title: The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study.
abstract: OBJECTIVE
  The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy.
  
  
  METHODS
  We carried out a descriptive epidemiological analysis of population-based data.
  
  
  METHODS
  We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country.
  
  
  RESULTS
  In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p<0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal β-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n=3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n=11) compared with cardiac controls.
  
  
  CONCLUSIONS
  The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.
authors: 1Centre for Maternal, Fetal and Infant Research,Institute of Nursing and Health Research,Ulster University,Belfast,UK.
authors: Breidge
authors: B
authors: Boyle
authors: 2Paediatric Department,Hospital Lillebaelt,Kolding,Denmark.
authors: Ester
authors: E
authors: Garne
authors: 1Centre for Maternal, Fetal and Infant Research,Institute of Nursing and Health Research,Ulster University,Belfast,UK.
authors: Maria
authors: M
authors: Loane
authors: 3Division of Medical Genetics,CHUV,Lausanne,Switzerland.
authors: Marie-Claude
authors: MC
authors: Addor
authors: 4Registro Anomalías Congénitas de la CAPV, Public Health Division of Gipuzkoa,Instituto BIO-Donostia,Basque Government, CIBER Epidemiología y Salud Pública - CIBERESP,Bilbao,Spain.
authors: Larraitz
authors: L
authors: Arriola
authors: 5Foundation for the Promotion of Health and Biomedical Research in the Valencian Region,Rare Diseases Research Area,Valencia,Spain.
authors: Clara
authors: C
authors: Cavero-Carbonell
authors: 6Department of Health Information and Research Guardamangia,Malta.
authors: Miriam
authors: M
authors: Gatt
authors: 7Paris Registry of Congenital Malformations INSERM U953,Paris,France.
authors: Nathalie
authors: N
authors: Lelong
authors: 8Health Service Executive, Kilkenny,Ireland.
authors: Catherine
authors: C
authors: Lynch
authors: 9Department of Environment,PIH,Antwerp,Province of Antwerp,Belgium.
authors: Vera
authors: V
authors: Nelen
authors: 10Registro IMER - IMER Registry (Emila Romagna Registry of Birth Defects),Azienda Ospedaliero - Universitaria di FerraraCorso Giovecca,Ferrara,Italy.
authors: Amanda J
authors: AJ
authors: Neville
authors: 11Health Service Executive, Cork,Ireland.
authors: Mary
authors: M
authors: O'Mahony
authors: 12CNR Institute of Clinical Physiology,Pisa,Italy.
authors: Anna
authors: A
authors: Pierini
authors: 13Medical Faculty,Malformation Monitoring Centre,Otto-von-Guericke University,Magdeburg,Saxony-Anhalt,Germany.
authors: Anke
authors: A
authors: Rissmann
authors: 14Public Health Wales. Swansea,UK.
authors: David
authors: D
authors: Tucker
authors: 15Khmelnytsky Regional Medical Genetic Centre,Rivne,Ukraine.
authors: Natalia
authors: N
authors: Zymak-Zakutnia
authors: 1Centre for Maternal, Fetal and Infant Research,Institute of Nursing and Health Research,Ulster University,Belfast,UK.
authors: Helen
authors: H
authors: Dolk
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects; D004437:Ebstein Anomaly / Q000453:epidemiology* / Q000209:etiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D005313:Fetal Death; D006801:Humans; D007231:Infant, Newborn; D008094:Lithium / Q000009:adverse effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D001523:Mental Disorders / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011261:Pregnancy Trimester, First; D012042:Registries; D055815:Young Adult; D017086:beta-Thalassemia / Q000209:etiology
chemical_list: D000928:Antidepressive Agents; D001569:Benzodiazepines; D008094:Lithium
keywords: Ebstein’s anomaly; antidepressants; mental illness; prevalence; psycholeptics