Neonatal Jaundice
Overview of Neonatal Jaundice
• The yellowish colouration (or yellowish discolouration) of the skin and or mucous
membranes, the result of accumulation of unconjugated (indirect) or conjugated (direct)
bilirubin or both
• Also known as neonatal hyperbilirubinaemia
• Is the most common condition that requires medical attention in newborns
• In some infants, serum unconjugated bilirubin levels may excessively rise, which raise a
concern because it is neurotoxic and can cause death and or lifelong neurologic sequelae
in infants who survive (kernicterus)
• Black infants are affected less often than white infants, and Asian infants have
particularly high rates of jaundice
• The risk of developing significant neonatal jaundice is higher in male infants
• The risk of significant neonatal jaundice is inversely proportional to gestational age.
Pathophysiology
• Bilirubin is produced in the reticuloendothelial system as the end product of heme
catabolism
o Approximately 75% of bilirubin is derived from haemoglobin
• Unconjugated bilirubin is transported in the plasma tightly bound to albumin
o Binding of bilirubin to albumin increases postnatally with age and is reduced in
infants who are ill
• Presence of binding competitors, such as certain drugs (e.g. cotrimoxazole) also decreases
the binding affinity of albumin for bilirubin
• A fraction of unconjugated bilirubin in serum is not bound to albumin (it is ‘free’)
• This free bilirubin is able to cross the blood-brain barrier, staining the basal ganglia and
leading to neurotoxicity
• Bilirubin is bound to glucuronic acid (conjugated) in the liver
• Physiological (unconjugated) jaundice results from:
o Bilirubin production elevated because of increased breakdown of foetal erythrocytes
o Excretory capacity of the liver is low both because of low concentrations of the
binding protein in the hepatocytes and because of low activity of glucuronyl
transferase (the enzyme responsible for binding bilirubin to glucuronic acid) thus
making bilirubin water soluble (conjugation)
• Pathological (unconjugated or conjugated) jaundice results from: o Increased production of unconjugated biribubin because of increased haemolysis (e.g.
in blood group incompatibilities, and in non-immune haemolytic disorders )
o Decreased clearance of bilirubin may play a role in several metabolic and endocrine
disorders
o Obstructive jaundice, as a result of obstruction to bile flow, occurs leading to
conjugated such as in biliary atresia (an extremely rare cause of newborn jaundice).
Risk Factors
• Genetics and familial risk/history
o Previous sibling with neonatal jaundice (particularly if the jaundice required
treatment)
o Family members with jaundice or known inherited syndromes
o Anaemia, splenectomy, or bile stones in family members
o Known heredity for haemolytic disorders
• Maternal factors, especially infants of diabetic mothers
• Incidence is higher in premature infants and in infants with low birth weight
• ABO and Rhesus blood group incompatibility
• Congenital infection (maternal illness suggestive of viral or other infection) .
Types and Causes of Neonatal Jaundice 1. Physiological Jaundice
• Normal transitional phenomenon in most infants (as explained in the pathophysiology
above)
• Presentation is typically on the second or third day of life
• Bilirubin levels are never higher than 205 μmol/litre (12 mg/100 ml)
2.Pathological Jaundice
• Jaundice that is visible during the first 24 hours of life
• Infants who present with jaundice after 3 to 4 days of life
• Severe jaundice or jaundice that continues beyond the first 1 to 2 weeks of life
Causes • Blood group incompatibilities (e.g. Rh, ABO)
• Non-immune haemolytic disorders (spherocytosis, G-6-PD deficiency)
• Immune-haemolytic anaemia
• Genetic causes such as Gilbert’s syndrome
• Galactosemia
• Polycythemia
• Hypothyroidism
• Obstructive jaundice (Conjugated hyperbilirubinaemia)
o Biliary atresia
o Hypertrophic pyloric stenos is
o Choledochal cyst
• Congenital infections with cytomegalovirus, toxoplasmosis, HIV and hepatitis B or C
(maternal history may be suggestive)
• Maternal drug intake
• Delayed cord clamping
• Birth trauma with bruising, cephalohaematoma (increased breakdown of heme products) .
Clinical Presentation • Yellow colour visible in the face and forehead, may apply pressure on the skin, since
blanching reveals the underlying colour.
o In dark-skinned individuals, may first notice under the tongue or in the sclera
• The jaundice then gradually becomes visible on the trunk and extremities
• More intense jaundice may be associated with drowsiness
• Overt neurologic findings, such as changes in muscle tone, seizures and high pitched cry
are danger signs and require immediate attention to prevent kernicterus
• Hepatosplenomegaly, petechiae, and microcephaly may be associated with haemolytic
anaemia, sepsis and congenital infections
• Passing clay (pale) coloured stool
• Weight loss or failure to gain weight
Investigations • Serum bilirubin (total, unconjugated and conjugated)
• Urine and stool analysis
• Additional investigations may be indicated in infants
o Presenting with jaundice on the first or after the third day of life
o Who are anaemic at birth
o In whom serum bilirubin levels are elevated enough to trigger treatment
o With jaundice persisting beyond the first 2 weeks of life
o In whom family, maternal, pregnancy, or history suggest the possibility of pathological jaundice
o Whose examination reveals findings not explained by simple physiologic
hyperbilirubinemia
• Additional investigations
o Blood type and Rh determination in mother and infant
o Direct antiglobulin test (DAT) in the infant (direct Coombs test)
o Haemoglobin and hematocrit values
o Serum albumin levels
o Liver function test (LFT)
o Toxoplasmosis, rubella cytomegalovirus, herpes simplex, HIV, hepatitis B & C,
Epstein Barr virus and syphilis (TORCHES) screening may be indicated in infants
with hepatosplenomegaly, petechiae, thrombocytopenia, or other evidence of
hepatocellular disease
o Abdominal ultrasonography for obstructive jaundice.
Treatment and Complications of Neonatal Jaundice • Phototherapy and exchange blood transfusion are the most widely used therapeutic
modalities in infants with neonatal jaundice
• Other treatment will depend on the underlying cause
Phototherapy
• Treating neonates with unconjugated jaundice to avoid neurotoxicity
o Total serum bilirubin levels > 350 µmol/L (20 mg/dL) in full-term infants
o Treatment is initiated at lower levels in premature infants because risk of bilirubin
encephalopathy occurs at lower total serum bilirubin levels than in mature infants
• Key points during phototherapy
o Infant should be naked except for nappy (if necessary) so as to irradiate a larger area
o Eyes should be covered to reduce risk of retinal damage
o Distance between the infant’s skin and the light source (fluorescent lamps with
wavelength of 450 nm) should be no greater than 50 cm (20 in).
o Phototherapy is safe, however, the following complications have been noted:
Insensible water loss- give fluid supplementation according to the infant’s needs,
usually 30 mls/kg/day (assess urine output and signs of dehydration)
Loose stools (or diarrhoea) which may also create a need for fluid
supplementation
• A child should be referred to hospital for this treatment
Exchange Transfusion
• For avoiding bilirubin neurotoxicity (encephalopathy) when other therapeutic modalities
have failed or are not sufficient
• A child should be referred to hospital for this treatment
Surgical Care
• Not indicated in infants with physiologic neonatal jaundice
• Indicated in biliary atresia (effective if performed before baby reaches 2 months)
• A child should be referred to hospital for this treatment.
Complications of Neonatal Jaundice 1. Bilirubin encephalopathy (see below)
Bilirubin Encephalopathy (Kernicterus) Brain damage as a result of hyperbirubinaemia, in which unconjugated bilirubin crosses
the blood brain barrier (BBB) and stains the basal ganglia
• Such staining can occur in the absence of severe hyperbilirubinemia, where factors
increasing permeability of BBB (e.g. infection) may play a role
• Acute bilirubin toxicity appears to occur in the first few days of life of the term infant
• Preterm infants may be at risk of toxicity for slightly longer than a few days
• Presentation
o Typical and non specific presentation
Decreased alertness
Hypotonia
Poor feeding
o Specific presentation
Hypertonia, backward arching of the neck, opisthotonus (backward arching of the
back), or both
Infants who progress to this phase develop long-term neurologic deficits
Hypotonia is a typical sign (infants aged > 1 wk)
o Chronic bilirubin encephalopathy (long term sequelae) includes abnormalities in:
Extrapyramidal (athetosis > chorea)
Visual (upward gaze)
Auditory systems (hearing loss)
Minor intellectual deficits can also occur
References • Behrman, R.E., & Kliegman, R.M. (2002). Nelson Essentials of Paediatrics. (4th ed.)
Pennsylvania: Saunders Company.