Cervicovaginal fluid proteomic analysis to identify potential biomarkers for preterm birth

Abstract Background Spontaneous preterm birth (SPTB) is a leading cause of neonatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could reduce the SPTB rate, but conventional methods such as obstetrical history and maternal cervical length screening identify only a minority of SPTB cases. Cervicovaginal fluid (CVF) might prove to be a useful, readily available biological fluid for identifying SPTB biomarkers. Objective To identify CVF biomarkers of early SPTB in a high-risk cohort of pregnant women with a history of SPTB using targeted and shotgun proteomic analyses. Study Design A nested case control study (cases = SPTB Results For targeted proteomics, CVF samples from 33 cases and 32 controls at 190/7-236/7 weeks, and 16 cases and 14 controls at 280/7-316/7 weeks from the same pregnancies, were analyzed. When samples were compared between cases and controls, the relative abundance of five proteins was greater (P=0.02-0.05) in cases at both visits, while the relative abundance of one protein was lower (P=0.03) in cases at both visits. For shotgun proteomics analyses, CVF samples were pooled for nine SPTB cases and nine term delivery controls at each study visit. Shotgun proteomics yielded 28 proteins that were detected at levels >2x higher and one protein that was detected at a level Conclusions Potential biomarkers of SPTB were identified by targeted and shotgun proteomics analyses in CVF samples from high-risk, asymptomatic women. Many of the proteins detected at higher levels in CVF samples from SPTB cases are extracellular matrix proteins and/or regulate cell membrane physiology. These proteins have substantial biological interest, but validation ELISA for five of these proteins did not yield clinically useful biomarkers for SPTB.