Infants born to women who took antidepressants during the first trimester of their pregnancies showed no increase in cardiac malformations overall or in specific cardiac defects that earlier research had linked to fetal exposure to the drugs, investigators have reported.
Previously, paroxetine and sertraline had been associated with congenital cardiac malformations, chiefly septal defects, but "considerable controversy" remains on the subject, the researchers noted in a report published online June 19 in the New England Journal of Medicine.
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Antidepressant use in the first trimester of pregnancy does not appear to be linked to infant heart conditions.
In the current large, population-based cohort study, the investigators drew from Medicaid records for 46 states and the District of Columbia and identified 949,504 completed pregnancies during a 7-year period. A total of 64,389 of these women (6.8%) used an antidepressant during their first trimester, including SSRIs, tricyclics, serotonin–norepinephrine reuptake inhibitors (SNRIs), and bupropion.
The SSRIs taken by women most frequently were sertraline, paroxetine, and fluoxetine, wrote Krista F. Huybrechts, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.
In the study’s initial analysis, cardiac malformations were diagnosed in 6,403 infants not exposed to antidepressants, for a rate of 72.3 malformations per 10,000 infants, and in 580 infants exposed to antidepressants, for a rate of 90.1 malformations per 10,000 infants. Once these data were adjusted to account for the effect of the underlying depression (indication bias), however, there was no association between the use of antidepressants in general and infant cardiac malformations, nor between specific antidepressants and specific cardiac malformations.
In particular, "we found no significant associations between paroxetine and right ventricular outflow tract obstruction or between sertraline and ventricular septal defect," Dr. Huybrechts and her associates said (N. Engl. J. Med. 2014 June 19 [doi:10.1056/NEJMoa1312828]).
In addition, numerous subgroup and sensitivity analyses found no such associations regardless of the women’s age, race, or use of monotherapy vs. polytherapy, and no dose-response relationships. In contrast, the data confirmed well-known associations between infant cardiac malformations and maternal diabetes, maternal use of anticonvulsants, and multiple gestations, which supports the premise that "the outcomes of interest were well captured in our study," the investigators said.
This study was supported by the Agency for Healthcare Research and Quality, the National Institute of Mental Health, and the National Institute of Child Health and Human Development. Dr. Huybrechts reported no financial conflicts of interest; her associates reported numerous ties to industry sources.