Jaundice is the yellow pigmentation of the skin that occurs with hyperbilirubinaemia. The bilirubin is formed from the breakdown of haem in red blood cells and is transported to the liver as unconjugated bilirubin, bound to albumin. In order to be excreted it needs to be made water soluble by conjugation in the liver. Conjugated bilirubin is then excreted in the bile into the duodenum, where some is reabsorbed (the enterohepatic circulation) and the remainder forms stercobilinogen, which gives the stools their yellow/brown pigment. Some of the reabsorbed conjugated bilirubin is excreted by the kidneys as urobilinogen.

Excessive haemolysis or impaired conjugation leads to a build-up of unconjugated bilirubin, and obstruction to drainage of bile leads to conjugated hyperbilirubinaemia. Unconjugated and unbound bilirubin is lipid soluble and can cross the blood–brain barrier.

Kernicterus

If free bilirubin crosses the blood–brain barrier in high concentrations it is deposited in the basal ganglia where it causes kernicterus. This causes an acute encephalopathy with irritability, high-pitched cry or coma. The neurotoxic damage to the basal ganglia can lead to the development of athetoid cerebral palsy. Kernicterus is now extremely rare due to better obstetric management of rhesus disease, careful monitoring of bilirubin levels and early treatment with phototherapy. Extremely sick preterm infants are still at risk of kernicterus, especially if they are acidotic or have a low serum albumin.

Treatment

Phototherapy (blue light at 450 nm wavelength) helps convert unconjugated bilirubin to biliverdin, an isomer which can be excreted by the kidneys. In rhesus or ABO incompatibility, if bilirubin levels rise significantly despite phototherapy, then an exchange transfusion is required to remove the bilirubin and the maternal IgG antibodies from the circulation. Intravenous immunoglobulin infusion can help prevent the need for exchange transfusion by blocking antibody receptor sites.

Physiological Jaundice

Jaundice in the neonatal period is very common and is usually due to liver immaturity. It is self-limiting as liver enzymes mature over the first week, and only occasionally needs phototherapy treatment. Nearly all preterm infants become jaundiced in the first days of life, due to the immature hepatocytes not being able to adequately conjugate bilirubin. This never requires exchange transfusion but may require phototherapy for a few days.

Breast-Milk Jaundice

Persistent jaundice in an otherwise well breast-fed infant with normal-coloured stools and urine is probably due to the inhibition of liver conjugation enzymes by substances in breast milk. It is a diagnosis of exclusion and a split bilirubin should be measured to exclude conjugated hyperbilirubinaemia. Breast-milk jaundice normally manifests itself by day 4–7 and can persist for 3 weeks to 3 months. Breast-milk jaundice should be distinguished from the severe jaundice and hypernatraemic dehydration that can occasionally occur in the first week of life due to failure to establish adequate lactation.

Haemolytic Disease of the Newborn

Haemolysis occurs when maternal IgG antibody crosses the placenta and reacts with fetal red blood cell antigens. The commonest causes are ABO or rhesus incompatibility. In rhesus disease the fetus is rhesus positive and the mother rhesus negative. The mother will have been sensitized by the passage of fetal red blood cells into her circulation at a previous delivery or during a threatened miscarriage. Rhesus-negative women are now routinely immunized with anti-D antibody at 28 weeks, to ‘mop up’ fetal red blood cells before they stimulate maternal IgG production. Fetal anaemia can lead to hydrops (severe oedema). In-utero blood transfusions can now be given (via the umbilical cord) in severe cases of haemolytic disease. After birth untreated fetuses are anaemic and rapidly develop severe jaundice. The management of severe disease is to deliver the baby before severe haemolysis has occurred and then to wash out the maternal antibodies (and the bilirubin) by performing a series of exchange transfusions, and by the aggressive use of early phototherapy. It is important to remember that the maternal IgG antibodies can persist in the baby’s circulation for many weeks, causing ongoing haemolysis and anaemia even after the jaundice is under control.

Biliary Atresia

Biliary atresia is a rare (1 in 10 000) but important condition caused by the absence of intra- or extrahepatic bile ducts. A conjugated hyperbilirubinaemia develops over weeks, and the stools become clay coloured. If undiagnosed the baby will develop liver failure and may die without a transplant. If detected within the first 6 weeks then a hepatoporto-enterostomy (Kasai procedure) can usually achieve adequate biliary drainage. Because of this it is recommended that any baby still jaundiced after 2 weeks has conjugated and unconjugated bilirubin levels checked. Those with a high conjugated fraction (>20% of total) should be referred urgently to a paediatric hepatologist for assessment.

Jaundice in Older Children

Jaundice is rare in older children. It is generally associated with hepatitis or with chronic liver disease. The commonest cause is hepatitis A infection. Other causes include chronic haemolysis due to hereditary spherocytosis or glucose-6-phosphate dehydrogenase (G6PD) deficiency, or liver disease such as autoimmune chronic hepatitis. Reye’s syndrome, an acute encephalopathy associated with fulminant liver failure, can be induced by aspirin, and this is therefore contraindicated in young children. Deliberate paracetamol overdose is an important cause of liver failure in older children. Some inherited metabolic disorders lead to progressive jaundice. In Wilson’s disease there is a defect in copper metabolism leading to neurodevelopmental delay and liver failure. Brown ‘Kayser–Fleischer’ rings may be visible in the cornea. Chronic hyperbilirubinaemia may be due to genetic enzyme defects such as Criggler–Najar disease (glucuronyl transferase deficiency) or abnormal hepatic uptake of bilirubin such as Gilbert’s syndrome.