No rise in major birth defects with lamotrigine

OB/GYN News, July 1, 2003 by Robert Finn

HONOLULU -- A prospective analysis of 10 years of pregnancy registry data has found no evidence that use of the anticonvulsant lamotrigine in the first trimester is associated with an increase in major birth defects, Dr. Mark S. Yerby reported.

Lamotrigine (Lamictal) is classified as Pregnancy Category C as a result of animal studies indicating teratogenic effects and is contraindicated in pregnancy But women with epilepsy often cannot easily be removed from lamotrigine when they become pregnant, he said at the annual meeting of the American Academy of Neurology.

He and his colleagues analyzed data from the GlaxoSmithKline International Lamotrigine Pregnancy Registry They included only women who were enrolled in the registry before the results of their pregnancies became known. The investigators used the Centers for Disease Control and Prevention definition of major birth defects.

Of the 248 qualifying pregnancies involving lamotrigine monotherapy in the registry as of September 2002, six infants had major birth defects. The risk of major birth defects was 2.4%. This compares favorably with general population rates of major birth defects, which range between 2% and 3%, said Dr. Yerby of North Pacific Epilepsy Research, Portland, Ore.

He added that the study was sufficiently powered to be able to detect a 2.05-fold increase in the proportion of major birth defects. Of the six major birth defects seen in this study, no two were alike, and the investigators noticed no pattern. The defects were esophageal malformation, cleft palate, cleft foot, hydronephrosis, anencephaly and atresia of the anus.

The investigators also identified 201 women taking lamotrigine polytherapy during the first trimester of pregnancy Of the 65 women taking lamotrigine polytherapy including valproic acid, 7 had infants (10.8%) with major birth defects. Of the 136 women taking lamotrigine polytherapy but not including valproic acid, 5 had infants (3.7%) with major birth defects.

Dr. Yerby urged physicians with patients who have been exposed to lamotrigine during pregnancy to register these pregnancies either with the GlaxoSmithKline registry (800-336-2176) or with the North American Antiepileptic Drug Pregnancy Registry (888-233-2334), but not both.