Phenytoin but not valproate directly affected in vitro trophoblast differentiation.
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.


METHODS
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.
Quenby
Siobhan M
SM
School of Reproductive and Developmental Medicine, University of Liverpool, UK. squenby@liv.ac.uk
Anin
Sheba
S
Bates
Michelle D
MD
Chadwick
David
D
Vince
Gill S
GS
Neilson
James P
JP
D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D010672:Phenytoin / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D014635:Valproic Acid; D010672:Phenytoin