Asymptomatic women with preterm birth have rising cervicovaginal CXCL10 across mid-trimester
The CXCR3 receptor chemokines (CXCL9, CXCL10 and CXCL11) are often implicated in chronic placental inflammation (CPI) associated with spontaneous preterm birth (sPTB). Overexpression of these and other chemocytokines in the cervicovaginal space may be indicative of chronic subclinical inflammation and risk of sPTB similar to their role in CPI. Hence, we measured the concentrations of CXCL9, CXCL10, CXCL11, TNF-α, Eotaxin and TNFR1 in cervicovaginal fluid (CVF) of asymptomatic pregnant women across mid-trimester and determined the ability of these chemocytokines to predict risk of sPTB before 37 weeks’ gestation.
CVF samples were collected from 51 asymptomatic high risk pregnant women at two gestational time points (GTPs): GTP1 – 20+0–22+6 weeks, n=51, preterm=17, term=34; and GTP2 – 26+0–28+6 weeks, n=45, preterm=14, term=31. Concentrations of chemocytokines were quantified by multiplexed bead-based immunoassay (Cytometric Bead Array, CBA), while fetal fibronectin (fFN) concentration was determined by 10Q Rapid analysis. The GTP1/GTP2 ratios of cytokines and fFN concentrations were compared between preterm- and term-delivered women using area under the Receiver Operating Characteristics curves (AUC) to predict risk of sPTB.
Four (23%) of the preterm women experienced preterm prelabour rupture of membranes. None of the measured cytokines differed between the groups at GTP1. At GTP2, only TNFR1 was higher in the term compared to preterm women (p=.049) and distinguished both groups (AUC=.88, p=.005, n=12). However, when expressed as a ratio of GTP1/GTP2, only CXCL10 was higher in the preterm than term women and was predictive of sPTB (AUC=.68, p=.044, n=45). Combination of the ratios of CXCL10 and fFN improved sPTB prediction (AUC=.74, p=.007). The concentrations of CXCL11, TNF-α, Eotaxin (in all samples) and TNFR1 (in some samples) could not be determined as they were either below or above the detection limit of the CBA.
These findings suggest increasing CVF CXCL10 with gestation in preterm women may indicate a chronic subclinical inflammation of gestational tissues that increase the risk of sPTB. If confirmed in larger cohort studies, early estimation of CVF CXCL10 alone or in combination with fFN may identify the risk of inflammation-associated sPTB in asymptomatic women and guide preventive and/or therapeutic interventions.