Abstracts

The international registry forms part of an epidemiologic safety program monitoring pregnancy outcomes in women exposed to lamotrigine that has been in operation since 1992. 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 pediatrician. 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. As of September 2004, fourteen MCMs were observed among 491 monotherapy exposures giving a risk of 2.9% (14/491, 95% CI 1.6% - 4.9%). This is similar to the risk in the US general population (approximately 2.2%) and in women with epilepsy on AED monotherapy (3.2% to 4.5%). The observed risk among 101 lamotrigine and valproate polytherapy exposures was 11.9% (95% CI 6.6% - 20.2%) and was 2.9% (95% CI 1.2% - 6.5%) among 206 exposures to lamotrigine polytherapy without valproate. These results will be updated to include data as of March 2005 prior to presentation. No consistent pattern of malformation types was observed. 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 higher frequency of major malformations following lamotrigine-valproate polytherapy exposure is consistent with publications on valproate monotherapy, though the registry is not powered to determine the individual contribution of each medication. 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. (Supported by GlaxoSmithKline Research and Development.)