title: Inflammation biomarkers in vaginal fluid and preterm delivery.
abstract: OBJECTIVE
  Which inflammation biomarkers detected in the vaginal fluid are most informative for identifying preterm delivery (PTD) risk?
  
  
  CONCLUSIONS
  Elevated interleukin (IL)-6 at mid-trimester was associated with increased odds of spontaneous PTD at <35 weeks and with PTD plus histologic chorioamnionitis (HCA), and had the greatest sensitivity for detecting these two PTD subtypes.
  
  
  BACKGROUND
  Maternal and/or fetal inflammation play a role in some preterm deliveries, therefore inflammation biomarkers might help to identify women at greater risk.
  
  
  METHODS
  We examined 1115 women from the Pregnancy Outcomes and Community Health Study, a cohort study conducted from September 1998 through June 2004, for whom data were available on mid-pregnancy inflammatory biomarkers.
  
  
  METHODS
  At enrollment at 16-27 weeks gestation, vaginal fluid samples were collected from a swab and 15 eluted biomarkers were measured using the Meso Scale Discovery multiplex electrochemiluminescence platform. Associations of biomarkers with PTD were examined, according to clinical circumstance, week at delivery and presence/absence of HCA. Weighted logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) adjusted for race. Sensitivity and specificity were compared between individual and multiple biomarkers, identified by a bootstrapping method.
  
  
  RESULTS
  Elevated IL-6 (>75th percentile) displayed the strongest association with spontaneous PTD <35 weeks (OR 2.3; CI 1.3-4.0) and PTD with HCA (OR 2.8; CI 1.4-6.0). The sensitivity of IL-6 to detect spontaneous PTD <35 weeks or PTD with HCA was 0.43 and 0.51, respectively, while specificity was 0.74 and 0.75, respectively. IL-6 plus IL1β, IL-6r, tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor increased specificity (range 0.84-0.88), but decreased sensitivity (range 0.28-0.34) to detect both PTD subtypes. Results were similar when a combination of IL-6 and bacterial vaginosis (BV) was explored. Thus, the use of multiple biomarkers did not detect PTD subtypes with a greater sensitivity than IL-6 alone, and IL-6 is a specific but non-sensitive marker for the detection of spontaneous PTD.
  
  
  CONCLUSIONS
  Our ability to find small effect size associations between PTD and inflammation biomarkers (OR <2.0) might have been limited by the modest number of less common PTD subtypes in our population (e.g. spontaneous delivery <35 weeks, PTD accompanied by HCA) and by relatively higher variability for some cytokines, for example tumor necrosis factor-α, IL-12p70, IL-10 and granulocyte-macrophage colony-stimulating factor, that are less stable and commonly undetectable or detectable at low levels in human vaginal secretions.
  
  
  CONCLUSIONS
  Larger studies are needed to further explore a role of inflammation biomarkers in combination with other risk factors, including specific BV-associated organisms, for the prediction of PTD subtypes.
  
  
  BACKGROUND
  This work was supported by the National Institute of Child Health and Human Development, National Institute of Nursing, March of Dimes Foundation, Thrasher Research Foundation and Centers for Disease Control and Prevention. The authors have no conflicts of interest.
authors: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, 5th floor Parran Hall, Pittsburgh, PA 15261, USA. depaolib@edc.pitt.edu
authors: Brandie D
authors: BD
authors: Taylor
authors: Claudia B
authors: CB
authors: Holzman
authors: Raina N
authors: RN
authors: Fichorova
authors: Yan
authors: Y
authors: Tian
authors: Nicole M
authors: NM
authors: Jones
authors: Wenjiang
authors: W
authors: Fu
authors: Patricia K
authors: PK
authors: Senagore
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000175:diagnosis* / Q000378:metabolism; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome; D012189:Retrospective Studies; D012307:Risk Factors; D014621:Vagina / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D015850:Interleukin-6