Expression of inflammatory, angiogenic, and extracellular matrix‐related mediators in the cervicovaginal fluid of women with preterm premature rupture of membranes: Relationship with acute histological chorioamnionitis

Abstract

AbstractProblemTo investigate whether altered expression of various inflammation‐, angiogenesis‐, and extracellular matrix‐related mediators in cervicovaginal fluid (CVF) could be independently associated with acute histological chorioamnionitis (HCA), microbial‐associated HCA, and funisitis in women with preterm premature rupture of membranes (PPROM).Method of StudyClinical data of 102 consecutive singleton pregnant women with PPROM at 23+0 to 34+0 weeks were retrospectively analyzed. CVF samples were collected upon admission. Levels of APRIL, DKK‐3, IGFBP‐1/2, IL‐6/8, lipocalin‐2, M‐CSF, MIP‐1α, MMP‐8/9, S100A8A9, TGFBI, TIMP‐1, TNFR2, uPA, and VDBP were determined by ELISA. Placentas were histologically examined after birth.ResultsMultivariate logistic regression analyses showed that: (1) elevated CVF levels of IL‐8 and TNFR2 were independently associated with acute HCA; (2) elevated CVF levels of IL‐6, IL‐8, M‐CSF, MMP‐8, and TNFR2 were independently associated with microbial‐associated HCA; and (3) elevated CVF IL‐8 and MMP‐8 levels were independently associated with funisitis when adjusted for gestational age. Areas under the curves of the aforementioned CVF biomarkers ranged within 0.61–0.77, thereby demonstrating poor to fair diagnostic capacity for these clinical endpoints. HCA risk significantly increased as the CVF levels of each inflammatory mediator increased (P for trend < 0.05).ConclusionsHerein, we identified several inflammatory biomarkers (IL‐6/8, M‐CSF, MMP‐8, and TNFR2) in the CVF that are independently associated with acute HCA, microbial‐associated HCA, and funisitis in women with PPROM. Furthermore, the degree of inflammatory response in the CVF, based on the levels of these proteins, demonstrated a direct relationship with HCA risk (especially risk severity).