A gestational monkey model: effects of phenytoin versus seizures on neonatal outcome

In the present research, an animal model was developed to ascertain the potential effects of gestational drug concentrations and/or maternal seizures on the neonate. The rhesus monkey (Macaca mulatta) was the species of choice as previous research has demonstrated its validity as a model for partial epilepsy. Phenytoin (PHT) was tested because it is effective in the treatment of partial epilepsy in patients and is efficacious in nonpregnant monkeys with focal motor seizures. Data were obtained on the outcomes of nine pregnancies from five mothers, all of whom received PHT during gestation. Infant motor and social development and maternal/offspring interactions were systematically monitored for 12 weeks postnatally. Results indicated that impairment of infant motor development was directly correlated with greater drug exposure during the third trimester of pregnancy and unrelated to maternal seizure frequency during gestation. Also, developmental problems were more serious in infants exposed to higher drug levels, including difficulty nursing, grasping, and/or clasping; an upper lip anomaly; fetal death in one case; and infant death in another. Though the sample size of this study was small and the methodology experimental, the findings indicate that the gestational model is a valuable paradigm with potential clinical relevance. The results also support the notion that high third-trimester phenytoin levels may have significant impact on newborn reflexes and initial development of gross motor skills.