Women with epilepsy who take a common drug (carbamazepine) to treat the illness are more likely to have an infant with spina bifida compared with women not taking antiepileptic drugs, finds a study published online by the BMJ.
Researchers led by the University of Groningen in the Netherlands carried out a review of all published studies to identify specific major malformations linked with carbamazepine use in the first three months of pregnancy.
Carbamazepine is one of the most commonly used anti-epilepsy drugs in Europe among women of reproductive age. The researchers’ material was derived from EUROCAT – a database containing information from 19 registers of pregnancy outcomes with major congenital malformations in Europe from 1995 to 2005. The data relates to almost four million European births, of which over 98,000 involved a major malformation.
The new study found that of the five identified indications in the literature, spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy. Spina bifida was 2.6 times more likely in infants of women who had taken carbamazepine compared with no antiepileptic drug, but the risk was smaller for carbamazepine than for valproic acid.
The authors did not conclude that carbamazepine was associated with other major malformations and said it was less risky than another frequently used antiepileptic drug, valproic acid.
They also stressed: “Although most antiepileptic drugs taken during pregnancy significantly increase the risk for one or more specific congenital malformations, the occurrence of these malformations is nevertheless rare … most exposed pregnancies result in a baby without malformation.”
For carbamazepine taken in the first three months of pregnancy, the overall risk of a major malformation was 3.3%.
The authors say that their earlier study on valproic acid (published in the New England Journal of Medicine in 2010) concluded that women on valproic acid were six times more likely to have a pregnancy outcome with spina bifida and seven times more likely to have an outcome with hypospadias (where a boy's urinary opening develops in the wrong part of the penis or in the scrotum) compared with women using other antiepileptic drug use.
The research team therefore agreed with the recent recommendation from the American Academy of Neurology that women should avoid valproic acid in pregnancy if possible.
The authors said that although the overall risk of birth defects was low for women taking antiepileptic drugs, they concluded: “The best option regarding antiepileptic drug treatment can be chosen only on an individual basis by the woman and neurologist before pregnancy, weighing the benefits of epilepsy control against the risk of teratogenicity.”