title: The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis.
abstract: OBJECTIVE
  The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category.
  
  
  METHODS
  A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.
  
  
  RESULTS
  Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.
  
  
  CONCLUSIONS
  Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.
authors.affiliation: Research Center, CHU Ste-Justine, Montreal, Quebec.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Anick
authors.initials: A
authors.lastname: Bérard
authors.affiliation: Research Center, CHU Ste-Justine, Montreal, Quebec.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Noha
authors.initials: N
authors.lastname: Iessa
authors.affiliation: Research Center, CHU Ste-Justine, Montreal, Quebec.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Chaabane
authors.affiliation: Research Center, CHU Ste-Justine, Montreal, Quebec.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Flory T
authors.initials: FT
authors.lastname: Muanda
authors.affiliation: Research Center, CHU Ste-Justine, Montreal, Quebec.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Takoua
authors.initials: T
authors.lastname: Boukhris
authors.affiliation: Research Center, CHU Ste-Justine, Montreal, Quebec.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Zhao
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced*; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects*; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: cardiac malformations; major malformations; meta-analysis; paroxetine; pregnancy