Antidepressant use during the first trimester of pregnancy was not associated with a greater risk of cardiac malformations in the offspring, a large cohort study showed.
The rate of cardiac malformations was 72.3 per 10,000 babies who were not exposed to antidepressants early in pregnancy and 90.1 per 10,000 babies whose mothers did take antidepressants, although the difference was not statistically significant in a propensity-matched analysis confined to women with diagnosed depression on Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
The findings were consistent for selective serotonin reuptake inhibitors (SSRIs) — the most commonly prescribed agents — and other antidepressants, the researchers reported in the June 19 issue of the New England Journal of Medicine.
This study can help inform the decision made by women and their physicians about the relative risks and benefits of using antidepressants during pregnancy.
The accumulated evidence suggests that the absolute risk is low, and this study indicates that there is no substantial increased risk of cardiac malformations associated with first trimester use of selective serotonin reuptake inhibitors or other antidepressants during pregnancy.
Previous studies have shown that 8% to 13% of pregnant women in the U.S. use antidepressants, with the rate increasing over time, and that there are possible relationships between prenatal exposure to the drugs and heart defects in the offspring. Results are mixed, however, and it has remained unclear … whether these associations are causal or due to systematic error or chance.
The analysis included 949,504 adolescents and women ages 12 to 55 who were enrolled in Medicaid from 3 months before the last menstrual period through 1 month after delivery of a live-born baby.
Overall, 6.8% of the women used antidepressants during the first trimester (with some exposed to more than one such medication an SSRI was used by 4.9%, a tricyclic antidepressant by 0.6%, a serotonin-norepinephrine reuptake inhibitor (SNRI) by 0.7%, bupropion by 0.9%, and other agents by 0.7%.
The most common SSRIs were sertraline, paroxetine, and fluoxetine.
When comparing babies born to women who used antidepressants in the first trimester with those born to mothers who did not, there were greater risks of cardiac defects associated with the use of SSRIs, SNRIs, and other antidepressants in unadjusted analyses.
Those risks were attenuated when the analyses were restricted to women with diagnosed depression and were rendered nonsignificant in fully adjusted analyses that used propensity-score matching among women with depression.
“Our results do not support earlier findings of an association between antidepressant use and cardiac anomalies, in particular findings with respect to the use of paroxetine and sertraline,” the authors wrote
Smoking, alcohol and drug use, poor maternal diet, obesity, and chronic conditions such as diabetes and hypertension are all more common in patients with depression than in those without depression, and are potential risk factors for congenital cardiac anomalies.
Women with depression and anxiety are more likely to have cardiac defects detected in their offspring because they tend to use more healthcare resources including ultrasonography, amniocentesis, and echocardiography of the infant during pregnancy compared with other women.
We have some limitations, however, including the restriction to women who had live births which resulted in missing cardiac malformations that caused fetal death or resulted in termination of the pregnancy and the potential for misclassification or residual confounding from incomplete or missing factors.
Im thinks the findings are applicable to the broader group of pregnant women. Medicaid cohorts tend to be younger and more racially diverse than the general population, but neither age nor race/ethnicity had significant interactions with the results.
DR JORGE BERNAL