An umbrella review of nine systematic reviews published today in BMJ shows no link between maternal acetaminophen (Tylenol) use during pregnancy and autism or attention deficit hyperactivity disorder (ADHD) in children.
The study, led by University of Liverpool researchers, involved a review of research published within the past 10 years, up to September 30, 2025, to evaluate the quality and validity of the evidence and the strength of any association between the use of acetaminophen (sold as paracetamol in many countries) during pregnancy and the risks of autism and ADHD.
The researchers noted that, in September, President Donald Trump advised pregnant women against using acetaminophen because of the drug's links to autism. Withholding acetaminophen, however, poses high fever risks for poor pregnancy outcomes, they said.
"The announcement caused considerable concern among pregnant women and mothers of children with autism," they wrote. "Worldwide, regulatory health agencies and expert bodies, such as the UK's Medicines and Healthcare Products Regulatory Agency, the European Medicines Agency, and the Australian Therapeutic Goods Administration, responded with reassurance about the safety of paracetamol use during pregnancy."
Potential bias, confounding factors
The systematic reviews included 40 primary studies (37 prospective cohorts, two case-control studies, and one ecological study), and four were meta-analyses. The primary studies overlapped considerably, covering many of the same studies (corrected covered area, 23%).
The reviews suggested a possible to strong tie between maternal acetaminophen intake and autism, ADHD, or both in children. Seven of the nine systematic reviews, however, urged caution with interpreting the results owing to a potential risk of bias and confounding in the included studies. Based on the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews) criteria, confidence in the review findings was low (two reviews) to critically low (seven).
Only one review included studies on autism and ADHD that appropriately adjusted for familial factors and unmeasured confounding through analyses controlled for siblings. And in those studies, the increased risk of autism (one study; hazard ratio [HR], 1.05) and ADHD (two; HRs, 1.07, 1.05 to 1.10 and 2.02, 1.17 to 3.25) seen in the whole-cohort analyses didn't persist in analyses controlled for siblings for autism (HR, 0.98, 0.93 to 1.04) or ADHD (HR, 0.98, 0.94 to 1.02 and 1.06, 0.51 to 2.05).
"This disappearance of association in the sibling analyses, previously observed in the whole cohort, suggests that shared family factors, such as parental mental health, genetic predisposition, and socioenvironmental background, explain much of the observed risk," the authors wrote.
No systematic review used the recommended tool (ROBINS-E or ROBINS-I) to evaluate the risk of bias in non-randomized trials.
Acetaminophen alternatives, maternal fever can harm fetus
"Existing systematic reviews on prenatal exposure to paracetamol and risk of autism and ADHD in offspring included heterogeneous studies, and many suggested a positive association," the researchers wrote. "But few reviews accounted for the study quality, appropriate control of relevant confounders, and rigorous ascertainment of drug use and outcomes in the primary studies when interpreting the evidence."
The current evidence base is insufficient to definitively link in utero exposure to paracetamol with autism and ADHD in childhood.
They recommended that regulatory agencies, clinicians, pregnant women, parents, and those affected by autism and ADHD be informed about the poor quality of the existing reviews and the likelihood that any positive associations were driven by familial confounding.
And because alternatives to acetaminophen, such as nonsteroidal anti-inflammatory drugs, adversely affect the fetal vascular system and can cause complications and because fever in pregnancy also can lead to poor outcomes, pregnant women should continue to take acetaminophen to treat pain and fever.
"The current evidence base is insufficient to definitively link in utero exposure to paracetamol with autism and ADHD in childhood," the researchers concluded. "High-quality studies that control for familial and unmeasured confounders can help improve evidence on the timing and duration of paracetamol exposure, and for other child neurodevelopmental outcomes."
