Is There a Risk of Cardiac Defects in Infants From Antidepressant Use in Pregnancy?

With clinical depression affecting 10 to 15 percent of pregnant women, the use of anti-depressant medications during pregnancy has increased over time. However in 2005, after conducting two epidemiologic studies, the U.S. Food and Drug Administration (FDA), issued a warning that early prenatal exposure to such treatment may increase the risk of congenital cardiac malformations.

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Following in the footsteps of subsequent research that have yielded diverse conclusions, a new study published June 18 in the New England Journal of Medicine sought to assess the risk of congenital cardiac defects after the use of specific antidepressants, with attention to the potential for confounding by the underlying depression and associated factors. However, the study found no significant increase in the risk of cardiac malformations among infants born to women who took antidepressants during the first trimester, as compared with infants born to women who did not have exposure to such agents.

The cohort study was led by Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, and looked at nationwide Medicaid Analytic eXtract from 2000 to 2007, drawing from 949,504 pregnant women who were enrolled in Medicaid during a period three months before their last menstrual period through one month after delivery and their live-born infants. Huybrechts and her co-authors then compared the risk of major cardiac defects among infants born to women who took antidepressants during the first trimester with the risk among infants born to women who did not use antidepressants, utilizing unadjusted analysis and analyses that restricted the cohort to women with depression and that used propensity-score adjustments to control depression severity and other potential confounders.

Results of the study showed that a total of 64,389 women (6.8 percent) used antidepressants during the first trimester. Overall, 6403 infants who were not exposed to antidepressants were born with a cardiac defect (72.3 cardiac malformations per 20,000 infants), compared with 580 infants that were exposed (90.1 cardiac malformations per 10,000 infants). In unadjusted analyses, the relative risk of any cardiac malformation was 1.25 with serotonin-reuptake inhibitors (95 percent confidence interval [CI], 1.13 to 1.38), 0.98 with tricyclic antidepressants (95 percent CI, 0.72 to 1.32), 1.51 with serotonin-norepinephrine reuptake inhibitors (95 percent CI, 1.20 to 1.90), 1.19 with bupropion (95 percent CI, 0.95 to 1.49), and 1.46 with other antidepressants (95 percent CI, 1.16 to 1.83). Restricting the cohort to women with a diagnosis of depression and adjusting the propensity score further only attenuated the associations.

In addition the study found that significantly increased risks were not observed in relation to specific cardiac defects previously hypothesized to be associated with such drug use, specific antidepressant medication classes or the most commonly used selective serotonin-reuptake inhibitors.

The authors conclude that, based on their results, “in making decisions about whether to continue or discontinue treatment with antidepressants during pregnancy, clinicians and women must balance the potential risks of treatment with the risks of not treating severe depression.” However, they add that “the accumulated evidence implies low absolute risks and argues against important cardiac teratogenic effects associated with the most commonly used antidepressant medications.”

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