Problem To determine whether altered levels of 13 plasma biomarkers, alone or in combination, could be independently associated with histologic chorioamnionitis (HCA) and microbial‐associated HCA (defined as the presence of HCA along with microbial invasion) in women with preterm labor (PTL). Methods of Study This was a retrospective cohort study involving 77 singleton pregnant women with PTL (23–34 gestational weeks) who delivered within 96 h of plasma and amniotic fluid (AF) sampling. DKK‐3, E‐selectin, Fas, haptoglobin, IGFBP‐1, kallistatin, MMP‐2, MMP‐8, pentraxin 3, progranulin, P‐selectin, SAA4, and TGFBI levels were assayed in plasma samples by ELISA. AF obtained via amniocentesis was used for microorganism identification. Results Multiple logistic regression analyses revealed significant associations between low plasma IGFBP‐1 levels and acute HCA, and between low plasma Fas and kallistatin levels, and elevated plasma P‐selectin levels and microbial‐associated HCA (all p < .05), after adjusting for gestational age. Using a stepwise regression procedure, a multi‐biomarker panel for microbial‐associated HCA was developed, which included plasma MMP‐2, kallistatin, and P‐selectin levels (area under the curve [AUC], .867). The AUC for this three‐marker panel was significantly or borderline significantly greater than that of any single variable included in the panel. However, a predictive model for acute HCA could not be developed because only one variable (MMP‐2) was selected. Conclusions These findings demonstrate that IGFBP‐1, Fas, kallistatin, and P‐selectin are associated with acute HCA and microbial‐associated HCA in women with PTL. Their combined use can significantly improve the diagnostic ability for the detection of microbial‐associated HCA.

ProblemTo examine whether the severity of spontaneous preterm birth (SPTB) risk after rescue cerclage for acute cervical insufficiency (CI) is linked to the degree of inflammatory response in the amniotic fluid (AF) based on the concentrations of various inflammatory proteins and prior obstetric history.Method of studyWe conducted a retrospective cohort study of 65 singleton pregnant women (17–25 weeks) who underwent rescue cerclage following the diagnosis of acute CI and were subjected to amniocentesis. EN‐RAGE, IL‐6, IL‐8, and IP‐10 as inflammatory mediators and kallistatin, MMP‐2/8, and uPA as extracellular matrix remodeling‐related molecules were assayed in the AF using ELISA. The level of each inflammatory mediator was divided into quartiles.ResultsIntra‐amniotic inflammation (IAI; AF IL‐6 level ≥2.6 ng/mL) was independently associated with SPTB after cerclage placement. The odds of SPTB at < 32 weeks, even after adjusting for confounders, increased significantly with each increasing quartile of baseline AF levels for each inflammatory mediator (p for trend < .05). Kaplan‐Meier survival curves showed that the cerclage‐to‐delivery intervals were significantly shorter as the quartiles of AF EN‐RAGE and MMP‐8 increased (log‐rank test, p < .01 each). Neither previous term birth nor prior PTB was associated with SPTB risk or cerclage‐to‐delivery interval after rescue cerclage. Multiparous women who experience CI after term birth showed significantly elevated levels of MMP‐8 and reduced kallistatin levels in the AF.ConclusionIn patients with CI, SPTB risk (especially risk severity) after rescue cerclage is associated with the degree of the inflammatory response in AF as well as the presence of IAI but not with prior obstetric history.

Problem This study aimed to determine whether various novel plasma mediators of immune regulation associated with inflammation could independently predict the clinical outcome of rescue cerclage in patients with cervical insufficiency (CI). Method of study A total of 41 singleton pregnant women (17–25 weeks) who underwent rescue cerclage for CI were retrospectively evaluated. Stored plasma samples were assayed for IGFBP‐1, ‐2, ‐3, IL‐6, latexin, LBP, lipocalin‐2, M‐CSF, MIP‐1α, MMP‐8, ‐9, pentraxin 3, resistin, S100A8, S100A8/A9, thrombospondin‐2, TIMP‐1, and TNFR2 levels. The primary outcome measures were spontaneous preterm birth (SPTB) at < 28 and < 34 weeks after cerclage placement. Results Multivariate Firth's logistic regression analysis revealed that high levels of IGFBP‐3 and S100A8/A9, and low levels of MIP‐1α were significantly associated with SPTB at < 28 weeks after cerclage placement, whereas only low MIP‐1α levels were significantly associated with SPTB at < 34 weeks, even after adjustment for baseline clinical covariates (e.g., cervical dilatation). For the prediction of SPTB at < 28 weeks, the area under the curves (AUC) of IGFBP‐3, MIP‐1α, and S100A8/A9 were of .686, .691, and .693, respectively. Similarly, the AUC of MIP‐1 α was of .659 to predict SPTB at < 34 weeks. Conclusions These findings suggest that plasma IGFBP‐3, MIP‐1α, and S100A8/A9 can represent noninvasive independent biomarkers for identifying women with CI at high risk for SPTB following rescue cerclage. Nonetheless, further in large, multicenter clinical studies should be performed to confirm the clinical value of these biomarkers.

Problem We aimed to determine whether altered levels of various extracellular matrix (ECM)‐related and serine protease proteins in the amniotic fluid (AF) are associated with imminent spontaneous preterm birth (SPTB; ≤7 days) and intra‐amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with early preterm labor (PTL). Method of study This retrospective cohort study included 252 women with singleton pregnancies undergoing transabdominal amniocentesis who demonstrated PTL (24–31 weeks). The AF was cultured for microorganism detection to characterize MIAC. IL‐6 concentrations were determined in the AF samples to identify IAI (≥2.6 ng/mL). The following mediators were measured in the AF samples using ELISA: kallistatin, lumican, MMP‐2, SPARC, TGFBI, and uPA. Results Kallistatin, MMP‐2, TGFBI, and uPA levels were significantly higher and SPARC and lumican levels were significantly lower in the AF of women who spontaneously delivered within 7 days than in the AF of those who delivered after 7 days; the levels of the first five mediators were independent of baseline clinical variables. In the multivariate analysis, elevated levels of kallistatin, MMP‐2, TGFBI, and uPA and low levels of lumican and SPARC in the AF were significantly associated with IAI/MIAC and MIAC, even after adjusting for the gestational age at sampling. The areas under the curves of the aforementioned biomarkers ranged from 0.58 to 0.87 for the diagnoses of each of the corresponding endpoints. Conclusion ECM‐related (SPARC, TGFBI, lumican, and MMP‐2) and serine protease (kallistatin and uPA) proteins in the AF are involved in preterm parturition and regulation of intra‐amniotic inflammatory/infectious responses in PTL.