Background: Observational studies have presented inconsistent findings on the association between gestational diabetes mellitus, gestational hypertension, and postpartum depression. This study used Mendelian randomization to examine the potential causal relationship between gestational diabetes mellitus, gestational hypertension, and postpartum depression. Methods: We obtained data from genome-wide association study databases. Single nucleotide polymorphisms associated with gestational diabetes mellitus (5,687 cases; 117,892 controls), gestational hypertension (7,686 cases; 115,893 controls), and postpartum depression (7,604 cases; 59,601 controls) were analyzed. Various Mendelian randomization methods were applied, including inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode. Sensitivity analyses such as the MR-Egger intercept test, funnel plot, MR-PRESSO analysis, Cochran’s Q test, and leave-one-out tests confirmed the robustness of our findings. The MR-Steiger test was applied to verify the causal direction from exposure to outcome. Results: Genetically predicted gestational diabetes mellitus was significantly associated with increased postpartum depression risk (IVW OR = 1.09; 95% CI: 1.03-1.14; p = 1.24×10−3), as was gestational hypertension (IVW OR = 1.08; 95% CI: 1.01-1.15; p = 0.01). Multiple sensitivity analyses further reinforced the validity of these findings. Multivariable Mendelian randomization adjusting for gestational hypertension confirmed the independent effect of gestational diabetes mellitus on postpartum depression and vice versa for gestational hypertension. Conclusion: Both gestational diabetes mellitus and gestational hypertension increase the incidence of postpartum depression. By focusing on interventions to manage these prenatal conditions, nursing professionals can play a crucial role in potentially reducing the incidence of postpartum depression.

The authors have declared no competing interest.

The author(s) received no specific funding for this work.

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