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Recent systematic review confirms the potential of biomarkers to predict preterm labour.1To identify plasma biomarkers that predict preterm/term labour.82 women with threatened preterm labour (23–35/40) were recruited. Plasma was taken at presentation and repeated ≤24 h following spontaneous delivery. 10 case-matched sets of women were analysed across 2 experiments (n = 30). Each set comprised of a standardised control, asymptomatic low-risk antenatal sample, antenatal and postnatal sample from a symptomatic woman delivering at term, and antenatal and postnatal sample from a symptomatic woman delivering preterm. The Orbitrap Mass Spectrometer analysed samples. Protein changes were observed through the comparison of pre/post delivery ratios.Two proteins were significantly up-regulated postnatally in every term sample: Haptoglobulin, Pappalysin-1 (p < 0.05). This effect was absent in preterm groups.5 proteins were significantly down-regulated in postnatal preterm samples, whilst up-regulated postnatally in term women; Alpha-2 macroglobulin, Ig kappa chain V-I region Lay, Ig kappa chain V-I region BAN, Corticosteroid-binding globulin, Cysteine-rich secretory protein 3 (p < 0.05).Alpha-2 macroglobulin was significantly up-regulated antenatally in a comparison of preterm women versus gestation-matched low-risk asymptomatic women (p < 0.05).Volcanic plots demonstrate that most proteins did not alter significantly (p > 0.05).Exclusive up-regulation of 2 proteins in term deliveries suggests potential variation in the underlying mechanisms of term versus preterm labour. Nevertheless, the majority of protein changes across mid-gestation are small. The significant up-regulation of Alpha-2 macroglobulin antenatally, represents a potential plasma biomarker of clinical use for the accurate diagnosis of preterm labour.