Over the last few years, we have reported on several studies which have suggested an  increased risk of certain types of cardiovascular malformations among children exposed to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. The first reports suggested a link between cardiac septal defects and exposure to paroxetine; other, but not all, studies have also shown an elevated risk of cardiac defects in children with prenatal exposure to other SSRIs.

Because there has not been consistency among the various reports, we are left with uncertainty regarding the actual risk. Some researchers have speculated that these disparate findings might reflect differences in methodologies used in the various studies or simply statistical variation. Some have suggested that other factors – not just exposure to antidepressant – may play a role here, such as exposure to tobacco, alcohol, other drugs, or poor prenatal care. A new study helps to quantify the risk of cardiac defects associated with prenatal exposure to antidepressants by taking into consideration some of these confounding factors.

In this cohort study, the researchers analyzed data from the nationwide Medicaid Analytic eXtract for the period 2000 through 2007. The analysis included 949,504 pregnant women who were enrolled in Medicaid during the period from 3 months before the last menstrual period through 1 month after delivery.

A total of 64,389 women (6.8%) used antidepressants during the first trimester of pregnancy. Overall, 6403 infants who were not exposed to antidepressants were born with a cardiac defect (72.3 per 10,000 infants), as compared with 580 infants with antidepressant exposure (90.1 per 10,000 infants). When the analysis was performed to account for potential confounders (e.g., depression severity, maternal medical illness, use of other medications), the difference in risk between the two groups was attenuated.

The relative risk of any cardiac defect associated with the use of SSRIs was 1.25 in the unadjusted analysis (95% confidence interval [CI], 1.13 to 1.38). The relative risk was 1.06 (95% CI, 0.93 to 1.22) in the fully adjusted analysis restricted to women with depression. Based on these findings, the authors concluded that there was no substantial increase in the risk of cardiac malformations attributable to antidepressant use during the first trimester of pregnancy.

Ruta Nonacs, MD PhD

Huybrechts KF, Palmsten K, Avorn J, Cohen LS, Holmes LB, Franklin JM, Mogun H, Levin R, Kowal M, Setoguchi S, Hernández-Díaz S. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014 Jun 19;370(25):2397-407.