With over 60 million people of childbearing potential in the United States and nearly four million births annually, the continued exclusion of pregnant individuals from clinical drug trials is a critical public health issue.[1] Despite 70 percent of pregnant – and 50 percent of lactating – individuals taking one or more medications, less than one percent of trials include these populations, compromising maternal and fetal health.[2]
The exclusion of pregnant individuals dates back to the 1950s, in which widespread thalidomide use caused severe fetal malformations and diethylstilbestrol-induced vaginal adenocarcinoma. In response, the U.S. Food and Drug Administration (FDA) excluded all women and other individuals of childbearing potential from participating in Phase 1 and early Phase 2 trials, when initial efficacy and safety data are collected and analyzed.[3] Pharmaceutical companies further extended their exclusion into Phase 3 and Phase 4, where safety and efficacy are confirmed and compared to standard treatments on large, diverse populations pre- and post-market.[4],[5]
It wasn’t until the 1990s that a congressional mandate required the inclusion of women of childbearing potential. Although the rates of inclusion among non-pregnant women within this population have steadily climbed since the mandate, rates of inclusion among pregnant individuals have remained steady. This is despite updated guidance from the FDA, National Institutes of Health, and Centers for Disease Control and Prevention advocating for their inclusion.[6]
In lieu of data from trials, pregnant individuals and their healthcare providers rely on post-market observational studies. These studies are often retrospective and may not capture all relevant variables and risks until there is widespread market adoption. Post-market surveillance takes an average of 27 years post-FDA approval to accurately and appropriately evaluate risk.[7]
The lack of timely data results in real consequences. Pregnant individuals take an average of 2.6 medications during pregnancy.[8] When medication is prescribed to these individuals, it is often done so without clear guidance on dosage or a full understanding of risks. This leads to prescriber and patient hesitancy in adjusting or accepting potentially lifesaving treatments.
Some may suggest that the requirement to include women of childbearing potential is sufficient to extrapolate safety and dosage data. However, pregnancy results in significant physiological changes that directly impact the pharmacokinetics and pharmacodynamics of medication (e.g., absorption, distribution, metabolism, and excretion).[9] For example, among some pregnant individuals undergoing chemotherapy, the typical dosage is metabolized and excreted so quickly that it never produces a therapeutic benefit, despite exposing the patient, and thereby the fetus, to its toxicities.[10]
The evidence is clear: such physiological changes mean that data from non-pregnant individuals cannot be reliably extrapolated to those who are pregnant.
The ethical arguments for exclusion also fall flat. Such arguments are grounded in the maternal-fetal conflict and the issue of informed consent. The maternal-fetal conflict is a situation where “the intent or actions of the pregnant [person] do not coincide with the needs, interests, or rights of [their] fetus as perceived by [their] caregivers.”[xi]
Physiologically, the health and well-being of the pregnant individual directly influence that of the fetus; they are not at odds.[xii] The maternal-fetal conflict is a social construct upheld by cultural, religious, and moral values, presenting a false dichotomy to researchers, policymakers, and clinicians. It is further complicated by the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization, which cleared the way for states to legally grant a fetus personhood.
There is also concern that the fetus cannot appropriately consent. A few issues arise with this concern. First, the fetus’s interests cannot be known. Rather, the pharmaceutical industry, clinicians, and the State project their judgement and values onto it. Furthermore, regulations and guidelines already exist on the safe inclusion of fetuses in trials (see: 21 CFR part 56, 21 CFR part 50, and 45 CFR part 46).
Second, upon birth, a child cannot consent to treatment until adolescence; parents and guardians make such decisions for them regardless. This creates a double standard; we hold pregnant individuals to a higher standard than we hold their partners and other parents, who make treatment decisions about their bodies and children every day.[xiii] It’s also worth noting that the FDA requires paternal consent for pregnant individuals to be enrolled in trials, with very few exceptions. By advocating for informed consent from a fetus, we negate the informed consent of the pregnant individual.
There are also legal arguments for pregnant individuals’ continued exclusion. Pharmaceutical companies are concerned about the liability they may take on should these individuals be included.; ultimately, a strawman argument. In fact, according to a report from the National Academies of Science, Engineering, and Medicine, no such claims were filed dating back to 1962. There were, however, many cases filed by pregnant individuals who used medications post-approval.[xiv] This would suggest that the exclusion of these individuals actually increases the risk of liability.
Continuing to withhold or otherwise prescribe treatments without adequate dosage information is an ethical concern. The 21st Century Cures Act takes a first step in establishing the Pregnant Women and Lactating Women Task Force (PRGLAC) to advise the U.S. Department of Health and Human Services on the inclusion of pregnant individuals. PRGLAC has since produced 15 recommendations, which serve as an excellent foundation for how to safely promote inclusion. For example, PRGLAC recommends leveraging the existing Vaccine Injury Compensation Program (VICP) as a model liability-mitigation strategy.[xv] PRGLAC’s charter expired in 2021; its recommendations now sit with the PRGLAC Implementation Working Group of Council; the last update provided by the group was in July 2024.[xvi]
Policymakers, researchers, pharmaceutical companies, clinicians, and patients must continue to support these recommendations and the broader dismantling of outdated, paternalistic, and patriarchal policies. Reenergizing the work of the PRGLAC Implementation Working Group of Council is the first step toward addressing this longstanding inequity to advance public health and protect the well-being of millions.
[1] Federal agencies refer exclusively to ‘women’. The author attempts to broaden the terms, as needed, throughout to acknowledge not all pregnant persons identify as such.
[2] Alyssa Bilinski and Natalia Emanuel. “Fewer than 1% of United States clinical drug trials enroll pregnant participants,” American Journal of Obstetrics & Gynecology 232, no. 4 (2025): 136-139, doi: 10.1016/j.ajog.2024.12.028.
[3] Jeanne Sheffield et al., “Designing drug trials: considerations for pregnant women,” Clinical Infectious Diseases 59, no. 7 (2014): 437-44, doi: 10.1093/cid/ciu709.
[4] Ibid.
[5] UC San Diego, “Learning to Navigate the Four Phases of Clinical Trails,” UC San Diego Extended Studies Blog, (2024), https://extendedstudies.ucsd.edu/news-events/extended-studies-blog/learning-to-navigate-the-four-phases-of-clinical-trials.
[6] Sheffield et al., “Designing Drug Trials”
[7] Anne Drapkin Lyerly. “Should pregnant women be included in clinical trials,” AAMC News, July 24, 2018, https://www.aamc.org/news/should-pregnant-women-be-included-clinical-trials.
[8] Sheffield et al., “Designing Drug Trials”
[9] Ibid.
[10] Anne Drapkin Lyerly et al., “The second wave: Toward responsible inclusion of pregnant women in research,” International Journal of Feminist Approaches to Bioethics, 1, no. 2 (2008): 5-22, doi: 10.1353/ijf.0.0047.
[xi] Marie McCormick and Joanna Siegel, Prenatal Care: Effectiveness and Implementation (Cambridge University Press, 1999), p. 285-6.
[xii] Lyerly, “Should Pregnant Women Be Included.”
[xiii] Ibid.
[xiv] National Academies of Science, Engineering, and Medicine, “Advancing Clinical Research with Pregnant and Lactating Populations: Overcoming Real and Perceived Liability Risks,” The National Academies Press, (2024), doi: 10.17226/27595.
[xv] National Institute of Child Health and Human Development Pregnant Women and Lactating Women Task Force, “List of Recommendations from the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC),” National Institutes of Health, (2019), https://www.nichd.nih.gov/about/advisory/PRGLAC/recommendations.
[xvi] National Institute of Child Health and Human Development Office of Legislation, Public Policy, and Ethics, “Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) Implementation Working Group of Council,” National Institutes of Health, (2024), https://www.nichd.nih.gov/about/advisory/council/PRGLAC-implementation-WG-of-council.