High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition

Morgan, Colin; Burgess, Laura

doi:10.1177/0148607115594009

Cited by 19 publications

(14 citation statements)

References 58 publications

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“…Remarkably, the combined plasma concentrations of leucine and isoleucine were less than normal human fetal plasma concentrations [37]. This was documented for more (non)essential amino acids in other studies [10,38] and might suggest that the current solutions are not optimal for VLBW infants, since even high doses do not result in plasma amino-acid concentrations that are sufficient to promote growth. Nevertheless, Poindexter et al [11] did document on significantly better growth outcomes at 36 weeks of PMA in VLBW infants who received greater early amino-acid supplementation (≥3 g/kg/day at ≤5 days of age) compared to lower late supply.…”

Section: Discussionmentioning

confidence: 96%

Low- versus High-Dose and Early versus Late Parenteral Amino-Acid Administration in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis

Leenders

Waard²,

Goudoever³

2017

Neonatology

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Objectives: Providing parenteral amino acids to very-low-birth-weight infants during the first weeks of life is critical for adequate growth and neurodevelopment. However, there is no consensus about what dose is appropriate or when to initiate supplementation. As a result, daily practice varies among neonatal intensive care units. The objective of our study was to determine the effects of early parenteral amino-acid supplementation (within 24 h of birth) versus later initiation and high dose (>3.0 g/kg/day) versus a lower dose on growth and morbidities. Methods: A systematic review and meta-analysis of publications identified by searching PubMed, EMBASE, and Cochrane databases was conducted. Randomized controlled studies were eligible if information on growth was available. Results: The search identified 14 studies. No differences were observed in growth or morbidity after early or high-dose amino-acid supplementation, but for several outcomes, meta-analysis was not possible due to study heterogeneity. Initiation of amino acids within the first 24 h of life appeared to be safe and well tolerated, and leads more rapidly to a positive nitrogen balance. Conclusions: Administering a high dose (>3.0 g/kg/day) or an early dose (≤24 h) of parenteral amino acids is safe and well tolerated but does not offer significant benefits on growth. Further large-scale randomized controlled trials in preterm infants are needed to study the effects of early and high-dose amino acids on growth and morbidity more consistently and extensively.

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Section: Discussionmentioning

confidence: 96%

Low- versus High-Dose and Early versus Late Parenteral Amino-Acid Administration in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis

Leenders

Waard²,

Goudoever³

2017

Neonatology

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“…Human milk protects against NEC123 and, although the preterm formulas currently used have concentrations of arginine similar to the human milk16, arginine intake might be different depending on the infants diet. Plasma arginine levels are likely to represent a balance between arginine intake, arginine synthesis, and the demands of protein synthesis and the multiple metabolic pathways for arginine utilization1437. Enteric arginine synthesis appears to be necessary to cover neonatal requirements, because mammalian milk is a relatively poor source of arginine, whereas its precursors proline and glutamine are abundant38.…”

Section: Discussionmentioning

confidence: 99%

“…CPS, ornithine aminotransferase, and argininosuccinate synthetase are key enzymes in the control of de novo intestinal synthesis of arginine, which are already expressed in the mid gestation human intestine38. However, hypoargininemia often develops in preterm infants, in particular if they are maintained on total parenteral nutrition, and it has been suggested that the intestine only produces arginine if substrate is supplied through enteral nutrition14373839. In situations of reduced availability of the substrate L-arginine or the cofactor BH 4 , NOS enzymatic activity becomes uncoupled, resulting in the production of superoxide instead of NO40.…”

Section: Discussionmentioning

confidence: 99%

Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study

Moonen

Cavallaro

Huizing

et al. 2016

Sci Rep

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The p.Thr1406Asn (rs1047891) polymorphism of the carbamoyl-phosphate synthetase 1 (CPS1) gene has been linked to functional consequences affecting the downstream availability of the nitric oxide precursor L-arginine. L-arginine concentrations are decreased in preterm infants with necrotizing enterocolitis (NEC). In this multicenter prospective study, we investigated the association of the p.Thr1406Asn polymorphism with NEC in 477 preterm infants (36 cases of NEC) from 4 European neonatal intensive care units (Maastricht, Las Palmas de Gran Canaria, Mantova, and Milan). Allele and genotype frequencies of the p.Thr1406Asn polymorphism did not significantly differ between the infants with and without NEC. In contrast, the minor A-allele was significantly less frequent in the group of 64 infants with the combined outcome NEC or death before 34 weeks of corrected gestational age than in the infants without the outcome (0.20 vs. 0.31, P = 0.03). In addition, a significant negative association of the A-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.54, 95% CI 0.29–0.99) and the additive (aOR 0.58, 95% CI 0.36–0.93) genetic models. In conclusion, our study provides further evidence that a functional variant of the CPS1 gene may contribute to NEC susceptibility.

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“…Plasma AA were collected in the second week of life in infants randomised to receive either 3.2 g/kg/d (standard) or 4.3 g/kg/d (high dose) par-enteral AA 2. A Spearman’s correlation analysis was run on the plasma data for the AA subgroups involved in argi-nine metabolic pathways to assess their relationship with arginine in the VPI population.…”

Section: Methodsmentioning

confidence: 99%

PP-32 Do plasma amino acid levels reflect arginine metabolism in parenteral nutrition (pn) dependent very preterm infants?

Premakumar

2017

Arch Dis Child

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BackgroundArginine plays an important role in several metabolic pathways as well as being a substrate for pro-tein synthesis. Arginine metabolism involves multi-com-partment processes that vary according to cell type/body organ. Enterocytes are a major site for arginine synthesis. The key amino acid (AA) metabolites of arginine synthesis pathways in the enterocytes of very preterm infants (VPIs) include glutamine, glutamate and proline with interme-diates ornithine and citrulline. The key arginine degrada-tion AA metabolite in the liver is ornithine. In contrast to these metabolically active AAs, histidine is presumed to be a metabolically inert AA and hence probably a useful indicator of non-metabolic factors (e.g. renal elimination). Newborn infants are dependent on enteral milk proteins for the AAs required for enterocyte arginine synthesis. However VPIs are dependent on parenteral nutrition (PN) and therefore parenteral AA for the first 2 weeks of life un-til milk feeds are established.MethodsSecondary analysis was performed on the plasma AA data collected during a previously published randomised controlled trial.1 Plasma AA were collected in the second week of life in infants randomised to receive either 3.2 g/kg/d (standard) or 4.3 g/kg/d (high dose) par-enteral AA.2 A Spearman’s correlation analysis was run on the plasma data for the AA subgroups involved in argi-nine metabolic pathways to assess their relationship with arginine in the VPI population. The data also underwent multivariate regression analysis (combining both groups) to test if any of these AA significantly predicted plasma arginine levels.ResultsPlasma AA levels were performed on median (IQR) day 9 (8-10) in both groups. Mean (95% confidence intervals) plasma arginine levels were 41 (25-57) and 35 (22-46) micromol/litre in the high and standard AA dose groups respectively (p=0.21) well below the reference range minimum (57µmol/L). Data analysis showed that arginine had the strongest positive correlation with or-nithine, r=0.602, n=107, p<0.001, followed by gluta-mine, r=0.564, n=107, p<0.001. A significant regression model was found [F(3,103)=24.318, p<0.001] with an R2=0.415ConclusionPlasma ornithine, glutamate and histidine are significant predictors of plasma arginine in PN depen-dent VPIs. This indicates that there are both metabolic and non-metabolic factors that play a role in determination of plasma arginine levels.

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High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition

Abstract: Plasma AA levels in PN-dependent VPIs indicate there is an imbalance in essential and CEAA provision in neonatal PN AA formulations that is not improved by increasing protein intake.

Cited by 19 publications

References 58 publications

Low- versus High-Dose and Early versus Late Parenteral Amino-Acid Administration in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis

Low- versus High-Dose and Early versus Late Parenteral Amino-Acid Administration in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis

Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study

PP-32 Do plasma amino acid levels reflect arginine metabolism in parenteral nutrition (pn) dependent very preterm infants?

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