Neonatal Hyperbilirubinemia and Long-Term Outcome: Another Look at the Collaborative Perinatal Project

Abstract

Objective. To examine the association between neonatal bilirubin levels and subsequent neurodevelopmental outcome. Design. Prospective cohort study. Setting. 12 US medical centers from 1959 (first births) to 1974 (last follow-up). Participants. 41 324 singleton white or black infants with birth weight ≥2500 g who had neonatal bilirubin measurements recorded and survived at least 1 year. Main outcome measures. Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) at age 7 years, blinded neurologic examination at age 7 years, and sensorineural hearing loss at age 8 years. Results. There was no association between IQ and bilirubin. For example, comparing children who had maximum bilirubin levels ≥342 µmol/L (20 mg/dL) with those who had lower bilirubin levels, adjusted mean IQs were 105.0 and 103.4 in whites (difference + 1.6; 95% confidence interval [CI]: –0.4 to + 3.5) and 91.0 and 93.3 in blacks (difference –2.3; 95% CI: –4.8 to +0.2). Abnormal neurologic examination results were reported in 12 of 268 children (4.5%) with bilirubin ≥342 µmol/L (20 mg/dL) compared with 1249 of 33 004 children (3.8%) with lower levels (relative risk [RR] = 1.2; 95% CI: 0.7 to 2.1). The frequency of abnormal or suspicious neurologic examination results increased in a stepwise fashion with increasing bilirubin level (P < .001), from 4346/29 258 (14.9%) of those with bilirubin levels <171 µmol/L (10 mg/dL) to 60/268 (22.4%) of those with bilirubin levels ≥342 µmol/L (20 mg/dL), apparently due to increasing minor motor abnormalities at higher bilirubin levels. Sensorineural hearing loss was not associated with high bilirubin levels (RR = 1.0; 95% CI: 0.3 to 3.0). Conclusions. Neonatal bilirubin levels seem to have little effect on IQ, definite neurologic abnormalities, or hearing loss. Higher bilirubin levels are associated with minor motor abnormalities, but the clinical importance of this finding is limited by the weakness of the association, the mild nature of the abnormalities, and the lack of evidence that they are prevented by treatment.