Head circumference in children of epileptic mothers: contributions of drug exposure and genetic background.

Head circumference after the first year of life was investigated in 144 children of epileptic mothers ('study group'). Fifty-two children had been exposed to phenytoin monotherapy, 19 to carbamazepine monotherapy, 27 to drug combinations including barbiturates, 29 to other drug combinations, and 17 children had not been exposed to antiepileptic drugs (AEDs) during pregnancy. The prevalence of microcephaly (2.1%) was no higher than that in the general population. Head circumference was measured at 5.5 years in 121 of the study group children, in 105 control children, and in the majority of their parents (118 mothers and 89 fathers in the study group, and 103 mothers and 65 fathers in the control group). The sex-adjusted head circumferences of the children showed a significant variation according to exposure subgroup, with the barbiturate and carbamazepine monotherapy exposed children having the lowest mean values. This result is similar to our previous findings in the same children at birth and at 18 months of age. Paternal head circumference was also below average in the same subgroups. After further adjustment for parental head circumference, the significant variation between the subgroups of children disappeared, even though the barbiturate exposed children continued to have the lowest mean value. Genetic causes may thus contribute to the relatively small head circumference in some AED exposed children of epileptic mothers. However, a mild drug effect in the barbiturate and carbamazepine exposed children cannot be excluded.