A Review on Drug-Induced Congenital Heart Defects: Teratogenicity, Mechanisms, and Prevention Strategies

Abstract

Congenital heart defects (CHDs) represent one of the most prevalent types of birth defects, affecting nearly 1% of live births globally. While genetic predispositions contribute to CHD incidence, increasing evidence highlights the critical role of teratogenic drug exposure during pregnancy. This review explores the teratogenic potential of various drug classes—including antiepileptics (valproic acid, phenytoin), isotretinoin, anticoagulants, ACE inhibitors, and select antipsychotics—in disrupting fetal cardiac development. The mechanisms underlying these drug-induced CHDs involve oxidative stress, disruption of cardiac signaling pathways, altered folate metabolism, and hemodynamic imbalances. Each agent exhibits unique pathophysiological pathways, such as histone deacetylase inhibition by valproic acid or retinoic acid-mediated gene dysregulation by isotretinoin, ultimately leading to structural heart anomalies. The review also outlines prevention strategies, emphasizing preconception counseling, alternative drug regimens, early screening, and rigorous pregnancy prevention programs. A comprehensive understanding of drug-related teratogenicity is crucial to ensuring maternal safety while minimizing fetal cardiovascular risks during gestation.