Acetaminophen
Sonya Collins
In September 2025, HHS announced actions it would take—including a letter to physicians and the beginning stage of a process for a safety label change—to address the potential risk of autism associated with prenatal acetaminophen exposure.
Acetaminophen is typically framed as the safest OTC analgesic during pregnancy; however, any shift may cause confusion and bring patients into the pharmacy with questions.
“I would continue to recommend acetaminophen for the shortest duration at the lowest dose, which is just good medication management during pregnancy,” said Nicole Cieri-Hutcherson, PharmD, a clinical associate professor at the University at Buffalo School of Pharmacy, who specializes in women’s health.
In an open letter to physicians, Martin Makary, MD, FDA commissioner, cited accumulating evidence of an association between prenatal acetaminophen exposure for autism and ADHD in children.
The letter acknowledged that the greatest risk was from chronic acetaminophen exposure in utero. Makary also noted that association does not equate to causation. Other studies, the letter said, find no link between prenatal acetaminophen exposure and autism risk.
The commissioner asked physicians to consider this information, especially when making recommendations to patients who are pregnant with low-grade fevers that may not warrant an analgesic. He urged physicians to minimize acetaminophen use in patients who are pregnant with low-grade fever while also remembering that it continues to be the safest analgesic, as ibuprofen and aspirin come with well-documented risks to the fetus.
Mixed findings
Multiple studies have addressed the topic of acetaminophen exposure in utero and autism risk.
“The largest trial did not find a link between prenatal acetaminophen use and autism when it controlled for other factors,” Cieri-Hutcherson said.
The large, randomized controlled trial published online in JAMA on April 9, 2024, included nearly 186,000 children and found no link between prenatal acetaminophen exposure and risk for autism, ADHD, and intellectual disability after controlling for genetic and environmental factors.
On the other hand, a meta-analysis of 46 studies published online August 14, 2025, in BMC Environmental Health, found an association between prenatal exposure to the analgesic and risk for autism. The study authors noted that while people who are pregnant should limit acetaminophen use, the analgesic is still the safest OTC option for reducing fever in this population. Untreated fever, the study authors noted, comes with its own risks, including neural tube defects and pre-term birth.
The findings of the meta-analysis led HHS to contact the study authors, who reiterated in a statement that their research showed association, not causation. The statement emphasized that the association was strongest in children who had had 4 weeks or more of prenatal exposure to the analgesic.
The authors also said, “Further research is needed to confirm the association and determine causality, but based on existing evidence, I believe that caution about acetaminophen use during pregnancy—especially heavy or prolonged use—is warranted.”
Counseling patients who are pregnant
The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) continue to recommend acetaminophen for pain or fever during pregnancy.
In statements released shortly after the HHS announcement on acetaminophen, both organizations described significant limitations to the research that has found an association between the analgesic and autism risk. ACOG stresses judicious use of the OTC pain reliever at the lowest effective dose for the shortest duration. The associations note that untreated fever, especially in the first trimester, raises risk of miscarriage, birth defects, and premature birth. Untreated pain can lead to depression, anxiety, and high BP, SMFM said.
“All our major organizations still recommend acetaminophen for fever,” Cieri-Hutcherson said, “But if patients are unwilling to take it, we recommend the same management strategies that we would for any patient: hydration, rest, cool compresses.”
It’s also important to address the underlying causes of fever or pain. “Some untreated infections are associated with birth defects, spontaneous miscarriage, or premature birth,” Cieri-Hutcherson said. “Headaches could be a warning sign of infection or blood clot.”
If the symptom for which a patient who is pregnant might take acetaminophen is a persistent one, Cieri-Hutcherson recommends referring them to their OB/GYN to identify the cause in order to receive appropriate treatment.
“Ideally, patients wouldn’t take any medications during pregnancy, but we know that patients do use them, so we want to make sure [they’re] using the safest ones.” ■