Article Text

Download PDFPDF

Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort
  1. Anick Bérard1,2,
  2. Jin-Ping Zhao1,2,
  3. Odile Sheehy1
  1. 1Research Center, CHU Sainte-Justine, Montreal, Quebec, Canada
  2. 2Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada
  1. Correspondence to Dr Anick Bérard; anick.berard{at}


Objective Antidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women.

Setting and participants Data were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included.

Outcome measures Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified.

Results 18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95% CI 1.07 to 4.38).

Conclusions Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression.


This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Previous presentation This research was presented in part at the 55th Annual Scientific Meeting of the Teratology Society, Montreal, Canada, 27 June to 1 July 2015.

  • Contributors AB contributed to the study design, data collection, analysis of data and preparation of the final document. J-PZ contributed to the study design, data collection, analysis of data and preparation of the final document. OS contributed to the study design, data collection, analysis of data and preparation of the final document. All authors read and approved the final document.

  • Funding This study was supported by the Canadian Institutes of Health Research (grant number 132750). AB is the recipient of a research chair from the Fonds de la recherche du Québec—Santé (FRQ-S). J-PZ is the recipient of a Quebec-China, postdoctoral fellowships from the Canadian Institutes of Health Research.

  • Competing interests AB is a consultant for plaintiffs in litigations involving antidepressants and birth defects. All authors have completed the ICMJE uniform disclosure form.

  • Ethics approval The study was approved by the Quebec Data Access Agency and the CHU Sainte-Justine Institutional Review Board (#1740 and #2976).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.