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Parenteral nutrition arginine supplementation in very preterm infants and early immune system development

Presented at the Neonatal Society 2018 Autumn Meeting.

Burgess L1,2, Flanagan B1, Wright H1, Davies J1, Turner M1,2, Morgan C2

1 University of Liverpool, UK
2 Liverpool Women’s Hospital, UK

Background: We have previously shown there is both overprovision of essential amino acids (AA) and underprovision of some conditionally essential AA, including arginine (Arg), in current neonatal parenteral nutrition (PN) formulations (1). We conducted a physiological study assessing a range of doses of arginine (6-15%) alongside routine PN to address arginine deficiency and investigate its role in immune function. We hypothesised that arginine supplementation would affect gene expression that is consistent with changes in immune function.

Methods: Very preterm infants (VPI) born <29 weeks’ gestation and/or <1200g were eligible for PN. Infants were assigned to receive standard PN only or standard PN alongside a range of doses of arginine supplementation until day 10 (D10) of life. Blood samples were taken on day 3 (D3) and D10 of life. Plasma AA levels were measured using ion exchange chromatography and RNA was extracted and used for microarray and qPCR. Funding: The Newborn Appeal, Liverpool Women’s Hospital. The Study received ethical and regulatory approval.

Results: The study included 26 infants with a mean gestation of 26+4 weeks’ and mean birth weight of 855g. 8 infants received standard PN only (6% arginine), 12 received 12% arginine and 6 received 15% arginine. Plasma arginine levels were significantly higher on D10 of life in the supplemented infants (mean 72.8 v 45.5μmol/L, p=0.03). Microarray analysis was used to examine changes in gene expression between D3 and D10 and found 215 differentially expressed genes (115 upregulated and 100 downregulated). KEGG and Ingenuity pathway analysis (IPA) link these changes to pathways involved in immune function including B cell differentiation and activation, phagocytosis and pathogen recognition. qPCR validation experiments confirm significant up regulation in expression of mRNA of: B cell differentiation factors APRIL (p<0.01) and BAFF (p<0.05); pathogen recognition receptors TLR2 (p<0.01) and TLR4 (p<0.01); and calprotectin component S100A9 (p<0.05).

Conclusion: Arginine supplementation can reduce arginine deficiency in PN dependent VPI. Infants with normal (versus low) plasma arginine levels exhibit changes in immune pathways similar to the temporal changes seen from D3 to D10. These gene expression changes are consistent with development of a functional immune system.

Corresponding author: l.burgess@doctors.org.uk

1. Morgan C, Burgess L. High protein intake does not prevent low plasma levels of conditionally essential amino acids in very preterm infants requiring parenteral nutrition.JPEN J Parenter Enteral Nutr. 2017 Mar;41(3):455

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