The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6

Abstract

Objective Intra-amniotic infection/inflammation are major causes of spontaneous preterm labor and delivery. However, diagnosis of intra-amniotic infection is challenging because most are subclinical and amniotic fluid (AF) cultures take several days before results are available. Several tests have been proposed for the rapid diagnosis of microbial invasion of the amniotic cavity (MIAC) or intra-amniotic inflammation. The aim of this study was to examine the diagnostic performance of the AF Mass Restricted (MR) score in comparison with interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8) for the identification of MIAC or inflammation. Methods AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n = 100). Intra-amniotic inflammation was defined as >100 white blood cells/mm3 (WBCs) in AF; MIAC was defined as a positive AF culture. AF IL-6 and MMP-8 were determined using ELISA. The MR score was obtained using the Surface-Enhanced Laser Desorption Ionization Time of Flight (SELDI-TOF) mass spectrometry. Sensitivity and specificity were calculated and logistic regression models were fit to construct receiver-operating characteristic (ROC) curves for the identification of each outcome. The McNemar’s test and paired sample non-parametric statistical techniques were used to test for differences in diagnostic performance metrics. Results (1) The prevalence of MIAC and intra-amniotic inflammation was 34% (34/100) and 40% (40/100), respectively; (2) there were no significant differences in sensitivity of the three tests under study (MR score, IL-6 or MMP-8) in the identification of either MIAC or intra-amniotic inflammation (using the following cutoffs: MR score >2, IL-6 >11.4 ng/mL, and MMP-8 >23 ng/mL); (3) there was no significant difference in the sensitivity among the three tests for the same outcomes when the false positive rate was fixed at 15%; (4) the specificity for IL-6 was not significantly different from that of the MR score in identifying either MIAC or intra-amniotic inflammation when using previously reported thresholds; and (5) there were no significant differences in the area under the ROC curve when comparing the MR score, IL-6 or MMP-8 in the identification of these outcomes. Conclusions IL-6 and the MR score have equivalent diagnostic performance in the identification of MIAC or intra-amniotic inflammation. Selection from among these three tests (MR score, IL-6 and MMP-8) for diagnostic purposes should be based on factors such as availability, reproducibility, and cost. The MR score requires a protein chip and a SELDI-TOF instrument which are not widely available or considered “state of the art”. In contrast, immunoassays for IL-6 can be performed in the majority of clinical laboratories.

Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques

“…The AF IL-6 concentrations were determined for research purposes, and such results were not used in patient management. We have previously reported the use of IL-6 for the assessment of intra-amniotic inflammation [44, 51, 61, 63, 75–91]. …”

Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance

“…Thus far, amniotic fluid concentrations of MMP-8 268, 269 and IL-6 101, 111, 124, 198, 270-272 appear to be the best predictors of pregnancy outcome and neonatal complications in patients with preterm labor and intact membranes 11, 12, 109, 112, 273, 274 , preterm PROM 13, 275 , as well as in those undergoing genetic amniocentesis for standard clinical indications 276-282 . Originally tested as researched methods, rapid analysis with point-of-care tests to identify intra-amniotic inflammation with cytokines 113, 130, 205, 283, 284 and MMP-8 is now possible 285-293 .…”

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

“…Several studies have investigated the diagnostic value of amniotic fluid and maternal serum biomarkers for the detection of chorioamnionitis in pregnant women undergoing amniocentesis. Elevated inflammatory markers such as interleukin 6 (IL-6), IL-8, matrix metalloproteinase 8 (MMP-8), MMP-9, and monocyte chemotactic proteins within amniotic fluid are positive predictors of intra-amniotic inflammation and/or clinical chorioamnionitis (15)(16)(17)(18)(19)(20)(21); however, these markers may have poor positive predictive values for the detection of subclinical, histologic chorioamnionitis and may be variably expressed within the amniotic fluid and fetal membranes during chorioamnionitis (22)(23)(24). Recently, Liu et al (25) reported that surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF-MS) for the detection of human neutrophil defensin 1 (HNP-1) and HNP-2 and calgranulins A and C within amniotic fluid was highly accurate for the diagnosis of subclinical chorioamnionitis, but further studies with larger patient cohorts are required to validate these findings.…”