The teratogenicity of hydantoins and barbiturates in humans, with considerations on the etiology of malformations and cerebral disturbances in the children of epileptic parents

Abstract

A total of 194 children of epileptic mothers and 71 children of epileptic fathers were examined for mental retardation, neurologic disturbances, major malformations, and acrofacial dysmorphias typical for hydantoin-barbiturate embryopathy (HB-E). HB-E was observed in nearly 7% of the children of mothers on anticonvulsants during pregnancy. Barbiturates and/or primidone were observed to induce the same dysmorphic features as hydantoins. The teratogenic potential of hydantoins may be slightly increased in combination with barbiturates/primidone. Neither the 71 children of epileptic fathers nor the 46 children of epileptic mothers without anticonvulsants exhibited symptoms of HB-E. The frequency of major, unspecific malformations was increased in children of epileptic mothers as well as in children of epileptic fathers as compared with the general population. Cerebral disturbances without dysmorphias were increased in children of mothers with and without anticonvulsants, but this was rarely the case in children of epileptic fathers. Cerebral disturbances were observed more often in children of mothers with seizures during pregnancy than in children of mothers without seizures. Multifactorial genetic influences on major malformations and influences of maternal seizures on cerebral disturbances in the offspring are likely.