Meta‐review of Drug Safety during Pregnancy: Teratogenic Risks, Mechanisms, and Risk Categories

Background: Pregnant women often require medications for preexisting or emergent conditions, yet fetal risk from drug exposure remains a critical concern. Teratogens—agents that induce permanent functional or structural abnormalities in the embryo or fetus—carry risks that depend on timing of exposure, maternal health, and inherent fetal/genetic vulnerability.Objective: This meta‐review synthesizes current evidence on the safety profile of drug categories during pregnancy. It examines teratogenicity mechanisms, exposure timing, and the utility of FDA risk classification to guide clinical decision‐making.Methods: A systematic search was performed across multiple databases for studies (randomized trials, observational cohorts, case‐reports, pharmacovigilance) evaluating fetal outcomes following drug exposure. Inclusion criteria required assessment of exposure period (preimplantation, embryonic, fetal), mechanistic data (e.g., folate metabolism, oxidative stress, homeobox gene involvement, paternal exposure), and approved FDA pregnancy risk categories.Results: The embryonic period (weeks 2–8 post fertilization) emerges as the most vulnerable time for structural teratogenesis; however, the fetal period remains sensitive, especially for neurodevelopmental effects (e.g. alcohol exposure). Drugs in FDA Category A/B (e.g. folic acid, metformin, amoxicillin) are associated with minimal or no observed fetal risk. Category C/D agents (e.g. amlodipine, losartan) show risk‐benefit trade-offs, with potential risk under certain conditions. Category X agents (e.g. atorvastatin, methotrexate) consistently demonstrate teratogenicity, warranting avoidance in pregnancy.Conclusions: Clinicians must weigh the benefits of drug therapy against fetal risk, considering specific timing, dose, and individual patient/fetal susceptibility. Enhanced reporting of human studies, better mechanistic research (including paternal contributions and molecular teratogenic pathways), and periodic reassessment of drug risk classifications are essential. Our findings support stronger guidelines and improved patient counseling to optimize maternal care with minimal fetal harm.