Plasma E-selectin and kallistatin as predictive markers of histologic chorioamnionitis in women with preterm premature rupture of membranes

Problem We aimed to assess the predictive potential of 12 plasma biomarkers to predict acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM) and to develop multi-biomarker panels based on these biomarkers in combination with widely used conventional laboratory markers. Method of study This was a retrospective cohort study involving 81 singleton pregnant women (24-34 weeks of gestation) who delivered within 96 h of blood sampling. White blood cell (WBC) count, differential counts, and C-reactive protein (CRP) levels were measured at admission. The levels of DKK-3, Fas, haptoglobin, IGFBP-2, kallistatin, MIP-1 alpha, MMP-2, MMP-8, pentraxin 3, progranulin, E-selectin, and P-selectin were evaluated by ELISA using stored plasma samples. The primary outcome measure was acute HCA. Results Multivariate analyses showed that low plasma E-selectin and kallistatin levels were independently associated with HCA occurrence after adjusting for gestational age. Using a stepwise regression analysis, a multi-biomarker panel comprising plasma E-selectin, serum CRP, and WBC was developed, which provided a good prediction of acute HCA in women with PPROM (area under the curve [AUC], 0.899), with a significantly higher AUC than that of any single variable included in the panel (P < 0.05). The plasma levels of DKK-3, Fas, haptoglobin, IGFBP-2, MIP-1 alpha, MMP-2, MMP-8, pentraxin 3, and P-selectin were not significantly associated with HCA occurrence. Conclusions This study identified E-selectin and kallistatin as potential plasma biomarkers associated with acute HCA in women with PPROM. Their combined analysis with serum CRP and WBC counts significantly improved acute HCA diagnosis.