ESPE Abstracts

Background: Fifteen years ago children born very preterm (<32 weeks of gestation) were reported to be insulin resistant. Neonatal intensive care has since improved considerably, but it is unclear whether this has affected long-term outcomes in those born preterm. Abnormalities in gut microbiome, which influence host metabolism, have been found in preterm newborns.

Objective and hypotheses: We aimed to assess whether children born very preterm still had lower insulin sensitivity than term controls, and whether there were differences in gut microbiome. We hypothesized that early life events in infants born very preterm lead to long-term alterations in gut microbiome, which contribute to later insulin resistance.

Method: Participants were pre-pubertal children aged 5–11 years born very preterm (n=51; 61% boys) or at term (37–41 weeks; n=50; 62% boys). Insulin sensitivity was assessed using frequently-sampled intravenous glucose tolerance tests and the Bergman’s minimal model. A fresh stool sample was collected from all children, and RNA extracted for assessment of gut microbiome composition and activity.

Results: Children born very preterm were lighter (weight SDS −0.16 vs 0.47; P=0.0005), shorter (height SDS 0.31 vs 0.92; P=0.0006), and leaner (BMI SDS −0.20 vs 0.29; P<0.0001) than term children. Notably, children born very preterm had lower insulin sensitivity than term controls (9.2 vs 12.5×10–4· min⁻¹(mU/l); P=0.0007), even after adjustment for confounders. Stool metatranscriptomics identified Coriobacteriaceae, particularly Collinsella spp., as being associated with preterm birth. There were also different microbiome activities in children born preterm, such as increased catabolism of glutamate and arginine, which are involved in glucose homeostasis.

Conclusion: Adverse metabolic programming (i.e. lower insulin sensitivity) remains a feature of pre-pubertal children born very preterm. Differences in gut microbiome composition and activity are also present in mid-childhood, suggesting a possible role of gut microbiome in defining the metabolic phenotype of those born preterm.