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Maternal Acetaminophen Use and Child Neurodevelopment

Pei-Chen Lee1, Yu-Hsuan Chuang1, Ya-Hui Hu1

  • 1Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

JAMA Pediatrics
|March 9, 2026
PubMed

Insights

Maternal acetaminophen use during pregnancy showed associations with offspring ADHD and ASDs in a large cohort. However, sibling analyses revealed no link, suggesting unaddressed biases may affect findings on acetaminophen and neurodevelopmental outcomes.

Area of Science:

  • Neurodevelopmental Disorders
  • Perinatal Pharmacology
  • Epidemiology

Background:

  • Maternal acetaminophen use during pregnancy is common, but its association with offspring neurodevelopmental outcomes like ADHD and ASDs remains debated.
  • Previous studies have yielded conflicting results, highlighting the need for robust research designs to address confounding factors.

Purpose of the Study:

  • To investigate the association between maternal prenatal acetaminophen prescriptions and the risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) in offspring.
  • To evaluate these associations using both full cohort and sibling-matched analyses to control for genetic and environmental factors.

Main Methods:

  • A large cohort study in Taiwan analyzed 2,092,926 singleton births (2004-2015), with a subset of 1,231,819 having at least one sibling.
  • Maternal acetaminophen prescriptions were extracted from the National Health Insurance Research Database, defining use by at least two dispense records during pregnancy.
  • Offspring ADHD and ASD diagnoses were ascertained, and hazard ratios (HRs) were calculated, adjusting for confounders and performing sibling-matched and bidirectional analyses.

Main Results:

  • In the full cohort, prenatal acetaminophen prescriptions were associated with increased risks of offspring ADHD and ASDs, particularly with higher frequencies or doses.
  • Sibling-matched analyses, however, showed null associations between prenatal acetaminophen exposure and these neurodevelopmental disorders.
  • Bidirectional sibling analyses revealed a divergence, with positive associations when only the older sibling was exposed and negative associations when only the younger sibling was exposed.

Conclusions:

  • While the full cohort analysis suggested a link between maternal acetaminophen use and offspring ADHD/ASDs, sibling-matched analyses did not support this association.
  • The divergent findings in sibling analyses indicate potential unaddressed sources of bias, complicating definitive conclusions.
  • Further research is needed to clarify the complex relationship between prenatal acetaminophen exposure and offspring neurodevelopmental outcomes.
Abstract

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