Antidepressant use in pregnancy and the risk of cardiac defects.


This retrospective cohort study of nearly one million women found no significant increase in risk of cardiac defects attributable to first trimester antidepressant use, after adjusting for potential confounders. Unadjusted, the relative risk was 1.25.


  • N=949,504 pregnant women, drawn from the Medicaid Analytic eXtract (majority of U.S. states) from 2000-2007, of whom n=64,389 (6.8%) used antidepressants in the first trimester.
  • Exposure categories:
    • Any SSRI (n=46,144)
    • Paroxetine (n=11,126)
    • Sertraline (n=14,040)
    • Fluoxetine (n=11,048)
    • SNRI (n=6,904)
    • TCA (n=5,954)
    • Buproprion (n=8,856)
    • Other antidepressant (n=7,055)
  • Reference group: women without exposure to antidepressants during first trimester (n=885,115).
  • Outcomes:
    • Any cardiac malformation
    • Right ventricular outflow tract obstruction
    • Ventricular septal defect
    • Other cardiac malformation
  • Outcomes related to prematurity were excluded (e.g. patent ductus arteriosus).


  • Overall, the rate of cardiac defects per 100,000 infants born were:
    • 72.3 infants not exposed to antidepressants
    • 90.1 infants exposed to antidepressants
  • After correcting for confounding variables, the associations were much less significant. For example, the relative risks of cardiac defect in those exposed to SSRIs compared with those not exposed were (95% CI):
    • 1.25 (1.13-1.38) unadjusted
    • 1.12 (1.00-1.26) after restricting to women with depression
    • 1.06 (0.93-1.22) after restricting to women with depression and using propensity-score adjustment to control for other potential confounders.


Huybrechts KF, Palmsten K, Avorn J, et al. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014;370(25):2397-2407. doi:10.1056/NEJMoa1312828.

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