Phenytoin and/or stiripentol in pregnancy: infant monkey hyperexcitability

A monkey (Macaca fascicularis) model was used to assess infant hyperexcitability after prenatal exposure to phenytoin (PHT, n = 4), stiripentol (STP, n = 5), or PHT + STP (n = 4). Adult female monkeys were equipped with tether systems and stomach catheters so that drug administration could start 1 month before mating and could be continued throughout gestation. During pregnancy, PHT and STP plasma levels were maintained between 4-12 and 4-10 micrograms/ml respectively (for both monotherapy and polytherapy). Infants were separated from mothers at birth and transferred to the University of Washington's (Seattle) Infant Primate Research Laboratory (IPRL) for postnatal care and testing. Data on a hyperexcitability scale were obtained during cognitive testing for visual and cross-modal recognition memory in 13 infant monkeys when they were between 2 weeks and 3 months of age. The data indicated that infants prenatally exposed to PHT, whether alone or in combination with STP, were at increased risk for hyperexcitability (screeching, refusing to attend to stimuli, lack of visual orientation). This was not true of infants prenatally exposed to STP monotherapy (drug group differences, p < 0.05).