Perinatal Inflammation Influences but Does Not Arrest Rapid Immune Development in Preterm Babies

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this, there is limited understanding of the development of the immune system in those born prematurely and how it is influenced by perinatal factors. To investigate this, we prospectively and longitudinally followed a cohort of babies born before 32 weeks of gestation. We demonstrated that preterm babies, including those born extremely prematurely, were capable of rapidly acquiring adult levels of immune functionality; that immune maturation appeared to occur independently of the developing microbiome, which was highly heterogeneous across different infants; and that the biggest drivers of change in the trajectory of perinatal immune development was exposure to infection in utero or post-natally. Conspicuously, a unifying factor among infants who developed infection despite their growing immune potentials was an inability to mount adequate T cell CXCL8 responses. Because this defect was present at birth, it may predict those babies likely to have poor clinical outcomes.