The historical exclusion of pregnant individuals from crucial medical research, while well-intentioned, has inadvertently created a significant knowledge gap, leaving expectant mothers and their healthcare providers navigating critical decisions without adequate evidence. This omission has led to situations where the very people most in need of precise medical guidance are left to make choices based on limited information, potentially jeopardizing both maternal and fetal well-being. Moving forward, a paradigm shift is essential: integrating pregnant individuals into rigorous clinical investigations is not merely a matter of inclusivity but a scientific and ethical imperative. Such inclusion promises to foster a more comprehensive understanding of drug effects during pregnancy, ultimately safeguarding a vulnerable population and advancing the broader landscape of public health.

The Urgent Need for Inclusivity in Pregnancy-Related Medical Research

In a compelling narrative highlighting the perils of insufficient data, Alyssa Bilinski, a distinguished Peterson family assistant professor of health policy, recounted the experience of her co-author, Natalia Emanuel. During her pregnancy, Emanuel faced a daunting decision regarding inhaled corticosteroids for a respiratory ailment. Her obstetrician, while adhering to current best practices of shared decision-making, could only offer limited reassurance due to a significant lack of evidence on steroid use during pregnancy. This predicament underscored a systemic issue: although FDA-approved medications undergo rigorous testing, pregnant participants are routinely excluded from these foundational studies.

This widespread exclusion, affecting over 90 million women in the U.S. who have experienced childbirth, stems from a historical reluctance to expose pregnant individuals and their offspring to potential harm, largely influenced by the tragic thalidomide incident of the early 1960s. Thalidomide, an anti-nausea drug, caused severe birth defects in thousands of European babies, prompting strict FDA regulations requiring drug safety and efficacy evidence. While this led to the initial exclusion of all women of childbearing age from drug development trials, a policy that was later relaxed in the 1980s and reversed in 1993 for non-pregnant women, pregnancy remains a common exclusion criterion. Consequently, research indicates that fewer than 1% of clinical drug trials for women aged 18-45 involve pregnant participants.

The unintended consequences of this exclusionary practice are profound. Pregnant individuals commonly take an average of five medications, many without robust safety data specific to pregnancy. This void forces many to either forgo necessary treatments, risking their health and that of their babies, or proceed with medication in the absence of comprehensive information. The recent COVID-19 pandemic starkly illustrated this issue: the exclusion of pregnant participants from vaccine trials led to hesitant vaccine uptake among expectant mothers, tragically contributing to preventable maternal mortalities and stillbirths. Expert estimations suggest that including pregnant individuals in these trials could have averted a substantial percentage of COVID-19-related maternal deaths and stillbirths in 2021 alone.

Despite mounting calls from clinicians, advocates, and governmental bodies to enhance the evidence base for pregnancy, the inclusion rate of pregnant participants in randomized controlled trials has stagnated over the past fifteen years. Addressing this critical issue necessitates comprehensive institutional reforms. Recommendations from esteemed organizations such as the National Academies of Science, Engineering, and Medicine, along with task forces from the FDA, propose solutions ranging from addressing liability concerns to reforming funding and timelines to accommodate the unique complexities and higher costs associated with trials involving pregnant individuals. Ultimately, ensuring the safety and well-being of pregnant participants through well-regulated research is paramount, mirroring the protections afforded to all trial volunteers who contribute to medical advancement. The aim is to gather vital information while minimizing risks to the fewest possible individuals, a commitment that current practices regrettably fall short of offering to pregnant individuals.

The ongoing challenge of integrating pregnant individuals into clinical research mirrors past struggles for inclusivity, particularly the decades-long battle to include women in drug trials. Just as those barriers were eventually overcome, there is a strong and justifiable hope that within a reasonable timeframe, the current deficit in rigorous pregnancy-specific medical evidence will become a relic of the past. The stakes are too high, and the potential for improved health outcomes too great, to perpetuate an outdated and potentially harmful system. The lessons of history, combined with the clear benefits of comprehensive data, should propel us toward a future where pregnant individuals are routinely and safely included in the medical research that directly impacts their health and the health of generations to come. This shift represents not just a scientific advance, but a profound commitment to equity and well-being in healthcare.