The chronic effects of a disease process such as partial epilepsy and its drug treatment(s) on maternal outcome in terms of the developing fetus and subsequent infant is a research area of considerable clinical importance. Anti-epileptic therapy, with rare exceptions, must continue in patients throughout gestation, and ascertainment of the potential effects of maternal drug concentrations on infants and their development in a suitable model is imperative. Preliminary studies of phenytoin (PHT) in alumina-gel rhesus (Macaca mulatta) have shown that a primate model is appropriate, as indicated by similarities of findings with those in the clinical literature (58, 59, 60). Pilot data on one valproate (VPA) and 9 PHT exposed rhesus infants have indicated that investigation of cognitive performance and brain development (myelination) is crucial to a complete understanding of the potential effects of these drugs. Recent clinical studies have also indicated the need for follow-up of infant and child mental development (30, 31). The proposed project will utilize our validated monkey-pregnancy paradigm to investigate the effects of valproate and phenytoin on neonatal development including neonatal maturation in terms of: 1) neurological status - (development of myelination); 2) mental performance - (cognitive development). The proposed project, based on previous PHT research (58, 59, 60) and ongoing studies of VPA will provide a complete analysis of the potential effects of these two important drugs on the developing fetus and subsequent infant.
