Abstracts

Rationale: The aim of this international registry is to characterize the overall risk of major congenital malformations (MCM) associated with exposure to lamotrigine. The registry forms part of an epidemiologic safety program monitoring pregnancy outcomes in women exposed to lamotrigine that has been in operation since 1992.Methods: Physicians report exposure to lamotrigine during pregnancy and subsequent outcomes on a voluntary basis. Prospective reporting (prior to any knowledge regarding the possible outcome of the pregnancy) early in pregnancy is encouraged. Major congenital malformations (MCMs) are classified according to the Centers for Disease Control criteria and are reviewed by a paediatrician. The percentage of MCMs is calculated using only prospective first trimester lamotrigine monotherapy and polytherapy exposures. Conclusions are developed and endorsed by a scientific advisory committee.Results: As of March 2007, 27 MCMs were observed among 1053 first trimester monotherapy exposures yielding a risk of 2.6% (95% CI 1.7% - 3.8%). This compares with risks in the United States general population of 1.6% – 2.7% (Brigham and Women’s Surveillance program and Metropolitan Atlanta Congenital Defects Program) and 3.3%-4.5% in cohorts of women exposed to anti-epileptic drug monotherapy from the literature. The observed risk among 139 lamotrigine and valproate polytherapy exposures was 10.8% (95% CI 6.4% - 17.5%) and was 2.7% (95% CI 1.3% - 5.2%) among 333 exposures to lamotrigine polytherapy without valproate. Conclusions: The current data do not indicate any substantial increase in the overall risk of major defects associated with prenatal lamotrigine exposure, though the sample size is insufficient to allow definitive conclusions concerning specific defect types. The registry is currently powered to detect a 1.6 fold increase in risk associated with monotherapy assuming a 2% background risk of all MCMs. The higher frequency of major malformations following lamotrigine-valproate polytherapy exposure is consistent with publications on valproate monotherapy. Continued registration of exposed pregnancies will enhance the statistical power of the study and the data available for physicians to assess the benefit-risk of lamotrigine use in pregnancy.