Including pregnant women in drug trials can lead to better health outcomes and reduce misinformation, experts say

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Last month’s announcement by the Trump administration linking Tylenol use during pregnancy to autism in children has reignited discussion on how drugs, their risks and their benefits are tested in women who are pregnant and breastfeeding.

This population has been historically excluded from clinical trials for drugs and treatments, mostly out of safety concerns for the mother and fetus.

But maternal health providers say that has created a gap in research on which medications are indeed dangerous, or safe and even necessary to take during pregnancy.

“Without some of this evidence, because of the exclusion of these populations from trials, we end up having a lot of conversations about risk benefit, theoretical risks based on the mechanism of how a medicine might work and what we think that might do,” said Dr. Sindhu Srinivas, an OB-GYN at Penn Medicine. “We’re left with a lot of conversations that aren’t guided always by the best information.”

In recent years, specialists from maternal fetal medicine, obstetrics and gynecology, pediatrics, mental health, and other fields have made a bigger push for drug trials to include more pregnant participants in order to create stronger confidence about medication use during this time.

The goal, Srinivas said, is to move away from automatic exclusion of pregnant participants from trials or studies and shift to a culture that protects women through research.

“When we think about enrolling patients in trials, it’s a discussion with the patient and it’s an informed consent,” she said. “So, the idea that pregnant people can’t, wouldn’t be able to have that conversation — it’s not that everybody would enroll, but you’d give people the option to enroll and it would be up to the individual, just like with any other person, to make that decision.”

Extreme caution in trial participation leads to gaps in research

The exclusion of pregnant women in clinical drug trials goes back decades, largely driven by concern and fear around the risks. Scientists and researchers became even more cautious following public drug incidents like the use of thalidomide.

The sedative medication was mostly used throughout Europe and Canada in the 1950s and 1960s. It was marketed as safe and effective for morning sickness and insomnia.

Doctors began prescribing it to pregnant women to address nausea, even though thalidomide was never tested in pregnant women in original clinical trials.

Researchers eventually discovered that the drug caused serious birth defects in infants. Between 10,000 and 20,000 babies worldwide were born with malformed or missing arms and legs.

The drug was pulled from the market. In the aftermath, clinical trials in many places, including in the U.S., became extremely cautious of testing medications in pregnant women.

Over the years, medical research and regulations have removed some of those severe reservations, but Srinivas said it’s been gradual.

The risks and benefits of medication use during pregnancy is still underresearched. A lot of what we know today is based on retrospective studies or data registries, which collect information on positive or negative outcomes after drugs come on the market and people start taking them.

Meanwhile, many women depend on treatments to manage mental health conditions, chronic diseases and pain. Srinivas said they sometimes succumb to a false cultural narrative that tells them all medication use during pregnancy is bad or harmful.

“Patients that have hypertension or diabetes or Crohn’s disease, not being on your medicines when you’re pregnant is actually quite harmful, not just to you, but also to the pregnancy,” she said.

This narrative and misconceptions about medication use during pregnancy can make mothers feel guilty, Srinivas said, and feel like they must choose between their own health and that of their infant when, ideally, both should be equally considered.

“It’s a pretty deep conversation about like, ‘How bad is your mental health disorder? Have you been hospitalized before?’ And then talking about all the risks of not being on medication when you have a pretty severe form of depression versus if it’s a little milder and you want to just kind of keep an eye on things,” she said. “It’s also not a one-size-fits-all approach. It’s really a conversation that’s pretty nuanced with that person.”

Efforts to make drug research more inclusive

Leading medical organizations and groups like the Society for Maternal and Fetal Medicine, the Coalition to Advance Maternal Therapeutics, the American College of Obstetricians and Gynecologists and the Society for Women’s Research all recommend including pregnant and breastfeeding people in drug research when appropriate.

A 2016 federal law created a special advisory group called the Task Force on Research Specific to Pregnant Women and Lactating Women and tasked members to identify gaps in research and make recommendations for future guidance.

A final report recommended declassifying pregnant women as a “vulnerable population” in research regulations, developing programs that prioritize the development of treatments specifically for pregnant and lactating people, and expanding the workforce of clinicians and researchers who specialize in obstetric and lactation therapies.

Some of those proposals have been achieved, but Srinivas said there’s more work to be done, especially in educating other health providers and patients on how maternal fetal specialists can help people make these decisions well before they even become pregnant.

“I’ve had a lot of conversations with patients that are like, ‘I’m not really sure I even want to do this, but I don’t know if I can,’” she said. “Those are exactly the kind of people that we see and that we like to see, to be able to help them make a good decision for themselves.”