Valproic acid transfer across human placental cotyledon during dual perfusion in vitro

Valproic acid (VPA ) is a well-known antiepileptic drug with a significant teratogenic effect when administered during pregnancy. To investigate the transplacental transport of VPA, we used an in vitro experiment of dual perfusion of a human placental cotyledon. Eighteen normal placentas at term were investigated; ten were treated with a therapeutic dose of VPA (initial level at maternal circulation 75 microgram/ml), while the remaining eight were supplied with toxic VPA doses (initial level at maternal circulation 225 microgram/ml). VPA concentrations in fetal compartment were lower than those in the maternal compartment at all timepoints with both doses applied. The maternal and foetal VPA concentrations were stable at 60 min and 120 min for the therapeutic dose of VPA (transfer percentages from the maternal to the fetal circulation were 22.7 +- 9.1 percent and 22.7 +- 7.1 percent, respectively). Interestingly, a significant decrease of VPA level in the maternal perfusate was observed after 120 min due to the slightly higher transfer of the drug to the foetal compartment. In conclusion, our data confirmed an easy and rapid transfer of VPA accross the placental barrier. Since the incidence of congenital malformations in infants correlates positively with VPA concentrations in maternal serum, monitoring of VPA should be mandatory due to possible harmful effects on the foetus.