Clinical consequences of severe hyperbilirubinemia

Raised serum bilirubin (hyperbilirubinemia) and consequent jaundice is common during the neonatal period; around half of all newborns become temporarily jaundiced during the first week or two of life. For the vast majority, serum bilirubin peaks no higher than around 250 µmol/L (14.6mg/dL) and jaundice quickly resolves with no long-term consequences. 

It remains important, however, to monitor serum bilirubin because in a small but unpredictable minority of neonates serum bilirubin rises to hazardous, neurotoxic levels. Rarely, bilirubin rises in excess of 500 µmol/L (29.2mg/dL) and such extreme levels are associated with high risk of kernicterus, a devastating chronic condition in which bilirubin-mediated irreversible brain damage results in cerebral palsy and loss of hearing. 

Although the link between extreme hyperbilirubinemia and permanent damage to the brain that kernicterus represents has been known for more than 50 years, it remains unclear if less severe hyperbilirubinemia has any adverse neurological effect.

A recently published prospective study of 140 neonates with severe hyperbilirubinemia (serum bilirubin >428 µmol/L) illuminates this gray area of neonatal care. Study authors compared outcome over 5 years of the 140 study patients (none of whom developed kernicterus) with that of 419 control neonates whose serum bilirubin never rose above 150 µmol/L. 

Prospective evaluation was based on hospital records; parental questionnaires enquiring about their infant’s development; and a formal intensive neurodevelopmental assessment by independent psychologists at 5 years of age. 

Analysis of results found no difference in outcome between the two groups. The authors conclude that their results indicate severe hyperbilirubinemia (serum bilirubin in the range 400-500 µmol/L) is not associated with any subtle neurodevelopmental deficiency.