Listen to the article
Pregnancy induces significant changes in a woman’s body, including shifts in hormone levels, blood circulation, and organ positioning. Notably, even the structure of the brain is affected as cortical gray matter decreases. These wide-ranging physiological alterations can alter drug metabolism and efficacy, raising concerns about the safety of pharmaceuticals for pregnant and breastfeeding individuals. Unfortunately, research on this critical population has been limited, largely due to historical exclusion from clinical studies.
A recent analysis by the World Health Organization underscored this gap, revealing that only 4% of clinical trials in the past decade have included pregnant women. In response, the FDA has issued draft guidance aimed at encouraging pharmaceutical companies to consider these populations during drug development.
Although the guidance does not require mandatory inclusion of pregnant and breastfeeding women, it serves as an important catalyst for discussion, according to Karen Yeo, Senior Vice President of Client and Regulatory Strategy at Certara. “The FDA emphasizes that pharma companies need to articulate how they plan to involve pregnant and breastfeeding women in upcoming trials,” Yeo noted.
“Clinicians are pushing back because if we don’t include pregnant women in trials, they don’t have the data to know how drugs impact them.”
Karen Yeo
SVP of client and regulatory strategy, Certara
The limited data on drug safety for pregnant women has led to widespread confusion, particularly amidst alarming claims about medications. For instance, misinformation about Tylenol and its alleged link to autism created significant backlash within both the scientific and medical communities.
In light of these concerns, the FDA has indicated plans to revise product labeling for acetaminophen based on potential associations highlighted during recent discussions. During the ongoing pandemic, emerging guidance regarding COVID-19 vaccines has further complicated perceptions about medication safety for pregnant women.
As the FDA seeks to reinforce its regulations, Yeo believes there is a growing urgency for drug companies to develop comprehensive plans for including expecting and nursing mothers in their clinical studies, starting at the submission phase.
Persistent Challenges in Research
Inclusion of women and minority groups in clinical trials has been a legal requirement since the NIH Revitalization Act of 1993, with further advancements made by the 21st Century Cures Act in 2016. However, barriers—both cultural and ethical—have continued to impede progress. Researchers often worry about the potential risks to pregnant participants, which can complicate trial designs and raise concerns about liability.
Interestingly, despite the fact that up to 90% of pregnant women take medications, the CDC reports that safety data are available for fewer than 10% of drugs approved since 1980. This imbalance places a significant burden on healthcare providers when making medication recommendations for pregnant women, as noted by Yeo: “Clinicians are pushing back because if we don’t include pregnant women in trials, they don’t have the data to know how drugs impact them.”
Emerging technologies, including artificial intelligence, are beginning to address some of these long-standing gaps in knowledge. For instance, researchers at Icahn School of Medicine at Mount Sinai have created models to predict which drugs may lead to birth defects, offering insights even before a drug is deemed unsafe. Additionally, a new platform launched in the Netherlands provides dosage recommendations for pregnant women, utilizing a range of data sources, including placenta transfer studies.
Certara has also taken steps to collaborate with 37 pharmaceutical companies to develop computational platforms aimed at predicting drug interactions, dosing safety, and other important factors for pregnant patients. “Our pregnancy model accounts for changes like blood flow and drug metabolization in different trimesters,” Yeo explained, emphasizing the importance of tailoring this information for safe drug administration.
Despite advancements, randomized controlled trials remain necessary. Should the FDA finalize its draft guidance, it will require pharmaceutical companies to not only outline how they will involve pregnant and lactating women in clinical trials but also to provide specifics about the design of these studies. This includes clarifying whether the assessment will focus on maternal or infant exposure and detailing the sampling methods to be employed.
While the draft guidance does not compel the inclusion of pregnant individuals in trials, it represents a significant move toward creating a more equitable framework, marking a potential shift in the industry’s approach to maternal health.
