Causes

• Physiological jaundice:
  • Results from increased erythrocyte breakdown and immature liver function.
  • Presents at two or three days old, begins to disappear towards the end of the first week and has resolved by day 10.
  • The bilirubin level does not usually rise above 200 μmol/Land the baby remains well.
  • However the bilirubin level may go much higher if the baby is premature or if there is increased red cell breakdown, eg extensive bruising, cephalhaematoma.
• Early neonatal jaundice (onset less than 24 hours):
  • Haemolytic disease: eg haemolytic disease of the newborn (rhesus), ABO incompatibility, glucose-6-phosphate dehydrogenase deficiency, spherocytosis
  • Infection: congenital (eg toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex, syphilis) or postnatal infection
  • Increased haemolysis due to haematoma
  • Maternal autoimmune haemolytic anaemia: eg systemic lupus erythematosus
  • Crigler-Najjar syndrome or Dubin-Johnson syndrome
  • Gilbert's syndrome
• Prolonged jaundice (jaundice lasting for longer than 14 days in term infants and 21 days in preterm infants):
  • Infection, eg urinary tract infection
  • Hypothyroidism, hypopituitarism
  • Galactosaemia
  • Breast milk jaundice: baby is well and the jaundice usually resolves by six weeks but occasionally continues for up to four months
  • Gastrointestinal (GI): biliary atresia, choledochal cyst, neonatal hepatitis
• Conjugated hyperbilirubinaemia:
  • Infection
  • Parenteral nutrition
  • Cystic fibrosis
  • Metabolic: alpha-1-antitrypsin deficiency, galactosaemia, aminoacidurias, organoacidaemias
  • GI: biliary atresia, choledochal cyst, neonatal hepatitis
  • Endocrine: hypothyroidism, hypopituitarism

Risk factors

The risk of developing significant neonatal jaundice is increased in:

• Low birthweight: premature and small for dates
• Breast-fed babies
• Infants of mothers who have diabetes
• Male infants
• East Asians
• Populations living at high altitudes

Presentation

• Neonatal jaundice first becomes visible in the face and forehead. Blanching reveals the underlying colour. Jaundice then gradually becomes visible on the trunk and extremities.
• In most infants, yellow colour is the only finding on physical examination. More intense jaundice may be associated with drowsiness.
• Neurological signs, eg changes in muscle tone, seizures, or altered crying, require immediate attention to avoid kernicterus.
• Hepatosplenomegaly, petechiae, and microcephaly are associated with haemolytic anaemia, sepsis, and congenital infections.
• Hepatitis (eg congenital rubella, CMV, toxoplasmosis) and biliary atresia cause a raised conjugated bilirubin and have a marked jaundice and pale stools and dark urine, usually presenting in the third week of life.

Investigations

Usually, a total serum bilirubin level is the only testing required in a moderately jaundiced infant who presents on the second or third day of life and is otherwise well. Further investigation is essential for any baby who is also unwell, presents in the first 24 hours or has prolonged (after 10 days) jaundice.

• Serum bilirubin: total, conjugated, unconjugated.
• Liver function tests: hepatitis, cholestatic disease.
• Infection screen (must be excluded in any baby that is unwell or presents in the first 24 hours or after day 3): toxoplasmosis, rubella, cytomegalovirus and herpes simplex (TORCH) congenital infection screen, surface swabs including umbilicus, throat swabs, urine culture, blood culture, lumbar puncture, chest X-ray.
• Haemolysis:
  • Blood type and Rh determination in mother and infant
  • Direct Coombs' testing in the infant
  • Haemoglobin and haematocrit values
  • Peripheral blood film for erythrocyte morphology
  • Red cell enzyme assays: G6PD deficiency, pyruvate kinase deficiency
• Reducing substance in urine: screening test for galactosaemia (provided the infant has received sufficient quantities of milk).
• Thyroid function tests.
• Ultrasound, hepatobiliary imino-diacetic acid (HIDA) radionuclide scan, liver biopsy and laparotomy may be required for cholestatic jaundice in the differentiation between hepatitis and biliary atresia.

Management

• Treatment of the underlying cause.
• Increase fluid intake - usually oral but may require intravenous fluids depending on the cause and well-being of the baby.
• Phototherapy:
  • The indications and use of phototherapy vary between units and are dependent not only on the level of the serum bilirubin but also on the gestation of the baby, rate of rise of bilirubin, likely underlying cause and well-being of the baby. Phototherapy should be started immediately if a rapidly rising bilirubin is expected, eg haemolytic disease, and with jaundice at less than 24 hours.
  • The more premature the infant, the lower the levels of bilirubin that are tolerated. One formula for the phototherapy threshold is birthweight in kg x 100. In term babies, phototherapy should be given when the bilirubin rises above 300 μmol/L.^[1]
  • Essential care of a baby receiving phototherapy include ensuring maximum skin exposure, providing eye protection and eye care, carefully monitoring thermoregulation, maintaining adequate hydration and supporting parent-infant interaction.^[1] The main complications are separation from the mother, dehydration (fluid intake must be increased) and loose stools.
• Exchange transfusion via an umbilical artery or vein:
  • Indications depend on the clinical well-being (unwell babies are transfused earlier), cause, rate of increase in bilirubin and the gestational age of the baby.
  • Approximate levels indicating the need for exchange transfusion would be a serum bilirubin of 350 μmol/L for term babies, 300 μmol/L for infants weighing 2500 g, 250 μmol/L if 1500 g and 170 μmol/L if 1000 g.^[1]

Complications

• Kernicterus.

Prognosis

• Dependent on the underlying cause, but otherwise excellent with prompt diagnosis and treatment.
• Biliary atresia requires surgery before 60 days of life for a better prognosis.^[2]