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/mm(3) (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.