CURRENT TOPIC Anticonvulsants in pregnancy

Epilepsy and pregnancy Recurrent seizures affect at least 1% of women who are of childbearing age, but as the fertility of both men and women with epilepsy is slightly reduced,' about one in 200 pregnancies occurs in a woman with epilepsy. Most of these women are taking anticonvulsants regularly. Pregnancy has an unpredictable affect on seizure frequency.2 3 For half of the women with epilepsy there is no significant change in the frequency of convulsions when they become pregnant, but a quarter have more seizures than usual. That group includes many women who also tend to have more seizures when menstruating. An increase in the number of seizures during pregnancy is twice as likely if the fetus is male. (There are some women who only have seizures when carrying a male child and none when carrying a female.) Pregnancy itself is not particularly epileptogenic, however by chance epilepsy will sometimes present for the first time during pregnancy; such gestational epilepsy is more likely to be of a focal nature.4 Pregnancy affects the metabolism of anticonvulsant drugs in several ways. Those women who suffer severe hyperemesis early in pregnancy may fail to retain the usual dose of oral anticonvulsant, and thereby suffer an increase in seizures. Some drugs are less well absorbed during pregnancy, and for some there is a lower degree of protein binding.5 Drug metabolism itself is altered. Pregnancy induces hydroxylating enzymes that lower the level of anticonvulsants such as phenytoin and phenobarbitone.6 7 Fluid retention, and the extra tissues of the fetus and placenta that increase the volume of distribution of the anticonvulsant drug, may lower levels further.