title: The fetal safety of fluoxetine: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Fluoxetine is the selective serotonin reuptake inhibitor (SSRI) with the longest clinical use. Published reports regarding its fetal safety are contradictory. We aimed to establish the fetal safety of the drug.
  
  
  METHODS
  We performed a systematic review of the literature, searching PubMed, Medline, and Embase from inception to August 31, 2012, for cohort and case-control studies in which women were exposed to fluoxetine during the first trimester and compared outcomes with those of unexposed control subjects.
  
  
  RESULTS
  Twenty-one studies met the inclusion criteria. The odds ratio for major malformations associated with maternal fluoxetine use in cohort studies was 1.12 (95% CI 0.98 to 1.28). The studies included were homogeneous. Fifteen cohort studies evaluated cardiac malformations and yielded an overall odds ratio of 1.6 (95% CI 1.31 to 1.95). These studies also were homogeneous. In contrast, two case-control studies assessing cardiac malformations yielded a combined odds ratio of 0.63 (95% CI 0.39 to 1.03).
  
  
  CONCLUSIONS
  The apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias. Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations.
authors: The Motherisk Program, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto ON.
authors: Lauren
authors: L
authors: Riggin
authors: The Motherisk Program, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto ON.
authors: Zipora
authors: Z
authors: Frankel
authors: The Motherisk Program, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto ON.
authors: Myla
authors: M
authors: Moretti
authors: The Motherisk Program, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto ON.
authors: Anna
authors: A
authors: Pupco
authors: The Motherisk Program, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto ON.
authors: Gideon
authors: G
authors: Koren
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003863:Depression / Q000150:complications / Q000188:drug therapy; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects*; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D016239:MEDLINE; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications / Q000523:psychology; D011261:Pregnancy Trimester, First; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: SSRIs; fluoxetine; malformations; meta-analysis; pregnancy; selective serotonin reuptake inhibitor