Immune Impairment in Preterm Neonates and Its Impact on Morbidity

Sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, and neurodevelopmental impairment remain major challenges in preterm care. Increasing evidence suggests that immune immaturity and dysregulated inflammatory responses play central roles in determining vulnerability and outcomes in this high-risk group. This narrative review emphasizes the role of intrinsic deviations in immune development and its impact on disease. It is quite evident that there is a "host/patient factor" that determines clinical presentation, severity, response to standard therapy, and outcomes for any disease. The manuscript synthesizes current literature on key alterations in innate, adaptive, and humoral immunity in preterm neonates and discusses their contribution to morbidity. There is emerging information on immune ontogeny in preterm infants, including interactions with cytokine dysregulation and oxidative stress. Evidence linking immune alterations with clinical outcomes such as sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and neurodevelopmental injury is highlighted, with attention to the dearth of data relevant to low- and middle-income settings. Interpretation of immune-based screening tools, such as T-cell receptor excision circle-based newborn screening for primary immunodeficiency, is further complicated by physiological immune immaturity in preterm neonates. The review suggests areas that need further research and the potential role of precision medicine in this regard.