title: Compartmentalization of acute phase reactants Interleukin-6, C-Reactive Protein and Procalcitonin as biomarkers of intra-amniotic infection and chorioamnionitis.
abstract: BACKGROUND
  The arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-Reactive Protein (CRP) and Procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known.
  
  
  METHODS
  We used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionitis.
  
  
  RESULTS
  PCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers.
  
  
  CONCLUSIONS
  In women with subclinical IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, United States.
authors.forename: Antonette T
authors.initials: AT
authors.lastname: Dulay
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, United States; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, United States.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, United States.
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, United States.
authors.forename: Mert O
authors.initials: MO
authors.lastname: Bahtiyar
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Thung
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Cackovic
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States. Electronic address: catalin.buhimschi@osumc.edu.
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
mesh_terms: D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry / Q000382:microbiology; D058345:Asymptomatic Infections; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis* / Q000652:urine; D002116:Calcitonin / Q000032:analysis* / Q000097:blood / Q000652:urine; D015740:Calcitonin Gene-Related Peptide; D002821:Chorioamnionitis / Q000175:diagnosis* / Q000382:microbiology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005322:Premature Rupture of Fetal Membranes; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000032:analysis* / Q000097:blood / Q000652:urine; D007752:Obstetric Labor, Premature; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D047928:Premature Birth; D011498:Protein Precursors / Q000032:analysis* / Q000097:blood / Q000652:urine; D018746:Systemic Inflammatory Response Syndrome
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide
keywords: Inflammatory response syndrome; Intra-amniotic infection; Non-invasive biomarkers; Preterm birth