For years, clinicians worldwide have relied on acetaminophen as the go-to painkiller for pregnant patients. But observational research has raised questions about whether prenatal exposure to the drug might drive up the risk of autism spectrum or attention-deficit hyperactivity disorder. Never mind the political rhetoric that appears to ignore the overall body of evidence.
Now, a new systematic review and meta-analysis appearing in The Lancet Obstetrics, Gynaecology & Women’s Health, offers some of the clearest reassurance yet. Researchers examined and incorporated data from more than four dozen studies. They found no evidence that acetaminophen use during pregnancy increases the risk of autism, ADHD, or intellectual disability.
The review, led by an international team of obstetric and epidemiology researchers, comes amid renewed public debate over acetaminophen’s safety in pregnancy. That debate intensified in late 2025 after Trump Administration officials publicly declared a possible link between prenatal acetaminophen exposure and autism. They cited earlier reviews that reported small risk increases.
“Our findings do not indicate a clinically important increase in neurodevelopmental risk when acetaminophen is used as directed during pregnancy,” the authors conclude.
Why Earlier Studies Raised Red Flags
Acetaminophen remains one of the most widely used medications in pregnancy and is clinicians favor it over nonsteroidal anti-inflammatory drugs and opioids, which carry more apparent fetal risks.
Still, multiple observational studies over the past decade have claimed modest links between prenatal acetaminophen use and neurodevelopmental outcomes.
Many of those studies, however, relied on maternal self-reports, short follow-up periods, or conventional observational designs that conflate the effects of medication from the reasons the drug was taken in the first place. Fever, infection, pain, and underlying maternal health conditions are all associated with adverse pregnancy and neurodevelopmental outcomes.
That, of course, raises a methodological challenge. Are observed associations a direct result of the drug? Or are shared familial, genetic, or environmental factors responsible?
Methodology
To address that question, this new review prioritized evidence from sibling-comparison studies. The new approach embraced a design that compared siblings discordant for prenatal exposure, which helped control for shared genetics, home environment, and socioeconomic factors.
The researchers searched MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Library for cohort studies published through September 2025. They ultimately settled on the inclusion of 43 studies in the systematic review and 17 in the meta-analysis. All told, the research included data from hundreds of thousands of kids.
When the team limited the analysis to sibling-comparison studies with adjusted risk estimates, acetaminophen exposure during pregnancy failed to reveal a link to autism, or intellectual disability. The findings remained null when the authors limited analyses to studies judged to be at low risk of bias or those with more than five years of follow-up.
Conversely, small risk increases reported in some earlier meta-analyses largely disappeared once researchers considered familial confounding.
“These results suggest that previously reported associations are likely explained by residual confounding rather than a causal effect of acetaminophen,” the authors write.
Biological Plausibility. But Limited Evidence
Laboratory and animal studies have offered up multiple explanations as to how acetaminophen might influence fetal neurodevelopment. Theories blame oxidative stress, endocrine disruption, altered prostaglandin signaling, and even epigenetic changes. The drug crosses the placenta easily. And fetal concentrations can approach maternal levels.
But the authors point out that the existing research hasn’t established a causal pathway linking typical acetaminophen use in pregnancy to long-term neurodevelopmental outcomes. In large, registry-based human studies that incorporate sibling comparisons, the signal dissipates.
Clinical (and Public Health) Implications
The findings, the review’s authors contend, carry substantial practical weight. The World Health Organization lists acetaminophen on its list of essential medicines. And, in many settings, it remains the only safe and accessible option for treating fever or pain during pregnancy.
The new analysis aligns with guidance from major professional organizations – including the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynaecologists, and the Society for Maternal-Fetal Medicine – all of which continue to recommend acetaminophen as the first-line analgesic and antipyretic during pregnancy.
When used as directed, acetaminophen during pregnancy doesn’t appear to increase the risk of autism, ADHD, or any intellectual disability. And in a field often clouded by fear and fragmented evidence, the study offers something missing from the renewed debate over this treatment: clarity.
Further Reading
Trump, HHS Link Tylenol to Autism. Experts Push Back.
Prenatal Opioids Might Not Drive Autism, ADHD Risk
Maternal Use of Acetaminophen During Pregnancy and Neurodevelopmental Disorders in Offspring
