Abstract
BACKGROUND: The relationship between antidepressants, depression, and the incidence of postpartum hemorrhage (PPH) has been reported in observational studies, but the causal link between these factors remains unknown. Clarifying this relationship is important for treating depression during pregnancy and managing PPH. OBJECTIVE: We aimed to assess the causal relationship between antidepressants, depression, and PPH using a two-sample Mendelian randomization method. METHODS: Single nucleotide polymorphisms were identified from publicly available genetics summary databases (FinnGen database, access date: 28 December, 2023, version R9, phenocode: ANTIDEPRESSANTS, 195,321 participants; the genome-wide association studies [GWAS] catalog, access date: 3 April, 2024, GWAS ID: ebi-a-GCST90016607; Integrative Epidemiological Unit database, access date: 3 April, 2024, GWAS ID: ieu-a-1187) as alternative exposure factors for antidepressants and depression. Subsequently, inverse variance weighting, Mendelian randomization-Egger regression, weighted median, simple method, and weighted method were employed for Mendelian randomization analyses, and the results were validated for pleiotropy, heterogeneity, and sensitivity. RESULTS: The analyses employed three sets of genetic tools, comprising two sets of 9 and 32 single nucleotide polymorphisms that are strongly associated with depression and another set of 26 single nucleotide polymorphisms that are associated with antidepressants. The inverse variance weighting indicated that antidepressants are associated with PPH (odds ratio = 1.36, 95% confidence interval 1.10-1.69, p = 0.005). Conversely, none of the five methods of Mendelian randomization analysis identified an effect of depression on PPH. CONCLUSIONS: This Mendelian randomization analysis indicated that antidepressant use is associated with PPH. However, the evidence does not support a causal relationship between depression and PPH.