When Robyn Flynn, a 34-year-old expectant mom, saw headlines last week announcing that a team of scientists were recommending pregnant people practice precaution when taking acetaminophen, the active ingredient in Tylenol, she felt worried — and frustrated.
Flynn, who is four months pregnant, said her OB/GYN told her that she shouldn’t take Advil — the Food and Drug Administration recommends against using non-steroidal anti-inflammatory drugs at 20 weeks pregnant or later — and that if she experienced “any sort of pain,” then “Tylenol was the safest option.”
When she saw the scientists’ statement, she wondered, “Okay, what can I take when I’m in pain?”
Flynn said she takes Tylenol occasionally for headaches and also for the aches and pains of pregnancy. After trying to conceive with the help of IVF for three years, Flynn, who lives in Montreal, said she feels “this extra incentive to want to do everything possible to make sure my baby is healthy.” But at the same time, she knows “anxiety and stress is bad for the baby, too” and that she can’t suffer through every pain for the remaining five months of her pregnancy. It might not seem like long from the outside, she said, but “nine months is a very long time when you’re in it.”
Since hearing about the new recommendation, Flynn said she’s going to try to hold off on taking any more until she can speak with her OB/GYN.
On Thursday, an international group of 13 scientists published a statement in the journal Nature Reviews Endocrinology calling for pregnant people and their physicians to practice greater caution when taking or prescribing acetaminophen, also known as APAP. The team of scientists reported that “increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders.”
The active ingredient in more than 600 medications, including Tylenol, acetaminophen is one of the most commonly used medications in the world, and commonly used by pregnant people — taken by up to 65 percent of pregnant people in the United States and 50 percent globally. Pregnant people often take acetaminophen to reduce fever and relieve pain because the usual alternatives, ibuprofen or naproxen, are contraindicated during the third trimester of pregnancy, and limited data exists on the potential adverse effects of opiates. The American College of Obstetricians and Gynecologists and Centers for Disease Control and Prevention recommend pregnant people take acetaminophen for fever or pain.
Historically, clinical research has excluded pregnant people under the assumption that they make up a “vulnerable” population. Yasaswi Kislovskiy, a fellow with Physicians for Reproductive Health and an obstetrician-gynecologist practicing in Pittsburgh, notes that “events like limb differences in children whose birthing parent took thalidomide” — a sedative frequently prescribed to pregnant people in the 1950s that was later found to cause birth defects — “forced scientific and regulatory bodies to take precautions when providing medications to pregnant people.” While that caution is important, she said, “pregnant people have been unintentionally harmed by restricted access to good data,” especially because they are excluded from drug trials.
The National Institutes of Health (NIH) did not require researchers to include women and other minorities in clinical trials until 1993. However, pregnant people are still largely excluded from drug trials because they are perceived as a “vulnerable” population. There’s been some effort to change that, with NIH Office of Research on Women’s Health recommending in 2010 that pregnant people be defined as “scientifically complex” rather than “vulnerable.”
Shanna Swan, a reproductive epidemiologist with the Icahn School of Medicine at Mount Sinai who co-authored the new statement on acetaminophen use, said that she and her colleagues came forward with their recommendations in part because acetaminophen is so widely used.
“You have this situation where it’s very cheap, it’s very available,” she said. In her experience, if you ask a pregnant person what medications they’re taking, they won’t include Tylenol because they don’t consider it a medication of note.
“This is a precautionary statement,” Swan said. “I want to stress that because we’re not saying, Stop taking APAPs at all.” Noting that “limited medical alternatives exist to treat pain and fever” in pregnancy, she and her co-authors advised that pregnant people not stop taking acetaminophen entirely, but rather only use it when medically necessary, in consultation with their physician and at the lowest dose for the shortest possible time.
The statement’s authors note that acetaminophen remains an important medication because alternative fever reducers and pain relievers are limited — and both fever and pain can have negative impacts on both the pregnant parent and developing fetus. “Fever is a well-accepted risk factor for multiple disorders, including neural tube defects and later life cardiovascular disorders,” the statement reads, adding that “pharmacotherapy during pregnancy involves a benefit-risk assessment,” meaning that physicians must evaluate “the potential benefits to the mother and fetus and possible risks to the fetus.”
Christopher Zahn, vice president of practice activities for the American College of Obstetricians and Gynecologists, said in an email statement that the authors “are not recommending anything counter to what is already done by obstetrician-gynecologists when prescribing acetaminophen for a given clinical condition.” He added: “Physicians should not change clinical practice until definitive prospective research is done and, most importantly, patients should not be frightened away from the many benefits of acetaminophen.”
Kislovskiy also urged a benefit-risk analysis. “Pregnant people live in the world, they have pain, they have jobs, they have stress. There are few tools available to them to alleviate pain, and they should be able to make an informed choice between having pain and its possible adverse effects, or using acetaminophen and its possible adverse effects,” she said. “For every choice in pregnancy, I hope to aid patients in understanding based on the data that we have, what are the possible outcomes if I use this medication compared to the possibilities if I don’t use this medication.”
What Swan and her co-authors do recommend is that patients consult with their physicians about acetaminophen use; that physicians be aware of the risks and take them into account when they counsel their patients; and that researchers conduct more studies into APAP-use during pregnancy.
“This is a lost child, if you will, in terms of research that has no home,” Swan said. She said her colleagues are calling for deeper research into acetaminophen use during pregnancy, including studies that look more closely at the doses patients have taken.
“What is really important about the consensus statement from this group is that it highlights the crisis that pregnant people face when trying to understand what drugs are safe during pregnancy,” Kislovskiy said. “We desperately need more information on drugs and diseases in pregnancy, not to regulate people’s bodies but to offer choice and information.”
Flynn also wishes there was more research on the subject — studies that identified painkillers that are safe during pregnancy, for example. She’d like to see reproductive health research that takes pregnant people’s pain seriously, she said.
“This happens a lot with women’s health issues,” Flynn said. “Even if you’re not pregnant, if you just have period cramps or whatever, you’re told that that’s normal and that you just have to live with it.”