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Given the increased use of antidepressants during pregnancy over the last two decades, there is understandable concern about possible adverse effects on antenatally exposed offspring. Using data from the Quebec Pregnancy Cohort, Bérard et al claim that exposure to antidepressants during pregnancy elevates the risk of major congenital malformations (MCM) in exposed offspring (1). The study compares depressed/anxious women who took medication to depressed/anxious women who did not. The results presented are dramatic: 11.1% MCM in the unmedicated cohort and 12-13.4% in SSRI, SNRI, and TCA exposed cohorts, with paroxetine, citalopram, tricyclic antidepressants and venlafaxine associated with organ-specific defects.
But the authors’ conclusion that antidepressants cause major congenital malformations is not supported by their data. First, the study’s numbers for the unmedicated groups are far above the baseline risk of 3-5% generally cited in the literature. The authors state that this high percentage is due to “genetic risk factors stemming from the ‘founding’ French ancestors.” But the paper cited to support this claim—written by the same authors—says nothing of the kind. In fact, that study reports a rate of 3.6%, consistent with North American background risks (2).
Second, since no data are presented for healthy, unmedicated pregnancies, it is impossible to know how the two studied groups compare to general population risk. To us, it appears that whatever is...
Second, since no data are presented for healthy, unmedicated pregnancies, it is impossible to know how the two studied groups compare to general population risk. To us, it appears that whatever is raising the risk for major congenital malformations in the unmedicated group is raising the risk only slightly more in the exposed group. This suggests that antidepressant use may be a marker for more severe psychiatric illness. The authors’ results may well be confounded by indication – that is, depression and/or anxiety (rather than antidepressant exposure) may be associated with adverse outcomes in the offspring.
The authors conclude that “Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression.” We believe that the data support another conclusion: “Depression and/or anxiety may be associated with genetic, environmental, and behavioral variables that increase the risk of major congenital malformations.”
1. Berard, A, Zhao J-P, Sheehy O: Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort. BMJ Open 2017;7:e013372. Doi;10.1136/bmjopen-2016-013372.
2. Zhao J-P, Sheehy O, Berard A: Regional variations in the prevalence of major congenital malformations in Quebec: The importance of fetal growth environment. J Popul Ther Clin Pharmacol 2015;22(3);e198-e210;November 11, 2015.
It seems significant to note the high rate (over 10%) of major congenital malformations among unexposed and exposed pregnancies. It would be interesting to have the authors comment whether this compromises external validity, and possible reasons for such high rates.