Incidence of Congenital Malformations in Infants Born to Patients with Epilepsy: A Comparison of Pregnancy Registries and Cohort Study Data (S56.003)

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Objective: To compare rates of major congenital malformations (MCM) and ventricular septal defects (VSD) within the UCB AED Pregnancy Registry (UCB Registry) to rates from other sources. Background The UCB Registry is a study designed to monitor pregnant women exposed primarily to levetiracetam (Keppra®) and their offspring. Design/Methods: MCM and VSD rates were calculated from the UCB Registry (interim data from 2004 through February 2011) and compared to published rates from a general population surveillance system (MACDP) and epilepsy patient registries: EURAP, UK registry, and NAAED. Results: MCM rates among levetiracetam monotherapy exposures were 7.7% (UCB Registry), 1.6% (EURAP), 2.1% (NAAED) and 0% (UK registry). An overall MCM rate for other AED monotherapies of 5.5% was reported by EURAP. MCM rates for individual monotherapy exposures in the first trimester were reported by NAAED: 9.5% valproate, 5.6% phenobarbital, 3.4% topiramate, 3.0% phenytoin, 2.9% carbamazepine, and 1.9% lamotrigine. MCM rates among levetiracetam polytherapy exposures were 12.5% (UCB Registry), 6.9% (EURAP), and 3.3% (UK). EURAP reported an overall MCM rate for other AED polytherapies of 9.2%. In an independent review of 59 published studies (Meador et al, Neurology 2008;71:1109-1117), the MCM rate was 7.1% in epilepsy patients and 2.3% in healthy women. The MACDP MCM rate was 2.8% and the VSD rate was 0.4%. VSD rates in the UCB Registry ranged from 0.8%–1.2% (n=5). Among epilepsy registries, VSD data was only available from EURAP in which one VSD was identified. Conclusions: Among the various registries, differences in observed MCM and VSD rates, as well as differences in the presence and impact of concomitant medications with a higher risk of birth defects, might be attributed to variations in study design. When an internal comparator was available, the rates of MCM and VSD were no greater in levetiracetam-exposed patients than in those treated with other AEDs. Supported by: UCB Pharma. Disclosure: Dr. Montouris has received personal compensation for activities with UCB Pharma, Eisai, Lundbeck, Meridian, and Sunovion. Dr. Montouris has received person compensation in an editorial capacity for Epilepsia. Dr. Harden has received personal compensation for activities with UCB Pharma, Pfizer, and GlaxoSmithKline as a speaker. Dr. Harden has received research support from Forest Pharmaceuticals. Dr. Albano has received personal compensation for activities with UCB Pharma. Dr. Leppik has received personal compensation for activities with Caremark R11 and UCB Pharma, Inc. as a consultantDr. Leppik has received research support from UCB Pharmaceuticals. Dr. Miller has received personal compensation for activities with UCB Pharma as an employee.