More than 90 scientists, doctors, and public health researchers are calling on U.S. and European regulators to conduct new safety reviews of acetaminophen, pointing to mounting evidence that fetal exposure to the commonly used pain reliever could increase the risk of neurodevelopmental disorders and reproductive system effects.
Pregnant women should take as low a dose of Tylenol and other acetaminophen-containing drugs as possible, say the authors of a consensus statement published Thursday in Nature Reviews Endocrinology. Other recommendations include:
- The U.S. Food and Drug Administration (FDA) and Europe Medicines Agency should conduct new safety reviews of the drug;
- Acetaminophen-containing medicine labels should include recommendations for use during pregnancy;
- Acetaminophen-containing medicine should be sold only at pharmacies, as is already the case in some European countries;
- Additional epidemiological studies should be conducted that more accurately account for dosage, timing, and potentially confounding genetic factors.
Acetaminophen is the most common drug taken by pregnant women, with up to 65% of pregnant women in the U.S. saying they’ve used the medication, according to the statement authors. The pain reliever is a known endocrine disruptor—meaning it interferes with the proper functioning of hormones—leading to speculations that its widespread use could be contributing to rising rates of reproductive problems and neurodevelopmental disorders. That’s because hormones play a significant role in guiding reproductive organ and brain development.
Related: Tylenol’s active ingredient linked to language delay for baby girls
“We have to remember that these drugs are available everywhere, cheaply in huge bottles, and people take a lot of them,” said Shanna Swan, a professor of environmental medicine at Mount Sinai and co-author of the consensus statement, during a press briefing. “So, I think many people take these drugs without serious thought and without considering that they’re taking a medication which has side effects.”
The authors stress that acetaminophen remains an important option for high fever and severe pain for pregnant women, but note that the compound is not that effective at treating chronic pain and headaches.
Acetaminophen’s reproductive impacts
In recent years, researchers have started looking at acetaminophen’s endocrine-disrupting effects and potential links to neurodevelopmental disorders, like autism and ADHD. A 2020 birth cohort study found that babies with the highest levels of acetaminophen in umbilical cords had a twofold higher chance of having ADHD, and up to a threefold higher chance of having autism, according to the statement authors. While less is known about how exactly acetaminophen contributes to neurodevelopmental disorders, testosterone is known to play a role in brain development, said Swan. The drug has also been linked to language development delays in young girls.
But the FDA has yet to review how acetaminophen’s potential effects on fetal reproductive and genital systems—one of the factors prompting the new consensus statement’s authors to review existing epidemiological and animal studies from 1995-2020.
Related: Acetaminophen during pregnancy linked to autism
Acetaminophen use during pregnancy has been shown to have a range of effects on developing fetuses’ endocrine systems, including lower testosterone levels, an increased risk of undescended testicles and, according to newer research in animals, impacted ovary development, the authors said at the press briefing.
Dr. Xiaobin Wang, director of John Hopkins University’s Center on the Early Life Origins of Disease who was not affiliated with the statement, said that while “uncertainty remains about the causal relationship” between acetaminophen and adverse health effects, data from human and animal studies have raised serious concerns.
“For a long time, [acetaminophen] use during pregnancy was regarded to be safe,” Wang told EHN in an email interview. “I agree that it is time for regulatory bodies to reassess the safety of [acetaminophen], considering the widespread use of [acetaminophen] among pregnant women and growing concern on its potential adverse health effects on the developing fetus.”
Pain relief during pregnancy
With the FDA recently advising women not to take NSAIDs like ibuprofen during the second half of a pregnancy, pregnant women, who are also advised against taking opioids, have few options available for pain relief and fever management. High fever during pregnancy has been linked to neurological effects in offspring, while persistent pain can cause anxiety, depression and high blood pressure in pregnant women.
David Kristensen, a professor of neurology at the University of Copenhagen and co-author of the consensus statement, said this lack of alternative medications has, in part, made regulators concerned that issuing stronger warnings about acetaminophen could discourage women from taking needed medication.
“But I think what we believe is that it’s important to empower women to make their own decisions together with their clinicians or pharmacist,” he said at the press briefing.
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