Abstracts

This international registry is part of an epidemiologic safety program monitoring pregnancy outcomes in women exposed to lamotrigine. Physicians report exposure to lamotrigine during pregnancy and subsequent outcomes on a voluntary basis. Prospective (before there is any knowledge regarding the outcome) reporting early in pregnancy is encouraged as only the prospectively reported cases can be used to estimate incidence rates for outcomes. Major congenital malformations (MCMs) are classified according to the US Centers for Disease Control criteria and are reviewed by a pediatrician. The percentage of MCMs is calculated for prospective first trimester lamotrigine monotherapy and polytherapy exposures. Conclusions are developed and endorsed by a scientific advisory committee As of September 30, 2003, 10 MCMs were observed among 360 lamotrigine monotherapy exposures in the first trimester, a risk of 2.8% (95% CI 1.5% - 5.2%). This compares to risks of 2 to 3% in the general population and 3.3% to 4.5% in women with epilepsy on AED monotherapy. The current sample size is sufficient to detect, with 80% power, a 1.85 fold increase in the risk of major malformations at the 5% statistical level assuming a baseline risk of 3%. The observed risk among 76 lamotrigine and valproate polytherapy first trimester exposures was 10.5% (95% CI 5.0% - 20.2%) and was 3.1% (95% CI 1.1% - 7.4%) among 163 first trimester exposures to lamotrigine polytherapy without valproate. Although the registry is not powered to detect with any accuracy the risk of specific malformations, no consistent pattern of malformation types was observed. This is one of the largest studies examining pregnancy outcomes in prospectively reported first trimester exposures to monotherapy with lamotrigine. The risk of MCMs following lamotrigine monotherapy exposure is similar to that in the general population, though the sample size is insufficient to allow definitive conclusions. The higher frequency of MCMs following lamotrigine-valproate polytherapy exposure is consistent with published data on valproate monotherapy, though the registry is not powered to determine the individual contribution of each medication or to determine the effect of lamotrigine on the pregnancy risk associated with other antiepileptic drugs. Continued registration of exposed pregnancies will further enhance the statistical power of the study. (Supported by GlaxoSmithKline Epidemiology)