Autism and Acetaminophen Use during Pregnancy: Does Science Support the Claim of a Link?

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In light of the recent White House announcement and the FDA's new guidance regarding the potential link between acetaminophen use during pregnancy and an increased risk of autism and ADHD in children, several scientific bodies, including The American College of Obstetricians and Gynecologists and The World Health Organization have released statements highlighting the lack of scientific evidence underlying the White House and FDA’s stance. When policy has the potential to influence human health it is crucial to examine the existing scientific evidence critically.

The investigation of a potential link between the use of acetaminophen during pregnancy and an increased risk of certain neurodevelopmental conditions, such as autism and ADHD, started in the 1980’s. Since then, numerous scientific investigations have explored this potential connection with mixed results. Recently, a comprehensive analysis by Prada et al. evaluated 46 studies evaluating the association between maternal acetaminophen use and an increased risk of neurodevelopmental disorders (NDDs) in children. The authors indicate that 27 studies reported a positive association between prenatal acetaminophen use and NDDs, while 9 showed no significant link, and 4 indicated negative associations (a potential protective effect). This analysis concluded that there is evidence consistent with an association between prenatal acetaminophen exposure and increased incidence of NDDs. However, the study also highlighted substantial differences among the studies, such as study design and population studied, which led to a qualitative rather than a quantitative synthesis of the evidence.

On the other hand, Ahlqvist et al. performed one of the largest clinical studies evaluating this potential association, assessing NDDs in nearly 2.5 million children in Sweden. In this study, while initial models showed a slight increase in risk for autism, ADHD, and intellectual disability with acetaminophen use during pregnancy, sibling control analyses found no evidence of increased risk. Specifically, when comparing children whose mothers took acetaminophen during pregnancy that were at an increased risk of developing NDDs to their siblings who were not exposed to acetaminophen, the authors found the association disappeared. This suggests that shared environmental or genetic factors in these families may predispose these children to developing NDDs that are completely independent of maternal acetaminophen use. Additionally, the study also noted the lack of a dose-response pattern in sibling control analyses, further questioning the causal nature of the association. Finally, a variety of maternal characteristics that could be confounding factors were identified in the Ahlqvist study, including lower socioeconomic status (SES), higher body mass index (BMI), and a history of psychiatric conditions. These factors were shown to be associated with both increased acetaminophen use and a higher risk of neurodevelopmental disorders in children.

Another significant hurdle the scientific community has faced when investigating the potential link between acetaminophen and the development of NDDs are substantial methodological limitations within the field. Specifically, potential confounding by indication poses a significant problem when interpreting results from these studies. Mothers who take acetaminophen during pregnancy are doing so to manage infections, fevers, and pain. It is essential to manage these conditions as maternal infections during pregnancy can predispose children to developing NDDs. The question that remains to be answered still is, is the increased risk of children developing NDDs due to their mother having an infection or due to her taking acetaminophen? Additionally, these studies are largely reliant upon self-reported data without formal documentation of length, dose, or timing of the exposure. Collectively, these factors contribute to the variability in study findings and limits the scientific community’s ability to draw causal conclusions.

In conclusion, while evidence exists suggesting an association between prenatal acetaminophen use and increased risk of NDDs exists, the lack of definitive causal evidence and the presence of confounding factors necessitate cautious interpretation. Further research is needed to clarify these associations and explore potential mechanisms before a causal interpretation between acetaminophen use during pregnancy and the development of NDDs can be reached. Meanwhile, the WHO recommends that “all women continue to follow advice of their doctors or health workers, who can help assess individual circumstances and recommend necessary medicines. Any medicine should be used with caution during pregnancy, especially in the first three months, and in line with advice from health professionals.”

We will continue to cover the scientific studies regarding acetaminophen use and the development of NDDs in children as well as other key scientific topics covered in the “Make America Healthy Again” report.