A systematic review of 46 human studies found that prenatal acetaminophen exposure was associated with an increased risk of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder and autism spectrum disorder. Of the studies included, 27 reported positive associations, 9 showed no association, and 4 suggested protective effects, and the remaining 6 reported mixed results, as reported in the abstract.
“Our findings show that higher-quality studies are more likely to show a link between prenatal acetaminophen exposure and increased risks of autism and ADHD,” said lead author Diddier Prada, MD, PhD, Assistant Professor of Population Health Science and Policy, and Environmental Medicine and Climate Science, at the Icahn School of Medicine at Mount Sinai. “Given the widespread use of this medication, even a small increase in risk could have major public health implications.”
By outcome, 20 studies examined attention‑deficit/hyperactivity disorder (ADHD), 8 investigated autism spectrum disorder (ASD), and 18 assessed other developmental outcomes. A Swedish nationwide cohort of nearly 2.5 million births reported a hazard ratio of 1.07 for ADHD, while a sibling‑controlled analysis in the same population reported 0.98. A European multicenter cohort of 73,881 pregnancies reported an odds ratio of 1.21 for ADHD with prenatal acetaminophen use. Biomarker‑based studies tended to report larger associations—for example, higher cord‑blood acetaminophen metabolites were linked with elevated odds of ADHD, and a maternal‑plasma biomarker study reported increased odds of ADHD diagnoses and ADHD medication use.
ASD findings were similar, with several studies reporting increased risk. Research on communication disorders, motor delays, and behavioral problems produced mixed results, though higher-quality studies more often showed associations.
The authors also noted biological plausibility for the association, citing experimental evidence that acetaminophen crosses the placental barrier, can affect hormone‑dependent processes important for brain development, and has been linked to neurodevelopmental deficits in animal models
The review was conducted using Navigation Guide methodology—the first application of this framework to this literature, per the Mount Sinai release. PubMed was searched through February 25, 2025, with supplementary checks in ISI Web of Science and Google Scholar identifying no additional eligible human studies. Because of heterogeneity in study design, exposure definitions, and outcomes, results were synthesized qualitatively rather than via meta‑analysis.
The authors discussed methodological concerns with sibling‑controlled studies, including reduced statistical power (only exposure‑ and outcome‑discordant pairs contribute) and non‑differential exposure misclassification—limitations that can bias estimates toward the null and help explain attenuation in within‑family analyses.
Limitations included self‑reported medication use, potential confounding by indication (e.g., maternal fever/infection), and the limited number—but greater objectivity—of biomarker studies. The risk‑of‑bias scoring system assigns equal weight across domains, which may not reflect the relative importance of different bias sources; the authors conducted sensitivity analyses (e.g., re‑weighting confounding) to probe robustness.
Clinical implications: The authors point out that acetaminophen remains first-line in pregnancy; NSAIDs may pose teratogenic risks, particularly in the third trimester. Separately, untreated maternal fever and pain carry risks (e.g., neural tube defects, preterm birth). Rather than recommending complete avoidance, they advocate “judicious acetaminophen use—lowest effective dose, shortest duration—under medical guidance, tailored to individual risk–benefit assessments.” The abstract also uses stronger wording—calling for “appropriate and immediate steps” to advise limiting use—while still emphasizing clinician-guided, time-limited dosing. “Pregnant women should not stop taking medication without consulting their doctors,” Dr. Prada emphasized. “Untreated pain or fever can also harm the baby… consider non-drug options whenever possible.”
Overall, most studies indicated an association between prenatal acetaminophen exposure and increased risks of ADHD, ASD, and other neurodevelopmental disorders. The review prioritized evidence from robust prospective cohorts and biomarker studies, while noting that sibling-controlled analyses have limitations (reduced power, potential exposure misclassification) that may bias estimates toward the null.
Disclosures: Dr. Andrea A. Baccarelli served as an expert witness related to prenatal acetaminophen and neurodevelopment; see paper for full details.