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Thromb Haemost
DOI: 10.1055/a-2788-3102
Original Article: New Technologies, Diagnostic Tools and Drugs

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

Authors

  • Qian Li

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China

  • Xiating Li

    3   Diagnostic Science Centre, Alberta Precision Laboratories, Calgary, AB, Canada

  • Wenqing Zhai

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China

  • Huafang Wang

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China

  • Jun Deng

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China

  • Zhipeng Cheng

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China

  • Fengjuan Fan

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China

  • Shi Chen

    4   Department of Biobank, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

  • De Li

    4   Department of Biobank, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

  • Liang V. Tang‡   ‡

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China
    5   Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China

  • Yu Hu‡   ‡

    1   Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    2   Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan, Hubei, China
    5   Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China

Funding Information This study is supported by the National Natural Science Foundation of China (No. 82103827, No. 82470134), the Young Elite Scientists Sponsorship Program by CAST (2023QNRC001), and Program of National Key Research and Development Project of China (No. 2022YFC2304600, No. 2023YFC2509500).
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Graphical Abstract

Abstract

Background

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.

Material and Methods

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.

Results

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.

Conclusion

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.

Keywords

fibrinogen - hemoglobin - postpartum hemorrhage - pregnant women - uric acid

Data Availability Statement

The de-identified datasets generated and analyzed during the current study are not publicly available due to ethical restrictions. Reasonable requests for access of data and code of the statistical analyses may be directed to the corresponding authors and will be considered following review and approval by the relevant ethical committee.


Ethical Approval

This study was approved by the ethics committee of Tongji Medical College affiliated with Huazhong University of Science and Technology (no.: [2015] S014). Informed consent was not required since the information was retrieved through the medical records retrospectively.


‡ These authors contributed equally to this article.


Supplementary Material



Publication History

Received: 24 November 2025

Accepted after revision: 13 January 2026

Article published online:
28 January 2026

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