Neonatal Hyperbilirubinemia and Risk of Autism Spectrum Disorders

Abstract

Objective. To investigate the association between neonatal hyperbilirubinemia and autism spectrum disorders (ASD). Methods. We conducted a large case-control study nested within the cohort of singleton term infants born between 1995 and 1998 at a northern California Kaiser Permanente hospital. Case subjects (n = 338) were children with an ASD diagnosis recorded in Kaiser Permanente outpatient databases; control subjects (n = 1817) were children without an ASD diagnosis, who were randomly sampled and frequency-matched to case subjects according to gender, birth year, and birth hospital. Results. Approximately 28% of case and control subjects received ≥1 bilirubin test in the first 30 days of life. No case-control differences were observed for maximal bilirubin levels of ≥15 mg/dL (10.1% vs 12.1%), ≥20 mg/dL (2.1% vs 2.5%), or ≥25 mg/dL (0.3% vs 0.2%). Compared with children whose maximal neonatal bilirubin levels were <15 mg/dL or not measured, children with any degree of bilirubin level elevation were not at increased risk of ASD, after adjustment for gender, birth facility, maternal age, maternal race/ethnicity, maternal education, and gestational age (for bilirubin levels of 15-19.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.5-1.2; for bilirubin levels of 20-24.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.3-1.6; for bilirubin levels of ≥25 mg/dL: odds ratio: 1.1; 95% confidence interval: 0.1-11.2). Conclusion. These data suggest that neonatal hyperbilirubinemia is not a risk factor for ASD.