Advancing Maternal Health Through Inclusive Clinical Research: Why Pregnant and Lactating Women Must Be Part of Clinical Trials
For decades, pregnant and lactating women have been systematically excluded from clinical trials. Although well-intentioned—historically justified by the desire to “protect” mothers and their infants—this exclusion has created profound scientific, ethical, and public health consequences. Today, leading global health organizations, regulatory agencies, and research institutions agree: failing to include pregnant and breastfeeding women in clinical research is no longer ethically defensible, scientifically acceptable, or socially equitable.
A Persistent Gap in Evidence: The Consequences of Exclusion
Despite major advances in biomedical research, the vast majority of medical products used during pregnancy have never been adequately studied in pregnant or lactating women.
Key facts illustrate the scale of the problem:
- Only 4% of clinical trials in the past decade allowed pregnant women to participate.
- Less than 10% of FDA-approved drugs contain reliable data on safety during pregnancy.
- Up to 70% of pregnant women take at least one prescription medication.
- 98% of medicines approved between 2000–2010 lack sufficient fetal safety data.
This evidence gap leaves millions of women—and their healthcare providers—forced to choose between:
- Under-treating serious chronic or acute conditions (cardiovascular disease, autoimmune disease, depression, cancer, infections);
- Treating with medications without data, relying on best guesses rather than evidence.
Neither scenario supports safe, effective, or equitable care.
Why Pregnancy Demands Dedicated Research
Pregnancy is not a static state—it triggers profound physiological and metabolic changes that alter how drugs are absorbed, distributed, metabolized, and eliminated. These changes differ dramatically by trimester and can affect both therapeutic effect and risk profile.
Examples of physiological changes include:
- Increased blood volume and altered plasma protein binding
- Slower gastrointestinal transit
- Modified renal and hepatic drug clearance
- Placental transfer dynamics
- Changes in immune response and inflammatory pathways
- Lactation-specific metabolic adjustments
Without rigorous trial data, clinicians cannot accurately determine dosing, efficacy, or safety for pregnant or lactating patients. This compromises treatment for common conditions as well as high-risk situations, including infections such as Zika, influenza, RSV, HIV, and COVID-19.
Ethical and Legal Misconceptions: A Barrier No Longer Justified
Historically, fear of teratogenicity—magnified by the tragedy of thalidomide—has shaped an overly cautious approach to maternal research. However, modern science and regulatory frameworks bear little resemblance to those of the 1950s.
Today:
- Preclinical models rigorously test for teratogenicity and reproductive toxicity.
- International ethical guidelines (CIOMS, WHO, ICH) are clear: pregnant and lactating women should not be excluded without strong justification.
- A 2024 legal review shows virtually no liability cases arising from clinical trials involving pregnant or breastfeeding participants since 1962.
- In contrast, many lawsuits have followed adverse outcomes from medications used without trial data during pregnancy.
In other words:
Exclusion does not eliminate risk—it shifts risk outside the controlled setting of a clinical trial and into everyday clinical practice.
Economic and Structural Barriers
Sponsors hesitate to run trials in maternal populations due to perceived low financial returns:
- Pregnancy is a time-limited condition.
- Many maternal health needs occur in low- and middle-income countries (LMICs), where market profitability may be lower.
- Insurance and indemnification processes for maternal trials can be costly and complex.
- Research capacity in LMICs remains limited, with fewer established maternal health trial networks.
As a result, R&D pipelines for maternal health innovations remain chronically underfunded and slow-moving.
Community Engagement and Misconceptions
Beyond scientific and regulatory barriers, cultural and social factors also inhibit participation:
- Misconceptions about risk and fetal harm
- Limited awareness of research opportunities
- Lack of agency in decision-making
- Cultural norms and stigma
- Fragmented communication between healthcare providers and communities
Strengthening community literacy and participatory approaches is critical to build trust and support informed decision-making.
A Global Movement Toward Inclusion
In response to these gaps, progress is accelerating across international institutions:
WHO Initiatives
- The WHO Global Clinical Trials Forum (2023) formally placed the inclusion of pregnant and lactating women at the center of clinical trial reform.
- WHO established a Global Task Force aiming for ethical inclusion of these populations in clinical trials by 2030.
- Regulatory harmonization efforts are underway to create unified global guidance.
National Initiatives
Programs such as PregTrial (Canada) and ConcePTION are pioneering practical frameworks to safely integrate pregnant and breastfeeding women in trials for cardiovascular, autoimmune, psychiatric, and infectious diseases.
Regulatory Evolution
The FDA, Health Canada, and EMA support:
- Revised risk–benefit frameworks
- Pregnancy-specific trial designs
- Use of preclinical teratogenicity data to guide safe inclusion
- Clearer labeling standards
- Improved post-marketing surveillance for maternal use
- Released of ICH E21
Opportunities to Accelerate Progress
Meaningful change will require coordinated action across the entire clinical research ecosystem:
1. Harmonized Ethical and Regulatory Frameworks
Shift from “presumption of exclusion” to “presumption of inclusion.”
Provide clear guidance on protocol design, informed consent, and risk assessment.
Create global standards for developmental and reproductive toxicology models.
2. Coordinated Multi-Stakeholder Collaboration
Researchers, clinicians, regulators, industry, insurers, funders, and communities must collaborate.
Partnerships can streamline approvals and reduce bureaucracy and costs.
Successful examples include public–private partnerships enabling access to heat-stable carbetocin.
3. Strengthened Research Capacity, Especially in LMICs
Build maternal health trial networks with integrated global hubs.
Integrate innovative tools: PK/PD modeling, AI simulations, placenta and lactation studies, adaptive trial designs.
Enhance long-term mother–infant follow-up using real-world data systems.
4. Increased Funding and Strategic Investment
Less than 1% of biomedical research funding currently targets maternal health.
Coordinated global investments and shared funding portfolios are essential.
Funders must prioritize maternal health innovations and improve access pathways.
5. Community Engagement and Good Participatory Practice
Provide clear, culturally appropriate, and evidence-based education.
Include women, families, and community stakeholders in co-design and co-implementation.
Build trust through transparency and patient-centered communication.
A Human, Scientific, and Ethical Imperative
The real risk is not studying medical products in pregnant women—it is continuing not to study them.
Exclusion perpetuates:
- preventable maternal and perinatal morbidity and mortality
- inequitable access to safe, effective therapies
- delayed innovation and limited treatment options
- scientific blind spots and biased evidence
- mistrust among vulnerable populations
Inclusion, by contrast, supports:
- evidence-based care
- safer and more effective therapies
- improved health outcomes for mothers and infants
- accelerated innovation
- stronger global health equity
Conclusion: Time for a Paradigm Shift
To truly safeguard maternal and infant health, the clinical research ecosystem must adopt a new, evidence-driven paradigm—one that recognizes pregnant and lactating women as essential partners in clinical research, not as populations to be excluded.
By integrating inclusive trial design, regulatory harmonization, strengthened research capacity, and robust community engagement, we can ensure that future therapies are safe, effective, and equitable for all women, everywhere.
The question is no longer whether pregnant and breastfeeding women should be included in clinical research.
The question is how quickly the global research community can act to correct this long-standing inequity—and how many lives will be saved once we do.
