Association of early VEGF trajectories with bronchopulmonary dysplasia severity in preterm infants

To characterize longitudinal vascular endothelial growth factor (VEGF) trajectories and establish time-discriminative thresholds for bronchopulmonary dysplasia (BPD) severity stratification in extremely preterm neonates. Prospective observational cohort study with serial biomarker assessments. Tertiary neonatal intensive care unit in Suzhou, China (February 2022-January 2023). The cohort comprised 157 infants born at < 30 weeks' gestation with birth weights < 1250 g. After exclusions (n = 21), 136 infants completed the study protocol. BPD severity and weekly plasma VEGF levels (cord blood to postnatal day 28). Analyses included adjusted mixed-effects models for longitudinal trends and Receiver Operating Characteristic (ROC) curves with bootstrap 95% confidence intervals for discriminative accuracy. Infants developing moderate-to-severe BPD (n = 44) exhibited biphasic VEGF dysregulation: elevated cord blood levels (75.8 pg/mL, 95% CI: 63.2-88.4) followed by steep weekly decline (- 56.0 pg/mL/week, 95% CI: -62.5 to - 49.4), whereas no/mild BPD infants (n = 92) maintained stable trajectories (P < 0.001, partial η² = 0.67). Discriminative performance varied temporally: at birth (AUC 0.88, 95% CI: 0.82-0.93; threshold ≥ 338.6 pg/mL), Day 14 (AUC 0.75, 95% CI: 0.66-0.84; threshold ≤ 232.2 pg/mL) and at Day 21 (AUC 0.91, 95% CI: 0.85-0.96; threshold ≤ 217.5 pg/mL), bootstrap validation confirmed robustness. Longitudinal VEGF trajectories from a parsimonious mixed‑effects model identified infants who developed moderate‑to‑severe BPD, supporting potential for early risk stratification requiring validation.