Serum levels of valproic acid during delivery in mothers and in umbilical cord - correlation with birth length and weight

Aims. The data on the valproic acid transplacental transfer and risk to the fetus of exposure, remain sparse and only a limited number of studies have reported umbilical cord blood levels. Materials and Methods. Maternal and umbilical cord serum levels were analyzed at delivery in a cohort of 58 women, between the years 1991 - 2013. The request forms for routine therapeutic drug monitoring were used as the data source. Maternal levels and dosing information were used for estimating the maternal apparent oral clearance and the paired umbilical cord and maternal levels for estimation of umbilical cord/maternal level ratios. Results. The levels varied from 5.3 - 59.5 mg/L in maternal and 5.4 - 72.1 mg/L in umbilical cord serum. The umbilical cord/maternal level ratios ranged from 0.64 - 2.49. Significant correlation was found between maternal and umbilical cord levels. Significant inverse correlations were found between birth length, and both maternal and umbilical cord levels in monotherapy. Conclusions. There were large individual variations in umbilical cord/maternal level ratios of valproic acid. Neonatal length and weight were inversely related to maternal and umbilical cord levels, but not to dose. Therefore, therapeutic drug monitoring in mothers is more useful than the given dose for the estimation of fetal exposure and minimization of the risk of fetal effects.