Major Review Finds Links Between Acetaminophen Use In Pregnancy And ADHD, Autism Risk

NEW YORK –– For decades, acetaminophen, also known as paracetamol and sold under brand names like Tylenol, has been the go-to pain and fever reliever during pregnancy. Doctors have often considered it the safest choice, especially compared to other painkillers that can cause complications in later pregnancy. But a sweeping new review is raising fresh concerns about that long-held assumption.

Researchers reviewed 46 observational studies published over the past two decades, covering individual samples as small as just over 100 participants and as large as more than 2.4 million. They found that children whose mothers used acetaminophen during pregnancy were more likely to be diagnosed with neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

The systematic review, published in BMC Environmental Health, used a rigorous, structured approach called the Navigation Guide methodology to assess the strength and consistency of the evidence.

With more than half of pregnant women worldwide reaching for acetaminophen during pregnancy, these results affect millions of families. In the United States alone, millions of expectant mothers who believe they’re making the responsible choice for their unborn child may face an unexpected trade-off.

What the Review Found About Acetaminophen in Pregnancy

The research team examined 46 eligible studies. Of these, 27 found positive associations between prenatal acetaminophen use and developmental disorders, nine found no association, and four showed negative associations (protective effects).

Higher-quality studies were more likely to detect these links, and several identified a dose-response relationship. This means that the more often or longer a pregnant person used acetaminophen, the greater the likelihood of a child being diagnosed with certain conditions.

The review also found some inverse associations for other neurodevelopmental disorders in some studies, showing that children of acetaminophen-exposed pregnancies were less likely to have those conditions.

Could Something Else Explain the ADHD and Autism Connection?

A major question is whether the reasons for taking acetaminophen in the first place, be it fever, infection, or injury, might actually be behind the developmental outcomes. Several studies in the review accounted for this “confounding by indication,” and results showed minimal influence from it.

Some of the strongest evidence came from biomarker studies, which measured acetaminophen levels in umbilical cord blood or a newborn’s first stool (meconium) instead of relying on mothers’ recall. These studies consistently supported an association.

Animal and lab research offers possible explanations: acetaminophen readily crosses the placenta, reaching the fetus in less than an hour. Experiments suggest it can increase oxidative stress in developing brain tissue, disrupt hormone systems, and alter gene expression in ways that could affect brain development. The authors also discuss a “two-hit” model, in which acetaminophen exposure combined with another stressor may amplify risks; but they emphasize this framework is speculative and intended to guide further research, not as established fact.

What Pregnant Women Should Know Before Reaching for Pain Relief

This creates a genuine challenge for doctors and pregnant women. Other pain relievers, such as ibuprofen and aspirin, carry known risks in later pregnancy, which is why acetaminophen became the default recommendation.

The authors are not calling for acetaminophen to be avoided entirely. Instead, they recommend using the lowest effective dose for the shortest necessary time, and only under medical guidance.

The review also examined sibling-controlled studies, which compare brothers and sisters within the same family to control for shared genetics and environment. Findings here were mixed: one Norwegian sibling-controlled cohort study (Brandlistuen et al.) with 134 discordant pairs reported significant associations, while other sibling-controlled analyses (including a very large Swedish cohort) found no link. However, the Swedish analysis likely suffered from under-ascertainment of acetaminophen use, as other Swedish studies have reported much higher usage rates (around 56–63%).

Limitations and the Road Ahead

This is one of the most comprehensive reviews to date, but it has limitations. Many studies relied on self-reported medication use, which can be inaccurate. Differences in exposure measurement and outcome definitions meant the authors could not statistically combine the results into one overall figure. Publication bias, where studies showing an effect are more likely to be published, is also possible.

Importantly, these studies show associations, not proof of causation. Unmeasured factors could still explain some of the observed links. The authors recommend future research with direct exposure measurement, more robust sibling-comparison designs, and deeper investigation into biological mechanisms.

“Pregnant women should not stop taking medication without consulting their doctors,” lead author Dr. Diddier Prada, an assistant professor at the Icahn School of Medicine at Mount Sinai, said in a statement. “Untreated pain or fever can also harm the baby. Our study highlights the importance of discussing the safest approach with health care providers and considering non-drug options whenever possible.”

For now, the takeaway is awareness: acetaminophen remains an important option for managing pain and fever in pregnancy, but it should be used thoughtfully, and always with professional guidance.

Disclaimer: This article summarizes peer-reviewed research and is intended for informational purposes only. It does not provide medical advice. Pregnant individuals should consult a qualified healthcare provider before making any decisions about medication use.