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Association of first trimester peripheral blood count-derived immune markers with the risk of incident hypertensive disorders of pregnancy: a retrospective cohort study

Hypertension Research (2026)Cite this article

Abstract

Emerging evidence links maternal immune dysregulation to hypertensive disorders of pregnancy (HDP), yet gestational immune alterations preceding symptom onset remain unclear. This study aimed to evaluate the associations between first-trimester immune biomarkers and incident HDP risk across clinical subtypes. This retrospective cohort study enrolled pregnant women aged ≥18 years undergoing first-trimester antenatal screening at a tertiary hospital from March to November 2023. First-trimester peripheral immune markers—neutrophils, monocytes, lymphocytes, and platelets—were measured, with derived indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI). Outcomes included HDP, gestational hypertension (GHTN), and preeclampsia confirmed via electronic medical records. Multivariable logistic regression models were performed to evaluate the relationship between peripheral immune markers and outcomes. Among the 2739 pregnant women who met inclusion criteria, 195 developed HDP, including 96 GHTN and 99 preeclampsia. Multivariable logistic regression demonstrated that first-trimester neutrophils, monocytes, platelets, lymphocytes, SII, and AISI were independently and positively associated with HDP risk in a linear dose-response manner (all FDR P < 0.05), with platelets exhibiting the strongest association (OR T3 vs. T1: 2.20; per log-SD: OR = 1.55). Distinct biomarker profiles were identified between GHTN and preeclampsia: GHTN exhibited associations with neutrophils, platelets, SII, and AISI, while preeclampsia correlated with monocytes, platelets, lymphocytes, SII, and AISI (all FDR P < 0.05). Elevated first-trimester immune markers correlate with HDP, particularly platelet-related indices. Divergent immune signatures between GHTN and preeclampsia suggest subtype-specific pathophysiological mechanisms.

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Some or all datasets generated during or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

We extend our gratitude to all the pregnant women who participated in this study. Additionally, we sincerely thank the clinicians at Qingdao Women and Children’s Hospital, affiliated with Qingdao University, for their invaluable contributions in collecting samples and performing laboratory tests.

Funding

This work was supported by a grant from the Municipal Key Clinical Specialty Programs of Qingdao.

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, China

    Xiangjie Kong, Bing Hao, Yutong Jiao, Jingyi Wang, Yili Wu & Shan Kang

  2. Clinical laboratory, Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, China

    Zhenxiu Guo, Jianhong Dong & Shan Kang

  3. Department of Laboratory Medicine, Peking University People’s Hospital, Qingdao, China

    Zhenxiu Guo

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  1. Xiangjie Kong
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  2. Zhenxiu Guo
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Contributions

Conceptualization: Y-LW and X-JK; Data curation: Z-XG and J-HD; Formal analysis: BH and Y-TJ; Project administration: X-JK; Supervision: J-YW; Validation: SK; Roles/Writing—original draft: X-JK and SK; Writing—review & editing: All authors.

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Correspondence to Shan Kang.

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Kong, X., Guo, Z., Dong, J. et al. Association of first trimester peripheral blood count-derived immune markers with the risk of incident hypertensive disorders of pregnancy: a retrospective cohort study. Hypertens Res (2026). https://doi.org/10.1038/s41440-026-02571-2

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