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Objective We aimed to evaluate the correlation and agreement of interleukin (IL)-8 and matrix metalloproteinases (MMP-9) levels between cervicovaginal (CVF) and amniotic fluids (AF) in women with preterm labor (PTL) and to determine the clinical values of these proteins in CVF compared with those in AF. Study Design We designed a retrospective cohort study of 85 singleton pregnant women with PTL at 23 to 34 weeks, who underwent amniocentesis. The AF was cultured, and CVF samples were collected at the time of amniocentesis. Paired AF and CVF samples were assayed for IL-8 and MMP-9 by enzyme-linked immunoassay (ELISA) in duplicate on a single plate, using similar dilution ratios. Results A significant but weak correlation was found for IL-8 levels between AF and CVF (r = 0.333), while no correlation was found for MMP-9 levels between AF and CVF (r = −0.039). Intra-class correlation coefficient for the agreement of IL-8 levels between CVF and AF was 0.4335 and −0.279 for MMP-9, indicating a poor-to-fair level of agreement between the two measured values, respectively. IL-8 and MMP-9 levels in CVF were not associated with the risk of either microbial invasion of the amniotic cavity (MIAC) or spontaneous preterm delivery (SPTD) within 7 days, whereas those in AF provided good-to-excellent predictive values for these two outcomes (area under the curve [AUCs]: 0.82–0.95). AUCs for IL-8 and MMP-9 were significantly larger using AF rather than using CVF for the prediction of MIAC and SPTD. Conclusion In women with PTL, IL-8 and MMP-9 levels in CVF do not precisely reflect the levels of the corresponding proteins in AF. IL-8 and MMP-9 levels in CVF had poor predictive values for the risk of MIAC and SPTD and were significantly inferior to those in AF. Key Points IL-8 and MMP-9 levels in CVF do not precisely reflect levels of the corresponding proteins in AF. Diagnostic accuracy of IL-8 and MMP-9 in CVF alone is not sufficient to predict MIAC and SPTD. IL-8 and MMP-9 levels in AF provide good-to-excellent predictive values for these two outcomes. [ABSTRACT FROM AUTHOR]

Problem: To identify proteins present in the amniotic fluid (AF) that could be associated with spontaneous preterm birth (SPTB; delivery < 7 days) in women with preterm labor (PTL). Method of study: First, the AF proteome of 20 women with PTL and SPTB was compared with that of 20 matched women with term deliveries using an antibody microarray. Next, nine identified candidate biomarkers of SPTB were further validated in 267 singleton pregnant women with PTL who underwent amniocentesis at 26–33 weeks of gestation using ELISA, and whether the degree of expression of these proteins was associated with the risk severity for subsequent SPTB was retrospectively assessed. Results: Of the 507 proteins evaluated in the microarray analysis, 27 displayed significant intergroup differences. In particular, ELISA quantification confirmed that the expression of EN‐RAGE, IL‐6, IL‐8, IP‐10, lipocalin‐2, MMP‐8, MMP‐9, S100 A8/A9, and TNFR2 were all increased in the AF of women spontaneously delivering within 7 days of sampling compared with those delivering after 7 days. Moreover, the odds of SPTB within 7 days, even upon adjusting for confounders, tended to significantly increase with each increasing quartile of baseline AF levels of each protein (P‐value for trend <.05). Conclusion: Nine AF proteins were found to be independently associated with higher risk of subsequent SPTB in women with PTL, all of which were immune‐, inflammation‐, and extracellular matrix‐related proteins. Moreover, risk severity for this subsequent SPTB is closely related to the degree of expression of each of these proteins. [ABSTRACT FROM AUTHOR]

Problem: We aimed to identify amniotic fluid (AF) proteins associated with the subsequent rupture of membranes (ROM) occurring in the absence of active labor in women with threatened preterm labor (PTL) using an antibody microarray. Method of the study: This retrospective cohort study included 183 singleton pregnant women with PTL (24–33 weeks) who underwent amniocentesis. A nested case‐control study was conducted using AF samples from 20 women with subsequent ROM within 7 days of sampling (case subjects) and 20 gestational age‐matched women with term delivery (TD) without ROM (control subjects), via protein‐antibody microarray analysis. Seven candidate proteins of interest were validated via ELISA in the total cohort. Results: Seventeen proteins displayed significant intergroup differences. ELISA validation confirmed that the levels of EN‐RAGE, Fas, IL‐8, IP‐10, MMP‐8, and MMP‐9 were significantly higher, whereas IGFBP‐3 levels were significantly lower in the AF of women with subsequent ROM within 7 days of sampling than in that of women with TD without ROM. Moreover, the time interval from sampling to membrane rupture was significantly correlated with the expression levels of AF proteins, except for IL‐10. Conclusion: Using an antibody microarray, we identified various inflammatory, angiogenic, matrix‐degrading, and apoptosis‐related proteins in the AF that were associated with subsequent ROM occurring in the absence of active labor in women with threatened PTL. These findings provide novel insights into the molecular mechanisms underlying membrane rupture without active labor in threatened PTL. [ABSTRACT FROM AUTHOR]

We aimed to identify novel biomarkers in maternal plasma that predict spontaneous preterm delivery (SPTD) in women with preterm labor (PTL) using an antibody microarray and to develop the best prediction model for SPTD based on these biomarkers in combination with clinical and ultrasound factors. This retrospective cohort study included 215 women with singleton pregnancies and PTL (23–33 weeks) who gave plasma samples. In a nested case-control study design, plasma proteomes from SPTD (case subjects, n = 15) and term delivery (control subjects, n = 15) groups were differentially profiled using a membrane-based antibody microarray. Six candidate biomarkers of interest were validated by enzyme-linked immunosorbent assay (ELISA) in the total cohort (n = 215). Cervical lengths were also measured. The primary outcome measure was SPTD within 48 h after sampling. Twenty of the molecules studied displayed significant intergroup differences. Validation by ELISA confirmed significantly higher levels of plasma endostatin and lipopolysaccharide binding protein (LBP) in women who had SPTD within 48 h than in those delivering after 48 h. However, plasma macrophage inflammatory protein (MIP)-1α levels were significantly lower in women who delivered within 48 h. A combined model was developed to predict SPTD within 48 h using a stepwise regression procedure, which included plasma endostatin and LBP levels, nulliparity, and cervical length (area under the curve = 0.920). Plasma LBP, endostatin, and MIP-1α are potential new biomarkers for predicting imminent SPTD and a combined noninvasive model based on these biomarkers and clinical and ultrasound factors can accurately predict imminent SPTD in women with PTL. [ABSTRACT FROM AUTHOR]

Objective: To determine whether vitamin D-binding protein (VDBP) in cervicovaginal fluid (CVF) is independently predictive of intra-amniotic infection and imminent spontaneous preterm delivery (SPTD, delivery within 48 hours) in women with preterm labor with intact membranes (PTL) or preterm premature rupture of membranes (PPROM). Method: This was a single-center retrospective cohort study. CVF samples for VDBP assays were obtained along with serum C-reactive protein (CRP) levels immediately after amniocentesis in consecutive women with PTL (n = 148) or PPROM (n = 103) between 23.0 and 34.0 weeks of gestation. VDBP levels in CVF were determined by enzyme-linked immunosorbent assay kits. The primary outcome measures were intra-amniotic infection [defined as positive amniotic fluid (AF) culture] and SPTD within 48 hours after sampling. Results: In the multivariable analysis, elevated VDBP levels in CVF samples of PTL women were significantly associated with intra-amniotic infection and imminent preterm delivery, even after adjusting for potential confounders (e.g., gestational age at sampling, parity, and serum CRP). However, these relationships were not found in women with PPROM. In women with PTL, the areas under receiver operating characteristic curves of CVF VDBP level for predicting intra-amniotic infection and imminent preterm delivery were 0.66 and 0.71, with cut-off values of 1.76 μg/mL (sensitivity of 64.3% and specificity of 78.4%) and 1.37 μg/mL (sensitivity of 65.4% and specificity of 72.6%), respectively. The CVF VDBP levels were significantly higher in women with PPROM than in those with PTL. Conclusions: VDBP in the CVF independently predicts intra-amniotic infection and imminent preterm delivery in women with PTL, whereas in women with PPROM, an elevated VDBP level in CVF is not associated with increased risks of these two outcome variables. [ABSTRACT FROM AUTHOR]