Title The effect of increased Preterm Arginine INTake on biological pathways affecting immune function in infants requiring early parenteral nutrition (PAINT-18 )~Population Preterm infants <29 weeks gestation and/or <1200g~Number of infants 24 infants (completing the study) will be recruited over approximately 12 months~Number of sites One. Infants will be born at Liverpool Women's Hospital (LWH) or transferred to LWH within 48 hours of birth.~Study duration Informed consent will take place antenatally, where possible, or within 72 hours of birth. The first study related blood sample will be taken on day 3 of life with the last sample taken on day 30 of life. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).~Study intervention All infants will receive standard clinical treatment. 8 infants will receive PN with Vaminolact as the amino acid base, with 6.3% arginine content, and 16 infants will receive PN with additional arginine in the PN bag at a concentration of 18%. These 16 infants will be sub-stratified into two groups based on gestational age (23-26 weeks and 27-29 weeks).~Primary objective To examine the changes in gene expression present in arginine supplemented infants <29 weeks' gestation and/or <1200g between day 3 and day 10 of life. This 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 infants. The genes of interest are those involved in immune function and inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.~Secondary objectives~To examine the changes in gene expression present in arginine supplemented infants <29 weeks' gestation and/or <1200g between days 3, 10 and day 30 of life. This will be done via illumina RNA sequencing and statistical pathway analysis. The changes in gene expression will be compared with those seen between days 3, 10 and day 30 in unsupplemented infants. The genes of interest are those involved in immune function and inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.~Statistical pathway analysis will be used to identify genes and their relationship with key 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 compare the changes in metabolomic profiles of control and intervention infants during the first 30 days of life.~To compare growth (weight and head circumference) and body composition data including total body water (intracellular and extracellular distribution) and fat free mass during study period
PAINT18 is a nutrition study focusing on the effect of arginine supplementation on immune function in preterm 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 premature babies. The investigators will also investigate the effect of supplementing arginine on these genes. The investigators will undertake a single centre exploratory physiological study in 24 very premature infants receiving PN. 16 of these infants 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 of life. The investigators will take blood for analysis at prespecified intervals for RNA sequencing, ammonia and IGF-1 levels. RNA sequencing findings will allow the investigators to describe the effect of arginine on gene activity in preterm 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.