Children without in utero acetaminophen exposure were included as a reference group. Physician-based diagnoses of NDDs were performed using International Classification of Diseases, Ninth Revision and Tenth Revision codes, with measurements from psychometric instrument scales also included.
A diverse patient population was reported across the selected studies, alongside variations in follow-up duration. The definition of acetaminophen use was exposure during pregnancy in all of the included studies.
ADHD risk analysis shows no causal association
The link between acetaminophen use during pregnancy and offspring ADHD was assessed in 6 studies with heterogeneity of 67%. Overall, a 17% increase in ADHD risk was reported following acetaminophen exposure when determined by physician diagnosis or psychometric test, with an odds ratio (OR) of 1.17.
When defining ADHD by physician diagnosis alone, the OR was 1.16, vs 1.15 for psychometric tests alone, highlighting no change in findings. Additional ORs included:
- 1.17 when assessing exposure by maternal report during pregnancy
- 1.20 when assessing exposure by patient-chart data
Overall, statistical significance was only reported when using patient-chart data. Investigators noted that maternal recall has been proven more accurate vs patient-chart data for over-the-counter medicine. An OR of 0.97 was reported for ADHD following in utero acetaminophen exposure in studies using sibling designs, indicating no increase in risk.
Autism spectrum disorder and other NDDs unaffected
Autism spectrum disorder (ASD) risk was also not increased by prenatal acetaminophen use. When basing ASD on physician-based diagnoses, an OR of 1.10 was reported. While a statistically significant OR of 1.20 was reported for ASD based on a psychometric test, this association was only evaluated in 1 study.
No other NDDs were impacted by acetaminophen use during pregnancy. Additionally, language developmental disorder and psychomotor developmental disorder risks were not influenced by the duration of use during pregnancy. Overall, only a minor increase in ADHD risk was observed from acetaminophen exposure, which did not remain in sibling analyses.
“Future studies should be meticulously designed to account for exposure and outcome misclassifications, timing, dosage and duration as well as indication for use, and confounding; discordant-exposure sibling designs should be prioritized,” wrote investigators.
References
- Meta-analysis offers reassurance that pregnant women can safely use acetaminophen. Elsevier. November 6, 2025. Accessed November 13, 2025. https://www.eurekalert.org/news-releases/1104958.
- Bérard A, Cottin J, Leal LF, et al. Systematic review and meta-analysis: Acetaminophen use during pregnancy and the risk of neurodevelopmental disorders in childhood. Journal of the American Academy of Child & Adolescent Psychiatry. 2025. doi:10.1016/j.jaac.2025.09.031