Interaction of hemolysis and hyperbilirubinemia on neurodevelopmental outcomes in the collaborative perinatal project.

OBJECTIVE: Our objective was to reanalyze data from the Collaborative Perinatal Project to investigate whether bilirubin is more neurotoxic in newborns with a positive direct antiglobulin test. PATIENTS AND METHODS: The Collaborative Perinatal Project enrolled 54795 newborns at 12 centers in the United States between 1959 and 1966. We restricted our analysis to those with a birth weight of >/=2000 g and gestational age of >/=36 weeks who had follow-up at 7 to 8 years of age (n = 32808 for IQ testing; n = 33278 for neurologic examination, and n = 16354 for hearing testing). We examined the association between maximum total serum bilirubin levels and these 3 neurodevelopmental outcomes by using multiple linear and logistic regression models. We included interaction terms for the effect of bilirubin category and direct antiglobulin test result on the neurodevelopmental outcome.
RESULTS: Overall, maximum total serum bilirubin level was not a significant predictor of IQ scores. However, there was a statistically significant interaction between a positive direct antiglobulin test and a maximum total serum bilirubin level of >/=25 mg/dL on IQ scores (eg, full-scale IQ: -6.7 points). No similar direct antiglobulin test interaction was seen for those with those with a total serum bilirubin of 20 to 24.9 mg/dL (eg, full-scale IQ: -1.7 points). We found no evidence of an interaction between a positive direct antiglobulin test and total serum bilirubin levels on the risk of an abnormal or suspicious neurologic examination or sensorineural hearing loss.
CONCLUSIONS: In the Collaborative Perinatal Project, evidence of increased bilirubin toxicity in those with a positive direct antiglobulin test result was confined to an adverse association with IQ in those with total serum bilirubin of >/=25 mg/dL.