Prediction of spontaneous preterm birth in women with cervical insufficiency: Comprehensive analysis of multiple proteins in amniotic fluid

AimThe purpose of this study is to determine whether proinflammatory cytokines and matrix metalloproteinases (MMPs) in amniotic fluid (AF), alone or in combination with clinical risk factors, can predict spontaneous preterm delivery (SPTD) at < 34 weeks in women with cervical insufficiency. MethodsThis retrospective cohort study included 57 consecutive singleton pregnant women (17-28 gestational weeks) with cervical insufficiency who underwent amniocentesis. AF was assayed for five cytokines (interleukin [IL]-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1, and MIP-1) and five MMPs (MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9) using multiplex immunoassay kits. The primary outcome measure was SPTD at < 34 weeks. ResultsThe AF concentrations of MMP-1, MMP-3, MMP-8, MMP-9, IL-6, IL-8, MIP-1 and MIP-1 were significantly higher in women with SPTD at < 34 weeks. Women who had SPTD at < 34 weeks were younger, had significantly more advanced cervical dilatation at presentation and a higher rate of positive AF cultures. Using stepwise regression analysis, a combined prediction model was developed that included maternal age, cervical dilatation at presentation, AF MMP-1 and AF MMP-8 (area under the curve [AUC] 0.951). The AUC for this model was significantly greater than for any single protein alone in AF or for each of the clinical risk factors alone. ConclusionA model combining proteins in AF and clinical factors can improve the accuracy of risk prediction for preterm birth and this combination is more accurate than each of the biomarkers alone in women with cervical insufficiency.