Immunophenotyping of very and extremely preterm infants at risk of developing sepsis and necrotising enterocolitis – a prospective, single-centre cohort study

BJECTIVE: To characterise adaptive immunity in very and extremely preterm neonates and assess potential immunological markers that predispose them to infection. STUDY DESIGN: Peripheral blood lymphocytes in 30 very to extremely preterm neonates (mean birth weight 815 g) were analysed using 9-colour flow cytometry at days of life 0–7, 8–14, and 15–28. Patients were prospectively recruited at the University Hospital of Zurich from 2021 to 2023. Statistical analyses included group comparisons and longitudinal assessments. RESULTS: Six of the thirty preterm neonates (20%) developed early- or late-onset sepsis, of whom one (3%) also exhibited signs of necrotising enterocolitis. T and B lymphocytes were predominantly composed of naïve T cells and unswitched CD27- B cells, respectively. The CD4/CD8 ratio was initially elevated, especially in extremely preterm neonates, and declined significantly after week 1. EPT neonates also had significantly fewer natural killer cells compared with very premature infants. Although no distinct immunological features were identified as predisposing to infection, B-cell proportions were significantly higher in infected neonates during the second week of life, possibly reflecting an immune response to infection. CONCLUSION: Adaptive immunity in preterm neonates is characterised by profound immaturity, including an almost complete absence of immunological memory and low CD8 T-cell frequency, which may limit effective pathogen elimination and increase susceptibility to infection. Immunophenotyping provides valuable insights into the immune processes in this vulnerable population and, when combined with clinical observations and routine laboratory findings, could aid in the earlier identification of high-risk neonates and guide targeted interventions.