Association of First-Trimester Maternal Biomarkers with Preeclampsia and Related Maternal and Fetal Severe Adverse Events.

To assess the association between known (PlGF, sFlt-1, betaHCG, PAPPA) and novel (cell-free DNA, cfDNA, and total endothelial and platelet microvesicles, MVs) maternal blood biomarkers measured at the first trimester with the later development of preeclampsia (PE) and PE-related severe adverse events (SAE), we conducted a retrospective case-control study including women with an established diagnosis of preeclampsia (cases) and healthy pregnant women (controls). Biomarkers were measured from first-trimester blood samples stored in a hospital biobank. 89 women, 54 women with PE and 35 controls were included. PlGF showed good performance for diagnosing overall preeclampsia (AUC: 0.71; 95% CI 0.59-0.82), early-onset preeclampsia (AUC 0.80; 95% CI 0.68-0.9) and fetal-neonatal SAEs (AUC: 0.73; 95% CI 0.63-0.84). Multivariate models including clinical variables, PlGF and other biomarkers showed good to very good discrimination for the development of PE, early-onset PE and fetal-neonatal SAEs (AUCs of 0.87, 0.89 and 0.79, respectively). Platelet-derived MVs were the best isolated biomarker for late-onset PE and, combined with systolic blood pressure, showed good discrimination (AUC: 0.81; 95% CI 0.71-0.92). For maternal SAEs, a model incorporating cfDNA and sFlt-1 provided excellent discrimination (AUC 0.92; 95% CI 0.82-1.00). Our findings suggest that multivariate models incorporating both clinical variables and first-trimester biomarkers may improve risk stratification for PE, especially for late-onset PE and for identifying women at risk of severe maternal or fetal complications. Notably, the inclusion of novel biomarkers such as cfDNA and MVs added value in clinical scenarios where the predictive performance of existing tools remains suboptimal.