Neonatal Jaundice :

is the yellow discoloration of mucous membranes and skin due to increased bilirubin levels.

Hyperbilirubinemia of It usually occurs during the first week of life and is most frequently caused by indirect
(unconjugated) hyperbilirubinemia that is physiologic in nature.
Visible jaundice occurs in the neonate when the serum bilirubin level exceeds 5 mg/dL.

the newborn
DR. SABREEN RA JOOB
G E N E R A L P E D I AT R I C I A N
5 TH Y E A R / P P U

Classification of jaundice
1. Physiologic jaundice:

2. Nonphysiologic jaundice. This term describes jaundice that is secondary to pathophysiologic

causes and may be further classified as follows:

a. Indirect hyperbilirubinemia

B. direct hyperbilirubinemia :
Common Causes of Indirect Hyperbilirubinemia:-
Physiologic Jaundice :
Physiologic Jaundice, Breast-feeding Jaundice, Breast milk Jaundice, Hemolytic diseases of
newborn (especially Rh & ABO incompatibility), Etiology : ↑ indirect bilirubin production from breakdown of fetal RBC combined with transient
limitation conjugation of bilirubin by the immature liver.
It is a diagnosis of exclusion.
Prematurity, Sepsis, Asphyxia, Polycythemia, Hypothyroidism, Down synd, Infant of diabetic
mother, Cephalohematoma, Delayed bowel movement, Family hx of physiologic jaundice, Drugs In Term infant, it usually started in the 2nd-3rd day of life, peaking in 2nd-4th day & gradually it
e.g. vit K3, Oxytocin (for induction of labor), Hypoalbuminemia, Displacement of bilirubin from its resolve after 5th-7th day.
binding sites on albumin due to acidosis or drugs e.g. Sulfizoxazol or by free fatty acids (due to
hypoglycemia or hypothermia),, Male gender, East Asian race & High altitude. It rarely reachs > 12 mg/dl.
In Preterm infant, it started in the 3rd-4th day of life, peaking in 4th7th day & gradually it
Common Causes of Direct Hyperbilirubinemia:- resolve after 7th-9th day. It rarely reachs > 15 mg/dl. Thus it tends to be slower & longer duration
with higher level.
Neonatal hepatitis, Cong bile duct disorders (atresia, paucity, Byler disease), Cholestasis, Inborn
errors of metabolism, CF, & Sepsis.

Treatment
Factors that suggest non-physiologic jaundice include:- .Physiologic jaundice is benign conditions that usually require no Rx except if other risk factors
are presented e.g. prematurity; therefore it may need phototherapy
1. Jaundice appears in the 1st day of life.
2. TSB > 12 mg/dl in term or > 15 mg/dl in preterm infant.
3. TSB that rapidly increasing > 5 mg/dl/day.
4. Direct bilirubin > 2 mg/dl at any time.
5. Jaundice that persist > 10-14 days.
6. Other factors include: family hx of hemolytic disease, pallor, hepatomegaly, splenomegaly,
vomiting, lethargy, poor feeding, excessive weight loss, abnormal vital signs, light-colored stools,
dark urine positive for bilirubin, failure of phototherapy to lower bilirubin, and signs of
kernicterus.
Breast-Milk Jaundice Breast-Feeding Jaundice:
* It is a rare condition that occurs in ≈ 2% of breast-fed term infants. It may be due to presence of It is more common than above (≈ 13%).
glucuronidase in some breast milk.
It can occur in the 1st week of life exaggerating the physiologic jaundice.
* It occurs after the 1st wk of life, peak in the 2nd or 3rd wk& then gradually resolve, although it
may persist as long as 10th wk of life at lower level. It may be due to decreased milk intake with dehydration and/or reduced caloric intake; it also
may be aggravated by giving glucose water (because it may ↓ milk intake).
*TSB can be as high as 10-30 mg/dl.
Rx.
Frequent breast-feeding including night feeding +/_ supplementation with formula feeding for 1-
2 days.

Rh INCOMPATIBILITY :
Pathophysiology :
The immune system to be sensitized requires at least 1 ml of fetal blood that enters maternal
circulation during labor or abortion →↑ IgM antibody initially which later replaced by IgG which
is readily crosses the placenta and causes hemolytic manifestations.
Therefore, HDN is rarely occurs in the 1st pregnancy, but it increasing with subsequent
pregnancies (although not always).
ABO incompatibility is partially protective against Rh incompatibility due to rapid removal of Rh-
positive cells from maternal circulation before sensitization by the pre-existing anti-A or anti-B
IgM maternal antibodies.

After birth, there may be blue berry-muffin rash (which represent dermal erythropoiesis).
Petechiea & purpura may be due to thrombocytopenia or DIC. Bilirubin pigment may stain the
cord, vernix & amniotic fluid.
Hypoglycemia frequently occur in severe disease which may be due to hyperinsulinemia!.
Clinical manifestations :
The severity is ranged from mild hemolysis to hydrops fetalis.
Severe anemia in the fetus → compensatory hyperplasia of erythropoietic tissue → massive
enlargement of the liver and spleen.
When the compensatory capacity of the hematopoietic system is exceeded, profound anemia
occurs and results in pallor, signs of cardiac decompensation (cardiomegaly, respiratory distress),
anasarca, and circulatory collapse.
The clinical picture of excessive abnormal fluid in ≥ 2 of fetal compartments (skin, pleura,
pericardium, placenta, peritoneum, amniotic fluid) is termed "Hydrops Fetalis" which frequently
results in death in utero or shortly after birth.
The severity of hydrops is related to the level of anemia and the degree of reduction in serum
albumin which is due in part to hepatic dysfunction.
INVESTIGATIONS :
ANTENATAL DIAGNOSIS :-
Serologic tests; expectant parents' blood types should be tested for potential incompatibility. Fetal Rh
status can be determined by isolating fetal cells (or fetal DNA) from the maternal circulation. Rh –ve
woman with previous hx of transfusions, abortion, or pregnancy should suggest the possibility of
sensitization,
thus measure maternal titer of IgG antibodies to D antigen at ≈14, 30, and 36 wk of gestation.
The presence of elevated antibody titers at the beginning of pregnancy, a rapid rise in titer, or titer ≥ 1
: 64 suggests significant hemolytic disease (although the exact titer correlates poorly with the severity
of disease).
2. Ultrasound; Real-time US can detect the progression of disease including hydrops. Doppler US can
confirm the severe disease by detect ↑ vascular resistance in the middle cerebral artery of fetus.
3. Amniocentesis was classically used to assess fetal hemolysis by measuring bilirubin in the amniotic
fluid. Percutaneous Umbilical Blood Sampling (PUBS) is used to measure bilirubin, Hb, pcv…etc; it also
can be used to transfuse packed RBC in severely affected fetus
 POSTNATAL DIAGNOSIS :-
. POSTNATAL Dx:-
1. Immediately after birth, take blood from the umbilical cord or from infant & test for TSB, ABO,
Rh, Hb, pcv as well as for the Direct Coombs test (which usually strongly +ve and may remain so
for a few days to several months). Bilirubin (especially indirect) can rapidly rise within 6 hr of life.
Hb is usually very low, but may be normal if compensatory hematopoiesis is adequate.
2. BLOOD FILM shows polychromasia, reticulocytosis & nucleated RBC. WBC may be ↑ &
platelets usually ↑ in severe disease.
3. Indirect Coombs test should also be done on the maternal blood not only to establish the
diagnosis but also for selection of the most compatible blood for exchange transfusion.
COMPLICATIONS :
Untreated severe disease either → death or kernicterus.
Late anemia; either hemolytic or hyporegenerative.
Rx by iron, erythropoietin or sometimes blood transfusion.
Rarely, inspissated bile syndrome; the cause is unclear, it → ↑ direct & indirect bilirubin, but
jaundice usually clears spontaneously within few weeks to months.
Prevention
Anti-D globulin IM injection; 300 μg (1 ml of RhoGAM) within 72 hr to the mother after delivery of Rh-
positive infant or after any condition that potentially causes feto-maternal transfusion.
* Note: The dose 300 μg can eliminate only ≈10 ml fetal RBC from the maternal circulation, thus for
larger transfusion, higher dose is required.
TREATMENT :
Antenatal ; If the fetus is near term, deliver. If preterm, assess lung maturity & treat with
corticosteroids, then deliver. If extremely preterm, do intravascular fetal transfusion of packed
RBC through the umbilical vein which can be repeated every month until delivery.
Postnatal Rx; If there is signs of severe disease, immediate resuscitation with supportive
measures e.g. O2 for respiratory distress, incubator for hypothermia, sodium bicarbonate for
acidosis & small transfusion with O –ve packed RBS for severe anemia (before ET).
In Rh incompatibility, the selection of blood group for exchange transfusion is either O–ve or
others (A or B) if both mother & infant were of the same group, but the Rh must always be –ve
ABO INCOMPATIBILITY
It is the most common cause of HDN, but it less severe than Rh incompatibility either because of
low antigenicity of ABO factors or the anti-A or anti-B antibody may bind to a non-erythrocytic
cells which contain A or B antigen.
Pathophysiology :. The mother is usually type O and the infant is type A or B. Although antibodies
against A and B factors occur without previous sensitization, i.e. “natural” antibodies, they are
usually IgM antibodies that do not cross the placenta. However, IgG antibodies to A antigen may
also be present which can cross the placenta, so A-O isoimmune hemolytic disease is more
common than B-O disease& may be found in first-born infants.
Mothers who have become sensitized against A or B factors from a previous incompatible
pregnancy may also exhibit IgG antibody.

Clinical manifestations :
Most cases are mild, but jaundice may be present in the 1st day & rise rapidly,
pallor usually is not present & hydrops is extremely rare.
TREATMENT :
ABO incompatibility usually requires only phototherapy, but some severe cases may require
exchange transfusions with type O blood & the same Rh type of the infant.
Some infants may exhibit slowly progressive anemia after several weeks of age which may
require transfusion of packed RBCs, thus post discharge monitoring of hemoglobin or Hct is
essential in newborn with ABO hemolytic disease.

Investigation :
Bl. gr. for the infant & mother.
TSB (especially indirect) is elevated.
Direct Coombs test is weakly to moderately positive.
CBP; Hb is normal or low, Reticulocytosis, Nucleated RBCs ↑, Polychromasia & Spherocytosis.

KERNICTERUS (Bilirubin Encephalopathy)

Etiology : Kernicterus is a neurologic syndrome resulting from the deposition of unconjugated
bilirubin in the basal ganglia & brainstem nuclei which become stained yellow then atrophy.
Risk factor for development of Kernicterus include any cause that leads to disruption of the
blood-brain barrier e.g. HDN, especially if associated with prematurity, sepsis, asphyxia, IVH,
drugs…etc.
Kernicterus is usually occurs in the 1st wk of life, but may be delayed depending on; the cause of
jaundice, infant's well being, level of unconjugated bilirubin & duration of exposure.
However, Kernicterus is unusual after the 4th day in term infant & 7th day in the preterm.
 Clinical Manifestation :

It usually appear 2–5 days after birth in term infants and as late as the 7th day in premature infants. It passes into several stages:-
A- ACUTE FORM:-
!. B- CHRONIC FORM:-
4. Later in the 1st yr; hypotonia, active deep tendon reflexes, obligatory tonic neck reflexes, opisthotonos,
1. 1st 1–2 days; features are non-specific e.g. lethargy, poor sucking, poor reflexes, hypotonia, convulsions, & delayed motor skills
and seizures.
2. Following days till end of 1st wk; patient deteriorate with hypertonia of extensor muscles only
5. In the 2nd yr; the opisthotonos and seizures abate, but irregular, involuntary movements,
(manifested as opisthotonos), twitching of the face or limbs, high-pitched cry, bulging fontanel,
muscle rigidity, and, in some infants, hypotonia increase steadily.
respiratory distress and fever.
3. After the 1st wk; patient develop hypertonia and stiffly extending their arms in an inward
rotation with the fists clenched as well as convulsions. Many infants who progress to these severe 6. At 3 yr of age; complete neurologic syndrome is often apparent which consists of bilateral
neurologic signs die (75%); the survivors are usually seriously damaged, but may appear to choreoathetosis with involuntary muscle spasms, extrapyramidal signs, seizures, mental
recover in the following 2–3 month. deficiency, dysarthric speech, high frequency hearing loss, squint and defective upward eye
movements..

Treatment of Neonatal Jaundice :

Prevention : There is no Rx for Kernicterus, but there are some situations that should be avoided PHOTOTHERAPY:
to prevent Kernicterus e.g.:-
PT is depends on high intensity of light in the visible spectrum maximally in the blue range (420–
1. Early discharge with no early follow-up.
470 nm) which also present in the sunlight.
2. Lack of concern regarding the presence of jaundice.
The bilirubin in skin absorbs light energy → 2 photochemical reactions:-
3. Underestimation of the severity of jaundice by visual assessment.
1. Reversible photo-isomerization reaction converting the toxic unconjugated bilirubin into an
4. Failure to check the TSB in infant with jaundiced in the 1st 24 hr. isomer called 4Z,15E-bilirubin which can then be excreted in bile without conjugation.
5. Failure to recognize the presence of risk factors for Kernicterus. 2. Irreversible structural isomer called Lumirubin, converted from native bilirubin and can be
excreted by the kidneys in the unconjugated state.
6. Failure to respond to parental concern regarding jaundice, poor feeding, or lethargy.
7. Delay in measuring TSB despite marked jaundice or delay in initiating PT or ET.
 EXCHANGE TRANSFUSION :is performed for rapidly rising bilirubin levels and dangerously
elevated bilirubin levels to prevent complications

Complications of phototherapy : IV Immunoglobulin :

It is an adjunctive therapy for NNJ due to isoimmune hemolytic disease when bilirubin is approaching
1. PT is contraindicated in the presence of Porphyria. exchange levels, it may act by reducing hemolysis.
2. Corneal damage due to light exposure, thus shields is required to close the eyes (but be careful not to close the
nose).
Dose is 0.5–1.0 g/kg/dose; repeated after 12 hr.
3. Dehydration due to loose stools & overheating with ↑ insensible water loss, thus patient need additional fluid,
especially when TSB is near ET.
4. Skin rash e.g. erythematous macular rash, purpuric rash (due to transient porphyrinemia).
Metalloporphyrins :
Bronze Baby syndrome is a dark, grayish brown discoloration due to presence of significant amount of conjugated
bilirubin, it may last for many months; however, phototherapy can be continue if needed Although it being evaluated as yet, it is potentially an important alternative therapy.
5. Anemia may develop due to continuous hemolysis which may need blood transfusion later on.
It acts as a competitive enzymatic inhibitor for heme-oxygenase which converts heme-protein to
Infants with HDN or TSB near the toxic level need to be checked every 4- 6 hr by measuring TSB, Hb, pcv & put it biliverdin which consequently converted to the unconjugated bilirubin.
on the Nomogram because PT may require 6-12 hr to have a measurable effect as well as the skin color after PT
cannot be relied on because the yellow discoloration may disappear . It have been used especially for ABO incompatibility, G6PD deficiency, or when blood products are
discouraged for ET; it given as single IM injection.

Direct hyperbilirubinemia
is a conjugated or direct bilirubin level that is >15% of the total bilirubin level. This is always That the most common cause is biliary atresia and neonatal hepatitis and the most common cause in NICU
pathologic in neonates is probably TPN use in the preterm infant.

* Conjugated hyperbilirubinemia is never normal or physiologic . Is always pathologic and must

be evaluated promptly .
* Early diagnosis is urgent and treatment is essential because it means a better outcome for the The goal is to complete evaluation by
infant and can be potentially lifesaving(eg biliary atresia) 45-60 days
To evaluate direct hyperbilirubinemia :
-hepatic and biliary ultrasound (to evaluate for biliary atresia and choledochal cyst),
-serologies for viral hepatitis,
-evaluation for metabolic disease, -
-evaluation for α-1-antitrypsin disease, and liver biopsy may be warranted -