To quantify the association between first-trimester antidepressant exposure and the risk of major congenital malformations (MCM) in a cohort of depressed women.

Data were obtained from the Quebec pregnancy cohort. 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. Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and other antidepressants), and types were individually compared to non-exposure during the first-trimester (depressed untreated). MCM overall and organ-specific malformations in the first year of life were identified.

Eighteen thousand four hundred and eighty-seven depressed pregnant women were included. Citalopram use during the first-trimester was increasing the risk of MCM (aOR 1.36, 95%CI 1.08, 1.73; 88 exposed cases). Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) were increasing the risk of certain organ specific defects: paroxetine was increasing the risk of cardiac defects (aOR 1.45, 95%CI 1.12, 1.88), and ventricular/atrial septal defects (aOR 1.39, 95%CI 1.00. 1.93); citalopram was increasing the risk of musculoskeletal defects (aOR 1.92, 95%CI 1.40. 2.62), and cranyosynostosis (aOR 3.95, 95%CI 2.08, 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95%CI 1.05, 5.72), and digestive defects (aOR 2.55, 95%CI 1.40. 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95%CI 1.07, 4.38).

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

COI: Disclosures and acknowledgments: AB is a consultant for plaintiffs in litigations involving antidepressants and birth defects. All other authors report no financial relationships with commercial interests. All authors have completed the ICMJE uniform disclosure form.