Cervicovaginal Fluid Protein Microarray for Detection of Microbial Invasion of the Amniotic Cavity in Preterm Labor

We aimed to identify cervicovaginal fluid (CVF) biomarkers that can detect microbial invasion of the amniotic cavity (MIAC) in women with preterm labor (PTL) with an antibody microarray and to develop the best combined model for detection of MIAC using these biomarkers in combination with conventional clinical variables. This retrospective cohort study included 168 singleton pregnant women with PTL (23-34 weeks) who underwent amniocentesis. AF was cultured, and CVF samples were obtained at the time of amniocentesis. An antibody microarray was used to analyze the CVF proteome (n = 40). The validation of four candidate biomarkers of interest was performed by enzyme-linked immunosorbent assay (ELISA) in the final cohort (n = 168). For comparison with candidate markers, CVF IL-6 concentration was also measured. Twenty-seven molecules studied exhibited intergroup differences. Validation by ELISA confirmed significantly higher levels of CVF DKK3, M-CSF, and TIMP-1, but not of IGFBP-2, independent of gestational age, in CVF of women with MIAC. The area under the curve (AUC) of DKK3, M-CSF, and TIMP-1 from CVF was not significantly different from the AUC of IL-6 from CVF for detecting MIAC in women with PTL. By using a stepwise regression analysis, a combined detection model was developed, which included the CVF M-CSF, TIMP-1, and gestational age at sampling (AUC = 0.823). An antibody microarray identified useful biomarkers (DKK3, M-CSF, and TIMP-1) in CVF for detection of MIAC, and a combined model including these biomarkers and gestational age can accurately detect MIAC in women with PTL.