Lamotrigine-birth defect link seen only in valproate combo.(Obstetrics)

WASHINGTON -- There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%, and the rate among those on polytherapy without valproate was 2.7%.

The rate among women on polytherapy with valproate was 11.8%--significantly higher than the background population rate of 2%-3%.