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. 2017 Jan 12;7(1):e013372.
doi: 10.1136/bmjopen-2016-013372.

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

Anick Bérard  1   2 , Jin-Ping Zhao  1   2 , Odile Sheehy  1
Affiliations

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

Anick Bérard et al. BMJ Open. .

Abstract

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.

Keywords: EPIDEMIOLOGY; PUBLIC HEALTH.

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Conflict of interest statement

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

Figures

Figure 1
Figure 1
Flow chart of the selection of the study cohort. *First day of the last menstrual period. SSRIs included citalopram, sertraline, paroxetine, fluoxetine and fluvoxamine; SNRI included venlafaxine; TCAs included amitriptyline, desipramine, doxepin, imipramine, nortriptyline, trimipramine and clomipramine; other antidepressants included: tryptophan, trazodone, buspirone, moclobemide, bupropion and mirtazapine. SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitors; TCA, tricyclic antidepressants.
Figure 2
Figure 2
Trend in the use of antidepressants, maternal depression/anxiety and prevalence of major congenital malformations in the overall Quebec Pregnancy Cohort. MCM, major congenital malformations.
See this image and copyright information in PMC

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