Early-pregnancy HDL-related inflammatory indices and risk of preeclampsia: A retrospective cohort study

Abstract

Background Preeclampsia (PE) is closely associated with dyslipidemia and inflammatory imbalance. High-density lipoprotein (HDL)-related inflammatory indices have demonstrated predictive potential in cardiovascular and metabolic diseases, but evidence regarding their role in PE remains limited. Objective This study aimed to investigate the associations between early-pregnancy HDL-related inflammatory indices, including the lymphocyte-to-HDL ratio (LHR), monocyte-to-HDL ratio (MHR), neutrophil-to-HDL ratio (NHR), and platelet-to-HDL ratio (PHR), and the risk of PE. Methods A total of 5,959 women with singleton pregnancies were retrospectively included. All participants underwent complete blood counts (CBC) and lipid profiling at 11–13 weeks of gestation, from which HDL-related inflammatory indices were calculated. Associations between these indices and PE risk were systematically evaluated using modified Poisson regression, restricted cubic splines (RCS), subgroup analyses, and sensitivity analyses. To assess their potential clinical utility, prediction models incorporating HDL-related inflammatory indices were developed and evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results Among 5,959 participants, 124 (2.08%) developed PE. Multivariable-adjusted analyses revealed that higher levels of LHR (RR = 1.99, 95% CI: 1.17–3.42, P  = 0.012), MHR (RR = 2.62, 95% CI: 1.58–4.35, P  < 0.001), NHR (RR = 2.87, 95% CI: 1.64–5.02, P  < 0.001), and PHR (RR = 2.57, 95% CI: 1.48–4.48, P  < 0.001) were significantly associated with increased PE risk. Quartile analyses demonstrated a dose-response relationship across categories ( P for trend < 0.05). RCS revealed U-shaped associations for LHR ( P  = 0.008) and NHR ( P  = 0.048), which became approximately linear after excluding extreme values. Subgroup analyses suggested stronger associations in women with gestational diabetes mellitus (GDM), advanced maternal age, or higher BMI, indicating potential effect modification. Sensitivity analyses confirmed the consistency of these associations. Incorporation of these indices modestly improved model discrimination (AUC 0.697) and provided limited clinical benefit in DCA. Conclusions Early-pregnancy HDL-related inflammatory indices, particularly MHR, NHR, and PHR, are significantly associated with increased PE risk. These indices reflect both lipid metabolism and inflammatory status, offering simple, accessible biomarkers for early risk stratification and potential supplementation of existing PE prediction strategies.