Prenatal Acetaminophen Use and Neurodevelopmental Disorders: Association Uncertain: JAMA
A cohort study from Taiwan found that maternal prenatal use of acetaminophen was associated with a higher risk of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) in children in the overall population analysis. However, this association disappeared in sibling-matched analyses, suggesting that other unmeasured factors or biases may explain the findings. Therefore, the study cannot establish a clear causal relationship between prenatal acetaminophen exposure and these neurodevelopmental disorders. The study was published in JAMA Pediatrics by Pei-Chen L. and colleagues.
A cohort study conducted in Taiwan observed that prenatal exposure to Acetaminophen is associated with an increased risk of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) in children in the population analysis.
However, when the analysis was conducted in the sibling-matched analysis, the associations were eliminated, suggesting the presence of other unmeasured variables and biases, and thus it is difficult to establish a cause-and-effect relationship between prenatal acetaminophen and ADHD and ASD
In this population-based cohort study, the authors assessed 2,092,926 singleton births in Taiwan between 2004 and 2015 using data from the National Health Insurance Research Database (NHIRD). Of the total births, 1,231,819 children had at least one sibling, thus allowing the authors to perform sibling-matched analysis and control for genetic and environmental influences.
Exposure to acetaminophen among pregnant women was identified using NHIRD records of prescriptions filled during pregnancy, defined as having at least two acetaminophen dispense records in the NHIRD database. Additionally, the total number of prescriptions and the estimated mean daily dispensed dose of acetaminophen were examined as exploratory variables for dose-response relationships.
Key findings:
• In this nationwide cohort study, researchers sought to evaluate the risk of ADHD and ASD in singleton births in Taiwan from 2004 to 2015, which comprised 2,092,926 births and 1,231,819 births with at least one sibling.
• Of the births in the nationwide cohort study, 48.3% (1,012,159 births) were exposed to at least two prescriptions of acetaminophen during pregnancy.
• Of the nationwide cohort study population, 23,557 (0.01%) were diagnosed with ASD and 116,387 (0.06%) were diagnosed with ADHD.
• The results showed that prenatal exposure to acetaminophen was associated with ADHD and ASD in the nationwide cohort study, especially when the number of prescriptions and the daily dose were increased.
• However, the results were negative when the exposure was assessed in the sibling-matched cohort analysis.
• In the bidirectional sibling analysis, the exposure was positively correlated with ADHD and ASD in the older sibling (HR = 1.33 and 1.75), and the exposure was negatively correlated with ADHD and ASD in the younger sibling (HR = 0.75 and 0.74).
An increased risk of ADHD and autism spectrum disorders was observed with the prescription of prenatal acetaminophen to the mother. However, this was not found when the sibling-matched approach was employed. The difference in results obtained using the two methods, which involve bidirectional comparisons, indicates that underlying sources of bias remain unaddressed, and as such, it is not possible to determine the link between the two.
Reference:
Lee P, Chuang Y, Hu Y, et al. Maternal Acetaminophen Use and Child Neurodevelopment. JAMA Pediatr. Published online March 09, 2026. doi:10.1001/jamapediatrics.2026.0071
