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

Pediatrics. 2009 Mar;123(3):1045-50. doi: 10.1542/peds.2007-3413.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Bilirubin / blood
  • Brain Damage, Chronic / diagnosis*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Coombs Test
  • Erythroblastosis, Fetal / diagnosis*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperbilirubinemia, Neonatal / diagnosis*
  • Infant
  • Infant, Newborn
  • Intelligence*
  • Male
  • Neurologic Examination


  • Bilirubin