Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia

OBJECTIVE: To demonstrate and validate the improvement of current risk stratification for bronchopulmonary dysplasia (BPD) early after birth by plasma protein markers (sialic acid-binding lg-like lectin 14 (SIGLEC-14), basal cell adhesion molecule (BCAM), angiopoietin-like 3 protein (ANGPTL-3)) in extremely premature infants. METHODS AND RESULTS: Proteome screening in first-week-of-life plasma samples of n- 52 preterm infants <32 weeks gestational age (GA) on two proteomic platforms (SomaLogic (R), Olink-Proteomics (R)) confirmed three biomarkers with significant predictive power: BCAM, SIGLEC-14, and ANGPTL-3. We demonstrate high sensitivity (0.92) and specificity (0.86) under consideration of GA, show the proteins' critical contribution to the predictive power of known clinical risk factors, e.g., birth weight and GA, and predicted the duration of mechanical ventilation, oxygen supplementation, as well as neonatal intensive care stay. We confirmed significant predictive power for BPD cases when switching to a clinically applicable method (enzyme-linked immunosorbent assay) in an independent sample set (n = 25, p < 0.001) and demonstrated disease specificity in different cohorts of neonatal and adult lung disease. CONCLUSION: While successfully addressing typical challenges of clinical biomarker studies, we demonstrated the potential of BCAM, SIGLEC-14, and ANGPTL-3 to inform future clinical decision making in the preterm infant at risk for BPD.

Automated summary

This study aims to improve the current risk stratification for BPD and validate the effectiveness of plasma protein markers. The research identified three biomarkers, BCAM, SIGLEC-14, and ANGPTL-3, that can predict the need for mechanical ventilation, oxygen supplementation, and length of neonatal intensive care stay in premature infants at risk for BPD.