Stage-specific neutrophil states in neonatal injury: from antimicrobial deficiency to pro-resolution repair.

Neonatal neutrophils are often described as immature effector cells with limited marrow reserves and reduced antimicrobial capacity. This account is clinically useful but incomplete: individual functions mature at different rates, neutrophil populations are heterogeneous, and observed phenotypes vary with gestational age, maternal health, tissue context, and time after injury. This Mini Review first places neonatal findings against canonical mature-neutrophil functions, then examines context-dependent programs in neonatal sepsis, hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. We use state as an operational, cross-sectional description supported by phenotypic, functional, or molecular evidence, without assuming a stable lineage or a proven conversion from inflammatory to reparative cells. Temporal change may instead reflect emergency granulopoiesis, selective recruitment, survival, clearance, or population replacement. Human neonatal studies show that chemotaxis and extracellular-trap formation are often developmentally constrained, whereas phagocytosis, oxidative burst, granule content, and degranulation can be relatively preserved under specific assay conditions. Disease models further reveal competing roles for neutrophils in pathogen control, thromboinflammation, angiogenic support, and resolution. Conflicting findings on extracellular traps in necrotizing enterocolitis illustrate why model, microbial burden, intervention timing, and whether an experiment prevents trap formation or removes established traps must be distinguished. No clinically validated neonatal neutrophil-state classifier exists. Routine laboratory values provide clinical context and trajectories, whereas proposed interventions targeting extracellular traps, myeloperoxidase, trained immunity, lipid mediators, or efferocytosis remain experimental. Taken together, the evidence favors a context-dependent approach that preserves antimicrobial defense while testing ways to limit tissue injury.