Objectives: To identify novel protein biomarkers and evaluate their combination with traditional inflammatory markers for early diagnosis of moderate-to-severe bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) preterm infants. Working Hypothesis: A combination of novel protein biomarkers and traditional inflammatory markers could improve early diagnostic accuracy for moderate-to-severe BPD. Study Design: Prospective cohort study. Patient Selection: 92 VLBW preterm infants (<1500g) were enrolled and categorized into mild BPD (n=42), moderate-to-severe BPD (n=30), and non-BPD (n=10) groups. Methodology: Blood samples were collected within 24 hours after birth. Peripheral inflammatory markers were measured, and plasma proteome was analyzed using Astral-DIA technology. Results: Proteomic analysis identified 127 differentially expressed proteins, with three proteins (IGFBP-2, S100A8, and IL-1Ra) showing the most significant changes in moderate-to-severe BPD. The combination of these three proteins achieved an AUC of 0.921 (95% CI: 0.864-0.978) for predicting moderate-to-severe BPD, outperforming traditional inflammatory markers including CRP (AUC=0.847). Integration of the protein panel with CRP further improved diagnostic accuracy (AUC=0.945). Conclusions: The study establishes a novel protein signature that, when combined with traditional inflammatory indicators, provides improved early diagnostic accuracy for moderate-to-severe BPD in VLBW infants.