Risk of vaginal bleeding after use of antidepressants in pregnancy: a study from the Norwegian Mother and Child Cohort Study

Introduction: Recent studies have suggested selective serotonin reuptake inhibitors (SSRIs) to be implicated in bleeding related outcomes from the gastrointestinal tract (GI), however little is known about bleeding outcomes from sites other than the GI tract, especially the gynecological system. Because vaginal bleeding during early and mid pregnancy is a marker of an at-risk pregnancy, we aimed to investigate the putative association between such outcomes and exposure to SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) during pregnancy. Methods: Three questionnaires (at gestational weeks 17 and 30, and six months after delivery) from the Norwegian Mother and Child Cohort Study (MoBa) and individual records in the Medical Birth Registry of Norway (MBRN) provided information about exposure to antidepressants, vaginal bleeding outcomes, mental health at two time points in pregnancy (gestational week 17 and 30) and maternal characteristics. Exposure was categorized according to use of SSRIs and/or SNRIs, with inclusion of a disease comparison group comprising women with persistent depressive symptoms at both gestational week 17 and 30 but not medicated. Multivariate logistic regression analysis was used to estimate the impact of exposure to antidepressants on adverse bleeding outcomes as crude and adjusted odds ratios with 95% confidence intervals. Results: The study population comprised 57,279 women. Of these, 1.0% reported use of SSRIs/SNRIs during pregnancy. Use of SSRIs/SNRIs during the first trimester was not associated with an increased risk of vaginal bleeding in early pregnancy of any kind (aOR:0.91, 95% CI:0.72-1.16), neither as trace of blood, blood loss in medium amounts or clots, nor bleeding more than once. Women in the disease comparison group were associated with a significant 32% increased risk of bleeding in medium amount or clots, 33% increased risk for recurrent bleeding episodes in early pregnancy, and bled significantly longer (in days) than the non-exposed. This very same group of women presented a moderate risk of vaginal bleeding even in mid pregnancy. Conclusions: The findings of the present study are reassuring: use of SSRIs/SNRIs during first and second trimesters is not associated with any increased risk of vaginal bleeding during pregnancy. On the contrary, women with persistent depressive symptoms during pregnancy but not medicated presented a 32-33% increased risk of vaginal blood loss in early as well as in mid pregnancy. The higher rates of vaginal bleeding among these women could be recognized as a sign of missed or threatened abortion. Nonetheless, depressed non-medicated women may present higher level of anxiety and stress, potentially leading to different health behaviors and different accuracy and attitudes in reporting.