November 13, 2025
2 min read
Key takeaways:
- Most studies indicated a possible link between prenatal acetaminophen use and autism or ADHD, but the quality of studies was poor.
- Increased risks also disappeared in sibling-controlled analyses.
Current evidence does not clearly link the use of acetaminophen during pregnancy to neurodevelopmental disorders in youth, according to an umbrella review published in BMJ.
The findings come after HHS in September said it would begin notifying physicians of an apparent risk and initiate the process of updating the label of acetaminophen (also known as paracetamol), the main ingredient in Tylenol (Kenvue), to warn about this risk.
Most studies indicated a possible link between prenatal acetaminophen use and autism or ADHD, but the quality of studies was poor. Image: Adobe Stock
HHS Secretary Robert F. Kennedy Jr. recently said the causative association between prenatal acetaminophen use and neurodevelopmental disorders “is not sufficient to say it definitely causes autism … but it is very suggestive,” according to reporting from The Hill.
Jameela Sheikh, a doctoral student at the University of Liverpool in the U.K., and colleagues noted that studies on this topic “vary in methodological quality, findings and the interpretation of evidence.”
“Given the heterogeneous quality and reporting of studies, a robust overview of existing evidence is urgently needed to guide health care professionals, women and families in interpreting the risks of paracetamol use during pregnancy,” they wrote.
The researchers analyzed nine systematic reviews assessing 40 randomized clinical trials and cohort, case-control or cross-sectional studies that reported on prenatal acetaminophen use and diagnosis of autism or ADHD in offspring.
Four of the systematic reviews included a meta-analysis.
Sheikh and colleagues found the reviews showed a “possible to strong association” between acetaminophen use and the two neurodevelopmental disorders, but several of the reviews advised for caution when interpreting the data due to a potential risk for confounding and bias in the studies.
“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,” they explained. “Also, the overlap of primary studies in these reviews was substantial.”
Just one review included studies that reported ADHD and autism in offspring and “appropriately adjusted for familial factors and unmeasured confounding through sibling-controlled analyses,” the researchers wrote. However, the increased risk for autism and ADHD observed did not persist in the sibling-controlled analyses in both studies.
“This disappearance … suggests that shared family factors, such as parental mental health, genetic predisposition, and socioenvironmental background, explain much of the observed risk,” Sheikh and colleagues wrote.
They said their confidence in the reviews’ findings “is low to critically low.”
The researchers acknowledged some limitations of their umbrella review, which included only assessing autism and ADHD as outcomes, and the potential misclassification of exposure or covariate details.
Ultimately, “given that alternative classes of drugs for relief of pain and fever, such as nonsteroidal anti-inflammatory drugs, are known to adversely affect the fetal vascular system and can cause complications such as oligohydramnios and premature closure of the ductus arteriosus, and considering the harmful effects of pyrexia on pregnancy, women should be advised to take paracetamol when needed to treat pain and pyrexia in pregnancy,” Sheikh and colleagues concluded.
They added that future studies assessing potential links “should ensure both reliable assessment of exposure and rigorous ascertainment of outcomes, address bias due to confounding that includes indication bias, and prioritize adjustment for genetic and shared environmental factors, preferably through sibling cohorts.”
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