Infant monkey hyperexcitability after prenatal exposure to antiepileptic compounds

Abstract

Purpose: A monkey (Macaca fascicularis) model was previously used to assess infant hyperexcitability after prenatal exposure to phenytoin (PHT), stiripentol (STP) or PHT+STP. To explore this issue further, we studied additional monkey infants in those groups, as well as groups prenatally exposed to carbamazepine (CBZ) in monotherapy (n = 5) or CBZ+STP polytherapy (n = 10).

Methods: The drug-exposed groups were compared with a group of control infants (n = 10) for whom procedures were matched except that there was no prenatal drug exposure. All adult female monkeys were equipped with tether systems and stomach catheters so that drug administration (or water for controls) could be initiated before they were mated and continued throughout pregnancy. During pregnancy, PHT, STP, and CBZ plasma levels were maintained between 4-12, 4-10, and 1-6 micrograms/ ml, respectively (for both monotherapy and polytherapy). At birth, infants were separated from mothers and transferred to the University of Washington's (Seattle, WA, U.S.A.) Infant Primate Research Laboratory (IPRL) for postnatal care and follow-up testing. During tests of recognition memory administered between 2 weeks and 3 months of age, infants were rated on a hyperexcitability scale.

Results: Previously reported data indicated that infants prenatally exposed to PHT, in monotherapy or polytherapy with STP, were at increased risk for hyperexcitability (screeching, refusing to attend to stimuli, lack of visual orientation). This was not the case for infants prenatally exposed to STP monotherapy.

Conclusions: Our results confirm previous findings and also demonstrate that infants prenatally exposed to CBZ or CBZ+STP, like controls, are not hyperexcitable during testing.