Key Points: Neonatal Jaundice

Neonatal Jaundice

(discussion found here in PDF)

Immature newborn brain is susceptible to toxicity from unconjugated bilirubin resulting in "Kernicterus" or "bilirubin brain damage". Jaundice is the visible manifestation of chemical bilirubinemia. In adults sclera appears jaundiced when serum bilirubin exceeds 2 mg/ dl. In neonates, evaluation of sclera is difficult because of physiological photophobia. Icterus, however, becomes apparent on the skin when serum bilirubin reaches more than 5 mg/ dl. Almost all neonates (60% Term and 80% Preterm) will have bilirubin greater than 5 mg/ dl in the first week of life and about 6% of term babies will have levels exceeding 15 mg/ dl.

Bilirubin Physiology
Source of production:
Bilirubin is derived from the breakdown of heme proteinswhich are present in hemoglobin, myoglobin and certain heme containingenzymes. Three fourths of the bilirubin comes from hemoglobin catabolism.One gram of hemoglobin results in the production of 34 mg of bilirubin. Anormal term newborn produces about 6-10 mg/kg/ day of bilirubin.
· Bilirubin is bound to albumin for transport in the blood. This bound bilirubin does not enter the central nervous system and is nontoxic.
· Upon reaching the liver, only bilirubin enters the liver cell and gets bound to ligandin which helps to transport it to the site of conjugation.
· Conjugation occurs with glucuronic acid to produce mono- and diglucuronides which are water soluble.
· The conjugated bilirubin is transported with the bile to the gut. In the sterile newborn gut, there is an enzyme called beta- glucuronidase which converts bilirubin glucuronide into unconjugated bilirubin which is reabsorbed into the circulation. This is called enterohepatic circulation and is particularly important in babies who are infrequently fed from birth. With frequent feeding early colonization of gut occurs. These bacteria reduce bilirubin glucuronide into stercobilin which is excreted in stool, thus inhibiting the enterohepatic circulation.

Assessment of jaundice
Clinical criteria:
It is very widely used and utilizes the principle that clinicaljaundice first becomes obvious in the face followed by a downward progression as it increases in intensity. Assessment of jaundice should be done in natural light. The finger is pressed on the baby's skin, preferably over a bony part, till it blanches. The underlying skin is noted for yellow color. Extent of jaundice thus detected gives a rough estimate of serum bilirubin. Clinical estimation of bilirubin by experienced person, though reliable, has to be confirmed by laboratory methods.

Physiological jaundice
Immaturity in bilirubin metabolism at multiple steps results in the occurrence of hyperbilirubinemia in the first few days of life. These are:
• Increased bilirubin load on the hepatic cell
• Defective uptake from plasma into liver cell
• Defective conjugation
• Decreased excretion
• Increased entero-hepatic circulation

Characteristics of physiological jaundice:
  • First appears between 24-72 hours of age
  • Maximum intensity seen on 4-5th day in term and 7th day in preterm neonates
  • Does not exceed 15 mg/ dl
  • Clinically undetectable after 14 days.
  • No treatment is required but baby should be observed closely for signs of worsening jaundice.

Pathological jaundice
Presence of any of the following signs denotes that the jaundice is pathological. Treatment is required in the form of phototherapy or exchange blood transfusion. One should investigate to find the cause of pathological jaundice.
  • Clinical jaundice detected before 24 hours of age
  • Rise in serum bilirubin by more than 5 mg/ dl/ day
  • Serum bilirubin more than 15 mg/ dl
  • Clinical jaundice persisting beyond 14 days of life
  • Clay/white colored stool and/or dark urine staining the clothes yellow
  • Direct bilirubin >2 mg/ dl at any time

Causes of jaundice
Hyperbilirubinemia in the first week of life is usually of the indirect variety. Causes are usually classified based on the time of onset of jaundice. While referring a baby with jaundice make sure that either the mother is referred or mother's blood sample is sent.

Appearing within 24 hours of age:
  • Hemolytic disease of newborn, Rh, ABO and minor group incompatibility
  • Infections, i.e., intrauterine viral, bacterial; malaria
  • G-6PD deficiency

Appearing between 24-72 hours of life:

  • Sepsis neonatorum
  • Polycythemia
  • Concealed hemorrhages: cephalhematoma, subarachnoid bleed, IVH.
  • Increased enterohepatic circulation
Appearing after 72 hours:
  • Sepsis neonatorum
  • Neonatal hepatitis
  • Extra hepatic biliary atresia
  • Breast milk jaundice
  • Metabolic disorders

The age of appearance may overlap and the above mentioned grouping is only a general classification. Infection must be ruled out in jaundice appearing any time after third day of life. Even after extensive investigations, cause remains uncertain in over one third of cases. Neonatal jaundice may be multifactorial in origin.

Risk factors of jaundice:
A simple pneumonic for risk factors is JAUNDICE
J - Jaundice within first 24 hrs of life
A - A sibling who was jaundiced as neonate
U - Unrecognized hemolysis
N – Non-optimal sucking/nursing
D - Deficiency of G6PD
I - infection
C – Cephalhematoma/bruising
E - East Asian/North Indian

Breast milk jaundice:
This condition may persist as a prolonged physiological jaundice or it may appear for-the first time after the first week. It is common in solely breast fed babies and the intensity peaks between 10-14 days of life. The bilirubin levels are never high enough to require exchange though phototherapy may occasionally be necessary. If bilirubin is less than 15 mg/ dl at 3 weeks one need not worry. But if bilirubin is > 15 mg/dl at 3 weeks, cessation of breast milk for 48 hours will decrease bilirubin levels dramatically and breast milk can be resumed without any risk of recurrence of jaundice. However, more frequent breast feeds without cessation results in improvement in many.

Workup for pathological jaundice
1. Review maternal and perinatal history
  • Family history of jaundice, liver disease
  • Previous sibling with jaundice for blood group incompatibility
  • Maternal illness during pregnancy
  • Previous history of malaria
  • Traumatic delivery, delayed cord clamping, oxytocin use
  • Birth asphyxia, delayed feeding, delay in meconium passage
  • Breast feeding
2. Physical examination
  • Prematurity
  • Small for gestation: polycythemia, hepato-splenomegaly, cataract, rash.
  • Extravascular bleed: cephalhematoma
  • Pallor: hemolysis, blood loss
  • Petechiae: sepsis, TORCH infections
  • Hepatosplenomegaly: Rh-isoimmunization, sepsis, TORCH infections

3. Laboratory tests (must in all*)
  • Serum bilirubin total and direct*
  • Blood group and Rh for mother and baby*
  • Direct Coomb’s test on infant
  • Hematocrit*
  • Peripheral smear for RBC morphology, evidence of hemolysis and reticulocyte count
  • Sepsis screen
  • Liver and thyroid function tests in cases with prolonged jaundice
  • TORCH titres

Management of jaundice is directed towards reducing the level of bilirubin and preventing CNS toxicity.
1. Prevention of hyperbilirubinemia
  • Early and frequent feeding
  • Adequate hydration
2. Reduction of bilirubin: This is achieved by phototherapy or/and exchange transfusion.
3. Phototherapy
This involves exposure of the naked baby to blue, cool white or green light of wave length 450-460 nm. The light waves convert the bilirubin to water soluble nontoxic forms which are then easily excreted. Every attempt should be made to find out the cause of jaundice.

Side effects of phototherapy
Increased insensible water loss:
  • Provide more frequent and for longer duration extra breast feeding.
Loose green stools:
  • weigh often and compensate with breast milk.
Skin rashes:
  • Harmless, no need to discontinue phototherapy;
Bronze baby syndrome:
  • occurs if baby has conjugated hyperbilirubinemia.
  • If so, discontinue phototherapy.
Hypo or hyperthermia:
  • monitor temperature frequently.

Exchange transfusion
It is still the most effective and reliable method to reduce serum bilirubin.
Anticipation and early referral to a higher centre is indicated.
Choice of blood for exchange blood transfusion
1. In ABO incompatibility:
  • Use O cells of same Rh type, ideal is to have O cells suspended in AB plasma.
2. In Rh isoimmunization:
  • In emergency use O-ve blood. Ideal is O -ve cells suspended in AB plasma. One may use baby blood group but Rh –ve blood also.
3. Other conditions:
  • Baby's blood group.

Maisel's chart
It is used for taking decision regarding treatment in cases of pathologicaljaundice. In presence of any of the following, treat as in next higher bilirubincategory.
• Perinatal asphyxia
• Respiratory distress
• Metabolic acidosis
• Hypothermia
• Low serum protein
• Birth weight <1500>Prolonged indirect jaundice
Following conditions may lead to prolonged indirect jaundice:
• Crigler Najjar Syndrome
• Breast milk jaundice
• Hypothyroidism
• Pyloric stenosis
• Ongoing hemolysis, malaria

Conjugated hyperbilirubinemia
This is rare in the newborn period and is defined as a direct bilirubin level of > 2mg/dl. It is important to document cause as it is never physiological.

Causes of conjugated hyperbilirubinemia:
1. Idiopathic neonatal hepatitis
2. Infections
  • Hepatitis B,
  • TORCH,
  • Sepsis

3. Malformations

  • Biliary atresia (extra and intrahepatic),
  • choledochal cyst,
  • bile duct stenosis.
4. Metabolic disorder
  • Galactosemia
  • Hereditary Fructose intolerance
  • Alpha-l antitrypsin deficiencyTyrosinemia
  • Glycogen storage disease type IV
  • Hypothyroidism
5. Total parenteral nutrition