Paracetamol and Pregnancy: From Pain Relief To The Risk Of ADHD And Autism

During pregnancy, the baby's brain is developing and highly vulnerable to external substances. Paracetamol is the most commonly used medication by pregnant women for pain and fever, and while considered safe, recent studies show that its frequent or prolonged use may be linked to a higher risk of neurological development problems in the child, such as ADHD and autism. Therefore, experts recommend that it be used only when truly necessary and always under medical supervision.

Pregnancy is an extremely delicate period for a baby's development. During this time, rapid and coordinated changes occur in the mother's body and the fetus, especially in the developing brain.

The central nervous system is still under construction, with neurons being born, connecting, and being "pruned" to make way for mature brain networks. Furthermore, the blood-brain barrier, which acts as a filter to protect the brain from potentially harmful substances, is not yet fully formed.

This means that the fetal brain is much more vulnerable to environmental exposures, such as chemicals, medications, and toxins. Even small changes in this process can have lasting consequences, resulting in difficulties with learning, behavior, and social interaction later in childhood.

These effects are grouped into a category called neurodevelopmental disorders (NDDs), which include, for example, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

Paracetamol, also known as acetaminophen, is currently the most widely used medication for pain and fever relief during pregnancy, as other common painkillers are associated with more serious risks, such as miscarriage or birth defects.

It is estimated that more than half of pregnant women worldwide use paracetamol at some point during pregnancy, and about 20% do so for prolonged periods, longer than 20 days. For many years, it was considered safe and even recommended by medical institutions such as the American College of Obstetricians and Gynecologists.

However, more recent studies have raised concerns about a possible link between frequent or prolonged use of the medication and an increased risk of neurodevelopmental disorders in children.

To carefully investigate this question, the researchers applied a methodology known as the Navigation Guide. This method was created to organize and evaluate observational studies in environmental health systematically and transparently, avoiding hasty conclusions.

The process begins with a detailed search of the scientific literature; in this case, all articles available in the PubMed database up to February 2025 were analyzed. The studies found are then evaluated according to rigorous criteria: risk of bias (i.e., whether there were flaws in the research design that could compromise the results), methodological quality, and strength of evidence (whether the findings are consistent and well-supported).

Because the studies were quite different from each other, rather than combining all the results into a single statistical analysis, the authors opted for a qualitative synthesis. This means they compared and discussed the findings together, highlighting patterns and differences between them, which is the procedure recommended by the Navigation Guide when there is a wide diversity of methods.

A total of 46 studies were included. Of these, 27 showed positive associations, that is, they found a significant link between prenatal acetaminophen use and the later development of ADHD, ASD, or related symptoms in their children.

Nine studies found no significant association, while four even suggested protective effects. Importantly, the studies considered to be of the highest quality were precisely those that most frequently indicated positive associations.

Thus, although not all studies reached the same conclusion, the prevailing trend indicates that there is indeed a link between fetal exposure to acetaminophen and an increased risk of attention deficit disorder.

This figure shows an assessment of the quality of studies investigating the relationship between paracetamol use during pregnancy and child developmental problems such as ADHD, autism, and other disorders. Each line represents an important aspect of the research, such as participant selection, data collection, control for potentially confounding factors, comprehensive analysis, and potential conflicts of interest. The colors indicate the level of confidence in these aspects: green indicates low risk of error, yellow indicates some concerns, red indicates high risk, and red (critical) indicates a high chance of error. In short, the figure helps understand which parts of the studies are most reliable and where there are weaknesses that could affect the results.

Given these results, the analysis concluded that there is a sufficiently consistent body of evidence to justify caution. The authors recommend that pregnant women limit paracetamol use to the minimum necessary, only when truly indicated, to reduce the risk of impacts on the baby's brain development.

This doesn't mean the medication should be avoided entirely, but rather that its use should be more judicious, under medical supervision, recognizing that even substances considered "safe" may not be completely risk-free when used during critical moments such as pregnancy.

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Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology

Diddier Prada, Beate Ritz, Ann Z. Bauer, and Andrea A. Baccarelli 

Environmental Health, volume 24, Article number: 56 (2025) 

https://doi.org/10.1186/s12940-025-01208-0

Abstract: 

Acetaminophen is the most commonly used over-the-counter pain and fever medication taken during pregnancy, with > 50% of pregnant women using acetaminophen worldwide. Numerous well-designed studies have indicated that pregnant mothers exposed to acetaminophen have children diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), at higher rates than children of pregnant mothers who were not exposed to acetaminophen. We applied the Navigation Guide methodology to the scientific literature to comprehensively and objectively examine the association between prenatal acetaminophen exposure and NDDs and related symptomology in offspring. We conducted a systematic PubMed search through February 25, 2025, using predefined inclusion criteria and rated studies based on risk of bias and strength of evidence. Due to substantial heterogeneity, we opted for a qualitative synthesis, consistent with the Navigation Guide’s focus on environmental health evidence. We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations. Overall, the majority of the studies reported positive associations of prenatal acetaminophen use with ADHD, ASD, or NDDs in offspring, with risk-of-bias and strength-of-evidence ratings informing the overall synthesis. Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring’s neurodevelopment.