Quantitative cervicovaginal fluid fetal fibronectin: A liquid biopsy for intra‐amniotic inflammation

AbstractIntroductionIntra‐amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra‐amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely‐used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra‐amniotic inflammation; and (2) an appropriate cut‐off value of a cervicovaginal fluid fFN concentration for the identification of intra‐amniotic inflammation.Material and MethodsThis prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra‐amniotic inflammation was defined as an amniotic fluid interleukin‐6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin‐6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra‐amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra‐amniotic inflammation were calculated.Results(1) Frequency of intra‐amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra‐amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83–0.96) for the identification of intra‐amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut‐off of 125 ng/mL had a significant higher predictive performance than the traditional cut‐off (50 ng/mL) for the identification of intra‐amniotic inflammation.ConclusionsQuantitative cervicovaginal fluid fFN with a cut‐off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra‐amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra‐amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra‐amniotic inflammation.