Volume 60, Number 8

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright © 2005
by Lippincott Williams & Wilkins CME REVIEWARTICLE 21
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total
of 36 AMA/PRA category 1 credit hours can be earned in 2005. Instructions for how CME credits can be earned appear on
the last page of the Table of Contents.

Management of Multiple Pregnancy:

Prenatal Care—Part I
Allen Ayres, MD, FACOG,* and Timothy R. B. Johnson, MD†
*Staff, Department of OB/GYN Naval Medical Center Portsmouth, MFM Division, Norfolk, Virginia; and
†Professor, Department of Obstetrics & Gynecology, and Chair, Department of Obstetrics & Gynecology,
University of Michigan, Ann Arbor, Michigan

Over the past 20 years, the number and rate of multiple births have dramatically increased in the
United States. The rise in multiple births is mainly attributable to the increased use of ovulation-
inducing drugs and the newly developed assisted reproductive technologies such as in vitro
fertilization. Multifetal gestation is associated with an increased risk of perinatal morbidity and
mortality. Multiple births account for an increasing percentage of low-birth-weight infants, preterm
births, and infant mortality. In this section, we address the management of the multifetal preg-
nancy, focusing on the maternal physiology, the diagnosis, the pregnancy outcomes, and the
antenatal management of multiple gestation.
Target Audience: Obstetricians & Gynecologists, Family Physicians
Learning Objectives: After completion of this article, the reader should be able to describe the effects
of the rising rate of multiple pregnancies on perinatal morbidity and mortality, to recall the complications
of diagnosing and treating abnormalities of multiple pregnancies, and to list the many changes that occur
in both the mother and the fetuses in multiple pregnancies.

Over the past 20 years, the number and rate of
multiple births have dramatically increased in the
United States. From 1980 to 1997, the twin birth rate
rose 52% (from 68,339 to 104,137), whereas the
triplet and higher-order multiple births increased
404% (from 1337 to 6737) (1). Specifically, this rise
in twin and triplet birth rates occurred in women aged
30 years and older, with the highest twin and triplet
birth rates occurring in women aged 45 to 49 years
(1). The rise in multiple births is mainly attributable
The authors have disclosed that they have no financial relation-
ships with or interests in any commercial companies pertaining to
this educational activity.
Wolters Kluwer Health has identified and resolved all faculty
conflicts of interest regarding this educational activity.
The views expressed in this article are those of the authors and
do not reflect the official policy or position of the Department of
Defense, Department of the Navy, or the U.S. Government.
Reprint requests to: Allen Ayres, MD, Staff, Department of OB/
GYN, Naval Medical Center Portsmouth, MFM Division, 1657
Powhatan St., Norfolk, VA 23511. E-mail: mfmayres@cox.net.
527
to the increased use of ovulation-inducing drugs and
the newly developed assisted reproductive technolo-
gies such as in vitro fertilization. Currently, the in-
cidence of twins, triplets, and higher-order multiple
gestations is 3% of all pregnancies (2).
Multifetal gestation is associated with an increased
risk of perinatal morbidity and mortality. Multiple
births account for an increasing percentage of low-
birth-weight infants, preterm births, and infant mor-
tality. From 1981 to 1997, the preterm birth rate for
twins rose from 40.9% to 55.0% and the percentage
of low-birth-weight infants increased from 11.9% to
14.1% (3). The fetal death rate for twin gestations is
higher compared with singleton fetal death rates,
15.5 per 1000 conceptions versus 4.3 per 1000 con-
ceptions, respectively (2). In addition, twin preg-
nancy increases the risk of maternal morbidity and
mortality, ie, a 2-fold risk of preeclampsia, postpar-
tum hemorrhage, and death and a 3-fold risk of
eclampsia compared with singleton gestations (4).
528 Obstetrical and Gynecological Survey
The obstetric care and management of multiple
gestations is often complicated, challenging the skills
of the practicing clinician. In this section, we address
the antenatal management of the multifetal preg-
nancy. In part II, the approaches to the unique com-
plications that can be associated with multiple ges-
tations will be reviewed.
TYPES AND GENESIS OF TWINNING
Twin gestations result from fertilization of 2 sep-
arate ova producing dizygotic or “fraternal” twins or
fertilization of 1 ovum, which subsequently divides,
giving rise to monozygotic or “identical” twins. The
dizygotic twins are not strictly a true twin pregnancy,
ie, the 2 fetuses do not have the identical genetic
makeup. On the other hand, in monozygotic twin-
ning, both fetuses are genetically the same. With
monozygotic twin pregnancies, the timing of the
division determines the outcome of the twinning
process:
1. Division occurring within the first 72 hours
after fertilization will result in 2 embryos, 2
amnions, and 2 chorions, which is a diamniotic,
dichorionic, monozygotic twin gestation. A sin-
gle fused placenta or 2 distinct placentas may
be present.
2. Division occurring between the fourth and
eighth day will produce 2 embryos and 2 am-
nions (an embryo in each separate amniotic
sac). The amniotic sacs will be covered by a
single chorion, giving rise to a diamniotic,
monochorionic, monozygotic twin gestation.
3. If the division occurs after the eighth day, 2
embryos will develop in a common amnion.
This is a monoamniotic, monochorionic,
monozygotic twin pregnancy.
4. Finally, division that occurs after day 12 (after
the embryonic disc is completed) results in a
monoamniotic, monochorionic, conjoined twin
gestation.
FACTORS INFLUENCING TWINNING
Worldwide, the frequency of monozygotic twin
births is relatively constant, ranging from 3 to 5 per
1000 births (5), and is mostly independent of race,
heredity, maternal age, and parity. Contrary to pre-
vious thoughts, recent studies demonstrate that infer-
tility treatment, ovulation induction, and assisted re-
production techniques can be responsible for
monozygotic twinning (6,7). On the other hand, the
incidence of dizygotic twinning is influenced by he-
redity, race, maternal age, parity, and infertility treat-
ment (fertility agents and assisted reproduction tech-
nology).
Heredity
The maternal family history of twinning is more
strongly associated with the incidence of dizygotic
twin gestation than the paternal family history. More-
over, if a woman is a dizygotic twin herself, her rate
of giving birth to twins is 1 set in 58 births (8).
Conversely, if the husband is a dizygotic twin and the
mother is not a twin, the rate of twin births is 1 set in
116 pregnancies. However, a report of an analysis of
950 zygosity-determined twin pairs shows that a
propensity to monozygotic twinning, as well as dizy-
gotic twinning, is inherited through the maternal line
and also found a paternal role in dizygotic, but not
monozygotic, twinning (9).
Race
Among different ethnic groups and races, the fre-
quency of multiple gestations varies. The rate of
dizygotic twin births in white women is 1 in 100
pregnancies, and in black women, it is 1 in 80 preg-
nancies (10). In Asia, twinning is less common, ie, 1
in 155 births (5).
Maternal Age and Parity
The frequency of dizygotic twin gestation in-
creases with advancing maternal age, peaking at age
37. At this age, the maximum hormonal stimulation
enhances the rate of double ovulation (11). After the
age of 37, the rate of twin pregnancies decreases as a
result of the reduction in hormonal production by the
aging ovarian follicles. Increasing parity is also as-
sociated with an increase in dizygotic twinning. In
Sweden, the frequency of multiple gestations in the
first pregnancy is 1.3%, but in the fourth pregnancy,
the frequency is 2.7% (12). In Nigeria, the frequency
of dizygotic twinning increased from 2% in primi-
gravid women to 6.6% in grand multiparous women
(6 or more) (13).
Infertility Treatment
The use of ovulation induction agents such as human
menopausal gonadotropin (hMG) with chorionic go-
nadotropin (hCG) and clomiphene increases the chance
of multiple ovulations and consequently enhances the
possibility of multiple gestations. The incidence of mul-
tiple pregnancies with the use of clomiphene ranges
from as low as 1.83% and to as high as 17% and with
hMG-hCG treatment from 18% to 53.5% (14). The
 Management of Multiple Pregnancy: Prenatal Care Y CME Review Article
majority of these multiple gestations are twins. Al-
though the major cause of triplet and quadruplet preg-
nancies is usually attributed to hMG therapy, literature
shows that clomiphene therapy may also be associated
with higher-order multiple gestations. In a review of 13
triplet and 2 quadruplet pregnancies, 9 of the patients
(82%) conceived using clomiphene (15). In addition,
ovulation induction using pulsatile gonadotropin-releas-
ing hormone is associated with approximately a 10%
incidence of multiple gestations, mostly twins (16,17).
Multifetal pregnancies resulting from ovulation in-
duction agents are usually the result of fertilization of
multiple ova. However, in the East Flanders Prospec-
tive Twin Study, results of zygosity determinations
for the twins and triplets occurring after artificial
induction of ovulation revealed that 13% of the twins
were monozygotic and 22% of the triplets contained
monozygotic twins (7). In addition, assisted repro-
duction technologies (ART) are associated with an
increased risk of monochorionic twinning. In a re-
view of 218 ART pregnancies, 71 (33%) were mul-
tifetal, of which 7 (9.8%) were monozygotic (6).
These studies suggest that infertility treatment with
ovulation induction agents and assisted reproduction
technologies increase both dizygotic and monozy-
gotic twinning.
MATERNAL PHYSIOLOGICAL CHANGES
The maternal physiological adjustments to multiple
gestations are usually greater than in a singleton
pregnancy. The average maternal blood volume in-
creases in late pregnancy by 40% to 50% in gesta-
tions with a single fetus, but in twin pregnancies, it
increases by 50% to 60%, which amounts to an extra
500 mL blood volume (18). In addition, compared
with a singleton pregnancy, the increase in red cell
mass in multiple gestations is less, thus producing a
more pronounced “physiological anemia.” After 20
weeks of gestation, the average hemoglobin concen-
tration in women with twins is 10 g/dL (19).
Assessment of cardiac function in twin pregnancies
using M-mode echocardiography shows an increase
in cardiac output compared with a singleton gesta-
tion, but no change in end-diastolic ventricular di-
mension. The increased cardiac output in twin preg-
nancy that occurs during the second and third
trimesters is the result of increased heart rate and
higher stroke volume (20). The arterial blood pres-
sure changes in women with twin pregnancies are
similar to the changes seen in a singleton pregnancy.
However, compared with singleton pregnancies at 20
weeks of gestation, the diastolic blood pressure in
529
twins is lower. Specifically, 74% of twins have a
diastolic pressure less than 80 mm Hg compared with
66% of singletons (19).
Uterine size is greatly increased in multiple gesta-
tions, resulting in more pronounced anatomic
changes that occur during pregnancy. The abdominal
organs can be compressed or displaced. Also, the
diaphragm can be elevated, compressing the lungs.
As a result of the size and weight of the large uterus,
the patient experiences more pressure symptoms and
more difficulty in ambulating and performing daily
tasks.
DIAGNOSIS OF MULTIPLE PREGNANCIES
Ultrasound
Ultrasound is an invaluable tool in the evaluation
and management of multiple gestations. With careful
use of sonography, practically all sets of twins should
be recognized. Ultrasound in the first trimester can
identify 2 separate gestational sacs characteristic of
an early twin pregnancy. To prevent the possibility of
scanning a single fetus twice and interpreting it as a
twin pregnancy, 2 fetal heads or 2 abdomens must be
seen in the same scanning plane. It not only is im-
portant to note the number of fetuses or embryos, but
also to carefully document the location or position of
each sac in the uterine cavity for future reference.
This will help to correctly identify the fetus under-
going ultrasound evaluation later in gestation.
Ultrasound is also helpful in determining the zy-
gosity of the twin pregnancy. If the twin gestation is
monoamniotic or monochorionic, then it is monozy-
gotic. However, if sonography shows a dichorionic,
diamniotic twin pregnancy, it could either be dizy-
gotic or monozygotic. Approximately one third of
monozygotic twins have a dichorionic placenta (21).
Also, ultrasound can help to determine the chorio-
nicity of twin pregnancies by using several sono-
graphic signs. Two separate placentas with a thick
dividing membrane of ⱖ2 mm suggest a dichorionic
pregnancy. Opposite genders of the fetuses are con-
sistent with a dizygotic twin gestation (22). It is
sometimes problematic to distinguish between 1
large placenta and 2 placentas that are side by side. In
this situation, identifying a triangular projection of
placental tissue between the layers of the dividing
membrane, called the twin peak sign, suggests 2
fused placentas instead of 1 large placenta. In mono-
chorionic pregnancies, the dividing membrane is thin
(⬍2 mm) and consists of only 2 layers. By using a
composite of the following ultrasound findings (pla-
530 Obstetrical and Gynecological Survey
cental number, twin peak sign, dividing membrane
thickness, and fetal sex), the chorionicity, amnionic-
ity, and zygosity can each be predicted with ⱖ91%
sensitivity and specificity (23).
History and Physical Findings
The following information obtained from the ma-
ternal history raises the possibility of a twin gestation
in the current pregnancy: previous twin pregnancy,
older maternal age, maternal family history of twins,
and higher parity. However, a pregnancy resulting
from use of ovulation-inducing agents or assisted
reproductive technologies has a strong likelihood of
being a twin or higher-order gestation.
The uterine size in a twin pregnancy in the second
trimester is larger than expected for gestational age
based on menstrual dating. Between 20 and 30 weeks
of gestation, the average fundal height in centimeters
for a twin pregnancy is 5 cm greater than expected
for a singleton pregnancy (24). However, other
causes of uterine size larger than dates include: hy-
dramnios, fetal macrosomia, leiomyoma, hydatidi-
form mole, and inaccurate menstrual dates.
Identification of a twin pregnancy may be done by
transabdominal palpation of fetal part, usually 2 fetal
heads, but it is difficult, particularly before the third
trimester or if the woman is obese. It is also possible
to diagnose twins by identifying 2 fetal hearts if their
heart rates are clearly different from each other and
from the maternal heart rate. Twins are associated
with an elevated maternal serum alpha-fetoprotein
level and a higher-than-average chorionic gonadotro-
pin, but these alone are not diagnostic. Presently,
there is no individual biochemical marker that will
reliably identify a multiple gestation.
PREGNANCY OUTCOMES OF MULTIPLE
GESTATIONS
‘Vanishing Twin’
The incidence of twin pregnancies is greater in the
first trimester than the incidence of twins at birth.
Multifetal pregnancies comprise more than 12% of
all natural conceptions, but only 2% survive to term
as twins and 12% result in single births (25). Fur-
thermore, the fetal loss rate before 24 weeks of
gestation is higher in monochorionic twin pregnancy
than in the dichorionic twin gestation, 12.2% versus
1.8%, respectively (26). In addition, in 21% to 70%
of spontaneous twin pregnancies diagnosed by ultra-
sound in the first trimester, 1 twin is lost or “van-
ishes” by the second trimester (27,28). This “vanish-
ing twin” phenomenon is often associated with
bleeding, but the prognosis of the remaining fetus is
good. The risk of spontaneous loss of the pregnancy
with a “vanishing twin” is similar to the risk in other
pregnancies that are complicated with first-trimester
bleeding (27). However, pregnancies complicated
with a “vanishing twin” are associated with an ele-
vation of the maternal serum alpha-fetoprotein level
and amniotic fluid alpha fetoprotein, and also a pos-
itive amniotic fluid acetylcholinesterase assay (29).
Abortion
Spontaneous abortion occurs more frequently in
twin gestations compared with singleton pregnan-
cies. The rate of twinning in pregnancies that spon-
taneously abort is from 1 in 35 to 1 in 44 (30,31). The
ratio of monozygotic to dizygotic in spontaneous
twin abortions is 17.5 to 1 with 88% of the twin
embryos and 21% of the twin fetuses being abnormal
(30).
Anomalies
Congenital malformations are more common in
twin and higher-order multifetal gestations than in
singleton pregnancies. Major malformations occur in
2.12% in twin pregnancies compared with 1.05% in
singleton pregnancies, and the incidence of minor
malformations in twins is 4.13% compared with
2.45% in singleton gestations (32). Furthermore, the
occurrence of malformations is higher in monozy-
gotic twins compared with dizygotic twins (3.1% to
1.9%, respectively) (33). The increased occurrence
of malformations in monozygotic twins compared
with dizygotic twins and singleton pregnancies is
primarily the result of an excess of structural defects
categorized into 3 types (34):
1. Defects that are part of the monozygotic twin-
ning such as conjoined twins and some amor-
phous twins.
2. Defects resulting from vascular interchange be-
tween monozygotic twins. These vascular con-
nections may result in reverse flow with acar-
diac status in 1 twin or vascular disruptions
from a deceased twin causing defects in the
surviving twin such as microcephaly, porence-
phalic cysts, hydranencephaly, aplasia cutis, or
limb amputation.
3. Deformations resulting from intrauterine
crowding during late gestation such as aberrant
 Management of Multiple Pregnancy: Prenatal Care Y CME Review Article
foot positioning. These deformations are usu-
ally transient, returning to normal after birth.
Twin pregnancies can be associated with an in-
creased amniotic fluid volume or hydramnios, which
can be evaluated by ultrasound. If hydramnios in a
twin gestation is identified by ultrasound in the
midtrimester, it may be transient or it could persist
and become chronic. The former is usually seen in
twin gestations with normal fetuses, whereas the twin
pregnancies complicated with chronic hydramnios
frequently have fetal anomalies (35).
Birth Weight
Compared with singleton pregnancies, the birth
weights of multifetal gestations are lower primarily
resulting from intrauterine growth restriction and/or
preterm delivery. An analysis of mean birth weights
of singletons and twins from 22 to 44 weeks of
gestation in Canada shows the average birth weight
of twins is 2491 g compared with 3464 g for single-
tons (36). In another study of twin and singleton
pregnancies, approximately 50% of the twins
weighed less than 2500 g at birth compared with only
5% of singletons. Also, in the same study population,
5.6% of the twins delivered at ⬍32 weeks of gesta-
tion compared with only 0.7% of singletons (37).
The growth of twins is similar to singletons up to
28 to 30 weeks of gestation. After 30 weeks of
gestation, the growth of twins starts to lag behind the
growth of singletons. By 36 gestational weeks, the
mean birth weight of twins is 2500 g compared with
2800 g for singletons (36).
Perinatal morbidity and mortality in twin pregnan-
cies is related to intrapair birth weight discordance.
The birth weight discordance of twins is calculated
by dividing the difference between the weights of the
2 fetuses by the weight of the largest fetus. Com-
pared with less than 5% birth weight discordance
category, the adjusted odds ratio with 95% confi-
dence interval for a stillborn fetus associated with a
10% to 19% birth weight discordance is 1.41. The
odds ratio for a stillborn fetus increases with increas-
ing intrapair weight discordance, reaching 4.29 for
40% or greater weight discordance (38). Also, the
association of fetal death with birth weight discor-
dance is seen in triplet pregnancies. A birth weight
discordance of 29% or greater is associated with a
significant risk of fetal death when compared with
less than 10% discordance; for the smallest, middle,
and largest triplets, the adjusted odds ratio are 10.88,
22.6, and 2.41, respectively (39).
531
There is evidence to suggest that uterine crowding
later in pregnancy plays a greater role in fetal growth
of twins and triplets than early implantation and
placentation. In a study comparing birth weights of
triplet, twin, and embryo-reduced pregnancies (re-
ductions performed before 12 weeks and leaving 2
fetuses), the birth weight of the embryo-reduced
pregnancies was similar to twins and significantly
larger than the triplets (40).
Duration of Gestation
The length of gestation decreases as the number of
fetuses increases. For twin pregnancies, half are de-
livered by 36 weeks and 90% by 37 to 39 weeks of
gestation (41). For triplets, the mean gestational age
at delivery is 33.5 weeks, with 90% and 24% deliv-
ered by 37 and 32 weeks, respectively (42). The
average gestational age at delivery for quadruplets is
31 weeks (42,43).
Preterm Delivery
Twin pregnancies have a higher rate of premature
delivery than singleton pregnancies. The causes of
preterm birth are divided into 3 categories: 1) spon-
taneous labor, 2) preterm premature rupture of the
membranes, and 3) indicated preterm births. Sponta-
neous labor accounts for 54% of twin preterm births,
and preterm premature rupture of the membranes
accounts for 22%. Lastly, 23% of preterm deliveries
are indicated in which the delivery is necessary for
maternal or fetal concerns (44). Moreover, preterm
twins do not have significantly more respiratory dis-
tress syndrome, intraventricular hemorrhage, or ne-
crotizing enterocolitis compared with same gesta-
tional age preterm singletons (44,45).
In contrast, the morbidity and mortality of preterm
twins with discordant growth are increased compared
with concordant growth preterm twins. The neonatal
mortality of the discordant preterm twin is 19% com-
pared with 2% for concordant preterm twin. Also, the
discordant preterm twin is more likely to have grade
3 or 4 intracranial hemorrhage and persistent ductus
arteriosus. Chronic twin–twin transfusion is the ma-
jor contributing factor for the increased neonatal
morbidity and mortality (46).
‘Term’ Twin Pregnancy
For twin pregnancies, the gestational age which is
considered “term” is unclear. The growth of twins
begins to decline after 38 weeks of gestation. Twins
born at 40 weeks gestation or later are smaller than
twins born at 38 and 39 weeks (47). The incidence of
perinatal death (stillbirth and neonatal deaths) in twin
532 Obstetrical and Gynecological Survey
gestations after 37 weeks is higher than in singleton
pregnancies. The lowest incidence of perinatal death
(10.5 per 1000 infants) is seen at 38 weeks in twin
pregnancies, which corresponds to the incidence of
perinatal death in singleton pregnancies at 43 weeks
of gestation. The perinatal death rate and intrauterine
growth restriction of twin pregnancies increase
substantially after 38 weeks of gestation (48,49).
These data suggest that twins are “postterm” after
38 weeks.
ANTEPARTUM MANAGEMENT OF
TWIN GESTATION
The ultimate goals of antepartum management of a
twin pregnancy are to prevent the delivery of mark-
edly preterm fetuses, to identify growth restriction in
1 or both fetuses to expedite their delivery before
they become moribund, to deliver the fetuses atrau-
matically, and to have expert anesthesia and neonatal
care available.
Nutrition and Weight Gain
Multiple pregnancies increase the requirements for
calories, protein, minerals, and vitamins. Evidence
suggests that the incorporation of dietetic services
into the antenatal care is beneficial. For a twin ges-
tation, a 35- to 40-lb total weight gain is recom-
mended. To achieve this weight gain would require,
on average, an additional 150 kcal per day above the
level for singleton pregnancy. A woman with triplets
should gain 50 lbs during her pregnancy. In addition,
as a result of the increased red cell mass, the need for
elemental dietary iron is increased. It is recom-
mended that a woman with a multifetal pregnancy
take 30 mg of iron and 300 ␮g of folate after the 12th
week of gestation (50).
Genetic Testing
With increasing maternal age, the incidence of both
twin gestations and fetal aneuploidy increases. In
monozygotic twin gestations, in which both fetuses
have the same karyotype, the risk of fetal aneuploidy
is the same as the age-related risk for a singleton.
However, in dizygotic twin pregnancies, the risk of
fetal aneuploidy is twice the maternal age risk for a
singleton pregnancy (51).
Scant information is available concerning maternal
serum screening for aneuploidy in twin gestations.
However, the average serum alpha-fetoprotein in
twins is 2.04 times higher than singleton pregnancies,
the mean unconjugated estriol is 1.64 times greater,
and the average human chorionic gonadotropin is
1.93 times higher (51,52). Currently, the reliability of
the serum screening for Down syndrome in twins is
unknown. In a small study of triplet and quadruplet
gestations, the average maternal serum alpha fetopro-
tein levels in triplets was 3 times that found in
singleton pregnancies and even higher in the quadru-
plet pregnancies (53). Using a cutoff of 4.5 MoM for
serum alpha fetoprotein in twin gestations, the detec-
tion rate for open neural tube defects is 50% to 85%
with a false-positive rate of 5% (51).
Midtrimester amniocentesis and first-trimester
chorionic villus sampling (CVS) are used for prenatal
diagnosis in twin gestations. Second-trimester am-
niocentesis under direct ultrasound guidance is not
associated with an excess pregnancy loss. Comparing
107 twins undergoing midtrimester genetic amnio-
centesis with 114 twins not undergoing amniocente-
sis (controls), the fetal loss rate was similar among
the cases and controls (3.5% vs. 3.2%, respectively),
and no losses occurred within 3 weeks of the proce-
dure (54). In the hands of experienced operators,
CVS is at least as safe and effective as amniocentesis
for prenatal diagnosis of twin gestations. A study
comparing 81 women with twins who had a midtri-
mester amniocentesis with 161 women who had CVS
showed that the loss of the entire pregnancy from the
time of sampling to 28 weeks of gestation in the
amniocentesis group was 2.9% and 3.2% in the CVS
group, which was not statistically significant (55). In
performing genetic amniocentesis in twin pregnan-
cies, care must be taken to sample each sac separately
and not to sample the same sac twice. Careful ultra-
sound examination to map and label fetal positions
relative to the maternal orientation, fetal membranes,
and placental localizations is of paramount impor-
tance. Genetic amniocentesis should be done under
direct ultrasound guidance. Instillation of indigo car-
mine or Evan’s blue into the first sac sampled can be
used to differentiate between the 2 fetal sacs before the
second sample is taken. Methylene blue dye should not
be used because of the risks of fetal hemolytic anemia,
small intestinal atresia, and fetal demise.
Hypertension
Twin pregnancies are complicated by an increase
in the incidence of hypertensive disorders, which
tend to occur earlier and be more severe than in
singleton pregnancies. In a recent case–control study
comparing 187 twin pregnancies with 187 singleton
pregnancies matched for gestational age, maternal
 Management of Multiple Pregnancy: Prenatal Care Y CME Review Article
age, and parity, the incidence of pregnancy-induced
hypertension was significantly higher in the twin
pregnancies (15% vs. 6.4%, respectively) (56). Fur-
thermore, twin pregnancy has a 4-fold increased risk
of preeclampsia independent of race and parity, and
the risk of preeclampsia in nulliparous twin gesta-
tions is 14 times that of a parous singleton pregnancy
(57). Comparing triplets with twins, the rate of over-
all preeclampsia is not significantly different (33.9%
vs. 22.6%), but the rate of severe preeclampsia is
significantly increased in triplet gestations compared
with twins (22.6% vs. 5.7%, respectively) (58).
Ultrasound Antepartum Surveillance
Fetal growth in twin and multifetal pregnancies
after 30 weeks of gestation lags behind the growth of
singleton pregnancies. Also, there can be unequal or
intrapair discordant growth. Therefore, serial ultra-
sounds at 2- to 4-week intervals are done to monitor
the interval growth of twin gestations in the third
trimester. Normal interval growth is reassuring, but
discordant growth would warrant further evaluations
to check the fetal status (59).
Amniotic fluid volume is another parameter that
should be evaluated by ultrasound. Oligohydramnios
may indicate uteroplacental insufficiency, necessitat-
ing further testing to check for fetal well-being. In
twin pregnancies, it may be difficult to quantify the
volume of amniotic fluid of both fetuses. The amni-
otic fluid volume can be assessed by measuring the
deepest vertical pocket in each sac or by measuring
the amniotic fluid index (AFI). Normative AFI mea-
surements for twin pregnancies are established based
on 282 sets of uncomplicated twins. The amniotic
fluid index is determined by adding the deepest ver-
tical pocket in each of the 4 quadrants defined by the
linea nigra and the umbilicus. Thus, an overall AFI is
obtained (60). If the AFI is abnormal, then the clini-
cian needs to discover which sac is responsible and
the possible cause.
Antepartum Tests of Fetal Well-Being
Ultrasound surveillance is the mainstay of moni-
toring fetal growth of twin pregnancies and deter-
mining amniotic fluid volume. The estimated fetal
weight provides the best discriminator for discordant
growth, but the estimation of amniotic fluid volume,
as stated earlier, is problematic. Tests for fetal well-
being in twin gestations include ultrasound assess-
ment of fetal growth and amniotic fluid volume,
Doppler velocimetry of the umbilical artery, non-
533
stress test, and biophysical profile. Of these 4, non-
stress test and Doppler velocimetry are more predic-
tive of fetal well-being than amniotic fluid volume
and biophysical profile (61). The amniotic fluid vol-
ume and the biophysical profile may not be as pre-
dictive as a result of the difficulty and inaccuracy of
the amniotic fluid volume estimation in twin gesta-
tions. However, in higher-order multiple gestations
(triplets and quadruplets), biophysical profile appears
to a reliable antepartum test of fetal well-being. In a
retrospective review of 18 triplets and 6 quadruplets
using the biophysical profile as the primary method
of fetal surveillance, there were 6 pregnancies deliv-
ered for nonreassuring biophysical profile testing
with good neonatal outcomes and 4 pregnancies had
poor neonatal outcomes despite a normal biophysical
profile test. However, all 4 of these pregnancies had
active changes in the pregnancy leading to delivery
(2 with worsening preeclampsia, 1 with abruptio
placenta, and 1 with preterm rupture of the mem-
branes with active labor) (62).
Duplex Doppler ultrasound measuring umbilical
venous blood flow and systolic/diastolic ratios is
useful in predicting and confirming concordant and
discordant growth in twins. In a study of 44 twin
pregnancies using duplex Doppler ultrasound to eval-
uate fetal growth, the sensitivity and specificity of
the test was 81.8% and 97.9%, respectively. The
positive predictive value of an abnormal Doppler
outcome was 90%, and the negative predictive value
was 95.6% (63). Furthermore, the finding of absent
end diastolic velocities on Doppler umbilical wave-
forms in triplet and quadruplet pregnancies is asso-
ciated with adverse perinatal outcomes such as low
birth weight, growth restriction, and perinatal mor-
tality (64).
Preterm Delivery
One of the major complications of twin pregnan-
cies is preterm delivery. Several management plans
and/or techniques and procedures have been pro-
posed to delay preterm labor and delivery in twins.
Routine Hospitalization With Bedrest
Routine hospitalization with bedrest is not helpful
in prolonging multifetal pregnancies. A study of 118
twin gestations between 28 and 30 weeks of preg-
nancy randomized either to hospitalization with be-
drest (58 patients) or to outpatient management with
no restriction on their activities (60 patients) was
conducted and the perinatal outcomes were com-
534 Obstetrical and Gynecological Survey
pared. There were no significant differences in the
gestational age at delivery between the 2 groups
(36.1 weeks for the hospitalization group and 35.9
weeks for the control group) or in neonatal morbid-
ity. However, the mean birth weight of the twins in
the hospitalized group was significantly greater than
the control group (2.43 kg vs. 2.30 kg, respectively)
(65). In addition, another study of 141 twin pregnan-
cies randomized to outpatient care with normal ac-
tivities or to hospitalization with restricted activities
showed no differences in mean birth weight or mean
gestational age at delivery between the 2 groups (66).
Also, there appears to be no benefit of routine hos-
pitalization with bedrest in triplet pregnancies. Peri-
natal outcomes were compared between 32 triplet
pregnancies managed as an outpatient on bedrest and
a historic cohort of 34 triplets managed as inpatients
in the hospital on bedrest. The mean gestational age
at delivery was 1 week longer in the hospitalized
group but not statistically significant (33.5 weeks vs.
32.5 weeks, respectively), but the average birth
weight was significantly greater in the hospitalized
cases (1942 g vs. 1718 g, respectively) (67).
Cervical Length Measurements
Cervical lengths in twin gestations may be a risk
factor for preterm birth. The cervical length is best
measured by transvaginal ultrasound with an empty
maternal bladder. A closed cervical length of 25 mm
is approximately the 10th percentile for singletons.
The finding of a closed cervical length of ⱕ25 mm at
24 weeks of gestation in twins is a predictor of
spontaneous preterm birth at ⬍32 weeks, ⬍35
weeks, and ⬍37 weeks. The odds ratios for sponta-
neous preterm births at these gestational ages are 6.9,
3.2, and 2.8, respectively (68). Another study of 215
twin pregnancies showed that, in patients with a
closed cervical length measurement of ⱕ25 mm at 23
weeks of gestation, spontaneous delivery occurred in
3.8%, 4.7%, 8.0%, and 17.5% at 28, 30, 32, and 34
weeks, respectively (69). Although cervical length
measurement by ultrasound is helpful as a predictor
of preterm delivery, its clinical usefulness as a rou-
tine evaluation is questionable because of the lack of
proven treatments affecting outcome (70).
Home Uterine Activity Monitoring
The usefulness of home uterine activity monitoring
(HUAM) as a screening test for preterm birth is
questionable. There have been multiple studies pub-
lished evaluating HUAM as a predictor of preterm
birth, but many had limitations with their research
design and varied in criteria for inclusion of patients
and in end points and outcomes. However, the U.S.
Preventive Services Task Force did an independent
review and concluded that HUAM was not effective
(71). Therefore, home uterine activity monitoring is
not currently recommended (70).
Tocolytic Therapy
Most randomized trials using beta-mimetics in
twin gestations have not shown any benefit in reduc-
ing preterm deliveries. The uterine activity was mon-
itored at home in 39 twin gestations, 20 triplets, and
10 quadruplets and showed that uterine activity in-
creased slightly within 48 hours of the onset of
preterm labor and significantly increased over base-
line during the 24 hours preceding the diagnosis of
preterm labor. Furthermore, treatment with oral to-
colytics did not have any effect on the crescendo of
uterine activity preceding preterm labor (72). In ad-
dition, a double-blind, controlled study of the pro-
phylactic use of oral salbutamol in 144 women
with twins (74 on salbutamol and 70 placebo)
showed no difference in the length of gestation,
birth weight, or fetal outcome between the study
and control groups (73).
Complications occur more often with the use of
tocolytic therapy in multiple gestations than in sin-
gletons. This is the result of a greater increase in
plasma volume and cardiac output that occurs in
twins compared with single gestations. Comparing
adverse maternal effects of treatment with intrave-
nous ritodrine for preterm labor with intact mem-
branes in 32 women with multifetal pregnancies (26
twins and 6 triplets) and 51 women with singleton
pregnancies showed that the incidence of maternal
cardiovascular complications was significantly
higher in the multifetal group (34.4% vs. 4.0%, re-
spectively) (74).
Cerclage
No significant benefit in the reduction of preterm
births of twin gestations has been shown with cervi-
cal cerclage placement in the midtrimester with a
pregnancy complicated with a shortened cervix. In a
prospective cohort study of 128 twin gestations, 21
patients who underwent cerclage for a cervical length
ⱕ25 mm were compared with 12 patients with the
same cervical length but did not have a cerclage
placed. Three were no statistically significant differ-
ence in preterm delivery between the 2 groups with
 Management of Multiple Pregnancy: Prenatal Care Y CME Review Article
the mean gestational age at delivery of 33.5 weeks
for the cerclage group and 32.8 weeks for the non-
cerclage group (75). Also, no reduction in preterm
delivery has been demonstrated with prophylactic
cerclage in triplet pregnancies. In a study comparing
20 triplet pregnancies with prophylactic cerclage
with 39 triplets with no cerclage, the mean gesta-
tional age at delivery in the cerclage group was not
significantly different than the noncerclage group,
32.8 weeks versus 31.5 weeks, respectively (76).
Preterm Corticosteroids
The use of corticosteroids to enhance fetal lung
maturation in multiple gestations in preterm labor
and impending delivery (⬍34 weeks gestation) is
recommended by the Consensus Development Con-
ference on the Effect of Corticosteroids for Fetal
Maturation sponsored by the National Institutes of
Health (77). In a review of 70 triplets, hyaline mem-
brane disease occurred in 13% of the group given
corticosteroids and in 31% of the untreated group.
The authors concluded that the data supported the use
of corticosteroids between 28 and 34 weeks for trip-
let pregnancies to reduce the incidence of hyaline
membrane disease of the newborn (78).
Fetal Lung Maturation
The data in the literature concerning acceleration
of fetal lung maturation in twin pregnancies is con-
flicting. However, in most cases, pulmonary matura-
tion is synchronous in twin gestations as measured by
lecithin-sphingomyelin ratio (L/S ratio). In a study of
42 twin pregnancies in which amniotic fluid was
obtained at the time of cesarean section, the L/S
ratios of the twin pairs were similar in numeric value
(regression line coefficient was 0.82 and slope of the
line was 0.87). In the same study, the mean L/S ratios
of the 42 twin gestations from 31 to 40 weeks ges-
tation were compared with 137 uncomplicated sin-
gleton pregnancies at comparable gestational ages.
At each biweekly interval from 31 to 36 weeks, twin
L/S ratios were significantly greater than those of
singletons (79). In contrast, in a matched cohort
study of 112 twin pregnancies matched to 224 sin-
gletons delivered because of refractory preterm la-
bor, there was no significant difference in the inci-
dence of respiratory distress syndrome (38% vs.
35%, respectively) or in the use of mechanical ven-
tilation (41% vs. 39%, respectively) between the 2
groups (80).
535
Preterm Premature Rupture of the Membranes
Like in singleton pregnancies, twin gestations com-
plicated with preterm premature rupture of the mem-
branes (PPROM) are managed expectantly. In a
matched cohort study, the perinatal outcomes were
compared between 99 twin pregnancies and 99 sin-
gletons with preterm premature rupture of the mem-
branes and managed expectantly. There were no sig-
nificant differences in latency to delivery, maternal
infectious morbidity, or average gestational age at
delivery between the 2 groups (81). Another study
comparing 131 singleton with 48 twin pregnancies
with PPROM between 20 and 36 weeks gestation
showed no difference in latency between the 2
groups (4.4 days vs. 3.4 days, respectively). How-
ever, the latency in twins was 1.2 days shorter if
PPROM occurred ⱖ30 weeks gestation (82).
Asynchronous Birth
There have been case reports of delayed delivery of
the retained fetus after the very preterm delivery of 1
of the fetuses. A review of 45 case reports in the
English literature of the management and outcomes
of asynchronous birth in multiple gestations showed
the survival rate of the first born was very poor, and
spontaneous rupture of the membranes was the most
common cause of the loss of the first born. The mean
period of retention of the surviving retained twin/
triplet was 48.9 days. In addition, no significant
difference in fetal outcome occurred with tocolysis,
cervical cerclage, or prophylactic use of antibiotics
(83). The risks of conservative management of asyn-
chronous birth in multiple gestations include infec-
tion and abruptio placenta. The patient should be
thoroughly counseled about these potential compli-
cations.
Vaginal Birth After Cesarean Section
Scant data is published concerning vaginal birth
after cesarean section in twin gestations. The studies
are retrospective, not randomized, controlled trials.
The maternal and neonatal outcomes of 210 twin
gestations with 1 prior low transverse cesarean sec-
tion, of which 118 underwent elective repeat cesar-
ean delivery (no labor) and 92 undertook a trial of
labor, were reviewed. There were no uterine ruptures
in the trial of labor group, and there were no signif-
icant differences in maternal or neonatal morbidity
between the 2 groups in the subset of patients ⱖ34
weeks gestation (84). This information can be used in
536 Obstetrical and Gynecological Survey
counseling the patient regarding a trial of labor with
twins and 1 prior low transverse cesarean section
along with a thorough discussion of the risks.
Timing of Delivery
As discussed in an earlier section, the growth of
twins begins to decline after 38 weeks of gestation.
The lowest incidence of perinatal death (10.5 per
1000 infants) is seen at 38 weeks in twin pregnan-
cies, which corresponds to the incidence of perinatal
death in singleton pregnancies at 43 weeks of gesta-
tion. After 38 weeks gestation, the perinatal death
rate and intrauterine growth restriction of twin preg-
nancies increase substantially (48,49). The data
would therefore suggest that twins are “postterm”
after 38 weeks. The ideal time of delivery for an
uncomplicated twin pregnancy is still uncertain.
However, the literature appears to support delivery
by 38 weeks of gestation. If elective delivery is
considered before 38 weeks of gestation, fetal lung
maturity should be assessed (2).
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