Over the past several months, President Trump and his Secretary of Health Robert F. Kennedy Jr. have made sweeping, unsubstantiated claims that Tylenol (acetaminophen) in pregnancy linked to autism and this SSRIs (antidepressants) may be associated with fetal harm. In the case of Tylenol, the few studies that claim to have found a link either do not control for confounding variables or find that the link disappears when they do this; the drug was also safe for children for decades. And scientists have actually studied SSRIs during pregnancy in quite some detail. But while these two types of drugs have been widely studied, they are the exception rather than the norm. In fact, most clinical trials and drug studies explicitly exclude pregnant women.
Because of this information vacuum, countless pregnant women refuse treatment that could relieve pain and actual harm, out of fear that it could potentially harm their fetus.
Scientists are understandably reticent to study drugs in pregnant women—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 post-marketing studies does not protect them – it does, researchers say. Scientific American Ultimately, clinicians have little information to help them treat pregnant women when they are ill. This needs to change, they say.
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“There is a growing consensus that we should think less about protecting pregnant women. from explore and think instead about the benefits of protecting people through research,” says Alyssa Bilinski, assistant professor of health policy at Brown University School of Public Health.
According to some estimates, more than 90 percent Pregnant women in the United States report taking at least one drug during pregnancy. At the same time, less than 1 percent Randomized clinical drug trials published between 2008 and 2023 included pregnant women, according to a study co-authored by Bilinski earlier this year.
Researchers believe this situation needs to change so that pregnant women can care for themselves while caring for their fetus.
The reason pregnant women are excluded from drug trials starts with thalidomide, a drug sold as a sleep aid that led to birth defects in 8,000–10,000 children worldwide. In the late 1950s and early 1960s, doctors prescribed thalidomide for morning sickness. (In the US, the Food and Drug Administration never approved thalidomide for the treatment of 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 closely monitored—something many had not done before. Bilinski said the FDA took this to mean the agency needed randomized studies showing safety and effectiveness. For many years, most drug trials excluded all women of childbearing age. Federal regulations classified pregnant women as a “vulnerable” population, meaning they were considered unable to consent to participate in a clinical trial.
“There is a growing consensus that we should think less about protecting pregnant women. from explore and think instead about the benefits of protecting people through explore.” —Alyssa Bilinski Associate Professor, Department of Health Policy
But experts, including the American College of Obstetricians and Gynecologists, have rejected this view, arguing that pregnant people are fully capable of giving informed consent. “It's a little shortsighted to say that not allowing pregnant women to participate in clinical trials actually protects them,” Bilinski says. In the absence of clinical trial data, when a drug is approved for the general population, doctors prescribe it to pregnant women as well—we simply don't have data on how safe and effective it is for them, she says. “So many, many people are still being exposed to drugs without even knowing the potential risk.”
The idea of excluding pregnant people from drug trials likely comes from a “well-intentioned desire to protect pregnant women and their babies,” says Shaheen Lokman, an assistant professor of immunology and infectious diseases at the Harvard T.H. School of Public Health. Chana. But “we must think about the mother’s health, and not just [see them] like a vessel for a baby.”
Because clinical trials excluded pregnant women, scientists do not know enough about the safety and effectiveness of drugs in this population. “And that leaves these groups 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 of Maternal-Fetal Medicine.
The decision to take a drug during pregnancy “must be balanced against what the harm is not only of the potential drug, if there is one, but also what the harm or benefit is of not taking the drug or not taking the vaccine,” Srinivas adds. She often talks with her patients about the risks and benefits of taking or staying on their medications. They don't want to put their fetus at risk from medications, but untreated conditions such as hypertension or diabetes are often more harmful—not only to the fetus, but also to the pregnant woman.
“You have to think about what would have happened to this mom and this pregnancy and this baby if the treatment or agent had not been prescribed. Because apparently people aren't just taking medications for fun—they're taking them for an underlying condition,” says Lockman, who has spent years developing guidelines to study the safety and effectiveness of medications in pregnant women with HIV or tuberculosis.
Earlier this year, Bilinski and her colleagues simulated the consequences of excluding pregnant women from randomized controlled trials. They found that the benefits of including pregnant women in such studies would far outweigh any negative consequences. For example, the researchers estimate that a clinical trial of thalidomide in 200 pregnant women would prevent birth defects in 99.6 percent of cases, or nearly 8,000 children. They found that including pregnant women in COVID vaccine trials would have prevented 20 percent of COVID-related maternal deaths and stillbirths in the US from March to November 2021.
So how can we fill this gap in knowledge about drug safety during pregnancy?
Scientists have some ideas. The 21st Century Cures Act, signed into law by then-President Barack Obama, established the Pregnant and Breastfeeding Women Research Task Force. (PRGLAC) to advise the HHS Secretary of gaps in this research. The task force recommended removing the “vulnerable” designation for pregnant women and issued draft guidance for the pharmaceutical industry. And the National Academies of Sciences, Engineering, and Medicine convened a commission that presented report recommendations to Congress and the Department of Health and Human Services last year. The report found that including pregnant and breastfeeding women in clinical drug trials does not pose a significant legal risk for pharmaceutical companies. However, it turned out that many pregnant women sued the companies after taking drugs already approved by the FDA, which the plaintiffs alleged caused birth defects, among other things. If companies had studied these drugs in pregnant women, some of these harms could have been avoided.
There are ways to ethically conduct drug research on people who are pregnant or breastfeeding. The gold standard of scientific evidence is a randomized controlled trial, which is more difficult to conduct in healthy pregnant women. But drug companies and researchers can enroll pregnant people in late-stage randomized trials of drugs that have already been proven safe in small studies and animal studies.
Most often, studies are observational in nature: they simply look at people who are already taking the drug and measure what effect it has on their health and the health of the fetus. But these studies are limited by the fact that populations of people who use drugs are inherently different from those who do not. There are more rigorous ways to conduct research, such as pre-enrolling people before they are born to avoid biasing memories and study results, and conducting studies on siblings who were differentially exposed to the drug in the womb.
“It's very, very difficult to do this study well from an observational standpoint, but it is possible,” Lockman says.
However, she stresses that not all drugs need to be tested on people who are pregnant or breastfeeding. Researchers should prioritize drugs that are taken to treat serious chronic diseases such as heart disease and cancer, deadly infections such as HIV, and fever. (Untreated infections and fevers are themselves linked to autism.) Antidepressants may be critical for the mental health of pregnant women. Poor mental health is a major contributing factor maternal mortality in the US A class of antidepressants known as SSRIs are actually relatively well studied in pregnancy.. Over the summer, the FDA convened a panel on the safety of some antidepressants during pregnancy, which attempted to cast doubt on these studies, ignoring the real harm of untreated depression or anxiety to pregnant women and their fetuses.
Trump said at a recent press conference about Tylenol and autism that women just need to “get over it.” Comments like these are at the heart of the medical establishment's long history. ignoring women's painwhich could further harm their health. In fact, many pregnant women already avoid taking medications, including those they need, because there is little to no evidence that the medications are safe for them and their fetus.
There is no easy solution—the solution will involve funding research to fill the gaps and providing drug manufacturers with guidance on how to safely enroll pregnant women in studies.
“There is no one on earth who would want to unnecessarily put a pregnant woman or fetus at risk,” Lockman says. “So what is the safest way to get information and help women stay informed about their care and make the best decisions?”
