Abstracts

Rationale: The registry forms part of an epidemiologic safety program to determine the risk of major congenital malformations (MCMs) associated with exposure to lamotrigine during pregnancy and has been in operation since 1992. Methods: Physicians report lamotrigine exposure during pregnancy and subsequent outcomes on a voluntary basis. Prospective reporting (prior to any knowledge regarding the possible pregnancy) early in pregnancy is encouraged. MCMs are classified according to the Centers for Disease Control criteria and are reviewed by a paediatrician. The percentage of MCMs is calculated using prospective first trimester lamotrigine monotherapy and polytherapy exposures. Conclusions are developed by a scientific advisory committee. Results: As of September 2007, 31 MCMs were observed among 1155 first trimester monotherapy exposures yielding a risk of 2.7% (95% CI 1.9% - 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 143 lamotrigine and valproate polytherapy exposures was 11.2% (95% CI 6.7% - 17.8%) and was 2.5% (95% CI 1.2% - 4.9%) among 355 exposures to lamotrigine polytherapy without valproate. Conclusions: The current data do not indicate any substantial increase in the overall risk of major malformations 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 1.5 fold increase in monotherapy associated risk assuming a 2% background MCM risk. The higher frequency of MCMs following lamotrigine-valproate polytherapy exposure is consistent with publications on valproate monotherapy. The registry has reached the milestone of 1000 first trimester monotherapy exposures and is adequately powered to meet its primary aim of detecting a signal of major teratogenicity.