title: Limited relationship between cervico-vaginal fluid cytokine profiles and cervical shortening in women at high risk of spontaneous preterm birth.
abstract: OBJECTIVE
  To determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship.
  
  
  METHODS
  This prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks' gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks' gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay.
  
  
  RESULTS
  All 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks' gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8-147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0-23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0-17.7; p<0.001].
  
  
  CONCLUSIONS
  Although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length.
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom. m.chandiramani@imperial.ac.uk
authors.forename: Manju
authors.initials: M
authors.lastname: Chandiramani
authors.forename: Paul T
authors.initials: PT
authors.lastname: Seed
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Orsi
authors.forename: Uma V
authors.initials: UV
authors.lastname: Ekbote
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Shennan
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Tribe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism*; D023802:Cerclage, Cervical; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D047928:Premature Birth / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000517:prevention & control / Q000601:surgery; D011374:Progesterone / Q000494:pharmacology; D012306:Risk; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D011374:Progesterone