Lactoferrin for Infants and Children: A Review of Its Mechanisms of Action and the Mixed Clinical Evidence

Infections remain a leading cause of illness and death in infants and young children, and the steady rise of antimicrobial resistance makes the search for safe host-directed agents more pressing. Lactoferrin, an iron-binding glycoprotein of the transferrin family, is abundant in human colostrum and is now produced at scale from bovine milk and by recombinant routes. This narrative review brings together experimental and clinical work on its use in pediatric infectious and inflammatory disease. We first outline its structure, natural sources and iron forms. We then describe how it acts against bacteria, viruses and fungi: by withholding iron, damaging microbial membranes, releasing the cationic peptide lactoferricin, degrading virulence factors and blocking biofilm formation. Its immunomodulatory side is discussed next, including neutralization of lipopolysaccharide, dampening of NF-κB-driven cytokine release, support of phagocyte and dendritic-cell function, and regulatory T-cell responses. A third section covers its effects on the immature gut, namely epithelial growth and maturation, barrier tightening and the promotion of bifidobacteria. The clinical record is then examined. Early trials in very-low-birth-weight neonates, led by an 11-center Italian trial, reported large falls in late-onset sepsis and necrotizing enterocolitis, but two large multicenter trials, ELFIN and LIFT, found no significant benefit. Newer small trials and pooled analyses still point to a low-certainty fall in late-onset sepsis. Trials in older infants and children suggest modest effects on the severity of diarrheal and respiratory illness. We close by discussing product quality, dosing, safety and the trial designs needed to settle where lactoferrin truly helps sick children.