Optimisation of Arginine Intake in Very Preterm Neonates on Neonatal Parenteral Nutrition Formulation

Premakumar, C ORCID: 0000-0001-6140-5069 (2019) Optimisation of Arginine Intake in Very Preterm Neonates on Neonatal Parenteral Nutrition Formulation. PhD thesis, University of Liverpool.

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Abstract

The overall aim of the thesis was to design and test modified neonatal parenteral nutrition (PN) formulations with additional arginine content in very preterm neonates (VPNs) dependent on PN. Review of the literature resulted in a dose concentration graph that suggested a percentage content of about 14% and absolute arginine intake of about 600mg/kg/day to achieve target plasma arginine levels ≥80 micromoles/L. Previous studies have reported that VPNs dependent on PN have low plasma arginine levels and an oversupply of essential amino acids (EAAs). The difficulties with assessing amino acid (AA) status were explored using published AA profiles. Modified PN formulations using two different base AA solutions, Vaminolact® and Primene®, containing 14% arginine were designed and manufactured in an aseptic, clean room setting. These formulations were tested in a stability testing study using common physical tests such as visual appearance, pH, optical rotation, UV absorbance and sub-visible particle count. This thesis included AA assay of PN formulations as a part of PN stability testing. It was included to monitor the AA content in the PN formulations tested. The results showed that the modified PN formulations with 14% arginine were stable for 90 days (without trace elements solution - Peditrace™) and 7 days (with Peditrace™). The AA assay results proved that the modified PN formulations contained 14% arginine as per the designed calculations and it also provided evidence that AA assay is a new, practical and reliable method to quality control arginine supplementation of PN formulations. The stability testing study also demonstrated that single sampling for each test point is crucial for PN stability testing to reduce the risk of contamination and oxidation to an extremely complex solution such as PN formulations. A clinical study (PAINT-NH4) compared the plasma AA profiles of VPNs on standard PN formulation (containing 6% arginine) versus intervention PN formulation (containing 14% arginine). The findings suggested that on Day 3, plasma arginine levels were significantly different between the treatment groups. Whereas on Day 10, plasma arginine levels were not significantly different. The high dependence on PN during first few days of life (Day 3) resulted in a significant impact from the intervention while the decreased PN dependency of the intervention group infants by Day 10 of life reduced the impact of the intervention and hence affected the plasma arginine levels. The comparison of the entire plasma profiles between the treatment groups in PAINT-NH4 illustrated that an increased arginine content while maintaining overall AA content (with reduction of all other AAs except arginine) resulted in rebalancing of the profiles to more closely resemble the reference range of healthy breastfed preterm infants. Plasma arginine levels increased whereas the oversupply of EAAs reduced. This indicated that rebalancing of AA content in PN formulations are reflected in the plasma AA profiles of VPNs. Although plasma arginine levels increased, the mean plasma arginine levels did not achieve the target levels above 80micromoles/L. Therefore, future work has been proposed to test a 18% arginine content solution with current AA intakes.

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	parenteral nutrition, neonate, premature, arginine
Divisions:	Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine
Depositing User:	Symplectic Admin
Date Deposited:	10 Aug 2020 12:42
Last Modified:	19 Jan 2023 00:26
DOI:	10.17638/03055041
Supervisors:	Turner, Mark ORCID: 0000-0002-5299-8656 Morgan, Colin
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3055041