Summary:Purpose: Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.Methods: Of a prospective study, "Epilepsy, pregnancy, and child development," children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.Results: Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.Conclusions: Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsylno-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.

The offspring of mothers with epilepsy are considered to be at developmental risk during pregnancy from: (1) generalized maternal seizures (hypoxia); (2) teratogenicity of antiepileptic drugs (AEDs); and (3) adverse socio‐familial conditions associated with having a chronically sick mother. Sixty‐seven children of mothers with epilepsy and 49 children from non‐affected mothers, matched for control variables, were followed from birth to adolescence (53 males, 63 females; mean age 14y 2mo, range 10‐20y). Prediction of intellectual performance of these children during adolescence was calculated from the following variables: maternal generalized seizures, prenatal exposure to AEDs, and quality of family stimulation (HOME Inventory) assessed in children at 2 years of age. Children who were prenatally exposed to AEDs achieved lower IQs than control children at adolescence. This effect was moderately significant for children who had been exposed to monotherapy (6 IQ points lower), but was considerable in those exposed to polytherapy (12 IQ points lower). Generalized seizures during pregnancy, observed in half the mothers, did not exacerbate this effect. Relative to prenatal risk status, the quality of the family environment had varied effects on intellectual development. Children with prenatal risks appeared to be more vulnerable to environmental disadvantage than control children, but they also showed longer‐lasting effects of environmental support.

Recent psychological research on infants and newborns led to discoveries of early competencies in young infants hitherto unbelievedby most scientists and difficult to account for in traditional models of child development. On the other hand, accumulated empirical longitudinal evidence challenged long-held preconceptions of the enduring impacts of early experience on later development. The risk concept, adapted from pediatrics and psychiatries, was introduced with the expectation of identifying those subgroups of infants that are of increased risk of later behaviouralor developmental maladaptation. The risk concept, however, turned out to be imprecise, having too many different meanings, being too abstract, and applicable only to populations or groups, not to individuals. Combinations of the risk concept with recently developed more sophisticated models of early development, such as transactive and systemic models ofdevelopment, include such concepts as vulnerability/resilience as stable personality characteristics, protection or risk as setting characteristics, and coping in the face of actual stress as situational process variables. Implications for prevention, intervention and early education are discussed with respect to some selected groups of infants considered at-risk.

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