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-1α, 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-1α, 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.