Abstracts

To characterize the overall risk of major congenital malformations (MCM) associated with exposure to lamotrigine. 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 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., As of September 2005, 20 MCMs were observed among 707 first trimester monotherapy exposures yeilding a risk of 2.8% (95% CI 1.8% - 4.4%). The observed risk among 118 lamotrigine and valproate polytherapy exposures was 11.8% (95% CI 6.8% - 19.3%) and was 2.7% (95% CI 1.2% - 5.8%) among 256 exposures to lamotrigine polytherapy without valproate. The mean and median monotherapy doses for subjects with MCMs respectively were 250.7 and 200 mg/day; the mean and median doses for those without defects were 281.1 and 200 mg/day. 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 was 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., (Supported by GlaxoSmithKline Research and Development.)