title: Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study.
abstract: 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.
authors.affiliation: WHO Collaborating Centre for the Epidemiologic Surveillance of Congenital Anomalies, Room 12L23, Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, Shore Road, Newtownabbey, BT37 0QB, UK.|School of Allied Health Sciences, University for Development Studies, Tamale, Ghana.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wemakor
authors.affiliation: WHO Collaborating Centre for the Epidemiologic Surveillance of Congenital Anomalies, Room 12L23, Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, Shore Road, Newtownabbey, BT37 0QB, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Casson
authors.affiliation: Hospital Lillebaelt, Kolding, Denmark.
authors.forename: Ester
authors.initials: E
authors.lastname: Garne
authors.affiliation: Department of Genetics, Eurocat Northern Netherlands, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Bakker
authors.affiliation: Service of Medical Genetics CHUV Lausanne, Lausanne, Switzerland.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Addor
authors.affiliation: Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública - CIBERESP, Madrid, Spain.
authors.forename: Larraitz
authors.initials: L
authors.lastname: Arriola
authors.affiliation: Department of Health Information and Research, Guardamangia, Malta.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gatt
authors.affiliation: Paris Registry of Congenital Malformations, INSERM U953, Paris, France.
authors.forename: Babak
authors.initials: B
authors.lastname: Khoshnood
authors.affiliation: Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway.|Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Klungsoyr
authors.affiliation: Provinciaal Instituut voor Hygiene, Antwerp, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Nelen
authors.affiliation: Health Service Executive, Cork, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Mahoney
authors.affiliation: Unit of Epidemiology, IFC CNR (Tuscany Registry of Birth Defects), Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pierini
authors.affiliation: Malformation Monitoring Centre, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Rissmann
authors.affiliation: Congenital Anomaly Register and Information Service, Public Health Wales, Swansea, Wales, UK.
authors.forename: David
authors.initials: D
authors.lastname: Tucker
authors.affiliation: WHO Collaborating Centre for the Epidemiologic Surveillance of Congenital Anomalies, Room 12L23, Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, Shore Road, Newtownabbey, BT37 0QB, UK.
authors.forename: Breidge
authors.initials: B
authors.lastname: Boyle
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Lolkje
authors.initials: L
authors.lastname: de Jong-van den Berg
authors.affiliation: WHO Collaborating Centre for the Epidemiologic Surveillance of Congenital Anomalies, Room 12L23, Centre for Maternal, Fetal and Infant Research, Institute of Nursing and Health Research, Ulster University, Shore Road, Newtownabbey, BT37 0QB, UK. H.Dolk@ulster.ac.uk.
authors.forename: Helen
authors.initials: H
authors.lastname: Dolk
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000453:epidemiology; D006345:Heart Septal Defects, Ventricular / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D011159:Population Surveillance; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000453:epidemiology / Q000523:psychology; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D012959:Socioeconomic Factors; D055815:Young Adult
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors
keywords: Congenital anomaly; Depression; Epidemiology; Medication; Registry; SSRI