ORAI1, FGF23, PP13, Palladin, and Supervillin as Potential Biomarkers in Late-Onset Pre- eclampsia: A Comparative Study in Maternal and Cord Blood Running Title: Potential Biomarkers in Late-Onset Pre-eclampsia

Background Pre-eclampsia continues to be a significant global health burden with complex pathophysiology, necessitating investigation of novel biomarkers to improve understanding, diagnosis and management of this pregnancy-specific disorder.To investigate the differential expression of Calcium Release-Activated Calcium Channel Protein 1 (ORAI1), Fibroblast Growth Factor 23 (FGF23), Placental Protein 13 (PP13), Palladin, and Supervillin in both maternal and umbilical cord blood as potential biomarkers for late-onset pre-eclampsia. Methods This cross-sectional, case-control study included 61 women with late-onset pre-eclampsia and 61 normotensive pregnant women undergoing cesarean delivery. Maternal blood samples were collected immediately prior to cesarean delivery, and umbilical cord blood was obtained immediately after delivery of the placenta. Protein concentrations in both circulatory compartments were measured using enzyme-linked immunosorbent assay. The unique study design with paired maternal-cord blood sampling provided insights into maternal-fetal protein transfer dynamics in pre-eclamptic conditions. Results Maternal and cord blood ORAI1 concentrations were significantly elevated in pre-eclampsia (p = 0.001 and p = 0.035, respectively), while FGF23 and PP13 were significantly decreased in maternal blood (p = 0.022 and p = 0.018, respectively). Maternal-to-cord blood concentration ratios for ORAI1 and FGF23 were significantly altered in pre-eclampsia (p = 0.038 and p = 0.021, respectively). ORAI1 showed the highest diagnostic accuracy (AUC = 0.733) and correlated positively with disease severity and negatively with birth weight. Combined ORAI1 and FGF23 assessment significantly enhanced diagnostic performance (AUC = 0.782). Conclusion The altered expression of ORAI1, FGF23, and PP13 in late-onset pre-eclampsia suggests disruptions in calcium signaling, phosphate metabolism, and placental function. The parallel measurement of these proteins in both maternal and cord blood provided unique insights into maternal-fetal interface dysfunction in pre-eclampsia. The superior performance of combined ORAI1 and FGF23 measurement underscores the value of a multi-marker approach in capturing pre-eclampsia's complex pathophysiology, potentially contributing to improved diagnostic strategies and therapeutic interventions.