The epidemiology of ebstein's anomaly in Europe: A registry-based study with special emphasis on medication exposure

Background: Ebstein's anomaly (EA) is a rare congenital malformation of the tricuspid valve and right ventricle of the heart. It has been associated with lithium and benzodiazepine exposure in pregnancy. Objectives: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe with reference to geographic and temporal variation in prevalence, associated malformations and syndromes, and risk factors including maternal age, parity, medical history, and medication exposure during pregnancy. Methods: Descriptive epidemiologic analysis of data from 15 EUROCAT Congenital Anomaly Registries in 12 European countries covering a population of 5.6 million births in 1982-2011 was carried out. EA cases included livebirths, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA). Prevalence rate per 10000 births was calculated. Odds ratios (OR) for exposure to maternal illnesses and medications in the first trimester of pregnancy were calculated using logistic regression, by comparing EA cases to non-EA and non-cardiac controls, excluding genetic syndromes. OR are adjusted for time period and country. Results: The prevalence of EA was 0.47 (95%CI 0.41- 0.53) per 10 000 births. Prevalence rose from 0.29 (95% CI 0.20-0.41) in the decade 1982-1991 to 0.55 (95%CI 0.46-0.67) in the decade 1992-2001 (p