JAMA Study Finds No Increased Risk of Autism or ADHD With Prenatal Acetaminophen Exposure
China: Researchers have found in a large population-based cohort study conducted in Hong Kong that maternal use of acetaminophen (paracetamol) during pregnancy was not associated with an increased risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children.
Using sibling-matched analyses, researchers showed that previously reported associations were likely influenced by maternal health conditions and shared familial factors rather than by the medication itself. Negative-control analyses further supported the absence of a causal relationship. These findings are consistent with earlier sibling-comparison studies and recent evidence from Denmark, reinforcing the view that prenatal acetaminophen exposure does not appear to increase the risk of ASD or ADHD.
The findings are from a population-based cohort study published in JAMA Internal Medicine. The study was led by Shan Luo from the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and colleagues.
Paracetamol is the recommended first-line analgesic and antipyretic during pregnancy. While earlier observational studies linked prenatal exposure to a higher risk of ASD and ADHD, these associations may have been influenced by shared familial and genetic factors. To minimize such bias, the researchers used a sibling-matched study design.
The study analyzed deidentified electronic health records from Hong Kong between 2001 and 2023. Among 708,020 mother-child pairs, 43.3% were exposed to paracetamol during pregnancy. Sibling-matched cohorts included 124,333 children for the ASD analysis and 97,285 children for the ADHD analysis, with exposure identified using electronic prescription records.
The study led to the following findings:
- In sibling-matched analyses, prenatal paracetamol exposure was not associated with an increased risk of autism spectrum disorder (ASD) (adjusted hazard ratio [aHR] 1.00; 95% CI, 0.91-1.11).
- Prenatal paracetamol exposure was also not linked to a higher risk of attention-deficit/hyperactivity disorder (ADHD) (aHR 1.01; 95% CI, 0.93-1.08).
- The null associations remained consistent regardless of the timing of exposure during pregnancy, cumulative dose, or pattern of use, including sporadic, intermittent, and persistent use.
- Sensitivity analyses yielded similar findings, supporting the robustness of the results.
- Conventional cohort analyses showed positive associations between prenatal paracetamol exposure and the risks of both ASD and ADHD, consistent with earlier observational studies.
- However, similar positive associations were also observed for prepregnancy paracetamol exposure, which is not biologically expected to influence fetal neurodevelopment.
The negative-control analyses suggest that the associations observed in conventional studies are likely due to shared familial factors, maternal health conditions, and other residual confounding rather than a causal effect of prenatal paracetamol exposure.
The researchers concluded that prenatal paracetamol use during pregnancy was not associated with an increased risk of ASD or ADHD in offspring. They noted that earlier positive associations were likely driven by residual familial confounding, providing further reassurance about the safety of clinically indicated paracetamol use during pregnancy with respect to these neurodevelopmental outcomes.
Reference:
Luo S, Gong Q, Ai Y, et al. Prenatal Acetaminophen (Paracetamol) Use and the Risk of Autism and/or Attention-Deficit/Hyperactivity Disorder Among Sibling-Matched Cohorts. JAMA Intern Med. Published online June 29, 2026. doi:10.1001/jamainternmed.2026.2215
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