Abstract

Valproic acid (VPA) is a well-established antiepileptic drug used worldwide. However, its teratogenic effects on neural tube development have raised significant concerns in both clinical and research settings. Therefore, the aim of this review was to comprehensively summarize the current knowledge regarding the teratogenic effects of VPA on neural tube development. Valproic acid is a simple branched-chain fatty acid with eight carbons, exhibits significant teratogenic effects when exposed during pregnancy. This can result in various neurodevelopmental abnormalities in offspring, collectively known as “fetal valproate syndrome.” These abnormalities include cleft palate, atrial septal defects, polydactyly, craniosynostosis, hypospadias, and spina bifida, observed in both humans and animals. The mechanisms underlying its teratogenicity involve disruption of folate metabolism via methyl enetetrahydrofolate reductase (MTHFR) inhibition, leading to increased homocysteine levels and folate deficiency. Valproic acid also induces oxidative stress, DNA damage, and inhibits histone deacetylases (HDACs), resulting in altered gene expression. Its antiangiogenic properties may contribute to its teratogenic effects. So, continued efforts are essential to understand the underlying mechanisms, develop preventive strategies, and enhance prenatal care to improve maternal and fetal health outcomes.

Keywords: Teratogenic effects of Valproic acid, Valproic acid