Neonatal

Definition hyperbilirubinemia
yellowish discoloration of skin and mucous membranes of the neonate.

The normal serum bilirubin in adult is 1 mg/dl.

clinical jaundice appears
in adults at a bilirubin level of 2 mg/dl
in neonates at a bilirubin level of 7 mg/dl.
Kramer's rule
zone 1 2 3 4 5

Total 6 9 12 15 15
bilirubin
Incidence

.65% of newborns are clinically jaundiced .

 Hb
From old RBCS

Bilirubin metabolism HEME

Heme Oxygenase

Iron BILIVERDIN
Biliverdin Reductase

LIVER
Enterohepatic circulation CO UCB
ALBUMIN

UCB UCB
LIGANDIN
Stercobilin LIVER - Glucorunidase UCB +
Urobilinogen & Glucoro
Urobilin CB nic acid

Bacterial flora

Stercobilinogen
 Bilirubin metabolism:
Bilirubin is the end product of the
catabolism of hem and is produced by the
breakdown of red blood cell hemoglobin.
Hemoglobin is hydrolyzed into heme and
globin
Globin entered into the amino acid pool.
Heme will be hydrolyzed into
protoporphyrin and iron:
 Iron will enter into iron pool
Protoporphyrin is oxidized by heme
oxygenase enzyme into biliverdin.
Biliverdin is then reduced by biliverdin
reductase into bilirubin
(unconjugated bilirubin) which will be
excreted in the blood.
 In the blood:
Bilirubin exists in several forms in the
blood but is predominantly bound to serum
albumin.
Free unconjugated bilirubin, and possibly
other forms may enter the central nervous
system and become toxic to the brain
cells.
 In the liver:
Bilirubin will be detached from albumin
and transported to the liver cells by special
mechanisms.
Bilirubin then is bound to ligandin for
transport to the smooth endoplasmic
reticulum for conjugation.
It is conjugated by uridine diphosphate
glucoronyl transferase enzyme.
 Conjugated bilirubin is water soluble and
can be excreted in the urine,
but most of them is excerted as a bile into
the intestine.
In children and adults, conjugated bilirubin
is further metabolized by bacteria in the
intestine and excreted in the feces.
 In the intestine:
On the other hand, most of the CB is reduced by
the action of intestinal bacterial flora, mainly
E.coli, into stercobilinogen (colorless) which will
be oxidized inside as well as outside the
intestine giving rise to stercobilin (brown in
colour).
Small fraction of CB is deconjugated by the
action of B-glucuronidase enzyme, present in
the intestine into UCB which will be reabsorbed
(entero-hepatic circulation of bilirubin).
Hyperbilirubinemia presents in one of two forms in the neonate

Conjugated Hyperbilirubinemia
Unconjugated Hyperbilirubinemia:
physiologic
pathologic.
Unconjugated Hyperbilirubinemia

Definition
Elevations of indirect serum bilirubin are related to
bilirubin load minus bilirubin excretion
and are therefore dependent on the gestational age
and chronological age of the infants
 Causes
1. Increased bilirubin load:
Hemolytic disease of the newborn most common cause
.
ABO incompatibility Spherocytosis
Rhesus incompatibility infantile pyknocytosis
G6PD deficiency sickle cell disease.
pyruvate kinase deficiency
Polycythemia
IDM
twin to twin transfusion
IUGR
blood extravasation
IVH, cephalhematoma and bruises
2. Defective transport:
defective ligandin
3. Defective conjugation:
Physiologic jaundice

Congenital
Crigler Najjar syndrome I& II

Acquired
asphyxia
acidosis
sepsiss
hypothermia
hypoglycemia
drugs
( aspirin, sulfonamides, frusemide and chloral hydrate).
4. Increased enterohepatic circulation :
Ileus
intestinal obstruction
congenital megacolon
 Breast milk jaundice.
it is characterized by high peak (10-30 mg/dl),
peaking by days 10-15 of life and slower decline in
the serum bilirubin concentration.
Factors associated with an abnormality of milk
itself may include:
pregnandiol in the milk, increased concentration of
fatty acids, or increased entero-hepatic-circulation
of bilirubin.
Interruption of breast feeding for 24-48 h at
unacceptable levels results in a rapid decline.
Exclusion criteria for physiologic jaundice:
Physiological Pathological
Onset 2nd-3rd day 1st 24 hours
Rate < 5 mg% / 24 >5 mg% / 24 hours
hours
Peak <12.9 mg% in full term >12.9 mg% in full term
< 15 mg in preterm > 15 mg in preterm

Duration 7 days in full term 14 Longer

days in preterm

Direct always < 1mg% may be >1mg%-

bilirubin
level
Exclusion criteria for physiologic
jaundice:
Unconjugated bilirubin level >12.9 mg/dl in term
infants
Unconjugated bilirubin level >15mg/dl in
preterm infants
Bilirubin level increasing at a rate >5 mg/dl/day.
Jaundice in the first day of life
Conjugated bilirubin >2 mg/dl
Clinical jaundice persisting > 1week in full-term
or > 2 weeks in preterm infants.
Causes of physiologic jaundice :
Increased bilirubin load: because larger
red blood cell volume, the shorter life
span of red blood cell, and increased
entero-hepatic circulation.
Defective uptake of bilirubin by the liver
Defective conjugation
Impaired excretion into bile
Overall impairment of liver function.
 Rh hemolytic disease of the
newborn (Rh-HDN):
If an Rh-ve mother get pregnant to an Rh
+ve fetus,
leakage of fetal RBCs across the placenta
into the maternal circulation may lead to
formation by the mother of IgG antibodies
directed against fetal antigens.
These Ig antibodies can cross the placenta
and induce destruction of fetal RBCs.
 However, they are not usually produced on the
first exposure to the antigen, but require initial
sensitization with an amplified response on the
second or subsequent exposures.
So, Rh-HDN dose not occur in the first baby
unless the mother was previously sensitized
from previous mismatched blood transfusion or
from feto-maternal bleeding at abortion or
amniocentesis.
 ABO-hemolytic disease of the
newborn:
ABO-HDN is caused by the reaction of
maternal anti-A or anti-B antigens on the
RBCs of the fetus or newborn infants.
It is usually seen in A or B infants born to
type O mothers.
 Clinical findings and diagnosis:
History:
1. Previous siblings
2. Family history .
3.Maternal illness during pregnancy
4.Maternal drugs.
5. Obstetric history.
6. Breast feeding.
7. Time of appearance.
 Physical examination:
Jaundice is often apparent in the face, especially the nose,
then descending to the trunk and lower extremities as
the degree of jaundice increases.
Jaundice can be demonstrated in some infants by
pressing lightly on the skin with a finger.

The examiner should search for:

Areas of bleeding e.g. cephalhematoma or ecchymosis

Hepatosplenomegaly may signify hemolytic disease
liver disease
infection
Signs of prematurity or postmaturity
Plethora: seen with polycythemia
CNS examination for early manifestations of bilirubin
encephalopathy
 Laboratory diagnosis
1- Total, Direct and indirect serum Bilirubin .
2- Hb content, haematocrite value, Reticulocytic
count, RBC morphology.
3- Blood type, Rh, direct coombs test of
the infant.
4- Blood type Rh, indirect coombs test of
the mother.
5- In prolonged jaundice, test for liver disease,
congenital infection,sepsis, metabolic defects,
hypothyroidism.
Others: G6PD screening, Osmotic fragility test,
liver function test, thyroid function test
, blood and urine culture, urine and amino acid
and organic acid measurements.
 *Hemoglobin level and Hb = Polycythemia
hematocrite

= Hemolytic disease
Hb

Reticulocytes Reticulocytes

Blood loss
*Coombs test

+ve -ve

Rh ABO Cell wall Enzyme

e.g.Spherocytosis G6PD
 Treatment

I. General treatment:
- Establish causes of the jaundice.
- Measure bilirubin level serially.
- Good hydration & adequate
caloric intake help the liver to
conjugate the bilirubin efficiently.
II. Specific treatment:
- Phototherapy.
- Exchange transfusion.
 Phototherapy
Types of Phototherapy

green light makes babies look sick

unpleasant to work in

Blue fluorescent tubes widely used

work best

White (daylight) fluorescent tubes less efficient

Fiberoptic light limited to surface area

 Basic principles

Bilirubin absorbs light primarily around 450 nm.

a dose-response relationship exists between
the amount of irradiation and reduction in serum bilirubin.

the energy delivered to the infant's skin decreases with increasing

distance between the infant and the light source.
This distance should not be greater than 50 cm (20 in).

the efficiency of phototherapy depends on

the amount of bilirubin that is irradiated.
Irradiating a large skin surface area is more
efficient than irradiating a small area.

Phototherapy is effective because :

Photo-oxidation was believed to be responsible for the beneficial
effect of phototherapy..
Configurational isomerization is a very rapid process that changes some
of bilirubin isomer to water-soluble isomers
 Technique of phototherapy

2 hours The infants are turned every

5-8cm
The infant should be naked except for diapers
The eyes should be covered to reduce risk of 45cm
retinal damage
The distance between the infant's skin and the
light source not more than 45cm
The space between the incubator and the lamp 5-
8cm
Skin color is not a guide to hyperbilirubinemia in infants undergoing phototherapy
complications

DEHYDRATION
DIARRHEEA
DERMATATOLOGICAL RASH
DAMAGE OF RETINA
DAMAGE TO TESTES
DEFECTIVE MATERNAL INFANT BONDING
 Exchange
transfusion

Mechanism
Exchange transfusion removes partially hemolyzed
and antibody _ coated RBCs as well as unattached
antibodies and replace them with donor RBCs lacking
the sensitizing antigen
 sndicationI
when phototherapy fails

correct anemia and prevent heart failure in hydropic infants

stop hemolysis and bilirubin production by removing antibody and sensitized RBCs.1

in hemolytic disease; immediate exchange is indicated if :

The cord bilirubin level is over 4.5 mg/dL and the cord
hemoglobin level is under 11 g/d
The bilirubin level is rising over 1mg/dL per hour despite phototherapy

The heamoglubin level is between 11 and 13 gm/dL and the bilirubin

level is rising over 0.5 mg/dL per hour despite phototherapy
The bilirubin level is 20 mg dL or it appears that it will reach 20 mg/dL
at the rate it is rising.
Volume of blood
)double blood volume is needed (285body weight

Type of blood used

In Rh incompatibility, Rh-ve group cross matched with the mother

In ABO incompatibility O+, O- group cross matched with the mother

blood
Other causes: infants blood group after cross matching.1
Complications
Embolization, thrombosis, infarction..1

Arrhythmia, heart failure, arrest.1

Electrolyte disturbances.1
Hyperkalemia, hypoglycemia, hypernatremia, hypocalcemia, acidosis

Infections: HIV, CMV, Hepatitis.1

Thrombocytopenia, anemia

Graft- versus-host disease.1

Miscellaneous: hypothermia, hyperthermia and possibly NEC .1

 Procedures:
Transferred blood
Umbilical vein

Syringe (10 ml)

Umbilical catheter
Tripartate valve

Removed blood
 Tripartate valve
Way from donor blood

Valve

Way to syringe

Valve

Way to removed blood

 Other
therapies
In infants with breast milk jaundice, interruption of breastfeeding
for 24-48 hours and feeding with breast milk substitutes often
helps to reduce the bilirubin level.

Prophylactic treatment of Rh-negative women with Rh immunoglobulin

Phenobarbital, an inducer of hepatic bilirubin metabolism

 Kernicterus (Bilirubin encephalopathy

Definition:
pathologic diagnosis refers to yellow staining of the brain by bilirubin
. together with evidence of neuronal injury
* The staining is most severe in: Basal ganglia.

Globus pallidus.
Putamen.
Caudate nuclei.

:Etiology

The lipid soluble UCB can cross the blood brain barrier and diffuse into the brain cells
 Clinical manifestations:

:Stage I
Poor Moro reflex, poor feeding, vomiting, high pitched cry, hypotonic and lethargy

:Stage II
Hypertonia, Opithotonous, seizures, fever, oculogyric crises, and paralysis of
upward gaze. Many infants die in this phase

Stage III

Hypotonia replaces hypertonia after about one week of age:

:Treatment

phototherapy until exchange starts

immediate exchange transfusion
 Conjugated hyperbilirubinemia
Neonatal cholestasis(

Caused by obstruction to the bile flow. The most common

causes are:
1.Neonatal hepatitis syndromes: ( intrahepatic cholestasis)
a. Idiopathic neonatal hepatitis.
b. Infectious hepatitis in a neonate.
c. Intrahepatic bile duct paucity.
2.Extrahepatic biliary atresia:
3.Metabolic diseases as galactosemia