43: Elevated mid-trimester maternal serum cytokines are associated with spontaneous preterm birth in women undergoing cerclage

Abstract

To examine the role of maternal serum inflammatory biomarkers in the mid-trimester in women undergoing cerclage and assess the differences in serum cytokines between women destined to deliver preterm versus those who deliver at term after cerclage placement. Prospective cohort study of singleton, non-anomalous pregnancies from 2016-2018 at a single tertiary institution who underwent a history-indicated, ultrasound-indicated (mid-trimester CL <25mm), or exam-indicated (asymptomatic cervical dilation) cerclage <24 weeks. Maternal blood was collected in the perioperative period. A custom magnetic bead Luminex cytokine assay was used to measure serum inflammatory cytokines (IL-1b, IL-6, IL-8, GCSF, MCP-1, TNF-a, MMP-8). Cytokine levels were compared between women with spontaneous preterm birth (SPTB) <37 weeks and those with term births. A statistical cut point was calculated for each cytokine to determine the optimal sensitivity and specificity of the cytokine in SPTB prediction. Women were classified as having a ‘high’ or ‘low’ result for each cytokine based on this cut point. Data were analyzed using t-test, chi2, Cox regression, and Kaplan-Meier curves. 42 women met inclusion criteria; 20 (47.6%) had SPTB and delivered at a median 29.6 (IQR 27.3-34.1) weeks. Samples were collected at a median of 0 (IQR -2 to 20) days after cerclage, at a median 17.6 (IQR 12.9-21.1) weeks’ gestation. Baseline characteristics were similar between SPTB and term births (Table). Maternal serum levels of IL-6, MCP-1, and MMP-8 were higher in women with SPTB (Table). Overall, 10 women (24%) had 0-1 high cytokine results, 15 (35%) had 2 or 3, and 17 (41%) had ³4 high cytokine results. A greater number of high inflammatory cytokines [Hazard Ratio (HR) 3.4, 95% CI 2.0-5.7)] and ultrasound- or exam-indication for cerclage (HR 3.5, 95% CI 1.7-7.4) were associated with earlier delivery GA. Increasing numbers of high cytokine results were associated with preterm delivery (Figure). Presence of ³4 high cytokine results was 75% sensitive and 91% specific for SPTB (AUC 0.84, 95% CI 0.71-0.97; PPV=88%, NPV=80%). Among women who undergo cerclage and lack signs or symptoms of labor or intra-amniotic infection, an elevated maternal serum cytokine profile drawn in the perioperative period is associated with SPTB. Confirmation and refinement of this panel may provide insight into improved selection of patients who may benefit from cervical cerclage.View Large Image Figure ViewerDownload Hi-res image Download (PPT)