Are cervicovaginal fluid inflammatory mediators associated with mid-trimester cervical shortening in women with prior spontaneous preterm birth?

The combination of prior spontaneous preterm birth (sPTB) and shortened cervical length (CL) markedly increases the risk of recurrent sPTB. The pathophysiology of cervical shortening is poorly understood but may involve local inflammatory mediators. We examined cervicovaginal fluid (CVF) concentrations of inflammatory mediators in women who developed CL <25mm versus those whose CL stayed ≥25 mm. We conducted a nested case-control study of women enrolled in a multicenter randomized trial of ultrasound-indicated cerclage for prevention of recurrent PTB. Women had serial CL’s from 16-22 wk. A CVF sample was collected using a polyester swab from the posterior fornix, placed in buffer and stored at -80C until thawed for analysis. Cases were women who developed CL<25 mm; controls maintained a CL ≥25 mm and delivered ≥37 wk. GM-CSF, IL-10, IL-1b. IL-4, IL-6, IL-8, MCP, TNF-α and MMP-1 were measured in duplicate using commercially available Luminex immunoassays. Groups were compared with the t-test. Statistical significance was assessed at α=0.005. CVF samples obtained at the time of the initial CL measurement (17.6wk±2.7wk) were available from 162 women who had a CL<25 mm and 299 women who maintained a CL≥25mm. Results are displayed in the Table. The concentration of TNF-α was significantly higher in women who developed cervical shortening. While IL-8 was higher in those with CL≥25mm, this difference was not significant. Concentrations of the other mediators, including MMP-1 which has a role in collagen remodeling, were similar between groups. Concentrations of TNF-α were higher in the CVF between 16 and 22 wk in women with a prior sPTB who developed a CL<25 mm. This may reflect a local inflammatory process in the pathway to CL shortening. Whether this inflammatory process and cervical shortening can be prevented warrants further investigation.