The Pregnancy Drug Gap: Why Doctors and Pregnant Patients Are Making Decisions in the Dark

More than 90% of pregnant people take medications during pregnancy, yet the safety and effectiveness of most drugs remain unknown because pregnant people have been largely excluded from clinical trials. This means doctors and pregnant patients often make critical medical decisions based on limited information, animal studies, or data collected after a drug is already on the market. The evidence gap is particularly stark: fewer than 1% of US drug trials between 2008 and 2023 specified that they included pregnant participants, and fewer than 0.4% of trials submitted in the European Union include pregnant people.

Why Were Pregnant People Excluded From Medical Research in the First Place?

The roots of this exclusion run deep. In the late 1950s, a drug called thalidomide was marketed in 46 countries as a morning-sickness treatment without being tested in pregnant people. The result was devastating: more than 10,000 children were born with missing or shortened limbs. After thalidomide was withdrawn in the early 1960s, drug regulation became much stricter, and pregnant people were classified as a "vulnerable population" alongside children and people unable to give informed consent. In 1977, the US Food and Drug Administration (FDA) barred not only pregnant people but also women of childbearing potential from participating in clinical trials altogether.

Although these policies began to shift in the late 1980s and early 1990s, pregnant people continued to be sidelined because of lingering concerns about protecting both mother and baby. The World Health Organization (WHO) now says that pregnant people should be considered "complex" rather than "vulnerable" and be included in trials when possible, but progress remains slow.

What Happens When Pregnant People Don't Have Evidence-Based Information?

The consequences are real and immediate. Kristin Wall, an epidemiologist at Emory University, faced this dilemma firsthand when she became pregnant during the COVID-19 pandemic. Her physician told her that little was known about the COVID-19 vaccine's safety and effectiveness in pregnant people, even though observational data suggested it was safe. She had to weigh the risks and benefits herself—a task that most pregnant people are not uniquely qualified to do.

The problem extends far beyond vaccines. When a drug's safety in pregnancy is unknown at the time of FDA approval, it takes an average of 27 years before there is enough evidence to confidently rate its safety. During those decades, pregnant people and their doctors must make decisions about medications for conditions ranging from nausea to depression to epilepsy with incomplete information.

Some medications are known to be safe during pregnancy, including certain anti-allergy drugs, some antidepressants, some antibiotics, and acetaminophen (Tylenol). Other drugs carry clear risks—for example, the anti-epilepsy drug sodium valproate can cause severe developmental disorders when taken during pregnancy. But for the vast majority of medicines approved over the past decade, the safety profile remains uncertain.

Which Medications Lack Clear Safety Data During Pregnancy?

The evidence gap is particularly concerning for common medications that pregnant people might need. These include:

• Anti-nausea treatments: Many medications used to manage pregnancy-related nausea have never been formally tested in pregnant people.
• Anti-inflammatory drugs: The safety of many pain relievers and anti-inflammatory medications during pregnancy remains uncertain.
• Medications approved in the past decade: The vast majority of drugs approved by the FDA in recent years have not been studied in pregnant populations.

This uncertainty forces pregnant people and their doctors into an impossible position: treat a medical condition with drugs whose risks are unknown, or leave the condition untreated. "Sometimes 'ask your doctor' is really good advice, because your doctor has a lot of information," explains Alyssa Bilinski, a statistician at Brown University. "But 'ask your doctor' cannot substitute for underinvestment in research over decades".

Denise Astill, who took sodium valproate during pregnancy before clear guidance advised against its use, understands the stakes. Her twin daughters were diagnosed at age four with a wide range of health conditions, including cognitive difficulties, hearing problems, kidney impairment, autism, and attention deficit hyperactivity disorder. She founded the charity Foetal Anti-Convulsant Syndrome New Zealand to offer guidance on taking anti-seizure medications in pregnancy. "Pregnant people should have the same access to evidence-based care as everyone else," she says. "Can we truly make an informed choice when our health system and research are based on men?"

Are Researchers Working to Close This Evidence Gap?

Yes, and progress is being made. Researchers like Kristin Wall have successfully designed and conducted trials that tested treatments for Ebola, HIV, and pregnancy-specific conditions in pregnant people—collecting reliable data while protecting the health of study participants and their babies. Based on that experience, they have developed tools and guidance to help other researchers include pregnant people in studies.

At the University at Buffalo, the Clinical and Translational Science Institute (CTSI) is advancing research that bridges the gap between laboratory discoveries and real-world patient care. In 2024 alone, clinical research at the institution sustained high levels with nearly 15,000 participants enrolled in 208 studies. The CTSI has trained 22 scholars in clinical and translational science research since 2016, who have published 495 articles and secured $34.1 million in extramural funding, largely from the National Institutes of Health (NIH).

The CTSI also emphasizes the importance of community engagement in research planning. Feedback from Community Engagement Studio sessions helps researchers plan more impactful studies that address real-world health needs. Additionally, the institute is connecting researchers with artificial intelligence (AI) tools to help solve societally challenging problems, including those related to pregnancy and maternal health.

Despite these advances, logistical, regulatory, and ethical barriers remain. There is no evidence yet that recent anti-pharmaceutical rhetoric has reduced the inclusion of pregnant people in trials, but experts worry that broader hesitancy about medications might slow efforts to close evidence gaps.

The path forward requires a fundamental shift in how medical research approaches pregnancy. Pregnant people are not a vulnerable population to be protected from research—they are a complex population whose health needs deserve the same rigorous, evidence-based investigation as everyone else. Until that happens, millions of pregnant people will continue making critical medical decisions with incomplete information, relying on guidance that may be decades out of date.