Systemic inflammation indices generated from first-trimester blood tests can be potential biomarkers for predicting preeclampsia

Journal of Human Hypertension ARTICLE www.nature.com/jhh OPEN Systemic inflammation indices generated from first-trimester blood tests can be potential biomarkers for predicting preeclampsia Yu Chen1,3, Jingyang Li1,3, Xiaoshuang Li1, Yihui Pan1, Ying Li1, Ying Gu1 ✉ and Qi Chen 2✉ 1234567890();,: © The Author(s) 2026 Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality, affecting 3 to 8% of pregnancies. Currently, no clinically useful predictive biomarker exists. Preeclampsia is characterised by systemic inflammatory responses that may be triggered by placental materials released into the maternal circulation, leading to an overly active maternal immune system. Recently, systemic inflammation indices have been used as indicators of inflammation in various diseases. Here, we investigated whether systemic inflammation indices derived from peripheral blood tests in the first trimester could serve as potential predictors of preeclampsia. Blood samples, ranging from 6 to 12 weeks, were collected from 109 women who later developed preeclampsia and 177 women who did not develop any complications. The counts of white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets were obtained, and systemic inflammation indices, including the systemic immune inflammation index (SII), the systemic inflammation response index (SIRI), the neutrophil-to-lymphocyte ratio (NLR), and the panimmune inflammation value (PIV), were calculated. Significantly higher counts of white blood cells, neutrophils, lymphocytes, and monocytes, but not eosinophils and basophils, were observed in women who later developed preeclampsia (p < 0.001). Additionally, all four indices were significantly elevated in women who later developed preeclampsia (p < 0.001). The increased indices were primarily associated with late-onset preeclampsia. No significant differences in these indices were observed between women who developed preeclampsia with or without severe features. Our study demonstrates that systemic inflammation indices derived from first-trimester blood tests may serve as additional predictors for preeclampsia when combined with other reported biomarkers. Journal of Human Hypertension; https://doi.org/10.1038/s41371-026-01169-y INTRODUCTION Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality worldwide, affecting 3 to 8% of all pregnancies [1]. Although the pathogenesis is not fully understood, placental hypoxia, placental inflammation, oxidative stress and metabolic dysfunctions are associated with the development of preeclampsia [2–4]. Despite its clinical significance, no reliable predictive biomarkers exist for early detection. The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is used as a potential predictive biomarker [5]. Preeclampsia is characterised by a systemic inflammatory response that may be potentially triggered by placental materials, such as placental extracellular vesicles (EVs) released into the maternal circulation, leading to excessive maternal immune activation [6]. Recently, systemic inflammation indices have been explored as early biomarkers in various diseases and clinical conditions, including pregnancy complications [7], as early biomarkers for inflammation-associated diseases [8, 9]. These systemic inflammation indices include the systemic immune inflammation index (SII), the systemic inflammation response index (SIRI), the neutrophil- to-lymphocyte ratio (NLR), and the pan-immune inflammation value (PIV). While lower counts of platelets are commonly observed in preeclampsia at the time of diagnosis (review in [10]), in the current literature, studies on systemic immune inflammation indices as predictive markers for preeclampsia remain inconclusive, potentially due to variations in sample size and sampling time [11–14]. Some studies indicated that a lower SII in the first trimester correlated with an increased risk of developing preeclampsia, but those studies were limited by their small sample sizes and incomplete data [15, 16]. Conversely, another study reported that increased SIRI and PIV, but not SII and NLR, measured in the first trimester, may serve as potential predictive markers for preeclampsia [17]. Preeclampsia is clinically classified into early-onset and lateonset forms with distinct underlying mechanisms. It has been known that the early-onset form is primarily associated with placental dysfunction resulting from defective placentation. On the other hand, the late-onset form is more associated with maternal factors, such as maternal metabolic dysfunction, suggesting relatively normal placental development. Additionally, 1 Department of Obstetrics, Wuxi Maternity and Child Health Care Hospital, Affiliated to Jiangnan University, Wuxi, China. 2Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand. 3These authors contributed equally: Yu Chen, Jingyang Li. ✉email: ; Received: 20 January 2026 Revised: 20 May 2026 Accepted: 29 May 2026 Y. Chen et al. 2 preeclampsia is also categorized into preeclampsia with or without severe features (formerly severe or mild preeclampsia) [18]. Preeclampsia with severe features is more strongly related to placental dysfunction, while preeclampsia without severe features is often driven by maternal factors (reviewed in [1]). Systemic immune inflammation indices are currently being investigated for predicting preeclampsia, as they can be obtained from a routine, non-invasive, and cost-effective blood test. However, no study has comprehensively evaluated their role in predicting preeclampsia in the first trimester while accounting for disease severity. Therefore, in this retrospective study with a relatively large sample size, we investigated whether systemic immune inflammation indices generated from peripheral blood tests in the first trimester could serve as potential predictive biomarkers for predicting preeclampsia. METHODS AND MATERIALS This retrospective study received approval from the Ethical Committee of Wuxi Maternity and Child Health Care Hospital, Jiangnan University, Wuxi, China (approval numbers:2024-06-1024-54). The Ethical Committee waived the patient’s consent form due to the data collected from the hospital database. This study was performed in accordance with the Medical Association Declaration of Helsinki. Study cohort In this retrospective study, women diagnosed with preeclampsia were identified in our hospital databases from January 2022 to December 2023. After excluding those who developed chronic hypertension (before 20 weeks of gestation), or had a history of chronic hypertension, or had a history of preeclampsia, or were conceived by in vitro fertilisation (IVF), a total of 109 pregnant women were included. Additionally, 177 pregnant women who did not develop any maternal or neonatal complications until delivery were includ (...truncated)