Plasma proteome profiling identifies predictive signatures for preterm birth risk

Preterm birth (PTB) is a major public health concern, and its associated complications account for 16.6% of deaths in children under five years. Over 50% of such deliveries are spontaneous, with unknown underlying causes. We identified significant changes in the plasma proteome across mid-trimester prior to the pre-term deliveries, indicating signals for identifying mothers at risk for PTB. Using quantitative LC-MS analysis and machine learning, we identified high plasma levels of Calcyophosin-2 (CAPS2) at 18-20 weeks of gestation in women who delivered preterm. Prediction model based on plasma CAPS2 level in a case-cohort (n=795) design accurately predicted high-risk sPTB with a detection rate of over 90% while reducing 40% false positivity and therefore avoiding subsequent unnecessary tests in them. Our findings strongly highlight CAPS2 as a novel candidate biomarker for prediction at early mid-trimester, accurately screening women at risk of preterm delivery, particularly in low-resource primary and secondary care settings where there are no existing screening programs for preterm birth.