Increased first-trimester CA125 levels associated with the development of preeclampsia

Preeclampsia (PE) remains a leading cause of maternal and fetal mortality, necessitating reliable first-trimester biomarkers for early identification and pathogenesis elucidation. This study aimed to evaluate the predictive performance of first-trimester serum CA125 for the PE development and to examine their longitudinal associations with blood pressure trajectories during pregnancy.

A nested case-control study was conducted within the prospective BiCoS cohort, including 70 PE cases and 70 matched controls. Serum CA125 levels were measured at 12.26 ± 0.44 weeks of gestation and compared using independent t-tests. Logistic regression models were built to assess the predictive performance of CA125 alone, clinical factors, and their combination. Model discrimination was evaluated by the area under the receiver operating characteristic curve (AUC), with internal validation via bootstrapping. Associations between CA125 and clinical parameters, including hepatic and renal function profiles, platelet counts, blood lipid levels and blood pressure, were examined using Pearson correlation analysis. Linear mixed-effects models were used to analyze the association between first-trimester CA125 and subsequent longitudinal blood pressure changes.

First-trimester serum CA125 levels were significantly elevated in the PE group compared to controls (25.44 ± 14.89 vs. 16.17 ± 9.61 U/mL, P < 0.0001), with particularly high levels observed in PE cases complicated by fetal growth restriction (34.94 ± 22.93 vs. 23.27 ± 11.61 U/mL, P = 0.010). Multivariable analysis confirmed that CA125 remained an independent predictor of PE after adjusting for clinical factors (adjusted OR 1.071, 95% CI 1.027-1.118, P < 0.001), along with parity and MAP. The combined model (CA125 + clinical factors) achieved superior discriminatory power (AUC 0.841, 95% CI 0.776-0.906) compared to the model with clinical factors (AUC 0.799), and demonstrated robustness upon internal validation (optimism-corrected AUC = 0.817). Cross-sectional correlation analysis revealed no significant associations between CA125 and a comprehensive panel of first-trimester hepatic, renal, metabolic, hematologic, or blood pressure parameters. Crucially, longitudinal mixed-effects models showed that higher first-trimester CA125 levels were significantly associated with steeper increases in both systolic blood pressure (interaction P = 0.015) and diastolic blood pressure (interaction P = 0.009) throughout gestation. The inclusion of CA125 significantly improved model fit for both SBP (χ² = 7.807, P = 0.005) and DBP (χ² = 7.024, P = 0.008), with interaction models demonstrating the best fit.

First-trimester serum CA125 serves as a robust and independent predictor of preeclampsia. Its integration with established clinical risk factors significantly improves predictive accuracy, facilitating early identification of of PE. The specific association of CA125 with accelerated blood pressure trajectories through gestation suggests its role as an early sentinel of aberrant placental-vascular pathophysiology. These findings position CA125 as a promising and practical biomarker for enhancing early risk stratification.