Antidepressants and fetal death: A systematic review and disproportionality analysis in the WHO safety database (VigiBaseⓇ)

•Exposure to ADs seems to be associated with fetal mortality.•This may exist more readily for exposure during the first trimester of pregnancy.•Citalopram, clomipramine and venlafaxine seem to be particularly involved.•Further research should investigate the safety of ADs during early pregnancy. Recent research suggests that fetal exposure to antidepressants (ADs) is significantly associated with fetal death, including stillbirth. However, there has been limited investigation into the timing of AD exposure during pregnancy, the specific effect of each drug, and the possibility of indication bias. To address these gaps in knowledge, we conducted a systematic review of literature and disproportionality analyses using the WHO Safety Database (VigiBaseⓇ). The systematic review provided evidence for increased risks of fetal death with exposure to any selective serotonin reuptake inhibitor (SSRI) at any time of pregnancy, stillbirth with exposure to any AD during the first trimester, and stillbirth with exposure to any SSRI during the first trimester. Disproportionality analyses revealed significant associations with citalopram, clomipramine, paroxetine, sertraline, and venlafaxine. Combining both sets of results, we conclude that exposure to ADs, especially during the first trimester of pregnancy, seems to be associated with fetal mortality, and that ADs with highest placental transfer may be particularly involved. Further research should investigate the links between ADs during early pregnancy and fetal mortality.