U-shaped Association of Third-trimester Serum Uric Acid with Postpartum Hemorrhage: Statistical Mediation Effects of Hemoglobin, Fibrinogen, and D-dimer-A Multicenter Cohort Study.

Serum uric acid, a key metabolic marker, has been linked to pregnancy complications, yet its association with postpartum hemorrhage (PPH)-especially non-linear relationships and underlying mechanisms-remains uninvestigated.We conducted a multicentre cohort study (pregnant women) and nested case-control study (1:2 matching) in China (2017-2024). Third-trimester serum uric acid was measured. PPH was defined per World Health Organization criteria (≥500 mL vaginal/≥1000 mL cesarean blood loss). Logistic regression, restricted cubic spline (RCS) analysis, mediation analysis, and predictive model evaluation were performed.In the cohort, serum uric acid was stratified into quintiles (Q1:<251.0, Q2:251.0-289.6, Q3:289.7-327.0 [reference], Q4:327.1-377.9, Q5:≥378.0 μmol/L). Adjusted for confounders, Q1 (odds ratio [OR]=1.56, 1.18-2.08) and Q5 (OR=1.38, 1.03-1.85) had higher PPH risk vs. Q3. RCS revealed a significant U-shaped association (Pnon-linearity=0.0038) with inflection point at 281.4 (244.70-318.10) μmol/L-validated in nested case-control (n=1,551) and sensitivity analyses (excluding pre-enrolment hyperuricemia). Stratified analyses showed the U-shape was confined to non-GDM and non-preeclampsia subgroups. Mediation analysis demonstrated low serum uric acid (<281.4 μmol/L) was statistically associated with increased PPH risk via hemoglobin (16.75% statistical mediation effect) and fibrinogen (7.87%); high serum uric acid (≥281.4 μmol/L) showed a statistical association with PPH risk via D-dimer (13.60%). An extended PPH predictive model (traditional variables + uric acid + hemoglobin + fibrinogen + D-dimer) had higher area under the receiver operating characteristic curve (0.739 vs. 0.702) and net benefit (0-20% risk threshold) vs. traditional models.Third-trimester serum uric acid exhibits a U-shaped association with PPH risk in Chinese pregnant women (inflection point:281.4 μmol/L), confined to non-GDM/non-preeclampsia subgroups; these associations are supported by statistical mediation effects of hemoglobin, fibrinogen, and D-dimer.