During the past few months, President Trump and his health secretary, Robert F. Kennedy, Jr., have made sweeping, thinly evidenced claims that Tylenol (acetaminophen) in pregnancy is linked to autism and that SSRIs (antidepressants) might be linked to fetal damage. In the case of Tylenol, the few research studies that claim to find a link either don’t control for confounding variables or find that the link disappears when they do; the drug has also been safely prescribed to children for decades. And scientists actually have studied SSRIs in pregnancy fairly extensively. But while these two types of drugs have been widely studied, that’s more the exception than the norm. In fact, most clinical trials and drug studies explicitly exclude people who are pregnant.
Because of this information vacuum, untold numbers of pregnant people forego treatments that could alleviate pain and real harm out of fear that it might potentially harm their fetuses.
Scientists have understandably been reticent about studying medications in pregnant people—they must consider the potential risk to the fetus while trying to understand how a drug might benefit the person carrying it. But excluding pregnant people from clinical trials and postapproval studies doesn’t protect them—instead, researchers tell Scientific American, clinicians end up having little information to guide them in treating pregnant people when they are sick. That needs to change, they say.
On supporting science journalism
If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.
“There’s a growing consensus that we should be thinking less about protecting pregnant women from research and instead think about the benefits of protecting people through research,” says Alyssa Bilinski, an assistant professor of health policy at the Brown University School of Public Health.
By some estimates, more than 90 percent of pregnant people in the U.S. report taking at least one drug during pregnancy. At the same time, less than 1 percent of randomized clinical drug trials posted between 2008 and 2023 included pregnant people, according to a study Bilinski co-authored earlier this year.
Researchers believe this has to change so that people who are pregnant can take care of themselves while also taking care of their fetuses.
The reason people who are pregnant have been excluded from drug trials starts with thalidomide, a drug marketed as a sleep aid that led to birth defects in 8,000 to 10,000 children worldwide. Doctors prescribed thalidomide for morning sickness in the late 1950s and early 1960s. (In the U.S., Food and Drug Administration officials never approved thalidomide for sleep and nausea, but it was still available.) In response to the thalidomide tragedy, Congress passed an amendment to the Food, Drug and Cosmetic Act in 1962 that required clinical trials to be well-controlled—up until then, many were not. The FDA took this to mean the agency needed randomized trials showing safety and efficacy, Bilinski says. For many years, most drug trials excluded all women of childbearing age. Federal regulations designated pregnant women as a “vulnerable” population, meaning they were considered incapable of consenting to be part of a clinical trial.
“There’s a growing consensus that we should be thinking less about protecting pregnant women from research and instead think about the benefits of protecting people through research.” —Alyssa Bilinski, assistant professor of health policy
But experts—including the American College of Obstetricians and Gynecologists—have pushed back on this view, arguing that pregnant people are perfectly capable of providing informed consent. “It’s a little bit shortsighted to say that not including pregnant women in clinical trials actually protects them,” Bilinski says. In the absence of data from a clinical trial, when a drug is approved in the general population, clinicians prescribe it to pregnant people, too—we just don’t have data on how safe and effective it is for them, she says. “So lots and lots of people are still being exposed to medications without necessarily knowing the potential risk.”
The idea of excluding pregnant people from drug trials probably comes from “a well-intentioned desire to protect pregnant women and their babies,” says Shahin Lockman, an associate professor of immunology and infectious diseases at the Harvard T. H. Chan School of Public Health. But “we have to think about the mother’s health too, not just [see them] as a vessel for a baby.”
Because clinical trials have excluded pregnant people, scientists don’t know enough about the safety and efficacy of medications in that population—“and it leaves those populations with little information,” says Sindhu Srinivas, a professor of obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania and president of the Society for Maternal-Fetal Medicine.
The decision to take a drug while pregnant “has to be a balance of, what’s the harm not just of the potential medication, if there is one, but what’s the harm or the benefit of not taking the medication or not taking the vaccine,” Srinivas adds. She often has conversations with her patients about the risks and benefits of taking or staying on their medications. They don’t want to put their fetuses at risk from medication, but untreated conditions such as hypertension or diabetes are often more harmful—not just to the fetus but also to the pregnant person.
“You have to think about what would have happened to this mom and to this pregnancy and this baby if the treatment or agent were not given. Because presumably people are not taking meds just for the fun of it—they’re taking them for an underlying condition,” says Lockman, who has spent years developing guidance for how to study drug safety and efficacy in pregnant people with HIV or tuberculosis.
Earlier this year Bilinski and her colleagues modeled the effects of excluding pregnant people from randomized controlled trials. They found that the benefits of including pregnant people in such trials would have far exceeded any negative effects. For example, a clinical trial of thalidomide in 200 pregnant people would have prevented birth defects in 99.6 percent of cases, or nearly 8,000 children, the researchers estimated. And including pregnant people in trials of the COVID vaccines would have prevented 20 percent of COVID-related maternal deaths and stillbirths in the U.S. from March to November 2021, they found.
So how can we remedy this gap in knowledge about drug safety in pregnant people?
Scientists have some ideas. The 21st Century Cures Act, signed by then-President Barack Obama, established the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to advise the HHS secretary on gaps in this research. The task force recommended removing the “vulnerable” designation for pregnant people and issued some draft guidance to the drug industry. And the National Academies of Sciences, Engineering and Medicine convened a panel that put out a report last year of recommendations for Congress and the Department of Health and Human Services. The report found that including pregnant or lactating women in clinical trials of medications does not represent a significant legal risk to drug companies. It did find, however, that plenty of pregnant people have sued companies after taking drugs the FDA had already approved, which the plaintiffs claimed caused birth defects, among other harms. If companies had studied these drugs in pregnant women, some of those harms might have been avoided.
There are ways to conduct drug studies ethically in pregnant or breastfeeding people. The gold standard for scientific evidence is the randomized controlled trial, which is harder to do in healthy pregnant people. But drug companies and researchers could recruit pregnant people to participate in late-stage randomized trials of drugs that have already been tested for safety in smaller trials and animal studies.
More often, studies are observational—they simply look at people who are already taking a drug and measure what effects it has on their health and that of the fetus. But these studies are limited by the fact that populations of people taking a drug are inherently different from those who aren’t taking it. There are more rigorous ways to do studies, such as preregistering people before they give birth to avoid biasing recall and study outcomes, as well as conducting studies of siblings who were differentially exposed to the drug in the womb.
“Doing this research well from an observational perspective is very, very difficult, but it can be done,” Lockman says.
She stresses that not all drugs need to be tested in people who are pregnant or breastfeeding, however. Researchers should prioritize drugs that are taken to treat serious chronic illnesses such as heart disease and cancer, deadly infections such as HIV, and high fevers. (Untreated infections and fevers are themselves associated with autism.) Antidepressants can be critical for the mental health of someone who is pregnant—poor mental health is among the leading contributors to maternal mortality in the U.S. A class of antidepressants known as SSRIs has actually been relatively well-studied in pregnancy. Over the summer the FDA convened a panel on the safety of certain antidepressants in pregnancy that tried to cast doubt on this research, ignoring the real harms of not treating depression or anxiety for pregnant people themselves and for their fetuses.
Trump said in the recent press conference about Tylenol and autism that women just need to “tough it out.” Comments such as these underlie the medical establishment’s long history of dismissing women’s pain, which can further harm their health. In fact, many pregnant people already avoid taking medications, including ones they need, because there is little to no evidence that the drugs are safe for them and their fetus.
There’s no easy fix—the solution will involve funding research to fill in the gaps and providing guidance to drugmakers on how to include pregnant people in studies safely.
“There’s nobody on earth who wants to put pregnant woman or fetuses at risk unnecessarily,” Lockman says. “So what is the safest way of getting the information and helping women inform their care and make the best decisions they can?”
