Summary: A new systematic review conducted by researchers at the Icahn School of Medicine at Mount Sinai raises concerns about the safety of acetaminophen use during pregnancy. Applying the rigorous Navigation Guide review method, the team analyzed 46 studies involving more than 100,000 participants and found that higher-quality studies were more likely to report associations between prenatal acetaminophen exposure and increased risks of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).
Although the evidence does not prove that acetaminophen causes neurodevelopmental disorders, the review highlights plausible biological mechanisms — including oxidative stress, hormonal disruption, and epigenetic changes — by which acetaminophen could affect fetal brain development. The researchers recommend cautious, time-limited use of acetaminophen during pregnancy under medical supervision and call for updated clinical guidance and research into safer alternatives.
Key Facts
- Study scope: Systematic review of 46 studies including data from over 100,000 participants across multiple countries.
- Primary finding: Higher-quality studies more consistently report a link between prenatal acetaminophen exposure and increased risks of autism and ADHD.
- Clinical implication: Results support caution and medical oversight when using acetaminophen during pregnancy and signal the need for safer treatment options.
Source: Mount Sinai Hospital
Summary of the findings
Researchers at Mount Sinai examined the available scientific evidence to determine whether acetaminophen (paracetamol) use during pregnancy is associated with neurodevelopmental disorders in children. Acetaminophen is the most commonly used over-the-counter medication for pain and fever in pregnancy, with more than half of pregnant people worldwide reporting use. Given its widespread use and the potential for even small increases in risk to have major public health implications, the team applied a transparent, evidence-based framework to evaluate the literature.
The review used the Navigation Guide Systematic Review methodology, a recognized framework for synthesizing environmental health evidence. This approach evaluates each study’s design, potential biases, and overall quality, and it rates the strength and consistency of the body of evidence. Applying these criteria, the researchers found that studies judged to be higher quality were more likely to demonstrate positive associations between prenatal acetaminophen exposure and diagnoses or symptoms consistent with ASD, ADHD, and related neurodevelopmental disorders (NDDs).
Across the 46 studies included in the analysis, 27 reported positive associations, 9 reported null results, and 4 reported inverse associations. Because the studies varied substantially in design, exposure measurement, and outcome definitions, the review emphasizes qualitative synthesis informed by risk-of-bias assessments rather than a pooled quantitative estimate.
Possible biological mechanisms
The review discusses several biologically plausible mechanisms that might link prenatal acetaminophen exposure to altered neurodevelopment. Acetaminophen crosses the placenta and can reach the developing fetus. Experimental and mechanistic studies suggest that acetaminophen exposure could contribute to oxidative stress, interfere with hormonal signaling that guides brain development, and induce epigenetic changes that alter gene expression during critical windows of fetal neurodevelopment. While these mechanisms do not prove causation in humans, they strengthen the plausibility of an association and underscore the need for further research.
Clinical recommendations and public health implications
The authors advise that pregnant people should not stop taking medications without first consulting their healthcare provider. Untreated fever or severe pain can also pose risks during pregnancy. Instead, clinicians and patients should discuss the safest approach for symptom management, including non-drug measures when appropriate and limiting acetaminophen use to the lowest effective dose for the shortest necessary duration. The review supports updating clinical guidance to better balance potential benefits and risks and calls for research into safer alternatives for treating pain and fever in pregnancy.
Given rising global diagnoses of autism and ADHD, these findings may have important implications for public health policy, clinical practice, and patient education. The authors stress the urgent need for further high-quality research, including studies that refine exposure measurement, account for confounding factors, and explore timing and dose effects.
The study was conducted in collaboration with investigators from the University of California, Los Angeles; University of Massachusetts Lowell; and Harvard T.H. Chan School of Public Health.
Funding:
This research received support from the National Cancer Institute (U54CA267776), the National Institute of Environmental Health Sciences (R35ES031688), and the National Institute on Aging (U01AG088684).
About this Autism and neurodevelopment research news
Author: Mount Sinai Health System Press Office
Source: Mount Sinai Hospital
Contact: Mount Sinai Health System Press Office – Mount Sinai Hospital
Image: Image credited to Neuroscience News
Original research: Open access. “Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology” by Diddier Prada et al., published in BMC Environmental Health.
Abstract
Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology
Background
Acetaminophen is the most commonly used over-the-counter medication for pain and fever during pregnancy, with more than 50% of pregnant people worldwide reporting use. Multiple well-designed studies have reported that children born to mothers who used acetaminophen in pregnancy are diagnosed with neurodevelopmental disorders, including ASD and ADHD, at higher rates compared with children whose mothers did not report such use.
Methods
The authors applied the Navigation Guide methodology to systematically and transparently evaluate the literature on prenatal acetaminophen exposure and neurodevelopmental outcomes in offspring. A comprehensive search of the scientific literature through February 25, 2025 was conducted using predefined inclusion criteria. Each study was rated for risk of bias and overall quality, and given substantial heterogeneity among studies, the review emphasizes qualitative synthesis consistent with the Navigation Guide approach to environmental health evidence.
Results
Forty-six studies met inclusion criteria. Of these, 27 reported significant positive associations between prenatal acetaminophen use and NDDs or related symptoms, 9 reported no significant association, and 4 reported inverse associations. Studies rated as higher quality were more likely to show positive associations. Risk-of-bias and strength-of-evidence ratings guided the overall interpretation.
Conclusions
Using the Navigation Guide framework, the evidence is consistent with an association between prenatal acetaminophen exposure and increased incidence of neurodevelopmental disorders. The authors recommend prompt actions to inform clinical practice and public health guidance so that pregnant people are advised to limit acetaminophen use to what is medically necessary in order to help protect offspring neurodevelopment.