Drug-Induced Congenital Malformations: A Systematic Review and Meta-Analysis of Teratogenic Medications in Pregnancy

Background: Congenital malformations are a leading cause of neonatal morbidity and mortality. Several medications have known or suspected teratogenic effects which vary in strength and consistency. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. Databases (PubMed, Embase, Scopus) were searched for studies evaluating the association between drug exposure during pregnancy and congenital malformations. Study details, design, populations, interventions, outcomes, and effect estimates were extracted. Pooled relative risks and subgroup analyses were performed by drug class and outcome. Results: Benzodiazepines (RR 1.09; 95% CI 1.05–1.13), NSAIDs (RR 1.14; 95% CI 1.10–1.18), SSRIs (RR 1.11; 95% CI 1.03–1.19; 95% CI 1.11–1.37) and lithium (OR 1.81, 95% CI 1.35–2.41) were associated with increased risk of congenital malformations. Yet, topiramate was strongly associated with oral clefts (RR 5.16; 95% CI 1.94–13.73). Conclusion: Several commonly used medications in pregnancy are associated with increased risk of congenital malformations. These results emphasize the importance of maternal health care in clinical practice. Plain Language Summary Birth defects are a major cause of illness and death in newborns. We reviewed and analyzed evidence on medicines that may increase risks during pregnancy. Our findings showed that benzodiazepines, NSAIDs, and SSRIs were linked to a modest rise in birth defects. Lithium was more strongly associated with congenital heart problems, while topiramate showed a significant link to cleft lip and palate. These results highlight the importance of careful medical care and treatment decisions during pregnancy to help prevent malformations and protect maternal and child health.