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. They will also investigate the effect of supplementing arginine on these genes. The investigators will undertake a single centre exploratory physiological study in 12 very premature infants receiving PN. 4 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 10 days of life. They will take blood for analysis at prespecified intervals for microarray, ammonia and IGF-1 levels. Microarray findings will allow the investigators to describe the effect of arginine on gene activity in preterm infants.

Title:

Effect of Preterm Arginine INTake on biological pathways affecting immune function in infants requiring early parenteral nutrition (PAINT)

Population: Preterm infants <29 weeks gestation

Number of infants: 12 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 within 72 hours of birth. The first study related blood sample will be taken at this point and will determine arginine status (using blood ammonia and arginine levels) with the last sample taken on postnatal day 10. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).

Study intervention: All infants will receive standard clinical treatment. The study will involve 4 infants with normal arginine status, and 8 infants with evidence of arginine deficiency. Of these, 4 infants will receive standard PN and the study intervention of an additional arginine infusion of 10mg/kg/hr from day 3 until day 10, the other 8 infants will receive standard PN only.

Primary objective: To determine the alterations in gene expression present in infants <29 weeks gestation (and shown to be arginine deficient on day 3) between day 3 and day 10 in infants receiving additional arginine supplementation. The changes in gene expression will be compared with those seen between day 3 and day 10 in unsupplemented infants, with and without arginine deficiency. The genes of interest are those involved in T-cell function and associated inflammatory pathways.

Secondary objectives:

1. 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
2. To assess whether there is an association between high ammonia levels (as a measure of functional arginine deficiency) and T-cell dysfunction and associated inflammatory pathways.

Inclusion Criteria:

• Preterm infants born between 23 and 29 completed weeks gestation and admitted to the neonatal unit within 48 hours of birth

Exclusion Criteria:

• Infants who are unlikely to survive the first week after birth.
• Infants with early onset infection (<72 hours)
• Infants known (or suspected to have) a diagnosis of inborn error of metabolism or serious liver dysfunction
• Parents who are unable to give informed consent

No IPD will be made available