title: About one-half of early spontaneous preterm deliveries can be identified by a rapid matrix metalloproteinase-8 (MMP-8) bedside test at the time of mid-trimester genetic amniocentesis.
abstract: OBJECTIVE
  Mid-trimester amniocentesis continues to be used for the prenatal diagnosis of chromosomal anomalies and other genetic disorders. Analysis of amniotic fluid obtained at the time of mid-trimester genetic amniocentesis identifies those patients who are at risk for early spontaneous preterm delivery. This is based on a solid body of evidence that found subclinical intra-amniotic inflammation/infection to be causally linked to early spontaneous preterm birth. Although several biomarkers have been proposed to identify intra-amniotic inflammation, the accumulated data suggest that the determination of amniotic fluid matrix metalloproteinase-8 (MMP-8), or neutrophil collagenase, is a powerful predictor of spontaneous preterm delivery. MMP-8 is released by inflammatory cells in response to microbial products or "danger signals". A rapid point-of-care test has been developed to determine MMP-8 at the bedside within 20 min, and without the requirement of laboratory equipment. The objective of this study was to determine whether an elevation of MMP-8 in the amniotic fluid, measured by a rapid point-of-care test, can identify those patients at risk for spontaneous preterm delivery after a mid-trimester genetic amniocentesis.
  
  
  METHODS
  A case-control study was designed to obtain amniotic fluid from asymptomatic singleton pregnant women who underwent mid-trimester genetic amniocentesis. An MMP-8 bedside test was performed to analyze the amniotic fluid of 64 patients with early spontaneous preterm delivery (<30 weeks) and 128 matched controls with normal pregnancy outcomes.
  
  
  RESULTS
  (1) The MMP-8 bedside test (Yoon's MMP-8 Check™) was positive in 42.2% (27/64) of patients with spontaneous preterm delivery but in none (0/128) of the control cases (p < 0.001); (2) the MMP-8 bedside test had a sensitivity of 42.2%, and a specificity of 100% in the prediction of spontaneous preterm delivery (<30 weeks) following a mid-trimester genetic amniocentesis; and (3) among the patients with spontaneous preterm delivery, those with a positive MMP-8 bedside test had a significantly higher rate of spontaneous delivery within 2 weeks and 4 weeks of an amniocentesis [40.7% (11/27) versus 5.4% (2/37); 63.0% (17/27) versus 24.3% (9/37)] and a shorter interval-to-delivery period than those with a negative test [interval-to-delivery: median (range), 16 d (0-95 d) versus 42 d (2-91 d); p < 0.05 for each].
  
  
  CONCLUSIONS
  We conclude that 42% of patients with an early spontaneous preterm delivery (< 30 weeks) could be identified by a rapid MMP-8 bedside test at the time of their mid-trimester genetic amniocentesis. The MMP-8 bedside test is a powerful predictor of early spontaneous preterm birth in asymptomatic pregnant women.
authors.affiliation: a Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Republic of Korea .|b Department of Obstetrics and Gynecology , Seoul Metropolitan Government-Seoul National University Boramae Medical Center , Seoul , Republic of Korea .
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: c Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 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 , and.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: a Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Republic of Korea .
authors.forename: JoonHo
authors.initials: J
authors.lastname: Lee
authors.affiliation: c Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA .|g Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.affiliation: a Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Republic of Korea .
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Lee
authors.affiliation: c Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Bethesda, MD , and Detroit , MI , USA .|g 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 Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Republic of Korea .
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: a Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Republic of Korea .
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000649:Amniocentesis / Q000379:methods*; D000653:Amniotic Fluid / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D020784:Matrix Metalloproteinase 8 / Q000032:analysis*; D019095:Point-of-Care Systems; D011247:Pregnancy; D011256:Pregnancy Outcome; D011264:Pregnancy Trimesters; D047928:Premature Birth / Q000175:diagnosis / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8
keywords: Amniotic fluid; intra-amniotic inflammation/infection; point-of-care (POC) test; preterm parturition