Antiepileptic Drugs Have Dose-Dependent Tie to Birth Defects

Drugs at start of pregnancy linked to increased risk of birth defects, especially at higher dose

TUESDAY, June 7 (HealthDay News) -- Four commonly used antiepileptic drugs are associated with a dose-dependent increased risk of major birth defects when used at the beginning of pregnancy, according to a study published online June 6 in The Lancet Neurology.

In an observational cohort study, Torbjörn Tomson, M.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues monitored pregnancies exposed to monotherapy with varying doses of four common antiepileptic drugs: carbamazepine (1,402 pregnancies), lamotrigine (1,280), valproic acid (1,010), and phenobarbital (217). They excluded pregnancies that ended in spontaneous abortion or chromosomal or genetic abnormalities, those in which there were first-trimester treatment changes, and those involving other diseases or treatments that could affect fetal outcome.

By the end of the first year after birth, the investigators identified 230 pregnancies associated with major birth defects. They found an increase in the rate of birth defects with increasing dose at time of conception for all the drugs. The highest doses of valproic acid (1,500 mg per day or greater) and phenobarbital (150 mg per day or greater) posed the highest risk to the fetus, with low doses of lamotrigine (less than 300 mg per day) and carbamazepine (less than 400 mg per day) posing the lowest risk to the fetus. In addition, the risk of defects was four times greater for offspring with a parental history of major congenital malformations.

"The risk of major congenital malformations is influenced not only by type of antiepileptic drug, but also by dose and other variables, which should be taken into account in the management of epilepsy in women of childbearing potential," the authors write.

The study was funded by Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, and UCB; several authors disclosed financial relationships with these companies and various other pharmaceutical and/or medical device companies.

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