The challenge of including expectant mothers in clinical trials

Fewer than 1% of clinical trials in the USA include pregnant women, creating knowledge gaps on the use of medications during gestation

Marília Marasciulo

Abstract geometric composition in shades of blue, with black and white silhouettes of n expectant mother, healthcare professionals, and other people in the center. Fluid geometric elements—weaving lines, polygonal shapes, and fragments—intertwine, creating movement and suggesting barriers and gaps in knowledge.

Fewer than 1% of new drug trials in the USA include expectant mothers. This systematic exclusion creates critical gaps in evidence regarding the safety and effectiveness of medications used during pregnancy.

These findings were reported in a 2025 study by researchers from Brown University School of Public Health and the Federal Reserve Bank of New York, published in the American Journal of Obstetrics & Gynecology.

Of the 90,860 randomized clinical trials analyzed—all registered between 2008 and 2023—44,160 met the sampling criteria defined by the study’s authors. From this group, only 362 (0.8%) included pregnant women, while 33,249 (75%) explicitly excluded them, and 10,549 (24%) did not state whether pregnant women participated.

Why are pregnant women excluded from clinical trials?

Ethical and legal concerns: Women are rarely invited to participate in experimental research due to concerns about potential harm to unborn babies.
Legal liability: By preventively excluding pregnant women, pharmaceutical companies limit the risk of litigation resulting from adverse effects during pregnancy.
Methodological complexity: Physiological changes during pregnancy (hormonal, metabolic, and cardiovascular alterations) make study design and data interpretation more difficult.
Historical regulation: Conservative guidelines established after cases such as the thalidomide tragedy in the 1960s continue to influence current research protocols.
Costs and logistics: Costs are increased by the need for additional monitoring of mother and baby, extended follow-up, and special safety requirements.

Of the studies that enrolled pregnant women, 94% limited participation exclusively to this group and did not include other populations for comparison.

“Despite calls to improve the pregnancy evidence base, the inclusion of pregnant participants in randomized clinical trials has remained flat over recent years,” wrote researchers Alyssa Bilinski and Natalia Emanuel in the article.

AI Classification

The dataset encompassed all randomized clinical trials registered between 2008 and 2023 in the Aggregate Analysis of Clinical Trials (AACT), a database containing data from ClinicalTrials.gov, the leading public registry of American clinical trials.

The sample was limited to studies conducted in the US involving women between 18 and 45 years old, reducing the scope to 49% of the total.

The researchers classified each trial into one of three categories—”including pregnant women,” “excluding pregnant women,” or “unspecified”—based on an analysis of the title, abstract, and eligibility criteria described in the protocols.

Postpartum trials and studies related to abortion or fetal death were considered “excluded,” restricting the “included” category to trials where live birth was expected.

The initial screening was performed using ChatGPT, which was then validated manually, with a margin of error between 1.5% and 1.8%.

All trials classified as “unspecified” or “including pregnant women” were subjected to an additional manual review.

Randomized clinical trials involving expectant mothers were further divided into clinical categories—labor, pregnancy-related conditions, premature birth, infectious diseases, chronic conditions, and pregnancy symptoms—using GPT-4 for initial classification followed by manual verification.

For comparison, the study separately cataloged trials on infertility, erectile dysfunction, and abortion or fetal death.

Profile of clinical trials involving pregnant women

Of the 362 trials involving pregnant women, 38% were related to labor; 22% to pregnancy-related conditions; 15% to premature birth; 16% to infectious diseases; 5% to chronic conditions; and 2% to pregnancy symptoms.

“Although non-infectious chronic conditions affect a growing proportion of pregnancies, only 19 randomized clinical trials addressed this issue, in stark contrast to the many studies focused on other conditions, such as infertility and erectile dysfunction,” the authors point out.

Trials that included pregnant women tended to adopt open-label designs (without the use of a placebo) and focus on prevention, especially interventions to prevent premature birth, infections, or vertical transmission of HIV.

These studies rarely receive funding from the pharmaceutical industry.

The trials classified as “excluding pregnant women” or “unspecified” included 225 trials on infertility, 116 on erectile dysfunction, and 71 on abortion or fetal death.

In a subsample of 50 trials initially classified as “unspecified,” the manual review found no evidence that pregnant women were included; in 82% there were explicit indications of exclusion.

The authors highlight the ongoing need for robust evidence specific to pregnancy.

“More randomized clinical trials focusing on pregnancy are essential to expand the data available to healthcare professionals and ensure that pregnant women receive quality, evidence-based care,” they wrote.

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