Study into birth risks of epilepsy drugs

Four of the most frequently prescribed epilepsy drugs appear to increase the risk of serious birth defects when taken early in pregnancy, according to a new study reported in The Lancet Neurology.

The research found that the higher the dosage of carbamazepine (Tegretol, Epitol), lamotrigine (Lamictal), valproic acid (Depakote) and phenobarbital, the greater the risk of defects in foetuses, according to the international team of researchers. However, they emphasised that the vast majority of women in their study delivered healthy children.

For their 11-year study, the researchers used data from the International Registry of Antiepileptic Drugs and Pregnancy on nearly 4,000 pregnancies in 33 countries. In all, 230 pregnancies resulted in major birth defects by the end of the first year after birth. Low doses of lamotrigine (less than 300mg per day) and carbamazepine (less than 400mg per day) carried the smallest risk, the study found.

The greatest risk to the foetus was seen with the highest doses of valproic acid (1,500 mg a day or more) and phenobarbital (150 mg or more a day), the researchers said.

A family history of major birth defects quadrupled the risk, they found.

The researchers said that their study shows that dose selection is as crucial as the choice of drug and gives doctors the opportunity to prescribe the safest anti-seizure medication at the safest level for women with epilepsy who want to get pregnant.

Most women with epilepsy need to take anti-seizure medication or risk harming themselves or their baby. Previous studies found that valproic acid, in particular, might increase the risk of birth defects, but those studies did not look at individual doses. Nor did they take into account other influential factors, such as family history of birth defects or severity of epilepsy.

Read the full study, 'Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry'.