Limited Relationship between Cervico-Vaginal Fluid Cytokine Profiles and Cervical Shortening in Women at High Risk of Spontaneous Preterm Birth

Abstract

ObjectiveTo 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.MethodsThis 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.ResultsAll 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].ConclusionsAlthough 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.

Microbiologic and Inflammatory Markers of Periodontitis are Different to those of Preterm Birth

“…This finding was also described by Matoba et al who quantified twenty-seven types of cytokines in cord blood at different gestational ages and found that MCP-1 was the one that was most strongly associated with PTB [40]. Significantly higher levels of MCP-1 have also been measured in cervicovaginal fluid [41] …”

Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

“…Samples for AMP analysis were obtained from a subset of women recruited to a previously reported prospective observational study (the C ervical L ength and I nflammatory C hanges: CLIC study) [23] designed to assess the relationship between inflammation and cervical shortening in women at high risk (i.e. women with a previous history or late miscarriage or sPTB) of sPTB.…”

“…Cervical length was assessed in accordance with standardised guidelines [23]. In brief, a sagittal view of the cervix was obtained with the long axis view of the echogenic endocervical mucosa along the length of the canal, allowing identification of both the internal and external os.…”

Host Defense Peptide Expression in Human Cervical Cells and Regulation by 1,25-Dihydroxyvitamin D3 in the Presence of Cytokines and Bacterial Endotoxin

“…Several proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8 and TNFα, have been detected in cervico-vaginal fluid in women at high risk of sPTB and women in threatened preterm labour [3][4][5] .…”