Increased Levels of Interleukin-6 in Cervical Secretions and Assessment of the Uterine Cervix by Transvaginal Ultrasonography Predict Preterm Premature Rupture of the Membranes

Abstract

Objective: The objective of this study was to investigate the predictive factors of premature rupture of the membranes (preterm PROM). Methods: The study was undertaken with cervical secretions collected from 72 consenting singleton pregnant women between 20 and 33 weeks of gestation. The levels of interleukin (IL) 1α, IL-1β, IL-6, IL-8, matrix metalloproteinase (MMP) 1, MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinase (TIMP) 1, TIMP-2, granulocyte elastase, and fetal fibronectin in cervical diluted specimens were measured by immunoassay, and the uterine cervix was assessed by transvaginal ultrasonography. Demographic, obstetric, clinical, neonatal, and laboratory data were analyzed by univariate analysis, multiple logistic regression, and receiver operator characteristic curve analysis. Results: Preterm PROM occurred in 6 women, and 63 women delivered at term. Multiple logistic regression analysis indicated a significant independent association with preterm PROM for the cervical IL-6 levels and cervical length. The receiver operator characteristic curve analysis revealed that an IL-6 level of ≧240 pg/ml in cervical secretions and a cervical length of ≤28 mm had higher diagnostic performance in predicting preterm PROM. Conclusion: It is suggested that preterm PROM is associated with increased cervical IL-6 levels and a short cervix.

Human cervicovaginal fluid biomarkers to predict term and preterm labor

“…The heterogeneity of spontaneous PTB and the various clinical presentations (asymptomatic or symptomatic) provide significant challenges for the identification of a single biochemical marker to reliably predict all PTB (Menon et al, 2011 ; Bhat et al, 2013 ). The concept of utilizing multiple biochemical markers to improve labor prediction has been reported by our team (Heng et al, 2010a , 2014b ; Liong et al, 2015 ) and others (Rizzo et al, 1998 ; Goldenberg et al, 2001 ; Kishida et al, 2003 ; Grenache et al, 2004 ; Taylor et al, 2013 ). Other variations of using a diagnostic panel to predict PTB include incorporating peripheral blood results, gene expression profiles (Heng et al, 2014a ) as well as combining demographic, physical and behavioral parameters (e.g., cervical length or illicit drug use) (Hincz et al, 2002 ; Schmitz et al, 2006 ; Dutta and Norman, 2010 ; Bolt et al, 2011 ; Dekker et al, 2012 ; Fox et al, 2012 ; DeFranco et al, 2013 ).…”

Tocilizumab Inhibits Interleukin-6-Mediated Matrix Metalloproteinase-2 and -9 Secretions from Human Amnion Cells in Preterm Premature Rupture of Membranes

“…In a study performed by Rizzo et al [32] in patients with preterm labor, the IL-6 levels in cervical secretions were significantly correlated with the intra-amniotic levels of IL-6, and Kishida et al [33] reported that increased levels of IL-6 in cervical secretions and assessment of the uterine cervix by transvaginal ultrasonography predicted PPROM. These reports indicate the importance of IL-6 in PPROM and are supported by the findings of this study.…”

Biomarkers for the prediction of preterm delivery

“…Several studies on low‐risk women have shown increased predictive performance by the following combinations of biomarkers: CL with fFN (51,52), CL with cytokines (53), cytokines in combination with other biochemical markers (15,54), CRH with alpha‐fetoprotein (AFP) (40), vaginal pH with fFN (55), BV with fFN (56), and BV in combination with genetic susceptibility (57). The most promising study has been the Preterm Prediction Study, which evaluated the predictive abilities of five biomarkers (AFP, alkaline phosphatase, G‐CSF, fFN, and CL) in a case‐control study with 50 preterm deliveries (<32 weeks) and 127 matched term controls (58).…”