Abstract
Little is known about the biomarkers that can identify patient candidates suitable for rescue cerclage procedure. The purpose of the study was to identify novel biomarkers in amniotic fluid (AF) that can predict the outcome of rescue cerclage in patients with cervical insufficiency by using an antibody microarray. This case–control study was conducted using AF samples collected from singleton pregnant women who underwent rescue cerclage following a diagnosis of cervical insufficiency (19–25 weeks). Patients were divided into case (n=20) and control (n=20) groups based on the occurrence of spontaneous preterm delivery (SPTD) at <34 weeks of gestation after cerclage placement. The AF proteomes were analyzed using an antibody microarray for biomarker discovery work. Ten candidate biomarkers of interest were validated by enzyme-linked immunosorbent assay (ELISA). Thirty-one molecules studied showed significant intergroup differences (≥two-fold change in signal intensity). Validation by ELISA confirmed significantly higher levels of a proliferation-inducing ligand (APRIL), S100 calcium-binding protein A8/A9 complex (S100 A8/A9), tissue inhibitors of metalloproteinase-1 (TIMP-1), macrophage inflammatory protein-1α (MIP-1α), and interleukin-8 (IL-8) in women who had SPTD at <34 weeks. Of these, AF S100 A8/A9 and TIMP-1 levels were independent of other potentially confounding factors (e.g., cervical dilatation). S100 A8/A9 had the highest area under the curve (AUC) at 0.857. Using protein–antibody microarray technology, we identified differentially expressed proteins (DEPs) and several novel biomarkers (APRIL, IL-8, MIP-1α, S100 A8/A9, and TIMP-1) in AF from women who had SPTB at <34 weeks after cerclage for cervical insufficiency. These data can provide an insight into the molecular mechanisms underlying SPTD after rescue cerclage in patients with cervical insufficiency.
Highlights
Acute cervical insufficiency is defined as painless cervical dilatation in the second trimester and occurs at an incidence of 4.6 per 1000 births [1,2]
These studies have restricted their analysis to specific target markers that are generated in response to inflammation or infection, thereby highlighting the need to explore all factors underlying mechanisms of spontaneous preterm delivery (SPTD) occurring after cerclage placement in cervical insufficiency
The purpose of the study was to identify novel biomarkers in amniotic fluid (AF) using an antibody microarray that can predict the outcome of rescue cerclage in patients with cervical insufficiency
Summary
Acute cervical insufficiency is defined as painless cervical dilatation in the second trimester and occurs at an incidence of 4.6 per 1000 births [1,2]. The clinical utility of these biomarkers remains limited with respect to prognostic assessment and treatment guidance because (i) their diagnostic sensitivity, specificity, and cut-off values have not been determined, and (ii) it is uncertain whether they are affected by confounding factors such as cervical dilation [5,6,8]. These studies have restricted their analysis to specific target markers that are generated in response to inflammation or infection, thereby highlighting the need to explore all factors underlying mechanisms of SPTD occurring after cerclage placement in cervical insufficiency. This has prompted us to screen for novel additional biomarkers in studies with larger sample sizes to further refine prediction of the outcome of rescue cerclage for cervical insufficiency
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