title: Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence.
abstract: OBJECTIVE
  Depression is often not optimally treated during pregnancy, partially because of conflicting data regarding antidepressant medication risk. This meta-analysis was conducted to determine whether antenatal antidepressant exposure is associated with congenital malformations and to assess the effect of known methodological limitations.
  
  
  METHODS
  EMBASE, CINAHL, PsycINFO, and MEDLINE were searched from their start dates to June 2010. Keywords of various combinations were used, including, but not limited to depressive/mood disorder, pregnancy, antidepressant drug/agent, congenital malformation, and cardiac malformation.
  
  
  METHODS
  English language studies reporting congenital malformations associated with antidepressants were included. Of 3,074 abstracts reviewed, 735 studies were retrieved and 27 studies were included.
  
  
  METHODS
  Two reviewers working independently assessed article quality. Data on use of any antidepressant, including fluoxetine and paroxetine specifically, were extracted. Outcomes included congenital malformations, major congenital malformations, cardiovascular defects, septal heart defects (ventral septal defects and atrial septal defects), and ventral septal defects only.
  
  
  RESULTS
  Nineteen studies were above quality threshold and make up the primary meta-analyses. Pooled relative risks (RRs) were derived by using random-effects methods. Antidepressant exposure was not associated with congenital malformations (RR = 0.93; 95% CI, 0.85-1.02; P = .113) or major malformations (RR = 1.07; 95% CI, 0.99-1.17; P = .095). However, increased risk for cardiovascular malformations (RR = 1.36; 95% CI, 1.08-1.71; P = .008) and septal heart defects (RR = 1.40; 95% CI, 1.10-1.77; P = .005) were found; the RR for ventral septal defects was similar to septal defects, although not significant (RR = 1.54; 95% CI, 0.71-3.33; P = .274). Pooled effects were significant for paroxetine and cardiovascular malformations (RR = 1.43; 95% CI, 1.08-1.88; P = .012). These results are contrasted with those addressing methodological limitations but are typically consistent.
  
  
  CONCLUSIONS
  Overall, antidepressants do not appear to be associated with an increased risk of congenital malformations, but statistical significance was found for cardiovascular malformations. Results were robust in several sensitivity analyses. Given that the RRs are marginal, they may be the result of uncontrolled confounders. Although the RRs were statistically significant, none reached clinically significant levels.
authors: Women's Mood and Anxiety Clinic: Reproductive Transitions, Department of Psychiatry, FG 29, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. Sophie.Grigoriadis@sunnybrook.ca
authors: Sophie
authors: S
authors: Grigoriadis
authors: Emily H
authors: EH
authors: VonderPorten
authors: Lana
authors: L
authors: Mamisashvili
authors: Michael
authors: M
authors: Roerecke
authors: Jürgen
authors: J
authors: Rehm
authors: Cindy-Lee
authors: CL
authors: Dennis
authors: Gideon
authors: G
authors: Koren
authors: Meir
authors: M
authors: Steiner
authors: Patricia
authors: P
authors: Mousmanis
authors: Amy
authors: A
authors: Cheung
authors: Lori E
authors: LE
authors: Ross
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D019317:Evidence-Based Medicine / Q000639:trends; D005260:Female; D006330:Heart Defects, Congenital / Q000453:epidemiology*; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000928:Antidepressive Agents