title: Comparison of rapid MMP-8 and interleukin-6 point-of-care tests to identify intra-amniotic inflammation/infection and impending preterm delivery in patients with preterm labor and intact membranes.
abstract: OBJECTIVE
  Among patients presenting with preterm labor and intact membranes, those with intra-amniotic inflammation have adverse obstetrical and neonatal outcomes. The diagnosis of intra-amniotic inflammation can easily be made by detecting an elevated concentration of the cytokine interleukin (IL)-6 or the enzyme neutrophil collagenase, also known as matrix metalloproteinase (MMP)-8. The diagnostic performances of MMP-8 and IL-6 enzyme-linked immunosorbent assay tests are similar. Recently, a rapid test has become available for point-of-care determination of either MMP-8 or IL-6. The objectives of this study were to compare the diagnostic indices and predictive values between the rapid MMP-8 and IL-6 tests for the identification of intra-amniotic inflammation in patients with preterm labor and intact membranes.
  
  
  METHODS
  We performed a retrospective cohort study including 124 women with singleton pregnancies who presented with symptoms of preterm labor and underwent transabdominal amniocentesis for the evaluation of microbial invasion of the amniotic cavity (MIAC). MIAC was defined according to amniotic fluid culture results (aerobic and anaerobic bacteria as well as genital Mycoplasmas). Amniotic fluid white blood cell (WBC) counts were determined using a hemocytometer chamber. An elevated amniotic fluid MMP-8 concentration was assessed using Yoon's MMP-8 Check®(cutoff: 10 ng/mL). An elevated amniotic fluid IL-6 concentration was scored when there was a positive result for the lateral flow-based immunoassay (cutoff: ≥745 pg/mL and ≥1000 pg/mL). In order to objectively compare rapid MMP-8 and rapid IL-6 tests to identify intra-amniotic inflammation, an amniotic fluid WBC count of ≥50 cells/mm3was used to define intra-amniotic inflammation.
  
  
  RESULTS
  (1) The rapid tests had the same sensitivity for the detection of intra-amniotic inflammation [85.7% (18/21) for all]; (2) the specificity of the rapid MMP-8 test was higher than that of the rapid IL-6 test (cutoff: 745 pg/mL) for the identification of intra-amniotic inflammation [72.8% (75/103) vs. 64.1% (66/103); p < 0.05]; and (3) there were no differences in the sensitivity and specificity between the rapid MMP-8 test and the rapid IL-6 test (cutoff:1000 pg/mL) in the identification of intra-amniotic inflammation. Of 13 patients with discrepant results between the rapid MMP-8 and rapid IL-6 tests, two had a positive MMP-8 but a negative rapid IL-6 test, and both delivered preterm - one within 24 h, and the other within 10 days - and both had acute histologic chorioamnionitis. On the other hand, there were 11 patients with a positive rapid IL-6 but a negative rapid MMP-8 result: 10 delivered preterm, 3 had acute histologic chorioamnionitis and 1 had subacute chorionitis.
  
  
  CONCLUSIONS
  We conclude that the rapid MMP-8 test has a better specificity than the rapid IL-6 (cutoff: 745 pg/mL) assay for the detection of intra-amniotic infection. Moreover, we observed that among patients who were not identified as having intra-amniotic infection or inflammation by the standard cultivation technique and amniotic fluid WBC count, those who had a positive MMP-8 rapid test delivered preterm and had acute histologic chorioamnionitis.
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.|c Department of Obstetrics and Gynecology , Block E East Prince of Wales Hospital, The Chinese University of Hong Kong , Shatin New Territories , Hong Kong.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , University of Michigan , Ann Arbor , MI , USA.|e Department of Epidemiology and Biostatistics , Michigan State University , East Lansing , MI , USA.|f Center for Molecular Medicine and Genetics , Wayne State University , Detroit , MI , USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Docheva
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Noppadol
authors.initials: N
authors.lastname: Chaiyasit
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhatti
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Percy
authors.initials: P
authors.lastname: Pacora
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.affiliation: a Perinatology Research Branch , NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
mesh_terms: D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000166:cytology / Q000382:microbiology; D002821:Chorioamnionitis / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D020784:Matrix Metalloproteinase 8 / Q000032:analysis*; D007752:Obstetric Labor, Premature / Q000453:epidemiology / Q000378:metabolism; D019095:Point-of-Care Systems; D011247:Pregnancy; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8
keywords: Amniocentesis; biomarker; chorioamnionitis; funisitis; immunoassay; microbial invasion of the amniotic cavity; point-of-care test; pregnancy; prematurity; preterm birth