Interaction of Hemolysis and Hyperbilirubinemia on Neurodevelopmental Outcomes in the Collaborative Perinatal Project

Abstract

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. 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. 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. 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.