Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition.
BACKGROUND
Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil-containing lipid emulsions.


OBJECTIVE
The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content.


METHODS
We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial.


RESULTS
We randomly assigned 168 infants born at <31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: -108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: -0.8 cm (95% CI: -1.5, -0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes.


CONCLUSIONS
Imm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34.
Chelsea and Westminster National Health Service Foundation Trust, London, United Kingdom; Section of Neonatal Medicine, Department of Medicine, Imperial College London, s.uthaya@imperial.ac.uk.
Sabita
http://orcid.org/0000-0002-6112-2277
S
Uthaya
Imperial Clinical Trials Unit, School of Public Health, and.
Xinxue
X
Liu
Imperial Clinical Trials Unit, School of Public Health, and Clinical Trials and Evaluation Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom;
Daphne
D
Babalis
Comprehensive Clinical Trials Unit, University College London, London, United Kingdom;
Caroline J
CJ
Doré
Warwick Clinical Trials Unit, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom; and.
Jane
J
Warwick
Institute of Clinical Sciences, Imperial College London and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom; Department of Life Sciences, University of Westminster, London, United Kingdom.
Jimmy
J
Bell
Institute of Clinical Sciences, Imperial College London and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom; Department of Life Sciences, University of Westminster, London, United Kingdom.
Louise
L
Thomas
Imperial Clinical Trials Unit, School of Public Health, and.
Deborah
D
Ashby
Institute of Clinical Sciences, Imperial College London and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom;
Giuliana
G
Durighel
Institute of Clinical Sciences, Imperial College London and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom;
Ash
A
Ederies
Institute of Clinical Sciences, Imperial College London and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom;
Monica
M
Yanez-Lopez
Chelsea and Westminster National Health Service Foundation Trust, London, United Kingdom; Section of Neonatal Medicine, Department of Medicine, Imperial College London.
Neena
N
Modi
D050154:Adiposity; D000596:Amino Acids / Q000008:administration & dosage* / Q000009:adverse effects; D001823:Body Composition; D004311:Double-Blind Method; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage* / Q000737:chemistry; D005395:Fish Oils; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D000069463:Olive Oil; D010288:Parenteral Nutrition / Q000379:methods*; D013024:Soybean Oil; D016896:Treatment Outcome; D014280:Triglycerides
D000596:Amino Acids; D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D000069463:Olive Oil; D014280:Triglycerides; D013024:Soybean Oil
amino acid; body composition; intrahepatocellular lipid; lipid emulsion; parenteral nutrition; preterm infant; randomized controlled trial