Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood

1. Acetaminophen burden, as measured by cord plasma samples, was associated with increased, dose-dependent risk of childhood Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Evidence Rating Level: 2 (Good)

Fetal acetaminophen exposure has been found to increase risk of neurodevelopmental disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). However, because many of these prior studies have depended on maternal self-reports, this prospective cohort study of 996 mother-infant dyads is the first to analyze archived cord plasma samples of three acetaminophen metabolites: unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-_L-cystein-S-yl]-acetaminophen. This subset of the Boston Birth Cohort participating between 1998 and 2018 included children with physician-diagnosed ADHD (25.8%), ASD (6.6%), ADHD+ASD (4.2%), other neurodevelopmental disorders (30.5%), as well as neurotypical children (32.8%). Each plasma sample included detectable, unchanged levels of acetaminophen. The second tertile (OR 2.26, 95% CI 1.40 to 3.69) and third tertile (OR 2.86, 95% CI 1.77 to 4.67) of cord acetaminophen burden were associated with increased odds of ADHD. Similar results were found for those diagnosed with ASD, with increased odds in the second tertile (OR 2.14, 95% CI 0.93 to 5.13) and third tertile (OR 3.62, 95% CI 1.62 to 8.60). Analyses across confounders such as substance use, preterm birth, child age and sex, and maternal indication yielded consistent associations between acetaminophen burden and both ADHD (ORs 2.3 to 3.5) and ASD (ORs 1.6 to 4.1). As a study that relied on cord plasma biomarkers rather than self-reports of acetaminophen use, its findings suggest that in utero exposure to acetaminophen may be associated in a dose-dependent manner with increased odds of developing ADHD or ASD.

Click to read the study in JAMA Psychiatry

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