Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study

Anthony Wemakor, Karen Casson, Ester Garne, Marian Bakker, Marie-Claude Addor, Larraitz Arriola, Miriam Gatt, Babak Khoshnood, Kari Klungsoyr, Vera Nelen, Mary O'Mahoney, Anna Pierini, Anke Rissmann, David Tucker, Breidge Boyle, Lolkje de Jong-van den Berg, Helen Dolk

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Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors.

Original languageEnglish
Pages (from-to)1187-1198
Number of pages12
JournalEuropean Journal of Epidemiology
Issue number11
Early online date07 Jul 2015
Publication statusPublished - Nov 2015


  • Abnormalities, Drug-Induced
  • Adolescent
  • Adult
  • Case-Control Studies
  • Depression
  • Europe
  • Female
  • Gestational Age
  • Heart Defects, Congenital
  • Heart Septal Defects, Ventricular
  • Humans
  • Middle Aged
  • Population Surveillance
  • Pregnancy
  • Pregnancy Complications
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects
  • Registries
  • Risk Assessment
  • Risk Factors
  • Serotonin Uptake Inhibitors
  • Socioeconomic Factors
  • Young Adult

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