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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
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  • Published on:
    Antidepressant use during pregnancy and the risk of major malformations in a cohort of depressed women: Prevalence of major malformations and indication bias.
    • Anick Berard, Full Professor University of Montreal, Faculty of Pharmacy; CHU Ste-Justine, Research Center, Montreal, Quebec, Canada
    • Other Contributors:
      • Jinping Zhao, MD, PhD; Research Associate
      • Odile Sheehy, Research Assistant, Biostatistician

    Dear Editor,

    We thank Drs Burt, Rasminsky, Andrade, and Barros for their letters on our study published in BMJ Open in January 2017.1 We agree with them that our baseline prevalence of major malformations in the Quebec Pregnancy Cohort (QPC) is higher than the reported 3-5%. Bérard et Sheehy2 have described the QPC, and have presented baseline statistics showing that the baseline prevalence of major malformations in Quebec was 9.3%. We have disclosed that already in our Discussion section – ‘Our major congenital malformation population prevalence may seem somewhat higher than the routinely reported 3-5%, but in fact our rate is consistent with what is expected in the province of Quebec, due to high concentration of genetic risk factors stemming from the ‘founding’ French ancestors.’1,3 It is true that we are referencing another of our studies to highlight the Founders’ effect. Indeed, Zhao et al.3 have shown that the prevalence of major malformations in the province of Quebec vary by geographical regions, and are higher in the regions where the founding French ancestors first inhabited. This is a well know fact and is representative of specific genetic traits of those founding fathers. Again, this was well discussed and represented in Zhao et al.,3 and it is why we are referencing this study in Bérard et al.1 Bérard et al.1 further showed that the prevalence of major malformations among those with depression during pregnancy was even higher (greater than 11%). Howev...

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    Conflict of Interest:
    None declared.
  • Published on:
    Confounding by indication suggests another conclusion
    • Vivien K Burt, Professor Emeritus of Psychiatry, Geffen School of Medicine at UCLA University of California at Los Angeles
    • Other Contributors:
      • Sonya Rasminsky, Visiting Associate Professor of Psychiatry
      • Chittaranjan Andrade, Professor and Head, Department of Psychopharmacology

    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...

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    Conflict of Interest:
    Dr. Burt is a consultant, advisor or speaker for Sunovion, Takeda, Lundbeck and Otsuka. Dr. Andrade authors and receives authorship payments for a Critical Readings book series, published by MicroLabs and receives payments for developing educational materials of scientific initiatives such as the Behavioral and Neuroscience Academy of India and the Asian Society for Continuing Medical Education. Dr. Andrade was recently Principal Investigator for a multicenter, self-initiated, MDD-1 India study on antidepressant outcomes in first-episode depressed patients, which received logistic support from Cipla at recruiting sites; neither Dr. Andrade nor other investigators benefited financially from this study. Dr. Rasminksy reports no financial relationships with commercial interests.
  • Published on:
    High rate of malformation in cohort

    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.

    Conflict of Interest:
    None declared.