FDA pushes label change for acetaminophen in pregnancy, approves leucovorin calcium for CFD

On September 22, 2025, the US Food and Drug Administration (FDA) issued a pair of announcements with immediate implications for women's health.

The FDA announced the initiation of a label change for acetaminophen (Tylenol and similar products), reflecting data that prenatal exposure may be associated with increased risk of neurodevelopmental disorders.¹

The agency also approved leucovorin calcium (Wellcovorin) for the treatment of cerebral folate deficiency (CFD), a rare neurological condition with manifestations that include autistic features, seizures, and movement difficulties.²

Acetaminophen in Pregnancy

Acetaminophen remains the most commonly used over-the-counter analgesic and antipyretic in pregnancy. The FDA cited multiple large-scale studies, including the Nurses’ Health Study II and the Boston Birth Cohort, showing an association between maternal acetaminophen use and later diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).¹ The strongest associations were observed with prolonged, chronic use across gestation.¹

In an official statement,noted: *“The precautionary principle may lead many to avoid using acetaminophen during pregnancy, especially since most low-grade fevers do not require treatment. It remains reasonable, however, for pregnant women to use acetaminophen in certain scenarios," said Marty Makary, MD, MPH, commissioner of the FDA.

Although causality has not been established, the agency emphasized the importance of clinician awareness and shared decision-making. Untreated maternal fever itself has been linked with adverse outcomes, underscoring the need to weigh potential risks of both the drug and the condition being treated. Importantly, acetaminophen remains the only over-the-counter antipyretic approved for use in pregnancy, as aspirin and nonsteroidal anti-inflammatory drugs have well-documented adverse fetal effects.¹

Leucovorin Calcium for Cerebral Folate Deficiency

In parallel, the FDA approved leucovorin calcium for CFD after reviewing mechanistic studies and case reports published between 2009 and 2024.² This condition, characterized by impaired folate transport into the central nervous system, can present with developmental delay, seizures, and behavioral phenotypes consistent with ASD.²

“The FDA is collaborating with GSK to broaden the existing Wellcovorin label. This effort reflects the FDA’s commitment to identify opportunities to repurpose drugs to treat chronic diseases. The FDA remains committed to finding and treating the root causes of autism," Tidmarsh, MD, PhD, director of the FDA’s Center for Drug Evaluation and Research, stated

Implications for Obstetric Care

For obstetrician–gynecologists, the FDA’s announcement reinforces the need for clear counseling around acetaminophen use in pregnancy. Patients should be advised that:

• Acetaminophen remains the preferred OTC antipyretic in pregnancy.
• Risks appear greatest with chronic, long-term use.
• Most low-grade fevers may not require pharmacologic treatment.
• Untreated febrile illness also carries risk and may justify acetaminophen use.¹

Regarding CFD, although this approval has no direct impact on obstetric prescribing, the growing recognition of neurodevelopmental disorders linked to prenatal and early-life exposures underscores the importance of maternal health optimization and interprofessional collaboration with pediatricians and neurologists.

Conclusion

The FDA’s dual actions highlight an ongoing shift toward both risk mitigation in pregnancy and expanded treatment options for pediatric neurological conditions. For OB/GYNs, these developments reinforce the need for evidence-based counseling on acetaminophen use and awareness of evolving therapies for conditions contributing to the rising prevalence of ASD.

Editor's Note: Artificial Intelligence was used in the creation of this content.

References

1. US Food and Drug Administration. FDA Responds to Evidence of Possible Association Between Autism and Acetaminophen Use During Pregnancy. September 22, 2025. Accessed September 22, 2025. https://www.fda.gov/news-events/press-announcements/fda-responds-evidence-possible-association-between-autism-and-acetaminophen-use-during-pregnancy
2. US Food and Drug Administration. FDA Takes Action to Make a Treatment Available for Autism Symptoms. September 22, 2025. Accessed September 22, 2025. https://www.fda.gov/news-events/press-announcements/fda-takes-action-make-treatment-available-autism-symptoms
3. GSK. GSK to Submit Label Update for Wellcovorin (Leucovorin) at US FDA’s Request. September 22, 2025. Accessed September 22, 2025. https://www.gsk.com/en-gb/media/press-releases/gsk-to-submit-label-update-for-wellcovorin-leucovorin-at-us-fda-s-request/