Perinatal inflammation influences but does not arrest rapid immune development in preterm babies

S Kamdar,K Costeloe,K Ansbro,A Laing,M R Millar,W G Wade,D L Gibbons,R Hutchinson,P Fleming,F Stacey

doi:10.1038/s41467-020-14923-8

Abstract

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this risk, there is limited understanding of the development of the immune system in those born prematurely, and of how this development is influenced by perinatal factors. Here we prospectively and longitudinally follow a cohort of babies born before 32 weeks of gestation. We demonstrate that preterm babies, including those born extremely prematurely (<28 weeks), are capable of rapidly acquiring some adult levels of immune functionality, in which immune maturation occurs independently of the developing heterogeneous microbiome. By contrast, we observe a reduced percentage of CXCL8-producing T cells, but comparable levels of TNF-producing T cells, from babies exposed to in utero or postnatal infection, which precedes an unstable post-natal clinical course. These data show that rapid immune development is possible in preterm babies, but distinct identifiable differences in functionality may predict subsequent infection mediated outcomes.

Highlights

Infection and infection-related complications are important causes of death and morbidity following preterm birth
We demonstrate that preterm babies rapidly acquire some adult levels of immune function; have immune functions that progress towards but do not reach adult levels; or have immune functions, conspicuously C-X-C motif chemokine ligand 8 (CXCL8)-producing T cells, that remain significantly distinct from adults
Thirteen further infants were born to mothers with histological or clinically confirmed chorioamnionitis, all but one of these fulfilled the unstable criteria

Summary

Introduction

Infection and infection-related complications are important causes of death and morbidity following preterm birth. We observe a reduced percentage of CXCL8producing T cells, but comparable levels of TNF-producing T cells, from babies exposed to in utero or postnatal infection, which precedes an unstable post-natal clinical course These data show that rapid immune development is possible in preterm babies, but distinct identifiable differences in functionality may predict subsequent infection mediated outcomes. Infants born before 32 weeks gestational age (GA) show a greater susceptibility to asthma in later life and yet a decreased risk of developing food allergy[8,9] Despite these drivers, understanding of how the preterm immune system develops is incomplete, and the impacts on the developing immune system of exposure to infection in utero, as well as the postnatal clinical course, have not been comprehensively evaluated. This, in turn, may help reduce the burden posed by infection and lead to improved outcomes for babies born prematurely

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Conclusion