Published online February 1, 2005
PEDIATRICS Vol. 115 No. 2 February 2005, pp. e135-e138 (doi:10.1542/peds.2004-1870)
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ELECTRONIC ARTICLE

Neonatal Hyperbilirubinemia and Risk of Autism Spectrum Disorders

Lisa A. Croen, PhD*, Cathleen K. Yoshida, MS*, Roxana Odouli, MSPH* and Thomas B. Newman, MD, MPH{ddagger}

* Kaiser Permanente Division of Research, Oakland, California
{ddagger} Departments of Epidemiology and Biostatistics and of Pediatrics, University of California, San Francisco, California

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.

Key Words: autism spectrum disorders • hyperbilirubinemia • jaundice • pervasive developmental disorder • neonatal risk

Abbreviations: PDD-NOS, pervasive developmental disorder not otherwise specified • ASD, autism spectrum disorders • KP, Kaiser Permanente • ICD-9-CM, International Classification of Diseases, 9th Revision, Clinical Modification

Accepted Sep 29, 2004.