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CLIC: a longitudinal study of inflammatory markers and cervical change in women at risk of spontaneous preterm labour
  1. M Chandiramani1,
  2. PT Seed1,
  3. UV Ekbote2,
  4. NM Orsi2,
  5. PR Bennett3,
  6. AH Shennan1,
  7. RM Tribe1
  1. 1Maternal and Fetal Research Unit, Division of Reproduction and Endocrinology, King's College London, London, UK
  2. 2Institute of Molecular Medicine, St James's University Hospital, Leeds, UK
  3. 3Institute of Reproductive & Developmental Biology, Imperial College London, London, UK

Abstract

Background Infection is implicated in cervical shortening and spontaneous preterm labour (SPTL). Increased understanding of inflammatory events in the vaginal tract prior to cervical shortening is needed. The authors undertook a longitudinal observational study to determine the relation between inflammation and cervical shortening in women at risk of SPTL.

Methods Women (n=112) with at least one previous preterm delivery were recruited (14–24-week gestation) from two prematurity clinics and assessed (transvaginal cervical scans and cervico-vaginal fluid (CVF) swabs) every 2 weeks until 28 weeks. If cervical length shortened (<25 mm), women were randomised to cervical cerclage or progesterone and samples taken weekly. Concentrations of interleukin 1β (IL-1β), IL-4, IL-6, IL-7, IL-8, granulocyte colony-stimulating factor, granulocyte-macrophage colony stimulating factor (GM-CSF), interferon γ (IFNγ), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1β, tumour necrosis factor α (TNFα) were measured in CVF samples (n=477 from 78 women) using an 11-plex fluid-phase immunoassay. Log-transformed data were analysed using STATA, results expressed as ratios (95% CI).

Results Women destined to develop a short cervix (n=37) exhibited higher CVF concentrations of GM-CSF (15.6 times greater, CI 1.7 to 144, p=0.015) and MCP-1 (4.9, CI 1.03 to 23, p=0.045) at <24 weeks' than controls (n=41). Progesterone treatment had little effect on cytokine concentrations, whereas the concentration of five cytokines was higher in women randomised to cerclage vs progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by an increase in cervical length of 11.4 mm (CI 7.3 to 15.4, p<0.001).

Conclusion GM-CSF and MCP-1 appear to be involved in processes leading to cervical shortening. Progesterone treatment has little impact on CVF markers of inflammation or cervical length.

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Footnotes

  • Funding Action Medical Research (SP4113).

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