June 4, 2020

Study Shows that Birth Defects Attributed to Valproate (Depakote®) Do Not Involve a Genetic Component

Abstract, published in Epilepsia

Objective: Sodium valproate (VPA), the most effective antiepileptic drug for patients with genetic generalized epilepsy (GGE), that is, generalized epilepsy cause by a mutation,  dramatically increases the risk of a range of birth defects. Although the mechanisms underlying these birth defects are not known, they may involve genetic risk factors. This study aimed to develop an animal model of VPA-induced birth defects.

Results: The team used three different rat models of epilepsy, each of which had a different genetic mutation. VPA-exposed pups showed significant reductions in weight, length, and whole-body development compared with controls. Specifically, VPA treatment altered the distances between individual vertebrae in the backbone in all three rat models, more frequently than in controls.

Significance: Exposure of embryos to VPA during pregnancy results in similar developmental and morphological abnormalities in three different rat models, indicating that the genetic underpinnings of epilepsy do not contribute markedly to VPA-induced birth defects. These models may be used in future studies to investigate mechanisms involved in the pathogenesis of antiepileptic drug–induced birth defects.

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