Clinical chorioamnionitis at term VIII: a rapid MMP-8 test for the identification of intra-amniotic inflammation

Abstract

Objective Clinical chorioamnionitis is the most common infection/inflammatory process diagnosed in labor and delivery units worldwide. The condition is a syndrome that can be caused by: 1) intra-amniotic infection; 2) intra-amniotic inflammation without demonstrable microorganisms (i.e., sterile intra-amniotic inflammation); and 3) maternal systemic inflammation that is not associated with intra-amniotic inflammation. The presence of intraamniotic inflammation is a risk factor for adverse maternal and neonatal outcomes in a broad range of obstetrical syndromes that includes clinical chorioamnionitis at term. Although the diagnosis of intra-amniotic infection has relied on culture results, such information is not immediately available for patient management. Therefore, the diagnosis of intra-amniotic inflammation could be helpful as a proxy for intra-amniotic infection, while results of microbiologic studies are pending. A rapid test is now available for the diagnosis of intraamniotic inflammation, based on the determination of neutrophil collagenase or matrix metalloproteinase-8 (MMP-8). The objectives of this study were to 1) evaluate the diagnostic indices of a rapid MMP-8 test for the identification of intra-amniotic inflammation/infection in patients with the diagnosis of clinical chorioamnionitis at term; and 2) compare the diagnostic performance of a rapid MMP-8 test to that of a conventional enzyme-linked immunosorbent assay (ELISA) interleukin (IL)-6 test for patients with clinical chorioamnionitis at term. Materials and Methods A retrospective cohort study was conducted. A transabdominal amniocentesis was performed in patients with clinical chorioamnionitis at term (n=44). Amniotic fluid was analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). Amniotic fluid IL-6 concentrations were determined by ELISA, and rapid MMP-8 results were determined by Yoon's MMP-8 Check®. Intra-amniotic inflammation was defined as an elevated amniotic fluid IL-6 concentration ≥2.6 ng/mL, and intra-amniotic infection was diagnosed by the presence of microorganisms in the amniotic fluid accompanied by intra-amniotic inflammation. The diagnostic indices of Yoon's MMP-8 Check® for the identification of intra-amniotic inflammation were calculated. In order to objectively compare Yoon's MMP-8 Check® to the ELISA IL-6 test for the identification of intra-amniotic inflammation, we used an amniotic fluid white blood cell (WBC) count ≥50 cells/mm3 to define intra-amniotic inflammation. Results 1) A positive rapid MMP-8 test had a sensitivity of 82.4% (28/34), specificity of 90% (9/10), positive predictive value of 96.6% (28/29), negative predictive value of 60% (9/15), positive likelihood ratio 8.2 (95% CI 1.3-53.2), and negative likelihood ratio 0.2 (95% CI 0.1-0.4) for the identification of intra-amniotic inflammation (prevalence 77.3%); 2) a positive rapid MMP-...

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

“…We observed that, regardless of membrane status, patients with MIAC had significantly higher concentrations of AF MMP-8 and IL-6 than those without MIAC, which is in line with previous IAI studies [19,20,22]. Moreover, cervical MMP-8 concentrations were higher in the subgroup of women without PPROM and with MIAC compared to women without PPROM and MIAC.…”

“…Over the last two decades, these biomarkers have been extensively studied as predictors of intra-amniotic inflammation (IAI) [13][14][15][16][17][18][19][20]. IAI is characterized by either sterile inflammation or inflammation due to microbial invasion of the amniotic cavity (MIAC) [21][22][23].…”

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation

“…These neutrophils actively participate in the mechanisms of host defense in the amniotic cavity by releasing cytokines [108] and anti-microbial molecules [111][112][113], performing phagocytosis [114], and forming neutrophil extracellular traps [115,116]. In addition, women with clinical chorioamnionitis at term and intra-amniotic infection present severe acute inflammatory lesions in the placenta [40,46,85,117], suggesting that both amniotic fluid neutrophils and the chorioamniotic membranes are a source of extracellular ASC in the amniotic cavity.…”

Inhibition of the NLRP3 inflammasome can prevent sterile intra-amniotic inflammation, preterm labor/birth, and adverse neonatal outcomes†

“…The current view is that most cases of spontaneous preterm labor with intra-amniotic inflammation occur in the absence of microorganisms and therefore represent a sterile inflammatory process [5][6][7][8][9]. We have coined the term "sterile intra-amniotic inflammation" to define the inflammatory process in which microorganisms cannot be detected by using both cultivation and molecular microbiology techniques in amniotic fluid [7,[10][11][12][13][14][15][16][17][18][19][20]. Sterile intraamniotic inflammation is also observed in women with an asymptomatic short cervix [10], preterm prelabor rupture of membranes [11], or clinical chorioamnionitis at term [12].…”