FDA Adopts Precautionary Principle, Announces new Guidance on Use of Acetaminophen

The U.S. Food and Drug Administration announced yesterday that it will require drug manufacturers to change the label to products containing acetaminophen to reflect an alleged association between taking the drug during pregnancy and certain diagnoses, such as autism and Attention Deficit Hyperactivity Disorder (ADHD) in children. They also sent a letter to physicians alerting them to this change.  In doing so, they relied on studies that show an apparent correlation between the drug and certain neurodivergent diagnoses. 

In the Notice to Physicians, the FDA acknowledged that causation has not been demonstrated – meaning there is no study that demonstrates that acetaminophen causes any actual harm. They also acknowledge that many studies show that there is no harm: 

While an association between acetaminophen and autism has been described in many studies, a causal relationship has not been established and there are contrary studies in the scientific literature.

Moreover, the Notice to Physicians stated that acetaminophen is the safest over the counter medication available to pregnant and nursing mothers and that high fevers can pose an actual risk to the fetus. 

This consideration should also be balanced with the fact that acetaminophen is the safest over-the-counter alternative in pregnancy among all analgesics and antipyretics; aspirin and ibuprofen have well-documented adverse impacts on the fetus.

The safety profile of acetaminophen during pregnancy is supported by several reputable organizations, including the Society for Maternal and Fetal Medicine and the Autism Science Foundation. These societies emphasize that acetaminophen remains a critical option for managing pain and fever in pregnant women, given its established safety compared to other analgesics that may pose risks to fetal development. Additionally, these scientific foundations underscore the lack of a scientific consensus on the causal relationship between prenatal acetaminophen use and the risk of autism and ADHD in children. It’s notable that FDA Commissioner Marty Makary cited the precautionary principle is driving this policy change. 

“Even with this body of evidence, the choice still belongs with parents. The precautionary principle may lead many to avoid using acetaminophen during pregnancy, especially since most low-grade fevers don’t require treatment. It remains reasonable, however, for pregnant women to use acetaminophen in certain scenarios.”

The precautionary principle suggests that when there is plausible risk of harm, but complete scientific understanding is not yet available, preventive measures should be taken to protect the public or environment from potential dangers. It has historically been a popular framework for making policy decisions in Europe.  Many academics suggest that this approach stifles innovation. 

Traditionally U.S. regulators, including the FDA, use a Benefit-Risk framework– which is a comprehensive framework that integrates various scientific and analytical methods to allocate resources effectively and make transparent, science-based regulatory decisions that enhance public safety. 

Using this framework, the FDA has interpreted “safe and effective” to mean that benefits outweigh risks. The present reliance on the precautionary principle is a significant shift and could be a harbinger of future decisions by the agency. 

This announcement could have impacts that reach beyond conversations with women and their physicians and extend into the courtroom.  Previously, class action litigation that alleged that acetaminophen causes autism was thrown out of court for lack of admissible evidence. However, a government pronouncement could tilt the scales in favor of plaintiffs. 

Stay tuned as we are closely following this issue and other regulatory developments that emerge from the Department of Health and Human Services (HHS).