Bronchopulmonary Dysplasia and the Oxidative Puzzle: Current and New Strategies for Neonatal Health

Significance: Bronchopulmonary dysplasia (BPD) remains a major chronic lung disease of prematurity and an important cause of long-term respiratory morbidity in preterm infants. As survival of extremely preterm infants has improved, the clinical burden of BPD has remained substantial. Redox dysregulation, characterized by an imbalance among oxidant exposure, antioxidant capacity, and adaptive signaling responses, represents a central pathogenic mechanism in BPD and contributes to impaired alveolar and vascular development, inflammatory amplification, and defective lung repair.Recent Advances: Current neonatal management strategies, including optimized respiratory support, careful oxygen targeting, nutritional support, caffeine therapy, and selective corticosteroid use, may reduce oxidant burden or modulate redox-sensitive injury pathways. In parallel, antioxidant-related interventions-including vitamins, trace elements, glutathione-related therapies, natural products, and pharmacological agents-have demonstrated biological plausibility.Critical Issues: Current interventions do not consistently correct the underlying redox imbalance of the immature lung. The clinical translation of antioxidant-related therapies remains limited and highly dependent on the level of evidence, intervention timing, and biological context. This review summarizes the role of redox dysregulation in the pathogenesis of BPD and critically examines the clinical and preclinical evidence for redox-related interventions.Future Directions: Emerging priorities include biomarker-guided therapy, omics-informed risk stratification, targeted pulmonary delivery, precision nutritional strategies, and integrated multimodal approaches. Future progress in BPD prevention and treatment will likely depend on integrating redox-informed approaches with established neonatal care, targeted interventions, and rigorous long-term clinical evaluation. Antioxid. Redox Signal. 00, 000-000.