Effects of antiepileptic drugs on delivery and early childhood--comparison among mono-therapies of valproic acid, phenytoin, carbamazepine and phenobarbital

The effects of antiepileptic drugs (AED) on infants during pregnancy and delivery were studied in a total of 82 epileptic mothers on various monotherapies; 29 cases receiving valproic acid (VPA), 20 receiving phenytoin (PHT), 18 on carbamazepine (CBZ) and 15 on phenobarbital (PB). While AED serum concentrations were low in most cases of VPA, PHT and PB except for one case of VPA which exceeded therapeutic limits, concentrations were within therapeutic levels in many cases of CBZ. Conclusion: When compared with normal controls, abnormal deliveries such as caesarian section were seen more frequently in epileptic mothers under AED treatment. In addition, infants in PB cases were shown to have significantly lower mean birth length, weight and head circumference, suggesting that PB may retard fetal growth. The incidence of malformation in cases of VPA, PHT, CBZ and PB, was 10.3%, 5.0%, 0% and 6.7%, respectively. There were five types of malformation: in VPA cases, spina bifida, Siamese twins and ventricular septal defect tended to be severe, while in PHT and PB cases, cor biloculare and hypospadias respectively were observed. In cases of VPA, serum levels in the umbilical cord were found to be 150% higher than those in the mother.