Anticonvulsant treatment, with rare exceptions, must continue in patients throughout gestation. An understanding of the effects of epilepsy and drug therapy on the developing fetus and neonate constitutes a research area of utmost clinical importance. Valproic acid (VPA) has become a widely used antiepileptic agent and there are clinical data to indicate placental transport during pregnancy and fetal side effects (e.g. spina bifida). Laboratory studies have confirmed differential placental transfer of VPA to the fetus in rhesus monkeys and demonstrated teratogenicity in rodents. Preliminary studies of phenytoin in alumina-gel rhesus have shown that a primate model is appropriate, as indicated by similarities of findings with those in the clinical literature. The question as to whether or not VPA is a suitable antiepiletic drug to prescribe during pregnancy is as yet unresolved. Investigations of its effects on neonatal outcome are indicated. The proposed project will utilize a validated monkey-pregnancy paradigm to investigate valproate exposure vs. maternal seizures on neonatal development in siblings. Parameters of maternal VPA pharmacokinetics during pregnancy and of neonatal development and social behavior will be investigated. Neonatal maturation in terms of a) social interactions (with mom and other monkeys), b) motor performance (reflexes, locomotion, etc.) and c) physical status (size at birth, growth rate) will be assessed as a function of VPA exposure and maternal kinetics. Studies of VPA in normal pregnant monkeys are currently ongoing and, together with the proposed research in epileptic monkeys, will allow separation of the effects of drug vs. seizures.
| Phillips, N K; Lockard, J S (1993) Phenytoin and/or stiripentol in pregnancy: infant monkey hyperexcitability. Epilepsia 34:1117-22 |
| Lockard, J S; Levy, R H (1988) Carbamazepine plus stiripentol: is polytherapy by design possible? Epilepsia 29:476-81 |
