Beyond the Neutrophil Count: Functional Profiling and Targeted Modulation of Neutrophils in Paediatric Care

Neutrophils are the most abundant leukocytes in childhood and form a critical component of innate immunity, particularly in early life when adaptive responses are still maturing. In paediatrics, both quantitative and qualitative disturbances in neutrophil number or function shape susceptibility to infection and inflammatory tissue injury. Emerging data from neonatal, sepsis, and allergic cohorts show that paediatric neutrophils exhibit distinct effector profiles and regulatory roles compared with adults, positioning them as central mediators of child health and disease.

This review synthesises current understanding of neutrophil biology across key paediatric settings, spanning sepsis, benign transient neutropenia, severe congenital neutropenia, neonatal brain injury, and allergic disease. In paediatric sepsis, quantitative and functional neutrophil abnormalities, including impaired trafficking, excess immature forms, dysregulated pattern-recognition signalling and excessive NETosis, contribute both to failure of pathogen control and to organ injury. In childhood neutropenia, transient post-viral marrow suppression contrasts sharply with congenital defects of granulopoiesis, in which granulocyte colony-stimulating factor therapy has transformed survival. Experimental and clinical data in hypoxic-ischaemic neonatal brain injury highlight biphasic neutrophil recruitment, with the initial phase responsible for tissue damage while the later reparative phase is beneficial. Beyond infection, neutrophils emerge as key players in asthma, allergic rhinitis, anaphylaxis, and food allergy, where neutrophilic endotypes, IgG-neutrophil pathways and degranulation signatures link environmental exposures, disease severity, and treatment response.

Neutrophils in children display age- and context-dependent plasticity, acting as indispensable defenders against infection yet potent drivers of tissue damage when dysregulated. Paediatric care should move beyond simple neutrophil counts towards functional and phenotypic profiling to distinguish protective from pathogenic activity and to guide therapeutic management. Future therapies should focus on selectively modulating neutrophil trafficking and neutrophil extracellular trap formation, particularly in sepsis, neonatal encephalopathy and severe allergic disease, while preserving host defence in this uniquely vulnerable population.