Abstracts

Rationale: The international registry formed part of an epidemiologic safety program, established in 1992, to monitor pregnancy outcomes in women exposed to lamotrigine. Methods: Physicians reported 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 was encouraged. Major congenital malformations (MCMs) were classified according to the Centers for Disease Control criteria and were reviewed by a pediatrician. The percentage of MCMs was calculated by trimester and according to monotherapy or polytherapy with/without valproate. Conclusions were developed and endorsed by a scientific advisory committee. Results: Between September 1992 and March 2010, 35 MCMs were observed among 1558 first trimester monotherapy exposures giving a risk of 2.2% (95% CI 1.6 % 3.1%). Assuming a baseline frequency of major defects of 2-3%, the 1558 first trimester monotherapy exposures provide 80% power to detect at least a 1.39 to 1.48 fold increase over the baseline rate. Up to maximum daily doses of 600 mg there was no effect on the rate of major defects. Above 600mg there were insufficient data to assess the effect of increasing dose. The observed risk among 150 lamotrigine and valproate polytherapy exposures was 10.7% (95% CI 6.4% 17.0%) and was 2.8% (95% CI 1.5% 5.0%) among 430 exposures to lamotrigine polytherapy without valproate. No consistent pattern of malformation types was observed. Conclusions: The Registry did not detect an appreciable increase in the risk of major congenital malformations following first trimester exposure to lamotrigine monotherapy. With a sample size of over 1500 first trimester monotherapy exposures the Registry met its primary objective of excluding major teratogenicity. However, increases in the risk of specific defect types cannot be ruled out. The higher frequency of major malformations following lamotrigine-valproate polytherapy exposure is similar to that reported with valproate monotherapy, though without an internal valproate comparison group conclusions cannot be drawn as to the relative contribution of each drug to that risk estimate. Monitoring of specific birth defects will continue through case control surveillance in the EUROCAT network.