrosis die. These lesions seem to
develop because of intrarenal vasospasm.

Classification
Placental abruption can be broadly classified into three grades that con'elate

with clinical and laboratory findings:

grade ! slight vaginal bleeding and some uterine

irritability are usually present
maternal blood pressure is unaffected
maternal fibrinogen level is normal
fetal heart rate pattern is normal

grade 2 0 external uterine bleeding is mild to moderate

0 uterus is irritable and tetanic contractions may

be present 0 maternal blood pressure is maintained, but the pulse
rate may be elevated and postural blood volume deficits may be
present 0 fibrinogen level is usually reduced to 150 to 250mg%
0 fetal heart rate often shows signs of fetal distress

grade 3 bleeding is moderate to severe but may be concealed

uterus is tetanic and painful

maternal hypotension is frequently present

fetal death has occurred
fibrinogen levels are often reduced to less than 150mg%
206

other coagulation abnormalities are present (thrombocytopenia,

factor depletion).

Signs and symptoms. Diagnosis Bleeding associated with pain that

varies in severity is characteristic of PSNIP. The pain may come on suddenly and
be severe and constant when there is a major separation or milder and intermittent
with a less severe lesion.

The blood may be dark or even clotted if it is retained within the uterine

cavity for a time before it is discharged into the vagina. Discharge may
consist only of blood-stained serum, which is squeezed out of retroplacental
clot. If there is a considerable amount of concealed bleeding the pain will
increase in severity as the uterus becomes distended and the muscular wall
is infiltrated with blood.

Ordinarly, it is not difficult to recognize the severe forms of abruptio

placentae, but milder degrees may be less obvious. In most instances, the
diagnosis can be made by history and clinical examination.

Abdominal examination

>* uterus feels firm and is tender to the touch; at the onset the
tenderness may be confined to a small area of the uterine wall, but eventually the
gentlest palpation at any point produces pain;

> if there is a considerable amount of concealed bleeding, the uterus

will gradually enlarge as the blood collects within its cavity and infiltrates the
muscular wall;

> uterus is hard and tetanically contracted and one may not be able
to outline fetal parts because of tenderness and the contracted uterus;

uterine contractions are usually of higher frequency but lower

amplitude than in normal labor.

The fetal heart tones may be normal if only a small amount of

placenta is separated or they may be completely absent in the more severe forms.

Vaginal examination should usually be performed as an aid in

diagnosis and to determine how delivery will be effected.

Sonography is appropriate only for minor degrees of separation as an

aid in clinical diagnosis.

Laboratory examinations >hemoglobin may be reduced, the level

depending on the amount of bleeding;

>the white blood cell count is often elevated to 20,000 or 30,000;

>a clotting defect is present in about 10% of cases and is most

common in severe abruption associated with either fetal death or brisk
hemorrhage ; whenever the diagnosis is entertained, coagulation studies (platelet
count, prothrombin time, partial thromboplastin time, fibrinogen, test for fibrin
split products) should be ordered promptly and repeated at regular intervals;

>while awaiting the results of formal coagulation studies,

information can be gathered by observing a tube of whole blood allowed to stand

21S

undisturbed (clot observation test) ; if a clot fails to form or forms and is promptly
lysed, a coagulation abnormality can be assumed.

Differential diagnosis Abruptio placentae can be confused with

placenta praevia, but in most instances it is possible to differentiate between them.

Abruptio

placentae

the bleeding usually is accompanied

by pain

the blood is usually dark

signs of shock may be out of

3proportion to visible bleeding

the first bleeding is often profuse

the uterus may be firm, tender and

5tetanicallv contracted

the fetus may be difficult to feel and

fetal heart tones may be irregular or
absent
the placenta cannot be felt

the patient may have acute or chronic

hypertensive disease, but the blood

pressure may be low because of
excessive bleeding
the urine may contain protein or the
patient may be oligo-anuric

a cloning defect may be present

the bleeding is painless unless labor

has started

the blood is bright red

observed bleeding and signs of shock
usually are comparable

the bleeding is usually slight at the

onset

the uterus is soft, not tender and may

5be contracting if labor has started

Placenta praevia

the fetus can be felt easily and fetal

heart tones are usually present

the placenta may be felt within the

cervical canal

there is usually no hypertensive disease

the urine is usually normal

the blood usually clots normally

Other abnormalities which can be differentiated: => uterine

rupture; => acute hydramnios; => twisted ovarian cyst; => peritonitis.

Management

Treatment for placental abruption will vary upon the status of the
mother and fetus. With the development of massive external bleeding, intense
therapy with oxygen and intravenous fluid, followed as rapidly as possible by an
appropriate volume of red blood cells.

208

 To combat hypovolemia successfully, blood must be available in large

quantities. If pulmonary congestion were to develop, Furosemide then

would be beneficial.

In the past, concern-mostly theoretical in origin- was expressed that

the use of Fibrinogen simply "added fuel to the tire" of disseminated intravascular
coagulation by imposing dire consequences of fibrin deposition and
microcirculation obstruction in vital organs. There is no good evidence, however,
that effective dose of fibrinogen causes this. Typically, 4g of Fibrinogen is an
effective dose and raises the plasma fibrinogen concentration by about 100mg/dl
(normal concentrations of plasma fibrinogen during pregnancy range between 300
and 700mg/dl).

A combination of fresh frozen plasma and cryoprecipitate will

replace the deficient plasma factors.
Heparin (to block disseminated intravascular coagulation) and Epsilonamino caproic acid (to try to control fibrinolysis) use is not recommended.
In most cases of placental abruption delivery will be the treatment of
choice. Considerable controversy remains regarding the appropriate method
of delivery in patients with this pathology. Vaginal delivery is more often
possible in multiparas than in primigrvidas, but one may be surprised by
the rapidity with which many primigrvidas deliver.

Electronic fetal monitoring is essential and cesarean section should

be performed promptly if evidence of fetal distress is detected.

Cesarean section, in the interest of the fetus, should be considered

with milder forms if bleeding and uterine tenderness are increasing and delivery is
not imminent.

In the presence of coagulation defects, the more extensive the

surgery, the more likely the hemorrhage is to be intensified. Therefore,
hysterectomy to attempt prophylactically to minimize blood loss is unwise. At
times, it must be performed because the uterus has been severely lacerated or
simply will not contract to effect hemostasis.

In more recent series, a fetal mortality of 17% and neonatal mortality

of 14% was reported. The principal causes of death are anoxia, complications of
prematurity and maternal hypertension.

Maternal mortality is about 1% and more. The important causes are :

hemorrhage, cardiac failure, acute renal failure, acute hepatic failure.

21S

 25.

PRETERM BIRTH

Definition
The fetus or newborn infant is referred to as a fetus at term or an infant at

term during the interval from the 38 to the 42 nd week after the onset of a
menstrual period that was followed, 2 weeks later, by ovulation.
The date of onset of the last normal menstrual period (LMP) is of clinical
importance for determining fetal age because it is usually known rather
precisely and when menstrual bleeding is spontaneous and previously
regular it is most often followed by ovulation and fertilization 2 weeks
later.
Before the 38lh (or between 28 to 37 weeks) week, preterm is the word best
applied to categorize the fetus and the pregnancy.
The World Health Organization, in 1961, added gestational age as a
criterion for premature infants defined as those born at 37 weeks or less.
The classic term prematurity refers to birth weight less than 2,500g. A
distinction was made between low birthweight (2,500 or less) and
prematurity (37 weeks or less).
Because of difficulty in accurately assigning gestational age, many-studies
have used a birth weight definition, equating a birth weight of less than
2,500g with preterm birth. Although birth weight and gestational age are
closely related, interchanging the two measures can lead to significant
errors (2,500g is not the mean weight for 37 weeks gestation but rather for
35 weeks gestation).

Although the term premature was used to designate the fetus or

infant before the 38th week of gestational age, premature should be used to
describe function.

Gestational age-specific neonatal mortality and morbidity Over the

past few decades, the answer to the question ''what is the lower limit of viability?"
has been a progressively earlier gestational age. Recent series reveal that 50 to
60% of 25 week gestation neonates survive as do up to 85% of 26 to 28 week
gestation neonates.

210

 Preterm infants are at risk for specific diseases relating to the immaturity of

various organ systems. Common complications include : respiratory

distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus,
intraventricular hemorrhage, necrotizing enterocolitis
Preterm infants were found to be at increased risk for serious
neurodevelopmental handicaps.
Obstetrical approaches to preterm labor and delivery are guided in large
part by expectations the obstetrician has for survival of the premature or
immature neonate, as well as the therapeutic alternatives available for
management of preterm labor.

Etiology
In most of instances, the precise cause or causes of labor before term are

not known. Listed below are some conditions that predispose to

prematurity:

> uterine malformations are at greater risk for preterm delivery: the
risk varies with the abnormality ; women with unicornuate or bicomuate uteri
have worse pregnancy outcomes than do women with a complete uterine septum;
uterine myomata have been associated with increased antepartum
bleeding and preterm labor;

> cervical incompetence leads to painless second-trimester cervical

dilatation and abortion; because of differences in definition and populations, the
absolute contribution of this entity to preterm delivery is, unclear;
a growing body of evidence suggests that maternal genital tract
infection and/or colonization may be among the most important preventable
causes of preterm birth; the association between chorioamnionitis and preterm
birth is well established, especially in the presence of PSRM;

> current pregnancy complications including multiple gestation,

polyhydramnios, placenta praevia or abruptio, marginal insertion of the umbilical
cord, placental insufficiency have been associated with preterm delivery;

>- the woman who previously gave birth remote from term is more
likely to do so again, even when no other predisposing factor is identified; there
is also a clear increase in subsequent preterm deliveries in women who have
experienced one or more second-trimester abortions;

>- there is still debate whether multiple first-trimester induced

abortions are associated with a higher preterm delivery rate;
systemic disease in the mother, when it is severe, may cause
preterm birth (urinary infections, hepatitis, toxoplasmosis, severe hypertension,
diabetes mellitus);

> reproducible risk factors include low socio-economic status,

maternal age of 18 years or less or of 40 years or more, nonwhite race, smoking;
occupations associated with great fatigue and long work hours may predispose to
preterm delivery, especially for women who have a history of prior poor

211

pregnancy outcomes; maternal smoking level correlates very significantly with

perinatal mortality, preterm delivery, PSRM and bleeding during pregnancy;

women who do not seek prenatal care are significantly more

likely to deliver before term regardless of social class; socially disadvantaged
women appear to gain the most from prenatal care;
> although stress may be etiologic in some cases of preterm labor, it is
difficult to evaluate inasmuch as the impact of life events is mediated by
social support and mental health;
> maternal nutritional status and weight gain in pregnancy are commonly
assumed to relate to neonatal birth weight and preterm delivery; certainly,
extremes of malnutrition and starvation lead to a decrease in birth weight;
of interest are the roles of copper and zinc balance in pregnancy; low
maternal serum zinc levels have been associated writh preterm labor and
low maternal and/or neonatal copper levels with preterm rupture of
membranes.

Identifying women at high risk to experience preterm labor is a

necessary first step in preventing preterm births. Several risk-scoring systems
have been developed based on the factors outlined above to identify women
likely to deliver preterm. Of these, the system devised by Papiernik has been the
most extensively applied.

Mechanisms of preterm labor

Delivery before term occurs because the events that normally should
not happen until term are triggered too early. The exact physiology of these
events in normal labor is unclear but we infer with little evidence that they are the
same in the case of preterm labor as in term labor.
A reduction in local progesterone, probably destabilizes lysosomal
membranes with release of the lysosomal enzyme phospholipase A2 which
cleaves AA from intracellular membranes and allows prostaglandin
synthesis, which then activates the myometrium by inhibiting uptake of
calcium.

The development of gap junctions between myometrial ceils is another

critical step in preparation for labor.

Chorioamnionitis increases synthesis of prostaglandins. Cytokines (among
which, Tumor Necrosis Factor) have the same effect.
A small proportion of preterm birth occurs because of incompetent cervix,
a poorly understood phenomenon where the cervix matures, softens and
painlessly dilates without apparent uterine contractions.

Intracellular^, calcium is stored in the sarcoplasmic reticulum and in

mitochondria. cAMP and progesterone promote calcium storage at these sites,
while PGF2 alpha and oxytocin stimulate its release.
In the control of myometrial contractility, the key process in actin-myosin
interaction, and thus contraction, is myosin light-chain kinase
phosphorilation. Factors regulating the activity of this enzyme are calcium
and cAMP. Calcium is essential for the activation of MLK and binds to the
kinase as calmodulin-calcium complex.
212

cAMP directly inhibits MLK function via phosphorilation. Levels of

cAMP are increased by the action of adenylate cyclase, which in turn is
stimulated by beta-adrenergic agents.

Therefore, beta-mimetic tocolytics act through adenylate cyclase to

increase cAMP, which inhibits MLK activity both by direct phosphorilation and
by reducing intracellular free calcium by inhibiting calcium release from storage
vesicles.

Clinical circumstances of preterm birth According to

P.G.Stubblefield (1984) seven different clinical circumstances were present:

=> early preterm labor with the cervix less than 5cm dilated and fetal
membranes intact; this group was further subdivided into those in very early labor
with cervical dilatation less than 3 cm and those further along with cervical
dilatations of 3-4cm;

=> advanced preterm labor with the cervix 5 or more centimeter

dilated and membranes intact;
PSRM without labor;
=> PSRM in labor;
vaginal bleeding of significant amount; maternal or fetal illness; => fetal
death (in utero) before hospital admission. Early differentiation between
true and false labor is often difficult before it is demonstrable cervical
effacement and dilatation. Progressive dilatation, of course, is indicative of
labor. A frequently used criterion for

labor is that of uterine contractions with a frequency of at least once every

10 minutes and a duration of 30 seconds or more.

As a consequence of the confusion and imprecision as to the diagnosis of
preterm labor, there has been corresponding uncertainity about the
effectiveness of most preterm labor treatment regimens. For exemple, most
attempts to prevent preterm delivery in patients with ruptured membranes
are less than satisfactory. Ruptured membranes definitively establish a
diagnosis of impending preterm delivery, whereas uterine contractions
alone may not be so predictive.

In addition to painful or painless uterine contractions, symptoms

such as pelvic pressure, watery or bloody vaginal discharge and pain in the low
back have been empirically associated with impending preterm birth.

Prevention of preterm birth Assuming that at least a proportion of

the women at risk for preterm deliveries can be identified, are there additional
approaches above routine prenatal care that can prevent preterm labor and birth in
these high-risk patients? *

Lack of prenatal care is found consistenly in association with LBW.

Uterine activity monitoring, using tocodynamometry, has received

considerable interest. Widespread clinical application of home uterine contraction
monitoring for the purpose of preventing preterm birth has provoked considerable
controversy in the USA. The dimensions of the controversy over the efficacy of

213

home uterine contraction monitoring can be sensed by reading reviews that have
appeared in major medical journals between 1989 and 1992.

The conclusion in all these reviews is that there is no consensus

concerning the effectiveness of home uterine contraction monitoring in the
prevention of preterm labor.
Reduced activity or bed rest in the late second and early third trimesters is
commonly recommended as a means of potentially decreasing preterm
births.

An increased rate of preterm delivery has been associated with group

B streptococci, Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma
urcalyticum, Trichomonas vaginalis, Treponema pallidum. However, the potential
benefits of antibiotic therapy remain unresolved.

Management of a number of medical complications such as severe

hypertension, diabetes mellitus, urinary infections is important to be realised.

The role of cerclage in patients with histories for cervical

incompetence or histories that clearly have an element of preterm labor is
controversial.

Parenteral progesterone, usually 17 alpha-hydroxyprogesterone

caproate (DELALUTIN) has been used for prophylaxis against preterm labor.
The prophylactic use of beta-mimetic agents before the onset of preterm labor has
not been extensively evaluated.

Treatment of preterm labor and delivery The challenge of

treating preterm labor clearly illustrates one of the

central dilemmas in Obstetrics today. In general , the more immature the
fetus, the greater the risks from labor and delivery.

As previously mentioned, early differentiation between true and false

labor is often difficult before there is cervical effacement and dilatation.
Unfortunately, by this time, attempts to arrest labor are often ineffective.
Successful arrest of preterm labor appears to require early
implementation. The treatment regimen that has been used most often is
bed rest.
Abnormalities of fetal heart rate and uterine contractions should be sought,
preferably by continuous electronical monitoring.
Beta-adrenergic receptor agonists (beta-mimetic tocolytics)
Sympathomimetic or adrenergic drugs act through either alpha or
beta receptors. Stimulation of beta receptors leads to smooth muscle
relaxation at all sites: vascular, gastrointestinal and uterine. There are two
classes of beta-adrenergic receptors:
beta 1 receptors (dominant in the heart and intestines); :=>beta 2
receptors (dominant in blood vessels, bronchioles,
myometrium).
A number of compounds, generally similar in structure to epinephrine,
have been evaluated in the search for one that ideally would provide
optimal stimulation of beta 2 adrenergic receptors on myometrial cells and
thus inhibit uterine contractions and simultaneously cause little or no

214

adverse effects from stimulation of adrenergic receptors elsewhere. Thus

far, no compound has exhibited these Utopian properties.

Compounds that have been or are being employed in attempts to

arrest preterm labor include RITODRINE, TERBUTALINE, FENOTEROL.

RITODRINE treatment significantly delayed delivery for 24 hours

or less. A likely explanation for the transient uterine tocolytic effects of
RITODRINE and ultimate failure of such therapy may be the phenomenon of
beta-adrenergic receptor function densitization.
The currently recommended protocol for intravenous therapy starts at 0,1
mg per minute and is increased by 0,05mg every 10 minutes up to a
maximum of 0,35/min. The rate is increased unless contractions cease, side
effects occur, or the maximum rate is reached. The infusion is then
maintained at that level for 12 hours after the cessation of contractions.

For oral therapy, initial dose is lOmg administered 30 minutes before

stopping infusion. Then lOmg every 2 hours, or 20mg every 4 hours, for 24 hours
may be administered. If the uterus remains quiescent, 10 to 20mg every 4 to 6
hours until further inhibition of labor is not indicated. Maximum dose is
120mg/day.

The infusion of RITODRINE, as well as the other beta-adrenergic

agonists, has resulted in frequent, and at times, serious side effects in the mother:

> tachycardia, headaches, emesis, fever;

> hypotension, electrocardiographic S-T segment depression;

> chest tightness or actual pain, pulmonary edema;

> metabolic effects : hyperglicemia, hypokalemia, ketoacidosis.

Absolute contraindications to the administration of beta mimetic

agents :
> maternal cardiac disease;
>eclampsia or preeclampsia;
> significant antepartum hemorrhage of any etiology; >chorioamnionitis;
> significant fetal growth retardation;
> uncontrolled maternal diabetes mellitus;
> uncontrolled hypertension.
Prostaglandin inhibitors
Antiprostaglandin agents (ASPIRIN, INDOMETHACIN, NAPROXEN,
MECLOFENAMIC ACID) may act by inhibiting the synthesis of PG or by
blocking the action of PG on target organs. Antiprostaglandins have been
the subject of considerable interest since it was appreciated that PG are
intimately involved in myometrial contractions that characterize normal
labor.
Magnesium sulfate
The role of magnesium is presumably that of an antagonist of calcium.
Intravenously administered MgSOa, 4g (20% solution) given as a loading
dose following by a continuous infusion of 2g/hour, will usually arrest
labor.
Calcium-channel blocking drugs

Calcium ions reach the cytoplasm through specific membrane

portals or channels and calcium-channel blockers act to inhibit the entry of
215

calcium. Recent reports have described NIFEDIPINE to be an effective tocolytic

agent.
Oxytocin antagonists
Experience with oxytocin antagonists (synthetic receptor that functions as a
competitive inhibitor for oxytocin) in humans is limited.

Glucocorticoids for enhancement of fetal pulmonary maturation

Infants born before 34 weeks had a significantly lowered incidence

of respiratory distress and neonatal mortality from hyaline membrane disease if
birth was delayed for at least 24 hours after completion of 24 hours of
corticosteroids given to the mother and up to 7 days after completion of steroid
therapy (intramuscular dexamethasone, 5mg every 12 hours for a total of up to
four doses). Not all workers have reported salutary effects from corticosteroid
administration. The major short-term side-effect is the risk of infection for both
the mother and infant.

Several centers have demonstrated a reduction in severity of acute

RDS with the intratracheal administration of surfactant.

Conduct of labor and delivery for the preterm infant Electronic

fetal monitoring gives information about fetal status. Changes in fetal heart rate
variability in the preterm fetus carry the same significance for risk of acidosis as
in term infants (pH is significantly less if variability is absent).

The course of labor in preterm gestation is shorter than that of term

pregnancy. The two predominant goals for the intrapartum management of the
premature fetus are: => avoidance of hypoxia (oxygen administration);

=> avoidance of birth trauma.

Episiotomy is recommended to minimize the forces of outlet

perineal resistance on the small soft head.

A former analysis found that the premature infants who had the best
outcome were the ones delivered by low forceps. Recent studies have not been
able to show this benefit.

The optimal method of delivery for the preterm infant continues to

be a source of debate. That the LBW nonvertex infant does better after a cesarean
birth is widely believed.

A critical technical point cannot be o ver stressed. One does not want
to avoid a traumatic vaginal delivery only to struggle and have a difficult
casarean birth because of an undeveloped lower uterine segment. There is
inadequate evidence to recommend routine cesarean birth for all LBW vertex
infants.

The focus of intrapartum care of preterm fetuses is to give the

newborn to the neonatologist in the best possible condition.

A physician proficient in resuscitative techniques who has been fully

oriented to the specific problems of the case should be present at delivery.

Hemorrhage from retained placental fragments is more frequent than

in term birth. The uterine cavity (placental site) is usually controlled by curettage.

216

26.
(PROLONGED)

POSTTERM

(POST

DATE)

PREGNANCY

Definition

A postterm pregnancy is one that persists for 42 weeks or more from the
onset of a menstrual period that was followed by ovulation 2 weeks later. Note
that this definition relates to the length of the pregnancy. Once again the value of
precise knowledge of the duration of gestation is evident, because, in general, the
longer the truly postterm fetus stays in utero, the greater the risk of a severely
compromised fetus and newborn infant. Incidence

The incidence of patients reaching 42 weeks gestation is estimated to

vary from 3 to 12%. With accurate gestational age estimation, the lower range is
more appropriate. Early prenatal examination and ultrasound clearly increase the
probability of accurate dating.

Etiology and physiopathology

There is a high incidence of large menstrual cycle length variation in

normal women. A relatively small proportion of pregnancies which reach 42
weeks evidence the fetal effects of postmaturity. Most pregnancies reliably 42
completed weeks beyond the last menses probably are not biologically prolonged.
However, there is no method available currently to identify these pregnancies.
The etiology of prolonged pregnancy is not completely
understood. Some rare conditions associated with prolonged pregnancy
include:

anencephaly; => fetal

adrenal hypoplasia; => absence of
fetal pituitary gland; => placental
sulfatase deficiency.
These clinical conditions share a common feature : the lack of the usually
high estrogen levels that characterize normal pregnancy. In the case of fetal
pituitary or adrenal insufficiency, the precursor hormone, DHEA sulfate, is
secreted in insufficient amounts for conversion to estradiol and

217

indirectly to estriol in the placenta. A classical example of the deficiency of

estrogen precursors is anencephaly.

Placental sulfatase deficiency is inherited as a sex-linked recessive

trait. In this condition, precursor hormone is produced by the fetal adrenal gland,
but the placenta lacks the enzyme to cleave the sulfate from DHEA-S, the initial
enzymatic step in the conversion of this biologically weak androgen into E2 and
E3.

Antepartum fetal risk and intrapartum fetal distress with postterm

pregnancies was not due to placental insufficiency, but rather was the
consequence of umbilical cord compression associated with oligoamnios. The
umbilical cord diameter, measured ultrasonographically, was predictive of
intrapartum fetal distress when decreased and especially if further associated with
oligoamnios.

The exact role of placental insufficiency is unclear but it has not been
identified even in those fetuses who were obviously postterm and growth retarded.

The postterm fetus may continue to gain weight in utero and thus be
an unusually large infant at birth. The fact that the fetus continues to grow serves
as an indication of uncompromised placental function.

The infant affected by prolonged gestation presents a somewhat

unique and characteristic appearance that was described by S.H.Clifford (1954)
and termed postmature :

>the infant is long but thin in girth and appears underweight from
loss of subcutaneous tissues;

>typically there are patchy areas of desquamation and the skin is

stained with meconium, although rarely the latter feature may be absent;

>the ventral surfaces os the hands and feet are wrinkled and the nails
are long and stained with meconium ("little old man" syndrome);

>the postterm infant is likely to be at risk for meconium aspiration

syndrome; the diminished amniotic fluid causes the meconium to be thicker and
more likely to obstruct airways; aspiration into the alveoli can cause significant
respiratory embarrassment and death. Diagnosis

The accurate diagnosis of a postterm pregnancy can be made only by

proper dating. The diagnosis allows concentration of management on the highestrisk patients.

A major problem of determining gestational age is that all methods of

estimating it lose accuracy in the third trimester, when fetal growth diminishes.

The obstetrician should review clinical parameters in all patients

since they are helpful in establishing gestational age at minimal cost. LMP is the
best clinical predictor of gestational age (estimate gestational age by comparing
the regularity, date, amount and length of menses).

An early pelvic examination may be helpful in confirming these

dates. Other clinical parameters include:

=> information concerning previous pregnancies (their duration at

delivery);

218

 => quickening (is a term that indicates the perception of fetal motion by the

mother; multiparas first feel movement at about the seventeenth week and
primigrvidas abut 2 weeks later);

=> first fetal heart sounds (19 to 20 weeks with fetoscope);

=> fimdal height at umbilicus (20 weeks).

Ultrasound has become the gold standard for the determination of
gestational age. Routine first and second trimester ultrasound decreases the
incidence of postterm pregnancy.

Ultrasound is clearly beneficial in patients without known or reliable

clinical data. Sonography is most accurate in early gestation. Measurement of
crown-rump length in early pregnancy correlates with accurate dates within 3 to 5
days. In the second trimester, the accuracy of ultrasound is plus-minus 1.5 weeks.

It is now common practice in the antepartum management of

postterm pregnancy to apply a variety of electronical and ultrasonic tests that have
been championed to predict fetal well-being:
contraction stress testing- fetal heart rate deceleration following
uterine contractions is associated with utero-placental insufficiency; oxytocin
challenge test (FIIR in response to oxytocin induced contractions) when is
negative, no periodic decelerations are recorded;
=>nonstress testing- fetal heart deceleration in response to spontaneous
fetal movement: currently, the nonstress test has become the most widely
used primary testing method for assessment of fetal well-being;

=> biophysical profile, based upon five variables:

fetal heart rate acceleration;
fetal breathing;
fetal movements;
fetal tone;
amniotic fluid volum;

Required quipement included a real-time ultrasound device and

Doppler ultrasound to record FHR ; normal variables were assigned a score of two
each and abnormal variable a score of zero ; thus, the highest score possible for a
normal fetus is 10.
As long as these tests remain normal, the fetus is considered to be in
minimal jeopardy and delivery is usually not attempted.
An amniotic fluid examination may be helpful in determining fetal maturity
but not actual fetal age.
Lecith in/sph ingomyelin rat io

After the thirty fifth week of pregnancy, the lecithin concentration

rises rapidly until term, whereas the sphingomyelin concentration decreases. High
lecithin concentration indicates fetal lung maturity. If the L/S ratio is at least 2/1,
the lung is probably mature.
Phosphatidylglycerol
Is,an amniotic fluid component synthesized almost exclusively by mature
fetal lung. This test is a more sensitive indicator of pulmonary maturity.

Obstetrical management of prolonged pregnancy can be planned

based on levels of urinary or plasma cstriol measurements. There are some
controversies because several investigators emphasized that estriol has little or no
clinical utility in the management of postterm pregnancies.

219

Several authors have suggested that the identification of diminished

amniotic fluid determined by various ultrasonic methods may be helpful to
identify a postterm fetus in jeopardy.
Antepartum management

The first major decision in management depends on the certainty of

the dates. The accuracy of the estimation of gestational age is important when
planning intervention.

hi patients with unsure dates, the same protocol for antenatal

surveillance should be followed as in well-dated pregnancies. Patients with a ripe
cervix may benefit from the induction of labor. However, these cases constitute a
minority of postdate pregnancies.

With confirmed dates and an unripe cervix, there are two alternatives
in management:
1. The most established method is to initiate antepartum surveillance
while awaiting spontaneous labor and/or spontaneous cervical ripening. m
1. The other approach is to administer PG gel for cervical ripening and
proceed with induction.

Some clinical trials with expectant management show an increase in

the cesarean section rate compared to that at term. This finding is attributed to the
increasing incidence of larger babies as well as fetal distress.

Others found uterine dysfunction and an increased cesarean section

rate in primigravid postterm pregnancies, independent of the induction of labor
and the size of the fetus.

Routine induction with oxytocin in postterm patients does not appear

to improve outcome because an unripe cervix is present in up to 80% of patients
reaching 42 weeks gestation. PG E2 gel applied locally to the cervix produces
softening, shortening, even dilatation. Ripening with PG may be not advisable if
there are abnormal decelerations, elevated baseline FHR or poor variability. The
next morning, oxytocin induction may be initiated with standard protocols if the
cervix has ripened. If the cervix remains unfavorable, a second dose (0.5mg PG
E2 gel) may be considered.

Previously most testing schemes suggested beginning testing at 42

weeks gestation since this represented the highest-risk population. Most
antepartum testing in the USA is done with the nonstress test, contraction stress
test and biophysical profile.
The assessment of amniotic fluid volume can be performed by using several
techniques.
Intrapartum management

Labor is a particularly dangerous time for the postterm fetus.

Electronic FHR and uterine contractions must be monitored very closely for rate
variations consistent with fetal distress.
The major complications in the intrapartum period are meconium staining,
macrosomia and hypoxia. Meconium staining is four times more common
in postterm pregnancy than in term gestations. There are two primary
reasons that meconium is more common in such postdate pregnancies:

=> first, the greater the length of time in utero, the greater chance for
activation of the mature vagal system with excretion of meconium;

=> second, hypoxia is more likely to occur in the infant who shows
the stigmata of dysmaturity and placental insufficiency.

220

Meconium aspiration syndrome may be prevented by aggressive

suctioning at the time of delivery of the head (suctioning of nasopharynx and
oropharynx).

Another important aspect of management is preventing birth trauma

associated with macrosomia. If clinical estimates indicate that the fetus is large or
the maternal pelvis is small, an ultrasound estimated fetal weight may be helpful:

Finally, consider primary cesarean section for suspected macrosomia

in patients with an estimated fetal weight greater than 4,000 (4,500)g, a marginal
pelvis or a previously difficult vaginal delivery.

Intrapartum asphyxia is also more common in the postterm

pregnancy, therefore, close observation of the FHR is necessary. Factors that
cause fetal distress are placental deterioration, long labor, oligoamnios. The
incidence of cesarean section for fetal distress increases from 5% to 15% in
patients who develop oligoamnios.
Cord compression is more likely in these gestations since the oligoamnios
is combined with a thin, easily compressible umbilical cord. Variable
decelerations result primarily from cord compression, not hypoxia.

Cesarean section is indicated when either hypotonic or hypertonic

dysfunctional labor is evident, when a cephalopelvic disproportion is evident,
when labor induction is unsuccesful (about 25% of cases) or when ese exist
previous postterm pregnancies with in utero fetal death.

Prognosis
The

rate of maternal, fetal and neonatal complications increases

exponentially with gestational age.
The primary maternal risk may be cesarean section with its possibilities to
favorise postpartum infection, hemorrhage from uterine hypotony,
prolonged hospitalization.
Maternal complications include trauma and postpartum hemorrhage from
the vaginal delivery of large babies. Vaginal side wall and cervical
lacerations are more common with instrumental deliveries of macrosomic
infants.

The complications cany the potential for urinary retention, fistula

formation, hemorrhage, infection and wound breakdown.

Neonatal complications from the postdate pregnancy include

postmaturity with placental insufficiency, birth trauma from macrosomia and
meconium aspiration syndrome.

Postmaturity represents the clinical condition of the infant in a

prolonged gestation. These fetuses are at increased risk for intruterine death.
Growth retardation subsequent to postmaturity is the result of uteroplacental
insufficiency from a small, aging, deteriorating placenta.

First, the placenta deprives the fetus of support for anabolic

processes. Fetal weight is reduced as the fetus energy stores in the adipose tissue
and liver. Diminished fetal plasma volume leads to oligoamnios. With further
deterioration the placenta loses respiratory function and the fetus faces asphyxiai
damage with possible stillbirth. Fortunately, long-term problems appear to arise
less often with postmaturity than other forms of growth retardation.

221

Although fetal growth can cease with postmaturity, a number of

fetuses, particularly males, continue growing and exceed 4,000g (25 to 30%).
Large infants frequently undergo prolonged labors and difficult deliveries and
have an increased risk of birth trauma.

Postdate pregnancy increases the risks for both fetus and mother.
Satisfactory outcome can be expected with appropriate pregnancy dating, fetal
surveillance, intervention when necessary and careful intrapartum and neonatal
management.

222

27. PLACENTA PRAEVIA

Definition

In placenta praevia, the placenta is located in the lower uterine

segment within the zone of effacement and dilatation of the cervix. Placenta
praevia constitutes an obstruction to the descent of the presenting part.

Frequency
The zygote that implants very low in the uterine cavity is likely to form a

placenta that at the outset lies in very close proximity to the internal
cervical os. The placenta so located usually migrates toward the fundus, or
it may remain in situ giving rise to placenta praevia.

Ultrasonic investigations of early pregnancies that subsequently

aborted have disclosed an unexpectedly large number of low-lying embryos.
Placenta praevia that becomes apparent clinically (by hemorrhage) is a
serious but not very common complication. Placenta praevia is diagnosed
about 1 in 200 deliveries (or 0.5/c). Contradictory statistics on the
incidence of the various degrees of placenta praevia mostly reflect the lack
of precision in definition and identification for the reasons already
discussed.

Only 20% are total (placenta over the entire cervix). About 90% of
cases will be parous. Among grand multiparas the incidence may be as high as
one in 20.

Placenta praevia is die most frequent cause of third trimester

bleeding.

Classification
A number of different clinical classifications of placenta praevia have been

proposed, all of which are based on the relationship of the placenta to the
cervix either prior to the onset of labor or at various stages of cervical
effacement and dilatation.
As the cervix dilates, the placenta will be drawn upward with the retracting
lower uterine segment. Late in labor, the placenta covers only part of the
opening.

223

We present an anatomical classification corresponding to the period

before the labor starts. Four degrees of the abnormality have been recognized:

2> low-lying placenta (laterally inserted placenta) in which the

placenta is implanted in the lower uterine segment so that the placental edge
actually does not reach the internal os but is in variable proximity to it;

> marginal placenta praevia, when the edge of the placenta is at

the margin of the internal o;

> partial placenta praevia. in which the internal os is partially

covered by placent;

>> total placenta praevia. when the internal cervical os is covered

completely by placenta (the placenta covers the os even when the cervix is fully
dilated, a situation which is also named "central" or "complete'* placenta
praevia).

This classification is made on the basis of findings at the initial

examination and may change in labor or as labor advances.

Etiology. Pathogenesis The reasons that the ovum implants in the

lower segment are not always obvious.

Defective decidual vascularization, the possible result of

inflammatory or atrophic changes (endometritis, hypoplasia, submucous myomas,
trauma) has been implicated in the development of placenta praevia.

Twin pregnancy, with its large placental bed, is prone to low

implantation of at least a part of the placenta.

Multiparity and advancing age increase the risk of placenta praevia.

The incidence of placenta praevia in women over 35 was 1 in 100 and for those
over 40 it was 1 in 50. Conversely, this incidence was 1 in 300 for women aged
20 to 29 (Parkland Hospital, USA, 1987-1988).

Prior cesarean sections or induced abortion increases the likelihood

of placenta praevia (fivefold increased incidence with a prior cesarean delivery).
The risk rises linearly with the number of prior sections.

Another contributory factor is an increased average surface area of a

placenta implanted in the lower uterine segment, possibly because these tissues
are less well suited for nidation.

Being a leading cause of third trimester hemorrhage, placenta praevia

presents itself classically as painless bleeding. Bleeding is thought to occur in
association with mechanical separation of the placenta from its implantation site,
either during the formation of the lower uterine segment or during effacement and
dilatation of the cervix in labor.
Uterus is unable to contract adequately to stop the flow of blood from the
open vessels. Another cause is rupture of poorly supported venous lake in
the decidua basalis that has become engorged with venous blood.

The source of bleeding is maternal blood and, in a little part, fetal

blood.

224

Placenta praevia may be associated with placenta accreta, or one of

its more advanced forms, placenta increta or percreta. The term placenta accreta is
used to describe any placental implantation in which there is abnormally firm
adherence to the uterine wall (placental villi are attached to the myometrium).

In placenta increta. placental villi invade the myometrium and in

placenta percreta they penetrate through the myometrium. The abnormal
adherence may involve all of the cotyledons or a single cotyledon.

Such abnormally firm attachement of the placenta might be

anticipated because of poorly developed decidua in the lower uterine segment.
According to S.L.Clark (1985), 5% of women with a placenta praevia also
had a clinically significant placenta accreta. For women with a prior
cesarean section, the incidence was about 25%.

Clinical findings and diagnosis

The most characteristic event in placenta praevia is painless hemorrhage

which usually does not appear until near the end of the second trimester or
after.
Frequently, bleeding has its onset without warning in a woman who had an
uneventful prenatal course. Occasionally, it makes its first appearance while
she is asleep and on awakening, she is surprised to find herself lying in
blood.

Fortunately, the initial bleeding is rarely so profuse as to prove fatal.

Usually, it ceases spontaneously, only to recur. In some cases, bleeding does not
appear until the onset of labor, when it may vary from slight to profuse
hemorrhage. The blood is bright red because it flows directly into the vagina from
the open sinuses just above the internal cervical os.
As the result of abnormal adherence, such as is seen with placenta accreta,
or an excessively large area of attachement, the process of placental
separation is sometimes impeded and then excessive hemorrhage is likely
after delivery of the infant.
Hemorrhage from the placental implantation site in the lower uterine
segment may continue after delivery of the placenta because the lower
uterine segment is more prone to contract poorly than is the body. Bleeding
may also result from lacerations in the friable cervix and lower uterine
segment.

Placenta praevia can be suspected from a history of painless bleeding

that begins during the last part of pregnancy. The reason for bleeding can be
determined only by examining the patient.
Abdominal examination
An exact diagnosis cannot be made by abdominal examination alone, but it
may provide suggestive information:

=> transverse lie and breech positions occur frequently with placenta
praevia;

225

 if the presenting part is high above the inlet and deviated anteriorly

or laterally and cannot be pushed into the pelvic inlet, placenta may be preventing
its descent.

Usually, the FHR is normal.

Vaginal examination

A sterile speculum examination should be performed to eliminate a

cervical lesion as the source of the bleeding.

A digital examination is never permissible unless the woman is in

an operating room with all the preparations for immediate cesarean section,
because the examination can cause toirential hemorrhage.

Such an examination should not be made unless delivery is planned

because it may cause bleeding of such a degree that immediate delivery becomes
necessary even though the fetus is immature.

After the fetus has reached a gestational age of 37 weeks, the

neonatal mortality rate is not greatly improved by further intrauterine
development. In such cases, the cause of vaginal bleeding may be ascertained by
pelvic examination but only under those conditions (in a operating room,
compatible blood available, an operating team ready to perform operation, a
pediatrician which can resuscitate the infant).
The simplest, most precise and safest method of placental localization is
provided by transabdominal sonography. Accuracies of as high as 98%
have been obtained. The use of transvaginal ultrasonography has
substantively improved diagnostic accuracy.

226

The concept of "placental migration" must be considered in ultrasonic

evaluation. As pregnancy advances, the lower uterine segment lengthens and the
placenta is drown upward with the enlarging uterus. The placenta will be normally
situated at term in almost all patients in whom an ultrasonic diagnosis of placenta
praevia is made during the early part of pregnancy. Differential diagnosis

Bleeding can be produced by benign or malignant lesions of the

cervix. These can be excluded during the course of the examination.

Endouterine bleeding causes, other than placenta praevia, include premature

separation of the normally implanted placenta, rupture of umbilical cord vessels,
premature labor. Treatment

To maintain a low materna! and infant mortality, the management of

placenta praevia must be planned individually for each patient.

Women with a placenta praevia may be considered as follows: =>

those in whom the fetus is preterm but there is no pressing need for delivery;
=> those in whom the fetus is reasonably mature: ==> those in
labor;

=> those in whom hemorrhage is so severe as to mandate delivery

despite fetal immaturity.

Management of the pregnancy complicated by placenta praevia and a

preterm fetus, but with no active bleeding, consists of delay in an environment
that provides safety for both mother and fetus. Hospitalization would be ideal.
However, the woman is usually discharged after bleeding ceased and the fetus is
judged to be healthy.

In this instance, the mother and her family must fully appreciate the
problems of placenta praevia and be prepared to transport her to the hospital
immediately if necessary.

When the pregnancy reaches the 37th week, the patient should usually
be delivered if evaluation indicates that the fetus is mature. Delayed treatment is
feasible only if the bleeding is slight and if compatible blood and facilities for
rapid treatment of hemorrhage are constantly available.

When the patient is to be delivered, vaginal examination, performed

with precautions outlined previously, will indicate the condition of the cervix,
presentation, type of placenta praevia, condition of the membranes so that the
proper method for delivery can be selected.

C
esare
an
sectio
n is
the
accep
ted
meth
od of
deliv
ery in
most
wom
en
with
place
nta
pracv
ia,
prima
rily
for
the
welfa
re of
the
moth
er.
Whe
n the
place
nta
lies
far
enou
gh
poste
riorly
that
the
lower
uterin
228

e
segm
ent
can
be
incise
d
trans
verse
ly
witho
ut
enco
unteri
ng
place
nta,
the
trans
verse
incisi
on is
prefe
rred.
Whe
n
place
nta
praev
ia is
anteri
or, a
vertic
al
uterin
e
incisi
on
may
be
safer.
In the coexistence of placenta praevia and accreta, other methods of
hemostasis are necessary:

=> oversewing the implantation site with chromic sutures;

=^> bilateral uterine artery ligation;

==> packing the lower uterine segment with gauze;

=> total abdominal hysterectomy.

The patient with total placenta praevia should be delivered by cesarean
section, even though the fetus is dead because the bleeding is profuse and
cannot be controlled.

If the fetus is dead, the cervix is soft and effaced, only a edge of
placenta can be felt and bleeding is minimal, vaginal delivery may be possible.
This is particularly true if labor has already started (induction is hazardous).

Vaginal delivery may also be possible in an occasional multipara with

a soft, effaced and partially dilated cervix and a minor degree of anterior placenta
praevia. If the membranes are ruptured, the fetal head will descend, exert pressure
against the placenta and compress the bleeding from uterine sinuses beneath it.
Vaginal delivery usually increases the hazard for the infant because
compression of the placenta by the presenting part obstructs fetal vessels. If
a large enough area of fetal circulation is eliminated, the infant will die of
anoxia. Electronic fetal monitoring is essential in patients who are allowed
to labor.
Vaginal delivery is most appropriate before the 28 th week when the baby has
little chance of surviving.

When the vaginal delivery is selected, there are several possible

methods for reducing maternal blood loss, but all are appropriate when the baby is
dead or has little chance of surviving:

>scalp traction with a long forceps (Willet forceps);

>when the breech presents and the cervix is partially dilated, one or
both legs can be pulled down, permitting the buttocks to tamponade the placenta.

Postpartum hemorrhage occurs more often because the lower segment

does not contract and control bleeding as well as the upper part of the uterus
and because the retained placental tissue are more frequent in placenta
praevia.

Supportive treatment. Prognosis

Lost blood must be replaced with blood. No other fluid will do. Maternal

mortality will be high if blood is not replaced promptly and adequately.

Plasma, glucose or saline solution may be used only as a temporary
measure while blood is being obtained.
A marked reduction in maternal mortality from placenta praevia has been
achieved since adequate transfusion and cesarean section were advocated
for its treatment. Maternal deaths are mostly from blood loss, thromboembolism or infectious complications.
The abandonment of hazardous vaginal maneuvers, the recognition of the
danger of injudicious vaginal examinations and the hospitalization of
patients at risk have virtually eliminated the principal maternal risk,
hypovolemic shock.
230

 The perinatal mortality rate associated with placenta praevia, in most

medical center?, has been 15-20%, or at least 10 times that of normal

pregnancy.

The principal causes of perinatal mortality are: >prematurity (a major

cause) and fetal growth retardation;
> intrauterine anoxia as a result of placental separation and prolapsed
cord;

>respiratory distress syndrome;

>exsanguination from placental injury;
> developmental anomalies (serious fetal malformations are more
common in placenta praevia).

28. RUPTURE OF THE UTERUS

Rupture of the pregnant uterus is a potential obstetric catastrophe and

a major cause of maternal death. In the category "uterine rupture'' are not included
cervical lacerations and accidental uterine perforations (abortificient maneuvers
or curettages).

Frequency

The incidence of uterine rupture may vary appreciably among

institutions. The frequency is related to antenatal care quality and to intrapartum
management characteristics.

Although the frequency of uterine rupture, from all causes, has

probably not decreased remarcably during the past several decades, the etiology
has changed appreciably and the outcome has improved significantly.

In a study of R.D.Eden (1986), from 1931 to 1950, incidence was 1

in 1280 deliveries compared with 1 in 2250 from 1973 to 1983. S.P. Rachagan
(New Zealand, 1991) reported an incidence of about 1 in 3,000 deliveries and
M.H.Rodriguez about 1 in 1650, in nearly 139,000 deliveries from Los Angeles
County (1989).

Etiology

Uterine rupture may develop as a result of preexisting injury or

anomaly, it may be associated with trauma, or it may complicate labor in a
previously unscarred uterus.

A. Uterine injury or anomaly sustained before current pregnancy :

# cesarean section or hysterotomy " previously repaired

uterine rupture 1. surgery involving * myomectomy the myometrium

i* cornual resection
in* metroplasty

232

 2.

coincidental >abortion with instrumentation

uterine trauma
>sharp or blunt trauma (accidents, bullets,
knives)

>silent rupture in previous pregnancy

3.

congenital pregnancy in undeveloped uterine

horn
anomaly

B. Uterine injury or abnormality during current pregnancy:

1.before delivery

A labor stimulations (oxytocin or PG)

^external trauma (excessive fundal pressure)

external version

A uterine overdistention (multiple

pregnancy, hydramnios)

delivery

fetal anomaly distending lower segment

(hydrocephalus) 2. during
* internal version, breech extraction

difficult forceps delivery

* difficult normal removal of placenta
* abnormal presentations
* contracted pelvis

*tumors involving the birth canal

*multiparity

^placenta increta or percreta ^gestational trophoblastic

neoplasia 3. utero-placental
-adenomyosis

pathology -^sacculation of entrapped

retroverted uterus
Kornual pregnancy Currently, the most common
cause of uterine rupture is separation of a previous cesarean section scar. Other
common predisposing factors to uterine rupture are previous traumatizing
operations or manipulations (uterine curettage, perforations).

Classification

Rupture of the uterus may communicate directly with the peritoneal

cavity, complete rupture, which include the entire thickness of the uterine wall.

Incomplete rupture is a laceration separated from peritoneal cavity

by the visceral peritoneum.
Complete ruptures may be classified as traumatic or spontaneous. These
ruptures usually occur during the course of labor.

Dehiscence of a uterine incision from previous surgery is usually an

incomplete or "occult" rupture, the separation does not involve all elements of the

233

previous uterine scar, the peritoneum overlying the defect is intact and bleeding is
absent or minimal.

The probability of rupture of a vertical uterine incision through the

body of the pregnant uterus is several times greater than that of a lower segment
scar and in about one third of cases the corporeal scar ruptures before labor.
Dehiscence of a lower segment cesarean section scar is much more
frequent than actual rupture. It is remarkable that these separated scars,
often called "windows" covered only by peritoneum, in many instances
appear to cause no difficulty in labor or after that.

Pathological anatomy
Rupture of the previously intact uterus at the time of labor most often

involves the lower uterine segment, especially at its left margin (because of
uterine dextroposition).

Although developing primarily in the lower uterine segment, it is not

unusual for the laceration to extend further upward into the body of the uterus or
downward through the cervix into vagina. At times, the bladder may also be
lacerated.
After complete rupture, the uterine contents escape into peritoneal cavity,
unless the presenting part is firmly engaged, when only a portion of the
fetus may be extruded from the uterus.
Incomplete ruptures frequently extend into the broad ligament. In such
circumstances hemorrhage tends to be less severe than in complete rupture
and the blood acumulates between the leaves of the broad ligament. The
bleeding results in a large retroperitoneal hematoma that may involve
sufficient blood loss to cause death.

With incomplete rupture, the products of conception may remain

within the uterus or assume a position between the leaves of the broad ligament.

Instances of uterine rupture have been observed in which

hemarrhage was slight. The rupture did not involve large arteries and the emptied
uterus contracted well after expulsion of the fetus and placenta into the peritonea!
cavity.
Clinical findings. Diagnosis
If rupture occurs during labor, the woman, usually after a period of

premonitory signs (abnormal hypertonic uterine contractions, suprapubic

pain and tenderness, anxious status), at the acme of a uterine contraction
suddenly complains of a sharp pain in the abdomen and may cry that
"something tore" inside her.
The so-called classical picture is that after these symptoms and signs have
appeared, there is cessation of uterine contractions and the patient, until
that point in intense agitation, suddenly experiences much relief. At the
same time, there may be external hemorrhage, although often it is slight.
The sudden appearance of gross hematuria is suggestive.
Other clinical elements are: disappearance of fetal heart tones, recession of
the presenting part, signs and symptoms of hypovolemic shock and
hemoperitoneum.
234

 Recent observations indicate that few women experience these classical

findings of uterine rupture. In still other women, the appearance is identical

to that of placental abruption. In others, rupture is unaccompanied by
appreciable pain and tenderness.

In some cases in which the fetal presenting part had entered the
pelvis with labor, there is loss of station detected by pelvic examination.
If the fetus is partly or totally extrauterine, abdominal palpation or vaginal
examination is helpful to identify the presenting part, which has moved
away from the pelvic inlet.

On vaginal examination, it is sometimes possible to palpate a tear in

the uterine wall through which the fingers can be passed into the peritoneal
cavity. In suspected cases, it is imperative that thorough examination be
performed by an experienced examiner before the suspicion is abandoned.

Sonography, performed on site, may be useful.

Uterine rupture due to obstetric trauma is usually not diagnosed until

after the infant's birth. The clinical picture depends on the site and extent of
rupture. Unfortunately, valuable time is often lost because the rupture was not
diagnosed at the time of the initial examination.

. Rupture of a cesarean scar

The current trend in some obstetrical units is to encourage a trial of labor in
anticipation of vaginal delivery in women who previously have been
delivered by one transverse cesarean section (this is not the case of our
clinic because we have the principle " once a section always a section") There is little information that deals with healing of cesarean section scars.
If the cut surfaces are closely apposed, the proliferation of connective
tissue is minima] and the normal relation of smooth muscle to connective
tissue is gradually reestablished, accounting for the occasional absence of
even a trace of a former incision.
The separation of the previous scar complicates about 1 in 200 trials
of labor. In most cases the separation is only a dehiscence and of little
consequence. However, ruptures may occur. Separation of a vertical scar is more
likely to result in severe hemorrhage with increased perinatal morbidity and
mortality.
A trial of labor following a previous cesarean section, especially of
the low transverse variety, would appear to be a safe option for the woman but the
safety is relative because significant morbidity still may accrue to both mother
and fetus even with assiduous observation during labor. Criteria for vaginal
delivery following previous cesarean section may include: => the patient
undergone only one previous cesarean section;
=> a low transverse uterine incision was used;
=> the original indication for cesarean was a cause not necessarily
recurring in subsequent pregnancies;
=> the postoperative course was benign;
=>the current pregnancy is not complicated by macrosomia,
malposition, multiple gestation or other conditions that would be likely to
preclude vaginal delivery.

Prevention of uterine rupture

235

Most of the cases of uterine rupture can be avoided by good obstetric

assessment and technique. Probably die most common error in judgement leading
to rupture is underestimation of fetal weight, resulting in traumatic delivery.

A good prenatal care and a correct execution of trial of labor are

important.
The most common technical error is the poorly supervised administration
of oxytocin during labor.

A frequent deficiency in operative technique is poor closure of a

cesarean section incision.

The indications, conditions and techniques in obstetrical maneuvres

must be strictly respected.

Treatment of uterine rupture

The life of the woman will depend most often on the speed and
efficiency with which hypovolemia can be corrected and hemorrhage controlled.

Whenever uterine rupture is diagnosed, it is mandatory that the

following functions be carried out immediately and simultaneously:

==> two effective, large-bore intravenous infusion catheters are

established and crystalloid solution, either lactated Ringer's or saline, is infused
vigorously;

=> type-specific whole blood is obtained in large quantities and its

rapid infusion is begun as soon as possible;

=^> a surgical team, including anesthesia personnel, is assembled to

perform suture or hysterectomy; there should be no delay in starting surgery;

=> pediatric personnel skilled in neonatal resuscitation are

summoned.

It is emphasized that hypovolemic shock may not be quickly

reversible until arterial bleeding has been surgically controlled. Blood must be
infused rapidly and the laparotomy begun. In desperate cases, compression
applied to the aorta may help to reduce the bleeding.
Hysterectomy is usually required, but in selected cases suture of the wound
may be performed. It is considered that total hystyerectomy is the surgical
procedure of choice, although transverse lower segment lacerations may be
dealt with adequately by repair of the injury.
In the presence of a large hematoma in the broad ligament, identification
and ligation of the uterine vessels can be extremely difficult (the ureter or
bladder can be injured).

Ligation of the internal iliac arteries reduces the hemorrhage

appreciably (in some women, pelvis vessel bleeding may continue even after
internal iliac artery ligation).
Complications.Prognosis

The complications of ruptured uterus are:

hemorrhage, circulatory collapse and shock;

disseminated intravascular coagulation;
postoperative infection, thrombophlebitis, peritonitis;
amniotic fluid embolus;
death (the maternal mortality rate is 10 to 40%);

236

 if the patient survives: pituitary failure (Sheehan syndrome),

infertility/sterility

vesico-vaginal fistula.
The chances for fetal survival are dismal and mortality rates in various
studies range from 50 to 75%.

If the fetus is alive at the time of the rupture, the only chance of
continued survival is afforded by immediate delivery, most often by laparotomy.
Otherwise, hypoxia from both, placental separation and maternal hypovolemia, is
inevitable.
Prompt diagnosis, immediate operation, the availability of large amounts of
blood and antimicrobial therapy have greatly improved the prognosis for
women with a rupture of the pregnant uterus.

237

 29.

FETAL DISTRESS

Definition

Fetal distress may be considered as a complex of signs indicating a

critical response to stress. It implies metabolic derangements-notably hypoxia and
acidosis-that affect the functions of vital organs to the point of temporary or
permanent injury or death.

Skillful monitoring will diagnose some degree of fetal distress

(perinatal jeopardy) in at least 20% of all obstetric patients.

Use of the word "distress" invocates any number of synonyms that

include "danger", "calamity", "suffering", "opression". The words "fetal distress"
are too broad and vague to be applied with any precision to clinical situations (for
example, some element of fetal distress is almost universal at some time during
normal human parturition).

Classification

Fetal distress may be chronic (during pregnancy) or acute (usually

developed during labor and delivery).

Prompt recognition of the symptoms of fetal distress and, when

necessary, decisive, well-planned intervention, are imperative for the reduction of
perinatal mortality and morbidity, especially to prevent permanent damage to the
central nervous system.

Unfortunately, the diagnostic criteria for fetal distress remain unclear

and the differential diagnosis must consider many possibilities.

Etiology

Factors which are involved during pregnancy

Chronic fetal distress implies an interval of fetal deprivation that

affects growth and development.

The distress may be caused by a reduction of placental perfusion, by

a placental abnormality or by deficient metabolism.

238

 Decreased placental perfusion may reflect any of the following conditions

in the mother (maternal causes):

vascular abnormality, as in hypertensive disease, preeclampsiaeclampsia or diabetes with pelvic vascular complications;
inadequate systemic circulation as in congenital or acquired heart
disease:
inadequate oxygenation of the blood as in chronic respiratory
diseases or by reason of residence at high altitude.
Chronic fetal distress due to placental abnormalities includes abnormal
inserted placenta, premature separation of normally implanted placenta,
placental insufficiency, premature placental aging and diabetes mellitus.
Possible fetal causes of jeopardy include multiple gestations, with possible
overdistension of the uterus and risk of premature delivery, as well as the
risk of twin to twin transfusion. Other fetal causes include : erythroblastosis
fetalis, postmaturity, congenital anomalies and infections, IUGR.

Other ovular etiological factors are : velamentous insertion of the umbilical

cord, hydramnios or oligoamnios, PSRM. Factors which act during labor
Excessive uterine contractions, often with negligible intervals of
relaxation, prevent appropriate uterine blood flow and oxygenation of the
fetal blood. Hypertonia may be induced by an injudicious use of oxytocin.

Hypotonic uterine dysfunction influence blood circulation from

intervillous space to maternal venous circulation.

Maternal causes of acute fetal distress include diverse aspects such

as decreased uterine blood flow (hypotension, shock, sudden heart failure) or
decreased blood oxygenation (hypoxia-hypercapnia).
Placenta and cord pathology include placenta praevia, abruptio placentae,
umbilical cord compression (knots, prolapse, loops), ruptured vasa praevia
or lack of sufficient placental reserve to tolerate labor (premature placental
aging, postmaturity).

Obstetrical maneuvers can represent a trauma when indications,

conditions and techniques arc not respected. Inappropriate use of drugs, during
labor, may have an unfavorable effect on fetus condition.

Physiopathohgy of fetal distress The actions of described factors can

induce against fetus 3 types of abnormal phenomena which maybe involved as
separate or associated:

chemical (hypoxia); ^
mechanical; infectious.
Fetal hypoxia
The major cause of cardiorespiratory depression is fetal hypoxia. The
fetus is entirely dependent on the mother for its supply of oxygen, which it obtains
from the maternal blood in the intervillous space.

Circulation of the blood through the placental sinuses is regulated by

the mother's arterial blood pressure and by the activity of the uterine muscle. Most
of this blood gravitates downward through the branching villi and leaves the
intervillous space by way of the venous openings at the base.

239

 Under normal circumstances, during a uterine contraction, the pressure

within the intervillous space is lower than the capillary pressure in the
placental villi, which is maintained by changes in fetal blood pressure.
This prevents the villi from collapsing and impending the flow of blood
through the fetal vessels and permits the exchange of materials back forth
between the fetal and the maternal circulations even during a contraction.

The fetal oxygen supply can be reduced by any of the following :

1.
Reduction in blood flow through the maternal vessels

The caliber of the arteries may be reduced by spasm in women with

hypertensive complications of pregnancy, thus limiting blood flow. It is estimated
that arterial blood flow can be reduced by as much as 50% in women with
hypertensive disease.
The flow of blood will also be impaired whenever the maternal systolic
blood pressure is lower than the amniotic fluid pressure. Fetal hypoxia is
likely to develop when maternal blood pressure levels fall below 60mm Hg.
2.
Reduction in blood flow through the uterine sinuses

Blood flow through intervillous space will be reduced if the veins or

arterioles are compressed over long periods of time by forceful, rapidly recurring
or prolonged uterine contractions. A reduction in maternal blood pressure will
have the same result.
3.
Reduction of the oxygen content of maternal blood

The available circulating maternal hemoglobin can be reduced by

profound chronic anemia or hemorrhage, thereby reducing the total oxygen
capacity.
4.
Alterations in fetal circulation

The circulation of blood through the vessels of the infant's body and
placenta is maintained by the fetal heart. Anything that alters normal cardiac
function will impair the circulation, as will compression of the umbilical cord.

Placental infarction or separation will decrease the total area

available for oxygen transfer from the maternal blood. If a considerable portion of
placenta is involved, the infant cannot survive.

Because of the continous passage of oxygen from the maternal blood

in the intervillous space to the fetus, the oxygen saturation of this blood resembles
that in the maternal capillaries.
Despite the relatively low P02, the fetus, normally, does not suffer from
lack of oxygen. The human fetus has a cardiac output considerably greater,
per unit of body weight, than does the adult.The high cardiac output, the
increased oxygen-carrying capacity of fetal blood and a higher
hemoglobin concentration than in adults compensate effectively for the
low oxygen tension.

At any given oxygen tension and at identical pH, fetal erythrocytes,

that contain mostly hemoglobin F, bind more oxygen than do erythrocytes that
contain, nearly all, hemoglobin A.

Fetal erythrocytes that are formed late in pregnancy contain less

hemoglobin F and more hemoglobin A than do the cells formed earlier. At term,
about three fourths of total hemoglobin is normally hemoglobin F.
240

Fetus has metabolic exchanges with low intensity and makes little
efforts to realise the thermoregulation.

The primary response of the healthy fetus to acute hypoxemia is a

profound stimulation of the vagus nerve secondary to the hypertension and
peripheral vasoconstriction. In addition, a stimulation of catecholamine secretion
occurs and the percentage of the cardiac output directed to the brain and
myocardium is increased.

Blood flow to the adrenals is also maintained or even increased and

the abundant stores of catecholamines play a critical role in maintaining
ventricular contractility.

Fetal cardiac muscle relies on its glycogen stores for continued

glycolysis during oxygen deprivation. Severe hypoxemia results in a fall in
cardiac output presumably due to decreased myocardal performance secondary to
the reduced delivery of oxygen to the heart.

Chronic placental insufficiency, with fetal growth retardation

secondary to reduced matemal-piacental perfusion is also associated with elevated
fetal levels of catecholamines which determine the circulatory changes to maintain
cerebral oxygenation.

As fetal adaptation reaches its limit, the fetus becomes metabolically

acidemic and these circumstances are associated with specific changes in FHR.

The changes in fetal metabolism caused by fetal hypoxia are

primarily mediated via increased catecholamine stimulation (S.B.Hooper,1995).
Fetal blood glucose concentrations rapidly increase to a maximum within 2h of
inducing fetal hypoxemia. This increase is due to an inhibition of insulin release,
leading to a reduction in glucose uptake and to increased glucose production and
release by fetal tissues, principally the liver.

Because the transfer of glucose from the mother to the fetus is

determined by the maternal-fetal glucose concentration gradient the increase in
fetal blood glucose concentrations, during hypoxemia, should lead to a decrease in
fetal glucose uptake from the mother.

The increase in fetal blood glucose concentrations induced by fetal

hypoxemia is not sustained if the period of hypoxemia is increased.

One of the most significant changes is the increase in circulating

lactate. Concentrations result from an increase in anaerobic metabolism of
glucose by hypoxic fetal tissues. Because of the associated metabolic acidosis,
the increase in fetal blood lactate concentrations has important consequences. A
reduction in pH reduces the affinity of oxygen for hemoglobin and, therefore,
reduces the oxygen-carrying capacity of blood.
There is gradual development of a metabolic acidosis, primarily as a result
of the accumulation of lactate.- This, probably, represents, also, anaerobic
glycolysis in those vascular beds where oxygen supply is limited.

At more severe degrees of asphyxia, when an adequate compensatory

increase in blood flow to the organs no longer occurs, the oxygen consumption
can no longer be maintained. This stage most likely precedes the final
bradycardia, hypotension and death in a relatively short time.

Mechanical injury

241

 Birth trauma may cause intracranial hemorrhage. The head of the fetus may

undergo appreciable molding during passage through the birth canaL The
skull bones, the dura mater and the brain itself permit some alteration in the
shape of the fetal head without untoward results. The dimensions of the
head are changed, with lengthening especially of the occipitofrontal
diameter of the skull.

Bridging veins from the cerebral cortex to the saggital sinus may tear
as the consequence of severe molding and marked overlap of the parietal bones or
of difficult forceps delivery.

Less common are ruptures of the internal cerebral veins, the vein of
Galen at its junction with the straight sinus. Compression of the skull can stretch
the tentorium cerebelli and may tear the vein of Galen or its tributaires.
The elimination of difficult forceps operations, the use of cesarean section
when there was cephalopelvic disproportion and the correct management of
breech delivery all contributed significantly to a reduction in the incidence
of all birth injuries, including intracranial hemorrhage.

Fetal infection
Bacteria, viruses or parasites may gain access transplacental^ or they may

cross the membranes even though intact. Fetal infections may develop early
in pregnancy to produce obvious stigmata at birth.
Conversely, organisms may colonize and infect the fetus during delivery.
Preterm rupture of membranes, prolonged labor and vaginal examinations
may increase the risk of neonatal infection. Infection occuring less than 72
hours of age is usually caused by bacteria acquired in utero or during
delivery.
The same vaginal organisms that lead to maternal infection can result in
congenital pneumonia, sepsis or meningitis.

Diagnosis A.

During pregnancy
Clinical findings
The first and most important step is to obtain a good history. The highest
risk of fetal distress or perinatal death usually occurs among those mothers
who suffer from multiple problems of social, biological and pathological
origin.

Some studies demonstrated the cumulative risks of adverse maternal

age, parity (more than 5), social class, smoking habits, complications of
pregnancy (such as preeclampsia), chronic illness, vaginal bleeding, diabetes etc.
The fetal heart tones can be heard first with an ordinary stethoscope at
about the eighteenth to twentieth week, low in the midline. The normal rate
varies from 120 to 140 beats/minute. However, rates of 90 to 150 are not
uncommon or necessarily abnormal.

242

Persistent periods (more than 10 minutes) of heart rate between 140

and 160 bpm is classified as a slight tachycardia, between 160 and 180 bpm as a
severe tachycardia and more than 180 bpm as a grave tachycardia.
Periods of fetal heart rate below 120 bpm are known as fetal bradycardia
(slight, between 120 and 100 bpm and very severe, less 100 bpm).
Persistent intervals of tachycardia or, especially, bradycardia are likely to be
associated with hypoxia.

Heart rate variability represents the . interplay between the cardioinhibitor

and cardioaccelerator centers in the fetal brain stem. It is unusual for a heart
rate under normal nervous system control to be steady at any one consistent
rate. Rather, there is considerable variation or short-term variability on a
beat-to-beat basis, usually ranging from 3 to 8 bpm around an imaginary
average heart rate.

The presence of normal fetal heart rate variability is one of the best
indicators of intact integration between the central nervous system and heart of the
fetus.
Fetal movement is one of the first objective signs of fetal life. These
movements are felt by the mother for the first time (quickening) between
the sixteenth and twentieth weeks of gestation and represent one of the
elements used for estimation of gestational age.

Many clinicians have used the mother's perception of fetal

movements as an index of fetal health. Most of the studies applying fetal
movements to clinical management have relied on the mother's subjective
perception. The accuracy of this method is variable and should be used only as an
alerting sign to the physician of the need for further antenatal fetal evaluation.

Meconium appearance in the amniotic fluid has long been thought

to be a sign of fetal distress. The actual significance of meconium passage in the
light of recent advances in antepartum and intrapartum surveillance techniques is
controversial. This passage, in the absence of abnormal FHR patterns, results in an
extremely low incidence of poor outcome.

Paraclinical tests

Ultrasound

The literature contains many tables and nomograms that describe the
normal growth of various fetal dimensions. Among the most commonly measured
dimensions are crown-rump length, biparietal diameter, abdominal circumference
and femur length.

A recurring theme in the potential practical applications of Doppler

ultrasound is the search to distinguish normal from abnormal pregnancies. Of
particular interest have been predictions of growth retardation, fetal hypoxia and
fetal distress.

A test to predict fetal hypoxia before or during labor would be of

great value and attempts have been made to apply Doppler velocimetry in this
capacity. Unfortunately, velocimetry has not yet been proved to be a good
predictor of antepartum or intrapartum fetal condition because of wide random
variations in results.
243

Biophysical profile

F.A.Mannin (1980) proposed the combined use of 5 fetal biophysical

variables as a more accurate means of assessing fetal health than any single
variable used alone. Required equipment include a real-time ultrasound device
and Doppler ultrasound to record FHR. The biophysical variables are:
FHR acceleration
fetal breathing
fetal movements
fetal tone
amniotic fluid volume

The nonstress test, fetal breathing movements and amniotic fluid volume
components are more predictive of pregnancy outcome. Amniocentesis

Amniocentesis is the most commonly performed invasive test for

prenatal diagnosis of genetic disease. It is also utilized for measuring other
markers of fetal health.

Amniocentesis, for prenatal diagnosis, has most often performed at

16 to 18 weeks' gestation, when it is likely to exist sufficient fetal cells to allow
successful culture. Cultured amniotic fluid cells can be utilized for cytogenetic
studies as well as enzyme and DNA analysis.

Since its development beginning in the early 1970s, chorion sampling

has become a widely accepted first-trimester alternative to amniocentesis for
prenatal diagnosis.

Amniotic fluid creatinine increases gradually during pregnancy as a

result of the increasing fetal muscle mass and fetal kidney maturation. Creatinine
levels of 2mg/l 00ml or more have been accepted as representing maturity.

Bilirubin in the amniotic fluid progressively decreases with

advancing gestational age in pregnancies not complicated by Rh disease. The
disappearance of its peak at 450um in spectrophotometry analysis at or after 36
weeks has been considered to represent maturity.

Cells are shed into the amniotic fluid from the fetus and the fetal
membranes. As pregnancy progresses, the cells containing lipid, which probably
arise from the fetal epidermis, increase in number. These cells can be identified by
staining them with blue Nile sulfate. When they exceed 20% of the total, it has
been considered a sign of fetal maturity.
The determination of the L/S ratio has proved to be the main technique for
measuring surfactant in the amniotic fluid. In normal pregnancies,
progressive changes in L/S ratio correlate well with gestational age.

The reliability and dependability of L/S ratio values equal or more

than 2 as evidence of functional pulmonary maturity have been confirmed. The
determination of phosphatidylglycerol may represent the most specific test for
lung maturity.
Percutaneous umbilical blood sampling has revolutionized the fields of
fetal physiology, diagnosis and therapy. Although genetic indications are
expanding most rapidly, diagnostic and treatment techniques for fetal
hypoxia, isoimmunization and infection are also being developed.

244

 Alphafetoprotein (AFP) is a glycoprotein synthesized by the fetus early in

gestation by the yolk sac and later by the gastrointestinal tract and liver. The
concentration of AFP is highest in both fetal serum and amniotic fluid
around the 13 th week and after, both fetal serum and amniotic fluid levels
normally decrease rapidly. The elevated levels suspect the possibility of a
neural-tube defect.
The determination of plasma or urinary estriols has been the most common
biochemical method used in the antenatal assessment of fetal well-being
during the past decades.

IUGR is associated with low concentrations of unconjugated and

total plasma E3 and reduced urinary E3 excretion. Pregnancies complicated by
postdatism can also be managed with the help of E3 determinations. Only serial
determinations can give adequate information about the status of the fetoplacental unit.

Human placental lactogen (HPL) concentration is significantly

correlated with the functional mass of the placenta. A value in "fetal danger zone"
(less than 4um/ml after 30 weeks gestation) indicates reduced placental function
or the presence of a small placenta which may indicate that a severely
compromised intrauterine environment may exist for the fetus.
The most commonly used tests in antepartum fetal surveillance are the
contraction stress test, the nonstress test and the biophysical profile.
CST is based on the response of the fetal heart rate to uterine contractions.
It relies on the premise that when fetal oxygenation is only marginally
adequate with the uterus at rest, oxigenation will be transiently worsened by
uterine contractions. The resultant intermittent fetal hypoxemia will, in turn,
lead to the fetal heart rate pattern of late decelerations.
In the fetus, as in the adult, the heartbeat is derived from an autorhythmic
atrial pacemaker. Undei normal conditions, the fetal heart rate is increased
or decreased on a beat-to-beat basis by autonomic influences mediated by
sympathetic or parasympathetic (vagal) impulses from centers in the brain
stem.
The NST is based on the premise that the heart rate of a fetus that is
not acidotic or neurologically depressed will temporarily accelerate with fetal
movement. Loss of reactivity is associated most commonly with a sleep cycle but
may result from any cause of central nervous system depression, including fetal
acidosis.

Biophysical profile testing consists of an NST with the addition of

four observations made by real-time ultrasound (1. reactive NST; 2. fetal
breathing movements; 3. fetal movement; 4. fetal tone; 5. amniotic fluid volume).
With this method, a score of 2 (normal) or O (abnormal) is assigned to each of the
five observations. A score of 8 or 10 is normal. A score of 6 is considered
equivocal (fetus should be rested in 12-24 hours). A score of 4 or less is abnormal.

The primary indication for biophysical antepartum tests of fetal wellbeing is a pregnancy at increased risk for antepartum demise (decreased fetal

245

movement, hypertensive disorders, diabetes mellitus, IUGR, postdate pregnancy,

isoimmunization, chronic renal disease, previous unexplained fetal demise etc).

B. During

labor Clinical
recognition

The possibility of fetal distress is suggested by :

auscultation of tachycardia, bradycardia or cardiac

arrhythmia passage of meconium by the fetus in vertex
presentation

fetal movement
modification Laboratory tests
Evaluation of acid-base status
The use of acid-base evaluation of the fetus is of clinical importance
because fetal pH status is directly related to tissue oxygenation, The pH is
affected both by short-term (respiratory) and long term (metabolic) changes.
The metabolic component of pH relates to the concentration of metabolic
acids (lactate and pyruvate) which result from anaerobic (in hypoxia state)
metabolism.

Technique of fetal scalp blood sampling is a simple maneuver. The

following are guidelines for pH measurements :

normal: 7.25 to 7.35

border line: 7.20 to 7.25
abnormal: below 7.20. Fetal heart rate
patterns
Periodic changes in fetal heart rate during labor have been classified
according to their relationship to uterine contractions.
In early decelerations, the onset of the decrease in rate begins with the
onset of the contraction and normal rate resumes as the uterus relaxes.
These decelerations are reflex, related to pressure on the fetal head and are
mediated by the vagus. They are not associated with a poor outcome.
In variable decelerations there is no constant relationship of the
deceleration to contractions. Variable decelerations are caused by cord
compression. They are reflex changes characterized by a sudden drop in the
FHR and a rapid return to normal. Whether this will cause a problem for the
fetus depends on the length of time the circulation is disturbed and the
reserve of the fetus.
The late deceleration begins after the contraction starts and recovery is
prolonged. These modifications are a sign of utero-placental insufficiency.
There is agreement that heart rate monitoring is based on clinical and
laboratory studies demonstrating that fetal hypoxia reliably produces
changes in FHR patterns.
The most widely used means (worldwide) of fetal assessment during labor
is the stethoscope. Even the most meticulous auscultatory monitoring is
subject to considerable human error.The fetal heart tones should be
recorded for 30 seconds immediately after a uterine contraction at least
every 30 minutes during the first stage of labor, every 15 minutes during the
second stage.
246

 There is some evidence that auscultatory monitoring will suffice for

determining the effect of labor on the fetus in situations where no risk

factors have been identified. Currently, electronic FHR monitoring may be
accomplished externally (from the maternal abdominal wall) or internally
(directly from the fetus). The commonest external method demonstrates
FHR by pulsed ultrasound (Doppler ultrasound). Direct fetal
electrocardiography and phonocardiography are other methods more
difficult technically than the first.

The fetal electrocardiographic impulse, obtained directly, potentially

provides the greatest amount of accurate information about FHR patterns.

Prolonged or increasingly more severe variable deceleration is a

warning sign. Late deceleration of the FHR, which may or may not be coupled
with accelerations, is of great importance because the presumed cause of this
pattern is the inability of the placenta to provide necessary exchange for normal
fetal metabolism.

Identification of the high-risk pregnancies The major issue in risk

identification is to understand that pregnancy is not physiologic since it can
produce death and increase the incidence of permanent damage to the survivors.
The prenatal care is the single most important medical issue in trying to
alter pregnancy outcome. Woman with a high risk pregnancy must be
included into a health care system with a group of concerned physicians.
The primigravid patient, in particular, is at high risk and should be seen
more frequently for prenatal care than the muciparous patient, especially
after 20 weeks gestation. A satisfactory interval rate should be every 2 or 3
weeks.

The maternal conditions in present pregnancy relate to broad

categories such as:

socio-economic status, age, general metabolic

status; reproductive tract abnormality;
blood incompatibility, uterine bleeding, infections;
fetal position, placenta and membranes;

cardiovascular disease etc.

The important point is to recognize that even though these are identified
under different categories, a woman who has a perfectly normal antepartum
course may for the first time develop an intrapartum problem, or,
conversely, she could have a high risk antepartum problem that could be
corrected and she would then have a normal intrapartum course.

Management of fetal distress

In an effort to reduce morbidity and mortality secondary to intrapartum

hypoxia, it seems reasonable to use and integrate all available fetal datacollecting systems.

As fetal heart rate monitoring is less able to identify the fetus that is
truly in distress, it appears justified to add intermittent fetal capillary blood
collection for acid-base values to supplement FHR monitoring.
247

Initial therapy for fetal distress is divided into four basic maneuvers:
1.
Position of the patient (supine to lateral)
A change of the mother's position may relieve pressure on the umbilical
cord. Uterine function may also be improved with the patient in a lateral
position (uterine blood flow is increased).
2.
Correct hypotension

The position change discussed above will usually correct the supine
hypotensive syndrome. Rapid administration of fluids intravenously will help to
restore the parturient's arterial pressure and increase blood flow in the intervillous
space.
3.
Decrease uterine activity

One of the more common causes of late deceleration is overuse of

oxytocin. Therefore, discontinue the administration if stimulation is in progress.
Moreover, oxytocin should not be given except by the intravenous route.
Decreased uterine activity permits better placental perfusion. 4. Induce maternal
hyperoxia

The administration of 02 to the mother has often been suggested

when the supply of 02 to the fetus is insufficient (fetal hypoxia), regardless of
whether this insufficiency occurs antepartum or intrapartum.

The principle of supplying the mother an overdose of what the fetus

is lacking appears to be simple and logical. However, during the last few years
opinions have been divided on the advantages and disadvantages of 02
administration in pregnancy and during labor.

Oxigen therapy should be administered in order to ameliorate the

fetal condition in labor but the other important treatments (such as change in
position, correction of hypotension, discontinuation of oxytocin, tocolysis, vaginal
examinations for prolapsed cord or termination of labor) have to be executed
without delay.

Although attempts may be made to correct acid-base by

administering sodium bicarbonate to the mother during labor, the transfer of fixed
alkali is relatively slow, and treatment is therefore unlikely to be of use when
given to the mother whose fetus is hypoxic and acidotic.

If the acidosis is severe, the "infant should be promptly delivered for

primary corrective therapy. Nevertheless, if maternal acidosis is the cause of fetal
acidosis, administering bicarbonate to the mother may be useful for both patients.

Hypertonic glucose may be administered when there is maternal

deprivation acidosis or hypoglicemia.
If the situation worsens, if the signs of probable fetal distress persist for 30
minutes, or if there is fetal distress despite conservative treatment,
immediate delivery is mandatory. Obstetric judgement must dictate how the
delivery will be accomplished in accordance with the presentation, position,
dilatation of the cervix, clinical course of labor. Obstetrical conditions to
perform cesarean section may also be checked.

248

If cesarean section is chosen, it must be done rapidly. The use of the

operation may be justifiably increased for fetal distress, diabetes mellitus,
isoimmunization, cord accidents, fetopelvic disproportion, previous uterine
operation, placenta praevia, abruptio placentae, abnormal presentations, cardiac
disorders classes I-IV, PEL

249

30. INTRA - UTERINE DEATH

Definition

The term intra-uterine death embraces cases before the 28th week of
pregnancy (missed abortion) and those occuring later which result in stillbirth.
A missed abortion is defined as retention of dead products of conception, in
utero, for several weeks. The rationale for an exact time period is not clear
and it serves no useful clinical purpose.
Maceration is a destructive aseptic process which first reveals itself by
blistering and peeling of the fetal skin. Macerated stillbirth nearly always
indicates death in pregnancy and not in labor and in most cases is caused by
anoxia.

Etiology

The causes of missed abortion are the same with spontaneous

abortion.
Among the causes of stillbirth, one of the commonest is preeclampsia
because of the hypertensive spasm of the vessels supplying the maternal
placental site. Chronic hypertension operates in like fashion.

Chronic nephritis, fortunately an uncommon complication, has a very

bad prognosis for the fetus who frequently dies from placental infarction and
anoxia before even the stage of viability is reached.

Hyperpirexia can affect the fetus directly.

Diabetic pregnancy and hemolytic disease are important causes too.

Fetal malformations may cause death before, during or after labor,
according to their nature and extent.

Postmaturity and placental insufficiency may act together.

Syphilis, a traditional cause, has been practically eradicated.

Other possible causes are : premature separation of normally inserted
placenta, placenta praevia, velamentous insertion, knots, loops, prolapse of
the umbilical cord, hydramnios, multifetal pregnancy.

250

 Diagnosis

In the typical instance of missed abortion, early pregnancy appears to

be normal, with amenorrhea, nausea and vomiting, breast changes and growth of
the uterus.
After fetal death, there may or may not be vaginal bleeding or other
symptoms denoting a threatened abortion. For a time, the uterus seems to
remain stationary in size, but mammary changes usually regress.

Thereafter, it becomes apparent that the uterus not only has ceased to
enlarge but also has become smaller. Many women have no symptoms during this
period except persistent amenorrhea.

After the 20,h week of pregnancy, if the accident occurs, the absence
of fetal heart sounds remains the mainstay of clinical diagnosis, supported by lack
of fetal movements and regression of uterine size.

Ultrasound diagnosis of death is recognised by an absent fetal heart

pattern. An attempt should always be made to determine the cause of the fetal
death because this may dictate further management.

Problems associated with the retained dead fetus

Three potential problems are associated with retention of the dead

fetus, these being infection, maternal distress and coagulopathy.

Infection is a potential risk. If the membranes remain intact, the risk

of infection remains very low.

Maternal psychological distress may be managed.

The coagulopathy is considered to result from fibrinogen

consumption following the release of thromboplastin from the retained products
of conception. Fibrinolysis may contribute to the bleeding diathesis as a
secondary event.

A prospective study indicated that gross disruption of the maternal

coagulation mechanism rarely developed before less than one month after fetal
death.

Typically, the fibrinogen concentration falls to levels that are normal

for the nonpregnant state, and in some cases the decrease continues to reach
potentially dangerous concentrations of lOOmg/dL or less.

Simultaneously, fibrin degradation products are elevated in serum.

The platelet count tends to decrease.

Correction of coagulation defects has been accomplished using

heparin under carefully controlled conditions in women with an intact circulation.
Heparin, appropriately administered, can block further pathological consumption
of fibrinogen and other clotting factors and thereby allow spontaneous repair of
the coagulation mechanism.

Treatment of active hemorrhage (if it is encountered at delivery)

consists in blood and lactated Ringer solution, initially administered.

Pregnancy termination with dead fetus

Near term, intravenously administered oxytocin is usually effective when

given in a dose that stimulates uterine activity. Remote from term, however,

251

it is less likely to prove effective unless given in high concentration and on

more than one occasion.

PGE2 given as a 20mg suppository to induce labor in pregnancy

complicated by fetal death is another option.

The intra-amniotic injection of hypertonic saline is not recommended

for evacuation of dead products of conception because the volume of amniotic
fluid is often reduced and coagulation defects may be induced or enhanced by this
solution.
Oxytocin should be used for induction of labor when cervix is favourable
(Bishop's score is more than 4) which generally equates to an advanced
gestation (>35 weeks). Intensive estrogen therapy, sometimes, succeeds
supposedly sensitising the uterus.

In the presence of a dead fetus cesarean section may be indicated in:

placenta praevia of a major degree;
severe cephalo-pelvic disproportion; previous cesarean section;

transverse presentation and no conditions to perform

version.

In some cases, hysterectomy is mandatory.

252

31. ANTENATAL CARE

Introduction

Pregnancy is a normal physiological state, not a disease state. It is

important for the physician to be familiar with the normal as well as with the
abnormal changes caused by pregnancy.

Prenatal care is intended to ensure:

that the mother reaches the end of pregnancy as healthy as, or even
healthier than she was at the outset;
that any physical or psychological problems are detected and treated.
Now the mother has the opportunity to discuss her anxieties and fears about
pregnancy and the right to be informed about proposed procedures;
that any complication of pregnancy is either prevented or early-detected
and managed adequately;
that the couples are prepared for childbirth and childrearing (including
receiving information about diet, childcare and family planning).
Antenatal care should be provided by family doctors as well as obstetric
specialists, helped by trained nurse-midwives who can play a major role in the
hospital outpatient obstetric care.
It is very important to establish a good relationship between the patient and
her medical advisers: doctor and midwife.
The goals of antenatal care are:
1)
- the diagnosis of pregnancy, calculation of the gestational age and
the
estimated date of confinement (EDC);
2) - the prognosis for the present pregnancy;
3) - the prognosis for delivery;
4) - the prognosis for the puerperium, the newborn and lactation;
5) - the prognosis for the future pregnancies.

The technique of antenatal care

a) The first antenatal ca*^ V'S-ff"

Ideally, each pregnant woman should be seen first before the 10 th

week of pregnancy. The advantages of this early visit are that a baseline can be

253

obtained, against which the physiological changes occurring in pregnancy

can be assessed and any abnormalities can be noted and treated before they have a
detrimental effect.
At this first visit, several matters are considered and the findings carefully
recorded:
A.
- A comprehensive history;
B.
- Physical examination;
C.
- Routine laboratory tests.

b) Visits up to term

The usual recommendation is that a normal pregnant woman should

be seen every 4 weeks up to the 28th week of pregnancy, every 2 weeks up to the
36th week and weekly from then till the baby is delivered. Patients who are
identified as being at "higher risk" require to be seen more often.

At each of these visits the examination consists of:

>- a general assessment;

> an assessment of the weight gain; up to 4-5 kg before the 20 th week of
pregnancy and after that a gain of 0,5 kg weekly are considered "ideal";

> an estimation of the woman's blood pressure. Since most normal

women have a blood pressure below this level, a systolic reading above 140 or a
diastolic reading above 90 are considered abnormal. But it is of great help to
know the expectant mother's pre-pregnancy blood pressure or at least the values in
the first trimester of pregnancy;

5> an obstetrical examination consisting of measuring the height of

the fundus of the uterus, noting the time of "quickening" and the fetal movements
and after the 28th week, checking the lie, the presentation and the position of the
baby and performing the auscultation of the fetal heart. At about the 37 th week of
pregnancy the pelvic assessment is best made by the obstetrician;

> the repeating of certain laboratory tests.

A. - History

I. - The history of present pregnancy and the calculation of the

estimated date of confinement (EDC)

The date of the first day of the last menstrual period (LMP) is
recorded and the patient is questioned about her menstrual cycle. If this is

of normal duration (25 to 34 days), it is easy to calculate the estimated

date of the childbirth. This calculation relies on the fact that the average
duration of
pregnancy is 266 days from the conception and 280 days from the first day

of die last menstrual period. Using Naegele's rule, the CDC is calculated by
adding 9 months plus seven days. This calculation is unreliable in women
with irregular menstrual cycle, in those using contraceptive pills who get
pregnant in the first postpill cycle ( as the ovulation may be delayed ) and
in women who are unncertain about their LMP.
254

In these cases, if the clinical examination is inconclusive, an

ultrasound examination should be made. Some obstetricians advise routine
ultrasound screening of all antenatal patients.

II.- Identification of risk factors

The goals of prenatal care are a healthy mother and a normal infant.
Thus, early identification and management of risk factors are essential so that
long term sequelae can be averted. The first task in risk identification and
management is a thorough historical assessment and, continuous assessment for
acute problems is imperative since many desease states can be unmasked by
pregnancy.
Nutrition

The pregnant woman of average weight requires about 2400 cal daily
and her diet must include:
- 70-100 g of animal and vegetable proteins containing all the essential
aminoacids;
- 300-500 g of carbohydrates as the first main source of energy;
- 1000 g of lipids, source of energy, including certain essential unsaturated fatty
acids, which the human is unable to synthesize, and the fat-soluble vitamins;
- minerals, essential for the normal metabolic processes: sodium (Na), potasium
(K), calcium (Ca), magnesium (Mg), phosphorus (P) and iron (Fe) and trace
elements; amongst these, only the iron defficiency is common;
- water and fat-soluble vitamins (vit D-400 u, daily).

The only supplements required are iron, vitamin D and folic acid.

Studies have implicated maternal folate defficiencies in several

reproductive problems as abruptio placentae, pregnancy-induced hypertension and
some fetal abnormalities such as neural cord defects.

Mothers who are underweight are at increased risk for: perinatal

morbidity and mortality, low birthweight infants, preterm delivery.

Obesity presents too a medical hazard to the pregnant woman and the
complications that are more likely to develop are: hypertension, diabetes, wound
complications, thromboembolism.

Environmental and ocupational factors

O Low socio-economic status is related to an increased risk of

perinatal morbidity and mortality, i - . ':

O Employment may be associated with an increased incidence of

preterm labor, especially for women in physically demanding or stressful jobs.

O Addiction to tobacco, drugs and alcohol leads to an increased risk

for: spontaneous abortion, prematurity, fetal death, low birthweight, etc.
Moreover, a pattern of abnormalities known as the fetal alcohol syndrome
including cranio-facial defects, limb and cardio-vascular defects, growth and
mental retardation, manifests in varying degrees of severity in the fetus. Mothers
who smoke have smaller infants ( average of 2550 g).
Medication

255

Any administrated drug reaches the fetus, therefore, if administrated, its

advantages must outweight the risks. General history

1). Family history. There seems to be a familial tendency for the

developement of multiple births, congenital abnormalities, diabetes, etc. 2). Age
is an identifiable risk factor, as:
maternal age less than 20 years increases the risk for premature birth,
fetal deaths, preeclampsia;

maternal age over 35 years increases the risk for first trimester
miscarriage, genetically abnormalities, maternal and fetal death, medical
complications, antepartum bleeding, preterm labor.

3). Medical history includes: chronic hypertension, cardiac diseases, renal

diseases, diabetes, venous thromboembolic disorders, infectious diseases, such as
rubella, syphilis, hepatitis B and gonon'hea, but also those with cytomegalovirus,
Heipes, Toxoplasmosis, HIV etc. All viral infections may induce abortion,
stillbirth, congenital anomalies. 4). Obstetric history should include:
a history of repeated spontaneous or induced abortions, knowing that
cervical trauma may place a woman at an increased risk for spontanous abortion,
incompetent cervix, preterm delivery;
a history of full term and premature deliveries, including the route of
each delivery. Special attention must be paid to noting a history of high parity
because of the increased risk for pueiperal hemorrhage, multiple gestation,
placenta praevia.
The length of each previous pregnancy as well as the sex and the weight of
the fetus must be recorded.
Complications of previous pregnancies and delieveries (such as premature
labor, premature rupture of membranes, shoulder dystocia, fetal or neonatal
death, perinatal morbidity, gestational diabetes and pregnancy-inducedhypertension) as well as abnormal occurrences in the puerperium of
previous confinements (such as postpartum hemorrhage, venous
thrombosis) and even whether the babies were breast-fed or not, must be
noted too.

B. - Physical examination

General examination should include an evaluation of the pregnant

woman's height, weight, blood pressure, eye fundus, breasts, heart, lungs,
abdomen, extremities and current nutritional status.
Pelvic examination

The speculum examination permits visualization of the vagina and

the cervix and the evaluation of the discharge and the cervical lesions by
performing a Pap smear.

Bimanual examination of the pelvis and the uterus will assess the
size of the uterus, the presentation and the clinical pelvimetry, and will exclude
tumours of the uterus, ovaries or of the bony pelvis.

Abdominal examination allows the ongoing evaluation of the fetal

growth, position and status.

256

C - Routine laboratory tests The following tests must be performed at the

first visit: => Blood: hemoglobin concentration (normal 10,5-15 g);
hematocrit (normal > 35%);

MCV and MCH, if the patient is from southern a

European,
African or Asian
country; ABO and Rhesus group;
Rh antibodies, if Rhesus negative;
irregular antibodies;
VDRL or similar, to exclude syphilis;
hepatitis B surface antigen (HBS Ag);
anti-rubella antibodies;
blood sugar;
=> Urine HI* urinalysis (specific gravity, protein, sugar, cells);
mi*- culture for bacteriuria; => Cervical cytology and culture from the
vaginal discharge. Further tests in pregnancy for all women: => irregular
antibody test is repeated at 36 weeks; => urinalysis is repeated monthly;
=> hemoglobin concentration and hematocrit are assessed at 30-36
weeks;

random blood sugar is evaluated at about 28 weeks; => for Rhesus-negative

women: Rh antibodies will be determined at 20, 24, 28, 32, 36 weeks.

Antenatal screening 1.
Routine ultrasound examination

Some obstetricians consider that every pregnant woman should be

screened by ultrasound either between the 10th and the 13th week or between the
16th and the 20th week. A further screening at about 34th week may also be advised.

Ultrasound screening between the 5th and the 7th week will detect an
intrauterine fetus. It is also helpful in diagnosing some cases of ectopic gestation,
particularly if a vaginal probe is used.
The screening between the 10th and the 13th week is useful for establishing
the gestational age with an accuracy of +/- 4 days in 95% of the patients
and it will confirm or exclude a trophoblastic tumour.
At 18th week of gestation, ultrasound screening can detect Down's
syndrome, neural tube defects and multiple pregnancy.
2. Screening for prenatal defects

Prenatal screening for Down's syndrome and other genetic

abnormalities may be performed by chorion villus sampling or by amniocentesis
followed by cell culture.

Chorionic villus sampling is performed between the 9th and the 11th
week of pregnancy. A sample of 20 mg of chorionic tissue is removed from the
placental edge by sucking it through a narrow cannula, introduced under
ultrasonic guidance. The kariotype of the sample can be detennined within 24
hours. Fetal loss is of 3%.

Amniocentesis is performed at 15 weeks of gestation. A needle is

thrust through the abdominal wall into the amniotic sac, guided by ultrasound in

257

order to avoid the placenta. The obtained amniotic fluid is centrifuged and the
fetal cells are cultivated. The kariotype may be obtained three weeks later.
Prenatal screening for open neural tube defects ( spina bifida and
anencephaly) is made by the measurement of alphafetoprotein, which is
much increased in the maternal serum and the amniotic fluid at the 16 th
week of pregnancy.
A more recent and reliable test is to measure the acetylcolinesterase level in
the amniotic fluid using a qualitative gel electrophoretic test. This enzyme
is released by the immature nerve terminals into the cerebrospinal fluid arid
in case of neural tube defect, into the amniotic fluid.

3. Biochemical tests

Some centres measure urinary estriol and serum HPL at intervals from the
th
30 week of pregnancy, but this routine screening had doubtfiil results. Anyway,
the serial values of estriol excretion is important. Less than 12 mg/24 hours
indicates fetal jeopardy. 4 Biophysical tests
a.
The nonstress test (NST) or fetal activity test (FAT) is a non invasive
test of fetal activity that correlates with fetal wellbeing. A reactive test, that is
normal, reveals three or more fetal movements over 30 minutes, with fetal
heart acceleration of at least 15 beats amplitude of 15 seconds duration.
b.
The contraction stress test (CST) is a test of fetal reactivity in
response
to oxytocin administered i.v., prior to labor, that indirectly measures placental
function. CST is performed when NST is nonreactive. A negative CST, that is
normal, consists in three uterine contractions over 10 minutes, with no
evidence in the fetal heart rate of late decelerations, severe variables or loss of
beat-to-beat variability.
c.
The biophysical profile is a combination of nonstress testing and
realtime ultrasound examination, used to study the dynamic intrauterine behavior
of the fetus. The biophysical profile or Manning score consists of five
variables that are scored by 0, 1 or 2. The maximal score is 10 and the
minimal is 0. In general, a score of 6 or more is acceptable. The five studied
variables are:

=> fetal breathing movements (there must be 30 seconds of sustained

breathing during a 30 minutes observation);

=> fetal movements or NST (there have to be 3 o\ more gross body

movements in a 30 minutes observation);
fetal tone (the presence of at least one episode of motion of a limb from a
position of flexion to extension and then rapid return to flexion);

=> fetal reactivity (there must be two or more fetal heart rate
accelerations of at least 15 b.p.m. lasting at least 15 seconds and associated with
fetal movements in a 10-20 minutes'observation);

^quantitative determination of the amniotic fluid volume (the

presence of a pocket of amniotic fluid that measures at least 2 cm in two
perpendicular planes, with fluid evident throughout the uterine cavity).

The utility of the biophysical profile is extensive. In some centers it

is used as the primary mode of antepartum surveillance.
258

Antenatal assessment The antenatal assessment of all these factors

should determine the obstetrician to classify the pregnant women in:

uncomplicated or normal pregnancies, that will be folio wed-up routinely;

-> high-risk pregnancies, presenting medical or obstetric problems that require

close and complexe surveillance by a medical team, at intervals determined by the
nature and severity of the problems.

Intrapartum assessment
Assessment of the pregnant women must continue into the intrapartum

period. Certain prenatal factors are associated with subsequent intrapartum

risk and outcome. It is important to identify the events associated with poor
outcome, so that the appropriate interventions may be taken to reduce
maternal and neonatal morbidity and mortality.
The prognosis for delivery is usully assessed after the 28th week of
pregnancy or at the onset of labor. It depends upon the following factors:

maternal factors:
-> age and parity -the teenage nulliparas, the older nulliparas (aged over 35)
and grand muciparous women (6 or more pregnancies) have a poor
prognosis;
medical history - associated acute or chronic pathology imply a
wretched prognosis;

obstetric history;

the size and shape of the bony pelvis:

the soft tissues of the pelvis (cervix, vagina, the pelvic floor, the
perineum);
the powers - abnormal uterine activity due to uterine postoperative
scars, tumors, malformations and the pathologic conditions of the anterior
abdominal wall;

fetal factors:
=> the fetus - the number, the size, the lie, the presentation, the position of
the presenting part, fetal wellbeing or distress and gross congenital
malformations are very important:

n> the placenta - its location and its pathology are of greatest
significance;
O the membranes - the fact of being ruptured or not and their pathology
should be considered;
r> the amniotic fluid - quantity, pathology;

O the umbilical cord - the fact of being prolapsed or not and its
length are very important.
Considering these factors, the pregnant women should be classified

259

 into;

^ patients who have a favourable prognosis for the vaginal delivery;

patients with a less favourable prognosis for the vaginal delivery,
amongst which it must be considered: very young and older nuliiparas, chronic
pathology associated to the pregnancy, breech presentation, multiple pregnancy,
polyhydramnios. These cases will be admitted in the maternity a few days (up to
7) before term;
patients with an unfavourable prognosis for the vaginal delivery:
preeclampsia, grand muciparous women, face and brow presentations, the
transverse lie, previous cesarian section, placenta praevia, fetal distress. These
patients will be admitted in the hospital anytime when needed, or at least 2 weeks
before EDC (estimated date of confinement).

260

32. PUERPERAL INFECTION

Definition

A rise in temperature to 38 C (100,4F) or over, maintained for 24

hours occurring in the puerperium, is generally considered indicative of puerperal
infection.
The definition is not entirely satisfactory, as patient may become infected
without being pyrexial, and it fails to distinguish between infection of the
genital tract and other form of infection, which may occur in the
puerperium.

Extragenital causes of puerperal fever include respiratory

complications, pyelonephritis, intense breast include respiratory complications,
pyelonephritis, intense breast engorgement, bacterial mastitis, thrombophlebitis,
and in cases of laparotomy, incisional wound abscess.

With these reservations, the incidence of infection in the puerperium

is 1 to 3%.

Diagnosis

History: interrogation of the patient and a study of her antenatal

record will show whether the infection was present before labor (a vaginal
infection, or anaemia in the antenatal period, or urinary infection).
The obstetric record will reveal the duration and character of the labor, if
the birth was spontaneous or required forceps, or caesarean incision, or the
lacerations of the genital tract.

Examination: a general examination of the patient is made, paying

special attention to the throat, heart, breasts and abdomen, and the legs (to exclude
venous thrombosis) before special investigations are performed.

Special investigation include a vaginal speculum examination the

taking of a high vaginal smear;

261

 a bimanual examination - to detect tenderness and swelling of the uterus or

adnexa;
a midstream specimen of urine, which is sent for microscopic examination
and culture;
hemoglobin and leucocyte examinations of the blood.

These investigations should enable the physician to localize the site

of the infection, but the bacterial cause must await the laboratory findings.

Bacteriology
Bacteria commonly responsible for female genital tract infections are: =>
aerobes: Group A, B and D streptococci, Ehterococus, Gram-negative
bacteria - Escherichia coli, Klebsiella and Proteus species, staphylococcus
aureus;

=> anaerobes: peptococcus species, Peptostretococous species,

Bacteroides bivius, B.fragilis, B.disiens, Clostridium species, Fusobacterium
species;

other: Mycoplasma hominis, Chlamydia trachomatis. Mode of

infection

In 60% of cases the infection is caused by bacteria, particularly

anaerobes, which normally inhabit the vagina. They only become pathogenic
when reduced maternal resistance, or damaged vaginal tissues permit the
anaerobes to grow by virtue of their proteolytic action on devitalized tissue.
Should the uterus contain placental remnants their growth is enhanced.

In the remaining 40% of cases the infections usually staphylococcal,

is introduced into the genital tract by the patient, the mode of transmission is
called autogenous.

If the bacteria are introduced by the attendants, or the environment it

is exogenous.

Exogenous infection is caused by bacteria introduced from some

source other than the patient. This is of importance because it is preventable.

Site and spread of infection The ability of the vaginal pathogens, or the

introduced bacteria, to invade will depend upon their virulence and the
resistance of the patient to invasion.

Patient who in pregnancy are anemic, have PTH, are diabetic, or

malnourished:
patients who in labor become dehydrated, exhausted, or shocked;
patients whose labor is prolonged, or have instrumental or operative
deliveries;
who have postabortum hemorrhage, are liable to have a reduced
resistance to bacteria.
Labor is traumatizing to the tissues of the vagina and cervix and devitalized
tissues offer the opportunity for bacterial growth.

The placental site must be considered a large wound, with much dead
tissue attached to it. and although a barrier to infection is created behind the
placental site, infection can be introduced easily through it.

TYPES AND CLINICAL FEATURES OF PUERPERAL INFECTION

262

Infection of vulva and vagina

Apart from infection of the episiotomy wound, infection of the lower

genital tract, arc uncommon, which is surprising because of the frequency

of trauma to the tissues during child-birth, and the proximity of the rectum.
Occasionally - a cotton wool or gauze sponge may be left in the vagina at
delivery. This can cause an offensive discharge and lead to low grade
infection.
Infection of an episiotomy wound, may be suspected, if the patient
complains of unusual perineal pain, or a discharge.
The wound edges are swollen and red. Treatment consists of local heat, and
if it is necessary, antibiotics are given.

The sutures have to be removed and a secondary repair made.

Cervicitis. The cervix is often traumatized during childbirth and may

readily become infected.
However, such an infection is usually associated with uterine infections,
and rarely causes any specific symptoms.

Endometritis and myometritis. Because of the vulnerable placental

site, infection of the endometrium, with spread into the myometrium, is the most
frequent cause of puerperal infection.

In most cases, the infection is limited to the endometrium, because of

the complex and efficient protective mechanisms.
The infection usually starts between the 3-rd and 6-th day after delivery,
and the clinical picture depends upon the virulence of the organisms.
In all cases, the lochia becomes darker in colour and increases in quantity
and has a bad smell. This is accompanied by pyrexia, shivering. Associated
with the infection are: headaches, malaise, tachicardia. Examinations show
a tender and large painful uterus.
Treatment is to ensure that good drainage from the uterus can occur and to
administer antibiotics.
Spreading
infection. Salpingitis.

Infection from the uterine cavity may spread upwards, to invole the uterine
tube, which becomes swollen and tender. Pelvic cellulitis*

Spread from the lower uterine cavity of the cervix may be lateral
through the uterine wall to involve the connective tissues of the cardinal
ligaments, leading to pelvic cellulitis.

The infection starts quietly, but once established usually in the 2 nd

week of the puerperium, causes lower abdominal pain. On examination the
abdomen is tender, and vaginal examination shows tenderness in the vaginal
fornix, with relative fixation of the cervix, hi many cases the condition is
indistinguishable from pelvic peritonitis.
Pelvic peritonitis

The patient is generally unwell, with pyrexia and disproportionate

tachycardia. There is low abdominal pain and tenderness, with tenderness in the
fornix and pain on manipulating the uterus. Vomiting and paralytic ileus may be
present, but guarding and rebound tenderness, are usually not marked.

263

Suppuration and local abcess fonnation, usually behind the uterus,

may occur. A pelvic abcess is characterized by swinging pyrexia and oedema in
the posterior fonnix. If large, the abscess may be felt on vaginal or rectal
examination. Inflammation and irritation of the adjacent rectum, commonly
results in diarrhoea. A pelvic abscess may burst spontaneously into the rectum or
posterior vaginal fornix, or can be drained by posterior colpotomy.
Generalized peritonitis

This usually only occurs after abdominal delivery after unrecognized

uterine rupture or bowel trauma, or if localized infection have been neglected.

The classic signs of pain, tenderness and rigidity, are commonly

absent in puerperal peritonitis, but the patient is clearly ill, toxic and aften
dehydrated. There is a high fever and rapid pulse. Vomiting is usual and bowel
sounds are absent.

Treatment depends on finding the cause, as well as the nature of the

organism and its sensitivity. Intravenous fluid'and electrolytis and gastric
aspiration are required. Unless there is rapid improvement, a laparotomy is
required, both for diagnostic purposes and for drainage and repair or removal of
damaged organs.

Septicemia may occur in women infected with virulent organisms

(group A hemolitic streptococci) or whose resistance is low. The patient becomes
acutely ill, with swinging pyrexia, a rapid pulse and mental confusion.
Thrombophlebitis of the uterine veins may arise, and showers of infected clots
may be carried to distant organs, particularly the lungs to produce further
symptoms. Prophylaxis
The incidence of puerperal infection can be reduced, if certain general
measures are undertaken. These are:
- in the antenatal period septic foci, should be treated;
- labor should be conducted with surgical asepsis; vaginal examinations
- in labor must only be performed after the hands have been scrubbed, and
sterile gloves worn.
Treatment
Antibiotic therapy

Swabs must be taken from all infected patients. The swab is then
examined to determine the predominant bacteria present, and sensitivity studies
are carried out.
The type of antibiotic, or combination of antibiotics chosen depends on the
severity of the infection.

If there is early severe sepsis intravenous administration of penicillin

G 10 mil u/24 hours every 4 hours intravenously must be given;
with Kanamicin (500 mg) or cefatoxin (2 g) every 12 hours and
metronidazole (500 mg every 8 hours);
or gentamicin 80 mg per dose, in 3 divided doses (240 mg/day)
is substitutes for kanamicin.
Generalized peritonitis

Treatment is laparotomy and large drainage with or without

hysterectomy and adnexectomy depending on the finding in the laparotomy.

264

33. POST PARTUM HEMORRHAGE (PPH)

Etiology of hemorrage in the early puerperium includes four causes:

1. * Inadequate uterine activity (uterine hypo or atony)
1. * Retention of placental tissue and membranes.
2. * Lacerations of the genital tract.
3. * Blood dyscrasias.
In these cases the placenta has been delivered, but bleeding persists. The
placenta should be inspected to see if it is complete. L Uterine hypo or
atony

Diagnosis

Hemorrhage can be:

internal; the blood has collected and distends the uterus; the fundus
rises, the uterus is soft; Pinard's globus is absent;
external hemorrhage;

mixed hemorrhage - internal
and external Treatment:
massage of the uterus with a slow firm rotary movement, with fingers
behind the fundus and the thumbs in front;
give an injection of ergometrine, or syntometrine, or an infusion with
oxytocin in Hartman's or glucose solution;
ice bag on the abdomen;
restoration of the patient's blood volume;
the uterus can be packed firmly with gauze.

If the bleeding continues - it is necessary to explore the cavity of the

uterus, by curettage and to detect if vaginal or cervical damage is present.

After the vulval area is cleansed, the speculum (valve) is applied

with two special forceps, the cervix is inspected, by passing the two forceps on
the entire surface of the cervix.

The uterus should be compressed by lifting the uterus out of the

pelvis, and compressing it between the hands and the spine.

265

 If bleeding persists histerectomy should be done with or without internal

iliac artery ligation.

2. Retention of placental or membrane tissue

Diagnosis the inspection of the placenta and membranes shows us if there

are lost placental or membrane fragments. Treatment
Curettage is only needed if portions of placental tissue or blood clots are
present.
An oxytocin must be injected prior to the operation and the infection must
be controlled with antibiotics.
3.
Laceration of the genital
tract
Perineal and vaginal tears

Four degrees of perineal laceration are recognized;

>- in the first degree there is damage to the skin of the fourchette and
the underlying muscle is expose;

>- in the second degree, the posterior vaginal wall and the perineal
muscles are torn to a varying extent but the anal sphincter is not damaged;

5> in the third degree - the anal sphincter is torn but the rectal
mucosa is intact;

> in the fourth degree the anal canal is opened and the tear may
spread up into the rectum.

Prevention of perineal and vaginal tears is done by a deliberate

episiotomy.

Method of repair

The" repair of a perineal tear of second degree and an episiotomy are

identical. Before starting the repair, it is essential to inspect the vagina, to ensure
that the apex of the vaginal wound can be seen.
Local infiltration with anesthesic (1% lignocaine or xylin) is injected into
the tissues through the wound.
A sanitary pad is inserted into the vagina; it must be removed at the
end of the operation. The patient in the lithotomy position, the legs and perineum
drapped with sterile drapes.
The needle is passed submucosally at the apex of the vaginal wound. It is
essential to close the apex of the wound.

Two methods are available:

O using continuous suture;

c> using interrupted sutures.

The perineal muscles are united with three (or more) interrupted sutures the deep muscles first, and then the superficial muscles.
If the rectum is involved, the rectal mucosa is first sutured, using a
submucosal continuous suture. It is essential to close the apex of the mucosal tear.
The anal sphincter, which always retracts, is sought and identified and is united
with two interrupted sutures. The remained of the repair is performed in the same
way as that after episiotomy.

The after care of a fourth degree tear is to give a low residue diet:
tea, soup, milk, yogurt without fruit, bread, meat.

266

Vaginal laceration

These are common after a difficult delivery (difficult forceps delivery). The
apex of the tear must be identified and is repaired under good light. Cervical tears

In a few cases tears of the cervix occur during delivery. The

commonest cause is delivery by forceps, before full dilatation of the cervix, or
following breach extraction. Less commonly tears may result from the forcible
expulsive efforts of the mother pushing the baby through the incompletely dilated
cervix, or from the injudicious use of oxytocin.

The bleeding is bright red, variable in amount and can be severe. It is

distinguished from placental site bleeding by the fact that it continues, even when
the uterus is well contracted.

Classification of the tears of the cervix includes tears: <=> in the

vaginal part of the cervix;

O above the vaginal part of the cervix; the tear above the vaginal part
of the cervic can extend to a lower segment of the uterus. Diagnosis

Patient in lithotomy position, a large speculum is put in the vagina,

and the anterior and posterior cervical lips are grasped by two forceps. The cervix
is usually edematous, bruised and the tear may be difficult to determine.

Treatment

If the tear is in the vaginal portion of the cervix, the first suture may
be placed at any convenient level and can be used for traction, to make the apex
of the tear more accessible. The tear is then sutured starting above the apex of the
tear going outwards.

The first suture may be placed at any convenient level and can be
used for traction. To make the apex of the tear more accessible. The tear is then
sutured starting above the apex of the tear to the external os.

If cervical tear is extended into the lower segment the pulse rate
rises, the blood pressure falls and signs of shock appear.

Treatment consist in opening the abdomen, operation which can be

performed quickest, and with least shock should be chosen. If the edge of the
rupture can be defined easily, they are freshened and the wound repaired. In most
cases a total hysterectomy is performed. 4. Blood dyscrasias

Hemorrhage is possible to appear after abruptio placenta and

retention of dead fetus.

In both cases a release of thromboplastine takes place with a change

in the mechanism of the coagulation factor (after the third stage haemoerrhage or
postpartum haemorrhage).

Diagnosis

Hemorrhage is continuous with fresh blood that not coagulate and forms no
clots. The patient shows signs of shock and hypovolemia. Treatment

The fresh blood (with coagulation factor) should be transfused,

fibrinogen should be administrated. After reanimation of the patient, hysterectomy
should be done, with or without internal iliac artery ligature.

267

34. VENOUS COMPLICATIONS IN PREGNANCY

AND PUERPERIUM

In pregnancy there is a 50% increase in the serum fibrinogen level, a

30% increase in platelets, a rise in the levels of factor VH, VIII and X, and a
reduction in fibrinolitic activity. Although the fibrinolytic activity returns abruptly
to normal at delivery, the other changes persist into the late puerperium, and
additionally there is an increase in platelet adhesiveness.

These chemical alterations in the blood of a pregnant and puerperal

woman disturb the coagulation: lysis balance in the direction of hypercoagulation.
This, together with die slowing of venous return from the legs in late pregnancy
and the puerperium, increases the likelihood of venous thrombosis.

Between 0,1 and 1,5% (USA and UK) of puerperal women may be
expected to develop venous thrombosis, which may occur in the superficial or
deep veins of the legs. It is common to distinguish two types:

i=> thrombophlebitis, in which a primary infective process is present;

O phlebothrombosis, in which the thrombus formation is due initially

to minor damage of the vessel wall, and which is aggravated by circulator)' stasis
and sepsis. The distinction is of doubtful validity and venous thrombosis
considered here will include both types.
Superficial venous thrombosis

This is the commonest from of venous thrombosis complicating

puerperium. It occurs in about 1% of patients and nearly always arises in existing
various veins.

The cause is the altered coagulability of the blood and the marked
venous stasis occurring in pregnancy and labor. Extension of the thrombus to
involve the deep veins rarely occurs.

Treatment is to apply a compressed bandage on the elevated leg, to

encourage activity, and to with hold antigoagulants, unless extension to deep vein
is diagnosed.

268

Deep venous thrombosis (DVT)

The disorder appears in pregnancy in 20% of cases. Women who are over
the age of 35, and who have been delivered by cesarean section, are
especially at risk. The thrombotic process may involve deep veins in the
calf, or may extend from the calf to the femural or pelvic veins. Only when
the latter occurs, there is a great risk of pulmonary embolism. In the UK,
pulmonary embolism is now the second cause of maternal death. One
patient in four developing an embolus will die.
Clinical signs are a poor guide to the diagnosis of deep venous thrombosis
and do not give any indication whether the trombus is stationary, lysing or
progressing.

The diagnosis is suggested by the presence of lowgrade pyrexia, a

raised pulse rate and the appearance of a feeling of uneasiness.

Examination of the leg is the most accurate clinical diagnostic

method and deep thrombosis is probable when pain and tenderness on firm
palpation of the calf muscles are detected. However, these signs may be absent.
Pain in the calf on dorsiflexion of the foot is Homans sign.

Because of the inadequasy of the clinical signs, and their diagnostic

inaccuaracy, deep venous thrombosis should not be diagnosed until further
investigation have been made. The most accurate method is radiographic
phlebography. This is expensive, invasive, may be painful and may induce venous
thrombosis.

A noninvasive technique, impedance plethysmography is nearly as

accurate.

If the clinical signs and the diagnostic tests suggest venous

thrombosis, anticoagulant treatment is needed throughout die remainder of the
antenatal period and for 6 weeks after delivery.

If pulmonary embolism is suspected on clinical grounds (pleural pain,

friction rub, or hemoptysis) a chest radiography, an electrocardiogram (to detect
changes indicating right ventricular strain) and pulmonary venography or isotope
perftision lung scan should be ordered. Treatment
Prophylaxis

There is no real evidence that anemia or dehydratation are

predisposing causes, but as general principles these should be prevented in
pregnancy and labor.

The main cause is stasis of blood induced by immobility, patients

must be allowed full mobility, as soon after vaginal delivery as possible, and the
immobile patient must be forced into activity. Since venous thrombosis is more
common after cesarean section, patients must be encouraged into movement.
Complaints of leg pain, tenderness must be treated seriousl) and further
investigations made.

Only patients who have had more than one episode of VT in the past should
be considered for prophylactic heparin treatment because of the risk of
demineralization of the bones. If the woman is obese, over the age 35 and has had
several episodes of VT, prophylactic heparin should be recommended, because
the risk of recurrence of VT; Curative treatment

269

Heparin
In pregnancy, Heparin is usually started by adding 20.000 U to 500 ml of
Dextrose 5% infused intravenous heparin may be replaced b> subcutaneous
injections of calcium heparin which are as effective and cause fewer
problems.

If VT is diagnosed after delivery Warfarin is started at the same time

as Heparin.
If the venous thrombosis is found to be iliofemoral in side, and fails to
respond to Heparin, or if pulmonary embolism occurs, expert advice should
be obtained. The choice lies between the use of streptokinase and surgery.
Streptokinase converts plasminogen into plasmin, which then attacks the
fibrin clot, splitting it into soluble fibrin degradation products, Since these
are patent, disturbances the coagulation, lysis balance, haemorrhages states
may occur with possible torrential uterine hemorrhage in the puerperium.
The place for surgery is very limited in uncomplicated deep venous
thrombosis, although pulmonary embolectomy may be life-saving in
certain cases of pulmonary embolism.

Other means of treatment V

Hie patient should remain in bed until fully hepariniztd, and until
tenderness has gone from the limb. The limb should be supported by a firm
crepe bandage or a properly fitted elastic stocking. During her stay in bed,
the limb should be elevated and analgesics given to counter the pain.

JI?
:
; " I
:,<.: ' F
'

"; r, ......

270

35. MAMMARY COMPLICATIONS AND

ABNORMALITIES OF LACTATION IN
PUERPERIUM

1 . Cracked nipples

Aggresive suckling by the baby allied to overfilling of the breasts,

can lead to fissures in the mucosa of the nipples (cracked nipples). These can be
very painful, and, if infected can lead to the development of acute mastitis. The
nipple should be treated witii clorhexidine cream during the day, compound
tincture of benzoin being applied at night. A nipple shield should be used to
protect the area during feeding.
2. Engorgement of the mammary glands

Usually, the milk secretion appears in the second or in the third day
after delivery: before this, some tensivcness, pain or even fever appear. Those
phenomena normally disappear when the milk secretion really begins. Their
persistance is pathological: the breasts remain hard and painful while palpating,
the fever persists, so that sometimes milking has to be interrupted.

Treatment:

Oxytocin may be administrated (2 u intra muscular). After this the

new-born will be breast fed. This treatment will be repeated twice a day, in the
next 2-3 days. Pressing the breasts manually or with artificial means for
eliminating the milk from the ducts and application of cold towels on the breasts
are other methods of treatment.
3. The infection of the breasts in puerperium
The diseases of the breasts during the puerperium are of great importance
because of their frequency and their implications in breasts-feeding.

Classification: I - Paramastities
II - Mastities I Paramastities are represented by:
a - lymphangitis
b - tuberous abcess

271

 c - premammary abcess d - retromammary abcesvs In these cases the

infection is localised at the level of the skin and the perimammary tissues.
a)
Acute lymphangitis is an infection spread from a creacked nipple or
from
another infected lesion of the nipples. The acusis of the patient are: fever,
shivering, tachicardia, one painful and tense breast.

Local examination: edema of the skin on the surface of the breast

corresponding to the lymphatics coming from the infected zone. Palpation of the
breast is veiy painful and sometimes painful axillary adenopathy may also be
present.

Treatment

Breast-feeding from the infected breast is arrested; we administrate

antibiotics (Penicillins and others from the same group of drugs), antipyretics,
antalgics, local placement of antiseptic solutions.
Usually, if the treatment is started promptly, the manifestations of the
disease disappear little by little.
b) Tuberous abcess is a localized infection which interests the areola. The
clinical manifestations are: fever, local pain, red colored skin. At palpation
we identify a well limited and painful mass (the accumulated puss).
c) Premammary and retromammary abeesses may rise some problems of
diagnosis and treatment. Clinically, the patient presents fever, shivering,
alteration of the general status. At the inspection of the breasts the skin is
red colored and oedema is present. At palpation a mass of variable
dimensions may be felt.

The collected puss may exteriorise on the surface of the skin.

In the retromammary abcess the clinical symptomatology is very much
alike, tire only difference is that the supurative process is an extended one,
die retromammary tissue is entirely or almost entirely involved, and the
general status of the patient is seriously alterated.

The treatment is mainly surgical and consists in incision, removal of

necrotic tissues and drainage. Surgery must be performed after the puss is
collected, under some protective antibioticotherapy selected on the base of
bacteriologic examination and antibiocram.
d)
Acute mastitis is characterized by the presence of inflammatory signs
on
the level of one breast (very rare of both breasts). Usually the infection is
localized in one lobule or lobe of the mammary gland.

Most frequently, mastitis debu.ates in the tenth or the fifteenth day of

the post-partum, brutally, with fever shivering, headache, tiredness, local pain.
The breast presents a red-colored zone of 3-4 cm in surface, and
seems, enlarged in volume. At palpation the skin is infiltrated and presents edema
(the presupuration phase) .

hi the supurative phase the general symptoms remain the same. At

the level of the breasts the pain is intense, sharp and pulsatile. At the inspection a

272

zone where the collected puss is acumulated may be observed and fluctuence is
present. In the axilla, mobile and pain full adenopathy can be felt.
' ' Pr'ophilaxy Consistsin respecting the hygienic principles while breastfeeding and the correct treatment of the cracked nipples.

The treatment is a surgical one, represented by large incision, with

excision of necrotic tissues and drainage in the maximum of fluctuence zone and
it will be a wide enough incision in order to eliminate the multiple accumulations
of p u s s , . . . . . . .* ...... ( .

Generally, a radiary incision is recommended, starting from the

areola and passing through the zone where maximum fluctuence is manifest. A
dranaige will be placed in order to maintain open the abcess and to assure the
elimination of the puss.:

Breast-feeding from the breast involved will be obligatorily arrested. ;

Antibioticdtherapy mttst be administrated, first wide spectrum ones and then
respecting the antibiogram. Antipiretic and antalgic drugs will be asociated.

Usually/when the treatment is correct, the evolution is favorable,

with a remaining scar within 2-3 weeks after incision.

' -

273

.*i."