An extensive review of existing studies, published in The BMJ on November 10, finds no clear evidence that using acetaminophen (Tylenol) during pregnancy increases the risk of autism or ADHD in children. The new analysis was conducted in response to growing public debate about the safety of acetaminophen use while pregnant.
Researchers reported that the reliability of earlier studies and reviews on this topic is rated as low to critically low. They noted that any apparent associations observed in past studies may be influenced by factors shared within families, such as genetics and environmental conditions, rather than by the medication itself.
Safety Guidance for Pregnant Women and Health Professionals
The study authors emphasize that regulators, healthcare providers, pregnant women, parents, and those affected by autism and ADHD should be aware of the poor quality of prior evidence. They recommend that acetaminophen continue to be used when needed to relieve pain or reduce fever during pregnancy, consistent with current medical advice.
Acetaminophen (called paracetamol outside the USA and Japan) remains the standard and recommended treatment for pain and fever in pregnancy and is considered safe by regulatory agencies around the world.
Previous systematic reviews exploring potential risks have been inconsistent in quality. Many did not properly adjust for key factors shared by family members, such as parental health or lifestyle, making it difficult to determine whether acetaminophen itself has any true impact on a baby’s brain development.
To clarify this uncertainty, the researchers conducted an “umbrella review” (a comprehensive summary of systematic reviews) to evaluate how strong and reliable the existing evidence is, and to examine whether there is a measurable association between acetaminophen use in pregnancy and the risk of autism or ADHD in children.
Reviewing Data From 40 Studies
The team identified nine systematic reviews that together covered 40 observational studies on acetaminophen exposure during pregnancy and later neurodevelopmental outcomes in children. Four of these reviews included meta-analyses (a statistical technique that combines data from multiple studies to produce a more precise estimate of effect).
Each review was carefully assessed for bias using recognized evaluation tools, and the researchers rated their confidence in the findings as high, moderate, low, or critically low. The amount of overlap between studies in the reviews was also recorded and found to be very high.
Although all reviews reported a possible to strong link between maternal acetaminophen use and autism or ADHD, seven of the nine reviews urged caution when interpreting those findings. Most warned that the results could be skewed by unmeasured factors, known as confounders, such as family genetics or parental health differences.
Overall, confidence in the findings was rated as low for two reviews and critically low for seven. Only one review included two studies that adequately controlled for shared genetic and environmental influences between siblings and accounted for other important factors, including parental mental health, background, and lifestyle.
Adjusted Results Show Little to No Link
In both of these well-controlled studies, any apparent connection between prenatal acetaminophen exposure and autism or ADHD risk largely disappeared or was significantly reduced after adjustments were made. The researchers suggest that these results indicate much of the previously observed risk can be explained by family-related factors rather than by the medication itself.
The authors acknowledge several limitations in the available research. The included reviews varied in scope and methodology, did not address dosage or timing of exposure, and focused only on autism and ADHD outcomes.
Even so, the new overview brings together all relevant evidence using established quality-assessment methods. It highlights what the authors describe as “the lack of robust evidence linking acetaminophen use in pregnancy and autism and ADHD in offspring.”
They conclude: “The current evidence base is insufficient to definitively link in utero exposure to acetaminophen with autism and ADHD in childhood. High quality studies that control for familial and unmeasured confounders can help improve evidence on the timing and duration of acetaminophen exposure, and for other child neurodevelopmental outcomes.”