The results of the Collaborative Project on Preterm and Small for Gestational Age Infants in the Netherlands, 1983, in regard to hyperbilirubinemia and neurodevelopmental outcome at two years of age are reported from the Division of Neonatology, Department of Pediatrics, University Hospital, Leiden, the Netherlands.
Children with minor and major handicaps had significantly greater maximal serum total bilirubin concentrations than children with a normal neurodevelopmental outcome (P = 0.02). An increase in prevalence of handicaps was found for each 50 mmol/L (2.9 mg/dL) increase of maximal serum total bilirubin concentration. The neurological abnormalities included cerebral palsy, seizures, hearing defects as well as retinopathy of prematurity. The risk of a handicap increased by 30% for each 2.9 mg/dL increase of maximal serum total bilirubin concentration (P = 0.02) suggesting a causal relationship. 
COMMENT. In the same issue, Newman TB and Maisels MJ comment that the strength of the association between bilirubin levels and brain damage in the present study was insufficiently precise to provide evidence of a strong causal relationship. The 95% confidence interval was wide, the association has not been consistent in other studies, and panic about bilirubin in the 6-12 mg/dL range is premature. They note that the NICHD collaborative phototherapy trial showed that bilirubin levels were reduced significantly by 4 mg/dL but this did not reduce the incidence of motor deficits or cerebral palsy and there was no effect on IQ scores. They estimate that even if the hyperbilirubinemia was toxic and causally related to neurologic damage, about 33 premature infants would need to be treated to prevent one case of neurologic handicap. To achieve similar benefit in term infants the number to be treated would be 333. Further studies are suggested.