title: Mid-trimester amniotic fluid pro-inflammatory biomarkers predict the risk of spontaneous preterm delivery in twins: a retrospective cohort study.
abstract: OBJECTIVE
  To evaluate the association between the concentrations of immune-related proteins in mid-trimester amniotic fluid (AF) and the subsequent risk of spontaneous preterm delivery in twins.
  
  
  METHODS
  The study population consisted of consecutive women with a twin pregnancy who underwent clinically indicated genetic amniocentesis at 15 to 20 weeks, and had a subsequent spontaneous delivery in the early preterm period (<32 weeks (cases)) or at term (37 to 42 weeks (controls)). AF was analyzed for cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13 and IL-15, interferon-γ, tumor necrosis factor-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-12), and chemokines (complement factor-D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, C-Reactive Protein, CCL2/MCP-1, Leptin, Resistin) using multiplex immunoassay kits. The association between AF protein levels and subsequent early preterm birth were examined.
  
  
  RESULTS
  A total of 96 sets of twins were enrolled, including 17 early preterm birth cases and 79 term controls. AF concentrations of IL-6, IL-8, MMP-3, MMP-8 and MMP-9, and CCL2/MCP-1 were significantly higher in cases than controls. Among these analytes, the combination of AF IL-8 and MMP-9 values had the highest predictive value for early preterm birth. The risk was 8% (10/132) for IL-8<1200 pg ml(-1) and MMP-9<1000 pg ml(-1), 30% (15/50) for IL-8>1200 pg ml(-1) or MMP-9>1000 pg ml(-1), and 90% (9/10) for IL-8>1200 pg ml(-1) and MMP-9>1000 pg ml(-1) (P<0.001).
  
  
  CONCLUSIONS
  High concentrations of IL-8 and MMP-9 in mid-trimester AF in twins predicted well the risk of early preterm birth.
authors: 1] Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea [2] Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
authors: S M
authors: SM
authors: Lee
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: J S
authors: JS
authors: Park
authors: Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA, USA.
authors: E R
authors: ER
authors: Norwitz
authors: Department of Biostatistics, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
authors: S
authors: S
authors: Oh
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: E J
authors: EJ
authors: Kim
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: S M
authors: SM
authors: Kim
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: J
authors: J
authors: Lee
authors: 1] Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea [2] Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
authors: B J
authors: BJ
authors: Kim
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: C-W
authors: CW
authors: Park
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: J K
authors: JK
authors: Jun
mesh_terms: D000328:Adult; D000649:Amniocentesis / Q000379:methods; D000653:Amniotic Fluid / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009321:Natural Childbirth / Q000379:methods*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000378:metabolism*; D047928:Premature Birth / Q000378:metabolism*; D012189:Retrospective Studies; D014427:Twins / Q000235:genetics
chemical_list: D015415:Biomarkers; D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D002097:C-Reactive Protein