This document provides information on neonatal hyperbilirubinemia or jaundice. It defines jaundice and discusses the mechanisms and risk factors for both physiologic and pathologic hyperbilirubinemia in newborns. It outlines the evaluation, management, and treatment of hyperbilirubinemia including phototherapy and exchange transfusion. The major points covered are the definition of jaundice, causes of increased and decreased bilirubin levels in newborns, clinical assessment and lab evaluation of hyperbilirubinemia, guidelines for phototherapy and exchange transfusion, and methods to optimize phototherapy treatment.

1. NEONATAL HYPERBILIRUBINEMIA
- DR. NAGESH LONIKAR

2. DEFINITION
JAUNDICE IS YELLOW COLOUR OF SCLERA AND SKIN CAUSED BY
DEPOSIT OF BILIRUBIN.
HYPERBILIRUBINEMIA is defined as a TB >95th percentile on the
hour specific nomogram
-Almost all newborn infants have a serum or plasma total bilirubin (TB)
level >1 mg/dL in contrast to normal adults in whom
the normal TB level is <1 mg/dL.
Approximately 85% of all term newborns and most preterm infants develop
clinical jaundice. ( SERUM BILIRUBIN > 5 mg/dl.)
Also, 6.1% of well term newborns have a peak
TB level >12.9 mg/dL.
A TB level >15 mg/dL is found in 3% of normal term infants.

3. Bilirubin metabolism

5. NONPATHOLOGIC HYPERBILIRUBINEMIA
The serum TB level of most newborn infants rises to >2 mg/dL in the
first week after birth.
In full-term infants -
a peak of 6 to 8 mg/dL by 3 to 5 days of age and then falls.
A rise to 12 mg/dL is in the physiologic range.
In preterm infants-
the peak may be 10 to 12 mg/dL on the fifth day after birth.
Levels <2 mg/dL may not be seen until 1 month of age in both
full-term and preterm infants.

6. MECHANISM OF NONPATHOLOGICAL JAUNDICE
1. Increased RBC volume per kilogram and decreased RBC survival
(90 days vs. 120 days) in infants compared to adults
2. Increased ineffective erythropoiesis and increased turnover of nonhemoglobin
heme proteins
B. Defective uptake of bilirubin from plasma caused by decreased ligandin
and binding of ligandin by other anions
C. Decreased clearance due to decreased UGT1A1 activity. In term infants at
7 days of age, UGT activity is approximately 1% that of adults and does not
reach adult levels until at least 3 months of age.
D. Decreased hepatic excretion of bilirubin.
Increased enterohepatic circulation caused by high levels of intestinal
β-glucuronidase, preponderance of bilirubin
monoglucuronide rather than diglucuronide,
decreased intestinal bacteria
decreased gut motility with poor evacuation of bilirubin-laden meconium

7. PATHOLOGIC HYPERBILIRUBINEMIA
1. Onset of jaundice before 24 hours of age.
2. An elevation of TB that requires phototherapy .
3. Rate of rise in total serum bilirubin (TSB) or
transcutaneous bilirubin (TcB) level of >0.2 mg/dL/hour.
4. Associated signs of illness such as -
vomiting, lethargy, poor feeding, excessive weight loss,
apnea, tachypnea, or temperature instability.
5. Jaundice persisting after 14 days in a term infant

8. Major risk factors for development of severe hyperbilirubinemia :
1. Predischarge TB in a high-risk zone
(>95th percentile for age in hours according to the Bhutani nomogram)
or high intermediate risk zone
2. Jaundice within the first 24 hours after birth.
3. Immune or other hemolytic disease.
4. Gestational age 35 to 36 weeks.
5. Previous sibling with jaundice.
6. Cephalohematoma or significant bruising.

9. Hour specific nomogram for predicting risk of developing severe jaundice

10. CAUSES / MECHANISM OF PATHOLOGIC HYPERBILIRUBINEMIA
1. OVER PRODUCTION OF BILIRUBIN.
2. UNDERSECRETION OF BILIRUBIN .
3. MIXED.

11. Intravascular hemolysis
Fetomaternal blood group
incompatibility (e.g., Rh, ABO)
Red cell structural defects
Hereditary spherocytosis
eliptocytosis, somatocytosis
Nonspherocytic hemolytic
Anemias.
Red cell enzyme deficiency
G6PD deficiency and drugs
Pyruvate-kinase deficiency
hemoglobinopathy
αThalassemia
–ß Thalassemia
Acquired hemolysis
vitamin K, nitrofurantonin,
sulfonamides, antimalarials,
penicillin, oxytocin,
bupivacaine, or infection
Extravascular hemolysis
Petechiae
Hematomas
Pulmonary, cerebral, or occult
Hemorrhage.
Polycythemia
Fetomaternal or fetofetal
transfusion
Delayed clamping of the
umbilical cord
Increased enterohepatic circulation
Pyloric stenosis*
Intestinal atresia or stenosis,
including annular pancreas
Hirschsprung disease
Meconium ileus and/or
meconium plug syndrome
overproduction

12. Metabolic and endocrine
conditions
Galactosemia
Familial nonhemolytic
jaundice types 1 and 2
(Crigler-Najjar syndrome)
Gilbert disease
Hypothyroidism
Tyrosinosis
Hypermethioninemia
Drugs and hormones
Novobiocin
Pregnanediol
Lucey-Driscoll syndrome
Infants of diabetic mothers
Prematurity
Hypopituitarism and
anencephaly
Obstructive disorders
Biliary atresia
Dubin-Johnson and Rotor
syndrome
Choledochal cyst
Cystic fibrosis (inspissated
bile)
Tumor or band(extrinsic
obstruction)
1-antitrypsin deficiency
Parenteral nutrition
Undersecretion

13. Sepsis
Intrauterine infections
Toxoplasmosis
Rubella
CID
Herpes simplex
Syphilis
Hepatitis
Respiratory distress syndrome
Hypoxia-ischemia
Infant of diabetic mother
Severe erythroblastosis fetalis
Mixed disorders

14. Breastfeeding failure jaundice.
typically occurs with lactation failure during the first postnatal week
that leads to insufficient intake-
weight loss .
hypernatremia.
Attributed mainly to the decreased intake of milk.
slower bilirubin elimination.
increased enterohepatic circulation.

15. BREAST MILK JAUNDICE.
Typically, it begins after the first 3 to 5 postnatal days,
peaks within 2 weeks of age, and if breastfeeding is continued,
gradually returns to normal levels over 3 to 12 weeks.
If breastfeeding is stopped, the bilirubin level may fall
rapidly in 48 hours. If nursing is then resumed, the bilirubin may rise
by 2 to 4 mg/dL but usually will not reach the previous high level
Associated with Gilbert disease or
perhaps a factor in human milk, possibly β-glucuronidase,
that deconjugates intestinal bilirubin and promotes its absorption.

16. Clinical evaluationfor hyperbilirubinemia
A. History
1. Family history
family history of jaundice,
anemia,
splenectomy,
early gallbladder disease .
suggests hereditary hemolytic anemia
(e.g., spherocytosis, glucose-6-phosphate
dehydrogenase [G6PD] deficiency).
b. A family history of liver disease may
suggest galactosemia, α1-antitrypsin deficiency,
tyrosinosis, hypermethioninemia, Gilbert disease,
Crigler-Najjar syndrome types I and
II, or cystic fibrosis

17. A sibling with jaundice or anemia may suggest
blood group incompatibility or breast milk jaundice.
2. Pregnancy history
a. viral or toxoplasmosis infection.
b. Infants of diabetic mothers .
c. Maternal drugs
1.interfere with bilirubin binding to albumin (sulfonamides)
2. may trigger hemolysis in a G6PD-deficient
infant (sulfonamides, nitrofurantoin, antimalarials).
d. Labor and delivery history
Birth trauma  cephalhematoma.
birth asphyxia
Delayed cord clamping  neonatal polycythemia  increased bilirubin load.
3. Infant history
a. Delayed or infrequent stooling  to increased enterohepatic circulation of bilirubin
b. Poor caloric intake may decrease bilirubin uptake by the liver.
c. Vomiting can be due to sepsis, pyloric stenosis, or galactosemia

18. Physical examination.
1. Lower gestational age.  more risk of bilirubin toxicity.
2. Small for gestational age (SGA)  polycythemia and intrauterine infections.
3. Microcephaly congenital infections.
4. Extravascular blood bruising, cephalohematoma, or other enclosed hemorrhage.
5. Pallor  hemolytic anemia or extravascular blood loss.
6. Petechiae may suggest congenital infection, sepsis, or erythroblastosis.
7. Hepatosplenomegaly  hemolytic anemia, congenital infection, or liver disease.
8. Omphalitis or other sign of infection.
9. Chorioretinitis  congenital infection.
10. Evidence of hypothyroidism

19. Dermal zones for estimation of Bilirubin toxicity
Serum levels of total bilirubin
( approximate)
Zone 1: =4-6 mg/dl
Zone 2: = 6-8 mg/dl
Zone 3:= 8-12 mg/dl
Zone 4: = 12-14 mg/dl
Zone 5: = > 15 mg/dl
However, visual inspection is not a reliable indicator of
serum TB level or the detection of rapidly rising levels,
especially in infants with dark skin,
&after starting phototherapy.
Jaundice typically progresses in a cephalocaudal direction,
starting in the face.
The highest bilirubin levels are typically associated with
jaundice below the knees and in
the hands.

20. SIGNS OF BILIRUBIN TOXICITY.
Acute bilirubin encephalopathy-
Three phases:
1. Early phase. Hypotonia, lethargy, high-pitched cry, and poor suck.
2. Intermediate phase. Hypertonia of extensor muscles (with opisthotonus,
rigidity, oculogyric crisis, and retrocollis), irritability, fever, and seizures.
3. Advanced phase. Pronounced opisthotonus
(although hypotonia replaces hypertonia after approximately 1 week of age)
shrill cry, apnea, seizures, coma,
death.

21. Risk Factors for Hyperbilirubinemia Neurotoxicity
Isoimmune hemolytic disease
G6PD deficiency
Asphyxia
Sepsis
Acidosis
Albumin <3.0 mg/dL
G6PD, glucose-6-phosphate dehydrogenase deficiency.

22. PATHOLOGY
yellow staining of the brain
neuronal injury.
Grossly, bilirubin staining is most commonly seen
in the basal ganglia,
cranial nerve nuclei,
brainstem nuclei,
cerebellar nuclei,
hippocampus,
anterior horn cells of the spinal cord.

23. Lab evaluation.
1 .Bilirubin = total , direct, indirect
2. The mother's blood type, Rh typing.
3.The infant's blood type, Rh, and direct Coombs test.
4.Peripheral smear for RBC morphology and reticulocyte count.
5Hematocrit & Hb  high = polycythemia
 low= blood loss from occult hemorrhage. Hemolytic disease.
6. G6PD LEVELS.
7. With prolonged jaundice,
tests for liver disease, congenital infections, sepsis, metabolic defects
hypothyroidism are indicated .
8. If direct bilirubin is elevated,
urinalysis and urine culture, urine for reducing substance
newborn screen for hypothyroidism and galactosemia.

24. Algorithm for lab evaluation.

25. MANAGEMENT OF UNCONJUGATED HYPERBILIRUBINEMIA
Initiation of therapy is directed by the hour-specific TB value,
modified by the
presence of any risk factors that increase the risk of brain damage.

26. GUIDELINES FOR INITIATING PHOTOTHERAPY
in full full term (38 week) and near term (35-38 week) infants

27. GUIDELINES FOR EXCHANGE TRANSFUSION
in full full term (38 week) and near term (35-38 week) infants

28. Gestational Age
(week)
Phototherapy.
Total Serum
Bilirubin (mg/dL)
Exchange
Transfusion.
Total Serum
Bilirubin (mg/dL)
<28 5-6 11-14
28 -29 6-8 12-14
30 -31 8-10 13-16
32 -33 10-12 15-18
34 -34 12-14 17-19
Guidelines for phototherapy and exchange transfusion in preterm baby

29. PHOTOTHERAPY
Mainstay of treatment against hyperbilirubinemia.
Highly effective and excellent safety.
Acts by converting insoluble bilirubin to soluble isomers
which are excreted in urine and feces .
MECHANISM:
1. Configurational isomerization.
2. Structural isomerization.
3. Photo oxidation.
TYPES OF PHOTOTHERAPY
1.CFL ( Compact fluroscent lamps)
2. Halogen bulbs
3. LED ( LIGHT EMITTING DIODES)
4.Fiberoptic light sources.
Best is LED phototherapy

30. MAXIMIZING EFFICACY OF PHOTOTHERAPY.
1. Periodic maintenance of phototherapy light.
2. Expose maximal surface area of body.
3. Ensure good hydration and nutrition of baby.
4. Light should fall perpendicularly on baby.
5. Minimize interruption of phototherapy
6. Ambient room temperature should be 25°- 28° C.
7. Remove all cloths except diapers of the baby.
8. Cover the babys eyes with an eye patch which should not block nostrils.
9. Use incubator if baby is preterm & < 2kg. To ensure euthermia.

31. Monitoring and stopping phototherapy
Measure total serum bilirubin every 12-24 hours.
Discontinue phototherapy once two TSB values fall below current
age specific cut offs.
Monitor clinically for rebound hyperbilirubinemia.

32. Exchange transfusion
Double volume exchange transfusion done if
1. TSB levels reach to age specific cut off for exchange transfuion.
2. Or baby shows s/o bilirubin encephalopathy irrespective of TSB levels.
Indications in Rh isoimmunization-
1. Cord bilirubin > 5mg/dL.
2. Cord Hb is < 10 g/Dl.
Technique
Umbilical catheterization.
Push pull method.
Double volume means= 160 ml/kg.