Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial
Background: Parenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations. Objective: To confirm the safety and demonstrate efficac...
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| Format: | Article |
| Language: | English |
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NIHR Journals Library
2016-03-01
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| Series: | Efficacy and Mechanism Evaluation |
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| Online Access: | https://doi.org/10.3310/eme03020 |
| _version_ | 1811332426274701312 |
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| author | Sabita Uthaya Xinxue Liu Daphne Babalis Caroline Dore Jane Warwick Jimmy Bell Louise Thomas Deborah Ashby Giuliana Durighel Ash Ederies Monica Yanez-Lopez Neena Modi |
| author_facet | Sabita Uthaya Xinxue Liu Daphne Babalis Caroline Dore Jane Warwick Jimmy Bell Louise Thomas Deborah Ashby Giuliana Durighel Ash Ederies Monica Yanez-Lopez Neena Modi |
| author_sort | Sabita Uthaya |
| collection | DOAJ |
| description | Background: Parenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations. Objective: To confirm the safety and demonstrate efficacy of the immediate introduction of the recommended daily intake of amino acids (Imm-RDI) and soya bean oil, medium-chain triglycerides, olive oil and fish oil lipid in PN to increase non-adipose (lean) body mass and decrease intrahepatocellular lipid (IHCL) content. Design: Multicentre, double-blind, 2 × 2 factorial and randomised controlled trial (RCT). Setting: Neonatal units in London and south-east England, UK. Participants: Extremely preterm infants born before 31 weeks of gestation without major congenital or life-threatening abnormalities who could to be randomised to receive PN within 24 hours of birth. Interventions: Infants were randomised within 24 hours of birth to receive PN containing either high [RDI of amino acids (Imm-RDI)] or low [incremental amino acids (Inc-AA) control] levels of amino acids. In addition, infants were randomised to receive either 20% SMOFlipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) or 20% Intralipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) (control). This resulted in four groups: (1) Inc-AA/Intralipid, (2) Inc-AA/SMOFlipid, (3) Imm-RDI/Intralipid and (4) Imm-RDI/SMOFlipid. The intervention was continued until infants were receiving 150 ml/kg/day of enteral feeds for 24 hours. Primary outcome measure: For the amino acid intervention, this was non-adipose or lean body mass measured by magnetic resonance imaging. For the lipid composition intervention, this was IHCL content as measured by hepatic magnetic resonance spectroscopy. Primary outcomes were measured at term age equivalent, between 37 and 44 weeks postmenstrual age. Results: We randomised 168 infants born before 31 weeks of gestation. We evaluated outcomes, at term, in 133 infants. There were no significant differences in non-adipose mass between the Imm-RDI and Inc-AA groups [adjusted mean difference 1.0 g, 95% confidence interval (CI) –108 to 111 g] or in levels of IHCLs between the SMOFlipid and Intralipid groups (adjusted mean SMOFlipid to Intralipid ratio 1.1, 95% CI 0.8 to 1.6). Infants receiving the Imm-RDI were more likely than Inc-AA infants to have blood urea nitrogen levels > 7 mmol/l [75% vs. 49% (p < 0.01)] and > 10 mmol/l [49% vs. 18% (p < 0.01)]. Furthermore, head circumference at term was smaller in the Imm-RDI group (mean difference –0.8 cm, 95% CI –1.5 to –0.1 cm; p = 0.02). There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, weight, length and mortality. Limitations: Not all eligible babies were available for recruitment, as pharmacy staff trained in clinical trial procedures were unavailable at weekends in three of the four centres. We were able to assess brain volumes in only one-third of participants, as imaging was carried out while the participants were sleeping naturally and we measured primary outcomes first and continued to brain imaging only if the infant remained asleep. Conclusions: Immediate delivery of the recommended daily intake of parenteral amino acids does not benefit body composition or growth to term and may be harmful; SMOFlipid does not affect IHCL content. Future work: The long-term functional outcomes of early administration of RDI of amino acids and the use of SMOFlipid, including neurodevelopment, body composition and metabolic health, should be evaluated. Trial registration: Current Controlled Trials ISRCTN29665319 and EudraCT 2009-016731-34. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. |
| first_indexed | 2024-04-13T16:35:47Z |
| format | Article |
| id | doaj.art-fee4f1a2de0a49d88bbf9401dde6baa3 |
| institution | Directory Open Access Journal |
| issn | 2050-4365 2050-4373 |
| language | English |
| last_indexed | 2024-04-13T16:35:47Z |
| publishDate | 2016-03-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Efficacy and Mechanism Evaluation |
| spelling | doaj.art-fee4f1a2de0a49d88bbf9401dde6baa32022-12-22T02:39:26ZengNIHR Journals LibraryEfficacy and Mechanism Evaluation2050-43652050-43732016-03-013210.3310/eme0302008/99/04Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trialSabita Uthaya0Xinxue Liu1Daphne Babalis2Caroline Dore3Jane Warwick4Jimmy Bell5Louise Thomas6Deborah Ashby7Giuliana Durighel8Ash Ederies9Monica Yanez-Lopez10Neena Modi11Chelsea and Westminster NHS Foundation Trust, London, UKImperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UKImperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UKUniversity College London Comprehensive Clinical Trials Unit, University College London, London, UKImperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UKMetabolic and Molecular Imaging Research Group, Medical Research Council Clinical Science Centre, Imperial College London, London, UKMetabolic and Molecular Imaging Research Group, Medical Research Council Clinical Science Centre, Imperial College London, London, UKDepartment of Medicine, Section of Infectious Diseases, Imperial College London, London, UKMetabolic and Molecular Imaging Research Group, Medical Research Council Clinical Science Centre, Imperial College London, London, UKInstitute of Clinical Sciences, Imperial College London and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UKClinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UKChelsea and Westminster NHS Foundation Trust, London, UKBackground: Parenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations. Objective: To confirm the safety and demonstrate efficacy of the immediate introduction of the recommended daily intake of amino acids (Imm-RDI) and soya bean oil, medium-chain triglycerides, olive oil and fish oil lipid in PN to increase non-adipose (lean) body mass and decrease intrahepatocellular lipid (IHCL) content. Design: Multicentre, double-blind, 2 × 2 factorial and randomised controlled trial (RCT). Setting: Neonatal units in London and south-east England, UK. Participants: Extremely preterm infants born before 31 weeks of gestation without major congenital or life-threatening abnormalities who could to be randomised to receive PN within 24 hours of birth. Interventions: Infants were randomised within 24 hours of birth to receive PN containing either high [RDI of amino acids (Imm-RDI)] or low [incremental amino acids (Inc-AA) control] levels of amino acids. In addition, infants were randomised to receive either 20% SMOFlipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) or 20% Intralipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) (control). This resulted in four groups: (1) Inc-AA/Intralipid, (2) Inc-AA/SMOFlipid, (3) Imm-RDI/Intralipid and (4) Imm-RDI/SMOFlipid. The intervention was continued until infants were receiving 150 ml/kg/day of enteral feeds for 24 hours. Primary outcome measure: For the amino acid intervention, this was non-adipose or lean body mass measured by magnetic resonance imaging. For the lipid composition intervention, this was IHCL content as measured by hepatic magnetic resonance spectroscopy. Primary outcomes were measured at term age equivalent, between 37 and 44 weeks postmenstrual age. Results: We randomised 168 infants born before 31 weeks of gestation. We evaluated outcomes, at term, in 133 infants. There were no significant differences in non-adipose mass between the Imm-RDI and Inc-AA groups [adjusted mean difference 1.0 g, 95% confidence interval (CI) –108 to 111 g] or in levels of IHCLs between the SMOFlipid and Intralipid groups (adjusted mean SMOFlipid to Intralipid ratio 1.1, 95% CI 0.8 to 1.6). Infants receiving the Imm-RDI were more likely than Inc-AA infants to have blood urea nitrogen levels > 7 mmol/l [75% vs. 49% (p < 0.01)] and > 10 mmol/l [49% vs. 18% (p < 0.01)]. Furthermore, head circumference at term was smaller in the Imm-RDI group (mean difference –0.8 cm, 95% CI –1.5 to –0.1 cm; p = 0.02). There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, weight, length and mortality. Limitations: Not all eligible babies were available for recruitment, as pharmacy staff trained in clinical trial procedures were unavailable at weekends in three of the four centres. We were able to assess brain volumes in only one-third of participants, as imaging was carried out while the participants were sleeping naturally and we measured primary outcomes first and continued to brain imaging only if the infant remained asleep. Conclusions: Immediate delivery of the recommended daily intake of parenteral amino acids does not benefit body composition or growth to term and may be harmful; SMOFlipid does not affect IHCL content. Future work: The long-term functional outcomes of early administration of RDI of amino acids and the use of SMOFlipid, including neurodevelopment, body composition and metabolic health, should be evaluated. Trial registration: Current Controlled Trials ISRCTN29665319 and EudraCT 2009-016731-34. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.https://doi.org/10.3310/eme03020parenteral nutritionamino acidspreterm infantsrandomised double-blind controlled trialintralipidsmoflipid |
| spellingShingle | Sabita Uthaya Xinxue Liu Daphne Babalis Caroline Dore Jane Warwick Jimmy Bell Louise Thomas Deborah Ashby Giuliana Durighel Ash Ederies Monica Yanez-Lopez Neena Modi Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial Efficacy and Mechanism Evaluation parenteral nutrition amino acids preterm infants randomised double-blind controlled trial intralipid smoflipid |
| title | Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial |
| title_full | Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial |
| title_fullStr | Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial |
| title_full_unstemmed | Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial |
| title_short | Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial |
| title_sort | nutritional evaluation and optimisation in neonates neon trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition a randomised double blind controlled trial |
| topic | parenteral nutrition amino acids preterm infants randomised double-blind controlled trial intralipid smoflipid |
| url | https://doi.org/10.3310/eme03020 |
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