Phenytoin but not valproate directly affected in vitro trophoblast differentiation

Abstract Objective Epilepsy has been associated with poor obstetric outcomes that could be the result of the epilepsy itself or a direct effect of anti-epileptic medication on placentation. The aim of this study was to investigate any direct effect of anti-epileptic drugs on an established, in vitro bioassay of trophoblast differentiation. Study design Primary extravillous trophoblast cells were cultured in the presence of phenytoin and sodium valproate at a range of concentrations with appropriate solvent controls. The formation of multinuclear giant cells was used as a marker of trophoblast differentiation. Results Phenytoin inhibited giant multinuclear cell formation in a dose-dependent manner; in contrast sodium valproate had no effect ( p = 0.011). Conclusions This study found that two anti-epileptic medications induced different effects on an in vitro trophoblast bioassay, suggesting that further research should be aimed at elucidating which anti-epileptic medication is most suitable for pregnant women.