Exclusion by Design: Regulatory Reform and Evolving Frameworks for Clinical Trials in Pregnancy

Maternal-fetal pharmacology remains a critically underdeveloped domain, largely because ethical, regulatory, and methodological barriers impede evidence generation in pregnant populations (hereafter women). Pregnant women continue to be routinely excluded from clinical trials, creating both a knowledge and an evidence gap that can adversely affect maternal and neonatal outcomes. Despite significant regulatory advances in both encouraging trial inclusion and improving labeling [1], for example through the implementation of the US Pregnancy and Lactation Labeling Rule, substantial gaps and a lack of harmonization persist in pharmacologic, safety, and efficacy data for medications used during pregnancy and lactation. This targeted commentary examines the current state of medication use in pregnant women and their fetuses, the regulatory landscape, and the challenges that impede the development of new research in maternal-fetal pharmacology. We also identify the regulatory conundrum in selected countries worldwide and propose new strategies to improve evidence generation and regulatory decision making for this protected population.