The role of prenatal exposure to antidepressants, anxiolytic, and hypnotics and its underlying illness on the risk of miscarriage using <scp>BIFAP</scp> database

Purpose: Despite the notable increase on the prescription of antidepressants and anxiolytics during pregnancy, recommendation on maintaining the treatment during prenatal period is still controversial. We aimed to separately assess the role of effects of the antidepressants and anxiolytic and the underlying illness, controlled by potential confounding associated with miscarriage onset. Methods: We used data from a validated pregnant cohort aged 15–49 years from 2002 to 2016 using BIFAP database. All confirmed miscarriages were used to perform a nested control analysis using conditional logistic regression. Women were classified according to use of each drug of interest into four mutually exclusive groups: nonusers, users only during prepregnancy, continuers, and initiators during first trimester. Adjusted odds ratios (aORs) for major confounders during pregnancy such as number of visits to primary care practitioners visits, obesity, smoking, HTA, diabetes with 95% confidence intervals were calculated. Results: Compared with nonusers, antidepressants continuers had the highest increased risk of miscarriage aOR (95%) of 1.29 (1.13–1.46), being continuers of paroxetine and fluoxetine the antidepressants with the strongest association. Likewise, continuers of anxiolytics and initiators showed an increased risk of 1.19 (1.04–1.37) and 1.30 (1.13–1.50). When separating the effect between the condition itself or the treatment, women exposed during first trimester, regardless treatment duration and/or the underlying illness, had the highest risk 1.27 (1.08–1.51) for antidepressants and 1.25 (1.13–1.39) for anxiolytics. Conclusions: Our analysis showed an association between prenatal exposure to antidepressants and anxiolytics and miscarriage onset after controlling by potential confounding adjusting for confounders and the underlying illness. This association was not supported for hypnotic medications. Further studies are warranted to evaluate the risk of miscarriage among subpopulation of pregnant women requiring these medications.