Human Milk, Protein Adequacy, and Neurodevelopment in Preterm Infants: A Narrative Review

Human milk is increasingly recognized not only as a source of nutrition but also as a biological regulator of organ development in preterm infants. Beyond supporting growth, human milk contains a complex array of bioactive components that influence intestinal maturation, immune function, vascular development, and brain development during a critical period of extrauterine adaptation. This narrative review summarizes current evidence regarding the role of human milk in multi-organ development in preterm infants. We review clinical and mechanistic studies demonstrating associations between human milk exposure and reduced risks of necrotizing enterocolitis, late-onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity. Particular attention is given to the interconnected gut-immune-lung-retina-brain axis and the biological pathways through which human milk may influence developmental outcomes. We further discuss the importance of early enteral feeding, adequate protein delivery, and human milk-derived fortification in supporting growth quality, lean mass accretion, head growth, and structural brain development. Emerging evidence suggests that nutritional strategies promoting early and sustained human milk exposure may contribute not only to protection from major prematurity-related morbidities but also to improved neurodevelopmental trajectories. By integrating current biological and clinical evidence, this review highlights the role of human milk as a foundation for developmental nutrition in preterm infants and provides a practical perspective for optimizing nutritional care in the neonatal intensive care unit.