Peripartum Magnesium Sulfate and Post-Delivery Depression: A Nationwide Cohort Study With 13-Year Follow-Up

OBJECTIVE: Although its potential antidepressant effects have been suggested, evidence on long-term outcomes for post-delivery depression remains limited. We evaluated whether peripartum intravenous magnesium sulfate (MgSO₄) is associated with a reduced risk of postpartum depression (PPD) within 12 months and its long-term trajectory over 13 years. METHODS: This nationwide retrospective cohort study included all women in South Korea who delivered between 2010 and 2014, excluding those with prior depression. Exposure was defined as intravenous MgSO₄ administration during delivery hospitalization. Propensity score (PS) matching (1:5) was used to balance baseline characteristics. We employed Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for both 12-month PPD and long-term depression (up to 13 years). RESULTS: Among 1,583,253 eligible mothers, 9,756 (0.6%) received MgSO₄. In the PS-matched cohort (9,682 exposed; 35,140 unexposed), there was no significant association between MgSO₄ and the primary outcome of 12-month PPD (HR, 1.11; 95% CI, 0.97-1.26; p=0.114). Similarly, the risk of long-term post-delivery depression showed no significant difference (HR, 1.02; 95% CI, 0.97-1.07; p=0.388). These findings were consistent in the dose-response analysis for 12-month PPD (HR, 1.10 per 10 g increase; 95% CI, 0.96- 1.24; p=0.144) and in subgroup analyses stratified by preeclampsia status. CONCLUSION: Peripartum MgSO₄ exposure was not associated with a reduced risk of either 12-month PPD or long-term post-delivery depression. Despite its biological plausibility, routine obstetric use of MgSO₄ does not appear to confer preventive mental health benefits for mothers in the general obstetric population.