EC Pharmacology and Toxicology

Most pregnant patients use prescription or over-the-counter medicines, yet high-quality human safety data remain limited and often inconsistently communicated. This narrative review synthesizes contemporary evidence on medication use in pregnancy and appraises the impact, implementation, and gaps of U.S. Food and Drug Administration (FDA) labeling reforms-especially the 2015 Pregnancy and Lactation Labeling Rule (PLLR). Epidemiologic studies show medication exposure is common and increasing, while robust human data lag; uncertainty, cultural factors, and clinician communication styles amplify perceived teratogenic risk and can undermine adherence. The PLLR replaced letter categories (A, B, C, D, X) with structured narrative sections (Pregnancy, Lactation, and Females/Males of Reproductive Potential) intended to reduce oversimplification and improve risk-benefit decisions. However, clinician awareness and use of PLLR content remain inconsistent, with persistent reliance on legacy categories and secondary databases. Post-approval evidence streams-pregnancy exposure registries and health-care utilization databases-now supply most human data, yet studies are frequently delayed, underpowered, or methodologically constrained, and labeling changes may take years. Internationally, FDA and European Medicines Agency labeling often diverge in language and directionality despite drawing on similar sources, further complicating counseling. Label modernization is necessary but insufficient. Priority actions include ethically including pregnant and lactating persons in clinical trials, accelerating harmonized post-approval evidence generation, standardizing clear communication that quantifies background versus drug-attributable risks, and educating clinicians to navigate PLLR narratives. Aligning evidence generation with effective risk communication is essential to support evidence-based prescribing and improve maternal-fetal safety.

 Keywords: Pregnancy and Lactation Labeling Rule; Letter Categories

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