title: Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with preterm prelabor rupture of membranes.
abstract: BACKGROUND
  Preterm prelabor rupture of membranes is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm prelabor rupture of membranes is not broadly used in clinical practice, and therefore, a shift toward a noninvasive amniotic fluid sampling method is needed.
  
  
  OBJECTIVE
  The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of-care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intraamniotic inflammation, and microbial-associated intraamniotic inflammation in patients with preterm prelabor rupture of membranes.
  
  
  METHODS
  A prospective cohort study was conducted in women with singleton gestation complicated by preterm prelabor rupture of membranes at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive polymerase chain reaction analysis. Intraamniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration ≥745 pg/mL.
  
  
  RESULTS
  Several results were obtained in this study. First, it was possible to perform the point-of-care assessment of interleukin-6 in vaginal fluid in 92% of the women (141 of 153), and only those women were included in the analyses. Second, the rate of microbial invasion of the amniotic cavity and intraamniotic inflammation was 26% (36 of 141) and 19% (27 of 141), respectively. Microbial-associated intraamniotic inflammation was identified in 12% of the women (17 of 141). Third, a strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; P < .0001). Fourth, the presence of microbial invasion of the amniotic cavity, intraamniotic inflammation, or microbial-associated intraamniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. Fifth, a vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity (sensitivity of 53% [19 of 36], specificity of 89% [93 of 104], positive predictive value of 63% [19 of 30], negative predictive value of 85% [93 of 110], positive likelihood ratio of 5.0 [95% confidence interval, 2.5-9.5], and negative likelihood ratio of 0.5 [95% confidence interval, 0.4-0.8]); intraamniotic inflammation (sensitivity of 74% [20/27], specificity of 91% [104/114], positive predictive value of 67% [20 of 30], negative predictive value of 94% [104 of 111], positive likelihood ratio of 8.4 [95% confidence interval, 4.5-15.9], and negative likelihood ratio of 0.3 [95% confidence interval, 0.2-0.5]); and microbial-associated intraamniotic inflammation (sensitivity of 100% [17 of 17], specificity of 90% [111 of 124), positive predictive value of 57% [17 of 30], negative predictive value of 100% [111 of 111], positive likelihood ratio of 9.5 [95% confidence interval, 5.7-16.0], and negative likelihood ratio of 0).
  
  
  CONCLUSIONS
  The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, noninvasive, and inexpensive method for the identification of intraamniotic inflammation and microbial-associated intraamniotic inflammation in preterm prelabor rupture of membranes pregnancies, showing good specificity and negative predictive value.
authors.affiliation: Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Musilova
authors.affiliation: Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Bestvina
authors.affiliation: Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Hudeckova
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital in Ostrava, Ostrava, Czech Republic; Department of Obstetrics and Gynecology, Faculty of Medicine, Ostrava University, Ostrava, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Michalec
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clinic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Centre for Biomedical Research on Rare Diseases (Centro de Investigación Biomédica en Red Enfermedades Raras), Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cobo
authors.affiliation: Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Bo
authors.initials: B
authors.lastname: Jacobsson
authors.affiliation: Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address: kacermar@fnhk.cz.
authors.forename: Marian
authors.initials: M
authors.lastname: Kacerovsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism* / Q000382:microbiology; D015415:Biomarkers / Q000378:metabolism; D002821:Chorioamnionitis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D005322:Premature Rupture of Fetal Membranes; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D019095:Point-of-Care Systems; D011247:Pregnancy; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014621:Vagina; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6
keywords: amniocentesis; amniotic fluid; biomarkers; cytokine; interleukin; intraamniotic inflammation; lateral flow-based immunoassay; microbial invasion of the amniotic cavity; noninvasive procedure; preterm; rapid test