title: Selective serotonin reuptake inhibitors and risk for major congenital anomalies.
abstract: OBJECTIVE
  To estimate the risk of major congenital anomalies after exposure to selective serotonin reuptake inhibitors during pregnancy.
  
  
  METHODS
  A retrospective cohort study based on national population-based registers (years 1996-2006) of births, congenital anomalies, and terminations of pregnancy because of severe fetal anomalies (maintained by National Institute for Health and Welfare, source offspring population n=635,583) and drug reimbursements (Social Insurance Institution) linked by a personal identification number. Offspring exposed to selective serotonin reuptake inhibitors during the first trimester (n=6,976) were compared with unexposed referent offspring.
  
  
  RESULTS
  Overall major congenital anomalies were not more common in selective serotonin reuptake inhibitor-exposed offspring compared with unexposed referent offspring (adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.96-1.22). Fluoxetine was associated with an increased risk of isolated ventricular septal defects (adjusted OR 2.03, 95% CI 1.28-3.21) and paroxetine was associated with an increased risk of right ventricular outflow tract defects (adjusted OR 4.68, 95% CI 1.48-14.74). Citalopram use was associated with neural tube defects (adjusted OR 2.46, 95% CI 1.20-5.07). Fetal alcohol spectrum disorders were 10-times more common in the selective serotonin reuptake inhibitor-exposed offspring than in unexposed referent offspring.
  
  
  CONCLUSIONS
  Fluoxetine use is associated with an increased risk of isolated ventricular septal defects and paroxetine is associated with right ventricular outflow tract defects. The absolute risk for these specific cardiac anomalies is small but should guide clinicians not to consider fluoxetine or paroxetine the first option when prescribing selective serotonin reuptake inhibitors to women planning pregnancy. Special attention should be given to alcohol use in pregnant women using selective serotonin reuptake inhibitors.
authors.affiliation: From the Teratology Information Service, Helsinki University Central Hospital and HUSLAB, Helsinki, Finland; the Department of Clinical Pharmacology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland; the National Institute for Health and Welfare, Helsinki, Finland; and the Nordic School of Public Health, Göteborg, Sweden.
authors.forename: Heli
authors.initials: H
authors.lastname: Malm
authors.forename: Miia
authors.initials: M
authors.lastname: Artama
authors.forename: Mika
authors.initials: M
authors.lastname: Gissler
authors.forename: Annukka
authors.initials: A
authors.lastname: Ritvanen
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking; D005260:Female; D005387:Finland; D005473:Fluoxetine / Q000009:adverse effects*; D006345:Heart Septal Defects, Ventricular / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects*; D011247:Pregnancy; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors