Amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double blind con

Lead Research Organisation: Chelsea & Westminster Hosp NHS Fdn Trust

Abstract

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Technical Summary

Scientific Abstract|Design: Multicentre, UK, randomised double blind controlled trial (RCT). Eligible infants will be randomised within 12 hours of birth to receive parenteral nutrition (PN) with Recommended Daily Intake of amino acids (intervention) or PN with incremental increase in amino acids (control) and either 20% lipid (control) or 20% SMOF lipid (intervention). Intralipid is a first generation intravenous emulsion that is the currently widely used formulation. SMOF lipid, a third generation emulsion (soy bean, medium chain triglycerides, olive and fish oil) has an improved ratio of n6 to n3 fatty acids that has been shown to be liver protective. Randomisation will be stratified by gestational age and centre. Enteral feeding will be commenced within 24 hours and advanced according to a pre-specified protocol that has previously been used by us in a RCT to control for potential differences arising from different feeding regimens. Dietary intakes will be captured from birth until discharge prospectively. PN will continue until the infant is tolerating full milk feeds. Enteral nutrition will be in the form of maternal expressed breast milk. If this is in short supply, standard preterm formula milk will be used as supplement. Research ethics approval and informed parental consent will be sought. The trial will be conducted in accordance with Good Clinical Practice. A Data Monitoring Committee and Trial Steering Committee will be set up. User input has been sought.|Setting: Neonatal Intensive Care units in North West London. Participants within this perinatal network cover wide socio economic and ethnic groups and are representative of those in the rest of the NHS. |Target Population: Preterm infants less than 31 weeks of gestation. These are infants who require nutritional support in the form of PN. Exclusion criteria: Infants with major congenital or life threatening anomalies.|Intervention being evaluated: The intervention being evaluated is PN. PN is the only means of delivering nutrition in extremely preterm infants in the immediate period after birth because of gastrointestinal immaturity and also when enteral feeding is contraindicated. Current practice in neonates is variable, inconsistent and not evidence based. Current practice results in significant deficits in protein which cannot be made up. Although RDI have been described for this group of infants (based on fetal growth rates from studies on fetal cadavers) the impact on body composition of providing this from birth has not previously been studied.|Measurements of outcomes and duration of follow up: |Primary outcome measure: Body composition at term or near term age equivalent, including lean body mass and adipose tissue mass measured by whole body magnetic resonance imaging (MRI) and Hepatic magnetic resonance spectroscopy (MRS) to measure intrahepatocellular lipid content (IHCL). |Secondary outcome measures: 1. Adipose tissue quantity and distribution. 2. Anthropometry; 3. Brain MRI (brain growth measured by cerebral volumes); 4. Metabolic index of insulin sensitivity at term age equivalent (QUICKI) calculated using fasting serum glucose and insulin; While measurement of weight, head circumference and length are inexpensive and routinely used to monitor growth, they do not reflect the composition of weight gain in relation to lean body and adipose tissue mass. It is not only the quantity but the distribution of lean and adipose tissue that is associated with metabolic health. The distribution of lean and adipose tissue mass is strongly influenced by diet and in turn affect metabolic health.| Therefore measurements of lean and adipose tissue mass are more clinically meaningful outcomes to measure following nutritional intervention. There are many ways to measure body composition. Several methods rely on assumptions and while they can measure absolute quantity of a certain tissue, they cannot measure the distribution. MRI and MRS are non invasive and valida
 
Guideline Title BAPM: The Provision of Parenteral Nutrition within Neonatal Services - A Framework for Practice December 2015
Description British Association of Perinatal Medicine: The Provision of Parenteral Nutrition within Neonatal Services - A Framework for Practice December 2015
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
URL http://www.bapm.org/publications/documents/guidelines/PN%20framework%20-%20draft%20for%20consultatio...
 
Description Citation in Cochrane Review (Lipid emulsions)
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
 
Guideline Title NICE Guideline Neonatal Parenteral Nutrition
Description Inclusion in NICE Guideline
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
 
Description Membership of NICE Committee on Neonatal Parenteral Nutrition
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description National Neonatal Parenteral Nutrition QIPP in London
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
Impact In progressing the National Neonatal Quality Innovation Productivity and Prevention programme in the London Neonatal Operational Delivery Network (ODN) a Core Nutrition Group was set up (including the CI of the study) and a decision was made to standardise parenteral nutrition within London. One of the two options of parenteral nutrition regimens was the trial regimen used in this trial. The aim of the exercise is not only to improve consistency in the prescribing, manufacturing and delivery of parenteral nutrition (PN) but NHS England aims to move towards central procurement of neonatal parenteral nutrition. In the North West London ODN all 6 hospitals have opted to use the trial PN.
 
Guideline Title Implementing Standard Parenteral Nutrition in London
Description Trial Parenteral Nutrition Formulation recommended for standard use in London
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Citation in clinical guidelines
 
Description Chelsea and Westminster Joint Research Committee
Amount £150,000 (GBP)
Organisation Chelsea and Westminster Hospital NHS Foundation Trust 
Sector Public
Country United Kingdom
Start  
 
Description EPIC Study
Amount £76,086 (GBP)
Organisation HCA Hospitals 
Sector Private
Country United Kingdom
Start 09/2019 
End 09/2022
 
Description HCA International Limited; Agreement for the appointment of clinical research fellows who will have resident medical officers at the Portland Hospital for women and children. Effect of Early Nutrition in Cardiac Re-modeling in Childhood (ENRiCh study).
Amount £76,086 (GBP)
Organisation HCA Hospitals 
Sector Private
Country United Kingdom
Start 03/2020 
End 03/2023
 
Description Metabolomic and Microbiota analyses 
Organisation Imperial College London
Department Computational and Systems Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Samples collected from the NEON Trial cohort were analysed by Prof Holmes team. Funding was from the Chelsea and Westminster Joint Research Committee.
Collaborator Contribution Supervision of PhD student and access to laboratory and supplies.
Impact In progress.
Start Year 2013
 
Description Stool Microbiota 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Access to samples from the NEON Trial for analysis.
Collaborator Contribution Supervision of PhD student. Funded by Chelsea and Westminster Hospital Joint Research Committee.
Impact In progress
Start Year 2015
 
Title NEON Standard Parenteral Nutrition 
Description The control group formulation tested in the NEON Trial is one of two parenteral nutrition regimens that have been recommended for use in London. All hospitals in the North West London Operational Delivery Network have adopted this regimen. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Implementing standardisation of parenteral nutrition in London has led to a central procurement framework which will result in significant cost saving for the NHS in London. 
URL http://www.isrctn.com/ISRCTN29665319