Title:~Arginine Supplementation and the Postoperative Immune REsponse (ASPIRE) in neonates~Population:~Preterm infants <30 weeks gestation requiring a laparotomy/major bowel surgery before discharge; Term and near term infants (born >35 weeks gestation) requiring a laparotomy/major bowel surgery in the first 3 days of life (gastroschisis; major bowel atresias expected to require at least 7 days PN).~Number of infants:~32 infants (completing the study) will be recruited over approximately 24 months: 16 in the preterm group and 16 in the term group.~Number of sites:~Two sites - Alder Hey Children's Hospital (AHCH) and Liverpool Women's Hospital (LWH) under the umbrella of the Neonatal Partnership. Eligible infants will undergo surgery at AHCH and will receive early postoperative care at either AHCH or LWH~Study duration:~Informed consent will take place preoperatively where possible, or within 72 hours of surgery. In the term group, antenatal recruitment will be attempted. The first study related blood sample will be taken on day 3 postoperatively with the last sample taken on day 30 post-operatively. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).~Study intervention:~All infants will receive standard clinical treatment. 8 preterm and 8 term infants will receive PN as determined by local clinical guidelines (6.3 or 8.4% arginine content). 8 preterm infants will receive PN with an additional arginine supplement aimed to achieve 18% arginine intake (allocated according to intervention PN stock availability). 8 term infants will receive arginine supplementation up to 18%.~Primary objective:~To examine the changes in gene expression present in arginine supplemented infants between day 3 and day 10 post-operatively. Thus will be done via illumina RNA sequencing and statistical pathway analysis. The changes in gene expression will be compared with those seen between day 3 and day 10 in unsupplemented preterm and term infants. The genes of interest are those involved in immune function and inflammatory pathways.~Secondary objectives:~To explore other biological pathways i) known to be involved in the pathogenesis of necrotising enterocolitis ii) involved in arginine metabolism iii) that are related to the insulin-IGF-I axis~To determine the changes in metabolomic profiles of these infants during the first 30 days postoperatively.~Growth and body composition data during study period.
ASPIRE is a nutrition study focusing on the effect of arginine supplementation on immune function in postoperative infants.~The investigators will explore the effect of current intravenous feeding (parenteral nutrition (PN)) formulations on blood arginine levels and the genes that are involved in body nutrition and fighting infection in babies who have had major bowel surgery. The investigators will also investigate the effect of supplementing arginine on these genes. The investigators will undertake an exploratory physiological study across two sites under which are part of a single neonatal partnership. 32 infants will be recruited; 16 preterm infants and 16 term/near term infants. 16 of these infants (8 preterm and 8 term/near term) will be supplemented with arginine. The investigators will record nutritional intake and routine biochemical testing data (which includes amino acid levels) collected over the first 30 days post surgery. The investigators will take blood for analysis at prespecified intervals for RNA sequencing, ammonia and metabolomics. RNA sequencing findings will allow the investigators to describe the effect of arginine on gene activity in postoperative infants~The investigators hypothesise that arginine supplementation will result in changes in gene expression that are consistent with changes in T-cell function and associated inflammatory pathways.