Neonatal Hyperbilirubinemia and Phototherapy Are Not Risk Factors for Autism

It has been hypothesized that neonatal hyperbilirubinemia and phototherapy might increase the risk for autism spectrum disorder (ASD). The former is supported by studies with significant limitations; the latter has been suggested from evidence linking DNA damage, altered cytokine levels, and increased oxidative stress with both phototherapy and ASD.

In a retrospective cohort study, total serum bilirubin and treatment with phototherapy were assessed through electronic medical records in 525,409 infants born at gestational age ≥35 weeks between 1995 and 2011 in a single healthcare system. ASD was diagnosed with a standardized instrument in an autism referral center or by general pediatricians.

Two percent of infants had hyperbilirubinemia (at least 1 total serum bilirubin measurement ≥20 mg/dL), and 8% underwent phototherapy. The incidence of ASD was 13 per 1000 births. In bivariate analysis, hyperbilirubinemia and phototherapy were independently associated with ASD, but after adjustment for potential sociodemographic confounders and birth weight, they were no longer significantly associated with ASD.