Abstracts

Rationale: The international registry forms part of an epidemiologic safety program, established in 1992, to monitor pregnancy outcomes in women exposed to lamotrigine. 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 by trimester and according to monotherapy or polytherapy with/without valproate. Conclusions are developed and endorsed by a scientific advisory committee. Results: As of September 2008, 33 MCMs were observed among 1337 first trimester monotherapy exposures giving a risk of 2.5% (95% CI 1.7% 3.5%). Assuming a baseline frequency of major defects of 2-3%, the 1337 first trimester monotherapy exposures provide 80% power to detect at least a 1.42 - 1.52 -fold increase over the baseline rate. . Up to maximum daily doses of 600 mg there was no effect on the incidence of major defects. The observed risk among 146 lamotrigine and valproate polytherapy exposures was 11.0% (95% CI 6.6% 17.5%) and was 2.3% (95% CI 1.1% 4.5%) among 392 exposures to lamotrigine polytherapy without valproate. No consistent pattern of malformation types was observed across all lamotrigine exposure groups. 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 regarding the safety of lamotrigine in pregnancy. The higher frequency of major malformations following lamotrigine-valproate polytherapy exposure is similar to that reported with valproate monotherapy. With a sample size of over 1,000 first trimester exposures the registry has met its primary objective of excluding major teratogenicty among offspring of lamotrigine-exposed women.