Abstract

TERATOGENICITY IN PREGNANCY: A REVIEW OF DRUGINDUCED BIRTH DEFECTS

Yeshashwini Naik* and Sudhamshu K. Tantry

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Abstract

Birth defects, affecting 3–4% of live births, result from genetic, physical, microbial, or chemical factors. Historic events, such as the rubella outbreak and the thalidomide tragedy, revealed that the placenta does not fully protect the fetus from teratogens. Drugs like ACE inhibitors, antibiotics (e.g., tetracyclines), anti-epileptics, benzodiazepines, NSAIDs, lithium, and chemotherapy agents are linked to severe structural and functional abnormalities in exposed fetuses. Mechanisms of teratogenesis include folate antagonism, oxidative stress, vascular disruption, endocrine imbalance, and receptor- or enzyme-mediated disruptions. For instance, folate antagonism impairs DNA synthesis, leading to neural tube defects, while oxidative stress causes DNA damage, resulting in congenital anomalies. Placental transport proteins, such as P-glycoprotein and BCRP, regulate drug transfer to the fetus, with polymorphisms significantly influencing teratogenic risks. Evaluation of these risks relies on animal studies, cohort and case-control studies, meta-analyses, and registries. Despite advances, challenges persist in risk assessment due to physiological changes during pregnancy, genetic variability in drug metabolism, and limited direct measurements of prenatal drug exposure. Understanding the mechanisms of teratogenesis and fostering effective risk management strategies, including patient education, robust pharmacovigilance, and the promotion of safer therapeutic alternatives, is critical to minimizing drug-induced birth defects. Further research is essential to better elucidate the role of transporter polymorphisms, improve clinical guidelines, and optimize drug safety for pregnant populations.

Keywords: Teratogenesis, Drug-induced birth defects, Placental transport proteins.