Parry S, Leite R, Esplin MS, et al. - Using targeted and shotgun proteomic analyses, researchers sought to determine cervicovaginal fluid biomarkers of early spontaneous preterm birth in a high-risk cohort of pregnant women with a history of spontaneous preterm birth. In this nested case control study (cases were spontaneous preterm birth < 34 weeks in the current pregnancy; controls were spontaneous labor and delivery at 39–41 weeks), collection of cervicovaginal fluid samples was performed at 3 study visits (10 ^0/7 to 18 ^6/7 weeks, 19 ^0/7 to 23 ^6/7 weeks, and 28 ^0/7 to 31 ^6/7 weeks). A history of at least 1 prior spontaneous preterm birth was reported in all participants. Targeted and shotgun proteomics analyses revealed potential biomarkers of spontaneous preterm birth in cervicovaginal fluid samples from high-risk, asymptomatic women. Cervicovaginal fluid samples from spontaneous preterm birth cases displayed higher level of many proteins; of these, many are extracellular matrix proteins and/or regulate cell membrane physiology. Despite substantial biological interest in these proteins, validation enzyme-linked immunosorbent assay for 5 of these proteins did not provide clinically valuable biomarkers for spontaneous preterm birth.