Inflammation-related immune proteins in maternal plasma as potential predictive biomarkers for rescue cerclage outcome in women with cervical insufficiency

Abstract

Problem: This study aimed to determine whether various novel plasma mediators of immune regulation associated with inflammation could independently predict the clinical outcome of rescue cerclage in patients with cervical insufficiency (CI).

Method of study: A total of 41 singleton pregnant women (17-25 weeks) who underwent rescue cerclage for CI were retrospectively evaluated. Stored plasma samples were assayed for IGFBP-1, -2, -3, IL-6, latexin, LBP, lipocalin-2, M-CSF, MIP-1α, MMP-8, -9, pentraxin 3, resistin, S100A8, S100A8/A9, thrombospondin-2, TIMP-1, and TNFR2 levels. The primary outcome measures were spontaneous preterm birth (SPTB) at < 28 and < 34 weeks after cerclage placement.

Results: Multivariate Firth's logistic regression analysis revealed that high levels of IGFBP-3 and S100A8/A9, and low levels of MIP-1α were significantly associated with SPTB at < 28 weeks after cerclage placement, whereas only low MIP-1α levels were significantly associated with SPTB at < 34 weeks, even after adjustment for baseline clinical covariates (e.g., cervical dilatation). For the prediction of SPTB at < 28 weeks, the area under the curves (AUC) of IGFBP-3, MIP-1α, and S100A8/A9 were of .686, .691, and .693, respectively. Similarly, the AUC of MIP-1 α was of .659 to predict SPTB at < 34 weeks.

Conclusions: These findings suggest that plasma IGFBP-3, MIP-1α, and S100A8/A9 can represent noninvasive independent biomarkers for identifying women with CI at high risk for SPTB following rescue cerclage. Nonetheless, further in large, multicenter clinical studies should be performed to confirm the clinical value of these biomarkers.

Keywords: biomarkers; cervical insufficiency; plasma; rescue cerclage; spontaneous preterm birth.