Another study challenges autism, ADHD concerns tied to prenatal acetaminophen

Clinical Takeaway: Reassure pregnant patients that acetaminophen remains an appropriate option for fever or pain when clinically indicated, while continuing to avoid unnecessary or prolonged use.

Patients may be anxious about using acetaminophen during pregnancy; these findings support counseling that indicated use remains appropriate when taken at the lowest effective dose for the shortest needed time.

A new population-based cohort study found no evidence that prescribed prenatal acetaminophen exposure was associated with autism spectrum disorder or ADHD in children after accounting for shared family factors.

The final cohorts included 124,333 children in the autism spectrum disorder analysis and 97,285 in the ADHD analysis. Children in the ASD cohort had a mean age of 9.3 years, and children in the ADHD cohort had a mean age of 7.6 years; sex distribution was nearly even in both cohorts.

In sibling-matched analyses, prenatal acetaminophen exposure was not associated with autism spectrum disorder, with an adjusted hazard ratio of 1.00 (95% confidence interval [CI], 0.91-1.11), or ADHD, with an adjusted hazard ratio of 1.01 (95% CI, 0.93-1.08). Null associations were consistent across timing of exposure, cumulative dose, and usage patterns, including sporadic, intermittent, and persistent use, and remained robust in sensitivity analyses.

The authors also found positive associations in conventional cohort analyses. Importantly, positive associations were also seen in negative control analyses of prepregnancy exposure: hazard ratio [HR] 1.12 (95% CI, 1.08-1.17) for ASD and HR 1.24 (95% CI, 1.20-1.28) for ADHD. That pattern supports the authors’ interpretation that positive signals in conventional analyses are likely explained by residual familial confounding rather than a causal effect of prenatal acetaminophen exposure.

“The collective evidence supports current regulatory guidance on the safety of indicated antenatal acetaminophen use,” the authors wrote, adding that acetaminophen “remains a safe and essential analgesic and antipyretic during pregnancy.”

The findings add to a growing body of sibling-comparison and high-quality review evidence suggesting that previously reported associations between prenatal acetaminophen and autism or ADHD are unlikely to be causal. A key limitation: the study captured prescribed medication use, so over-the-counter use may have been missed.

Source: Luo S, et al. 2026 June 29. JAMA Intern Med. Prenatal Acetaminophen (Paracetamol) Use and the Risk of Autism and/or Attention-Deficit/Hyperactivity Disorder Among Sibling-Matched Cohorts