Glutamine supplement with parenteral nutrition decreases whole body proteolysis in low birth weight infants

OBJECTIVES: To examine the effect of supplemental glutamine (0.6 g.kg -1 .d -1 ) on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW) infants receiving parenteral nutrition in the immediate neonatal period. STUDY DESIGN: Premature infants < or =32 weeks gestation with a birth weight from 694 to 1590 g were randomly assigned to either a glutamine-supplemented group (n = 10) or to a control group (n = 10). Tracer isotope studies were performed when the infants were 6 to 7 days old and had been receiving an amino acid intake of approximately 3.0 g.kg -1 .d -1 for at least 3 days. Whole body glutamine and nitrogen kinetics were measured with [5-15N]glutamine, [2H5]phenylalanine, [1-13C, 15 N]leucine, [15N2]urea, and GC-mass spectrometry. RESULTS: Supplemental glutamine was associated with a lower rate of appearance of glutamine ( P = .003), phenylalanine ( P = .001), and leucine C ( P = .003). There was no significant difference in leucine N turnover, urea turnover and plasma cortisol, and C-reactive protein levels in the 2 groups. CONCLUSION: Parenteral glutamine supplement in LBW infants was associated with lower whole-body protein breakdown. Because the decrease in whole body proteolysis is associated with protein accretion, parenteral glutamine supplement may be beneficial in selected populations of LBW infants.     

Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study.

Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28-30 wk; birth weight, 820-1610 g) receiving parenteral nutrition supplying 1.5 g x kg(-1) x d(-1) amino acids and approximately 60 nonprotein kcal x kg(-1) x d(-1) were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g x kg(-1) x d(-1); glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH(13)CO(3) to assess the recovery of (13)C in breath, immediately followed by a 3-h L-[1-(13)C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 +/- 94 versus 503 +/- 83 microM, mean +/- SD; p < 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (-16%, p < 0.05) and leucine oxidation (-35%, p < 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (-20%, p < 0.05), and 4) no change in protein balance (nonoxidative leucine disposal - leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants.     

两种肠道外营养方法在早产儿中的应用研究

目的 探讨早产儿应用两种肠道外营养(parenteral nutrition,PN)方法的疗效.方法 选择不能耐受完全胃肠道喂养的早产儿42例,随机分为观察组(22例)和对照组(20例).观察组患儿生后24 h内应用氨基酸,自1.0/g(kg·d)开始,每日递增1.0g/(kg·d),直至3.0/g(kg·d);48 h内应用脂肪乳,剂量及添加方法同氨基酸,生后第5天达全静脉营养.对照组患儿生后48 h应用氨基酸,自0.5g/(kg·d)开始,每日递增0.5g/(kg·d),直至3.0g/(kg·d);72 h后应用脂肪乳,剂量及添加方法同氨基酸,生后8～9 d达全静脉营养.两组患儿均监测营养效果,出生72 h内和第10天分别监测血生化指标,观察并发症发生情况.结果 观察组恢复至出生体质量时间、体质量下降幅度、PN时间、过渡到全胃肠道营养时间均较对照组短,差异有统计学意义(P＜0.01).并发症发生情况比较两组差异无统计学意义(x2=0.191,P＞0.05).两组患儿在血糖、总胆红素、尿素氮、二氧化碳结合力、总胆固醇等方面比较差异均无统计学意义(P＞0.05).结论 早产儿可以耐受生后24 h内早期足量的PN.     

The role of parenteral lipids in supporting gluconeogenesis in very premature infants

We have previously demonstrated that very premature infants receiving glucose at 17 micromol/kg min plus appropriate supply of parenteral lipids (Intralipid) and amino acids (TrophAmine) maintained normoglycemia by glucose produced primarily via gluconeogenesis. The present study addressed the individual roles of parenteral lipids and amino acids in supporting gluconeogenesis. Fourteen premature infants (993 +/- 36 g 27 +/- 1 wk) (mean +/- SE) were studied for 8 h on d 5 +/- 1 of life. All infants were receiving standard TPN prior to the study. At start of study, the glucose infusion rate was decreased to approximately 17 micromol/kg min and either Intralipid (g + AA; n = 8) or TrophAmine (g + IL; n = 6) was discontinued. Data from 14 previously studied infants receiving glucose (approximately 17 micromol/kg min) + TrophAmine + Intralipid (g + AA + IL) are included for comparison. Gluconeogenesis was measured by [U-13 C]glucose, (g + AA) and (8 infants of the g + AA + IL group) or [2-13C]glycerol, (g + IL) and (6 infants of the g + AA + IL group). Infants studied by the same method were compared. Withdrawal of Intralipid resulted in decreased gluconeogenesis, 6.3 +/- 0.9 (g +AA) vs. 8.4 +/- 0.7 micromol/kg min (g + AA + IL) (p = 0.03). Withdrawal of TrophAmine affected neither total gluconeogenesis, 7.5 +/- 0.8 vs. 7.9 +/- 0.9 micromol/kg min nor gluconeogenesis from glycerol, 4.4 +/- 0.6 vs. 4.9 +/- 0.7 micromol/kg min (g+ IL and g + AA + IL groups, respectively). In conclusion, in parenterally fed very premature infants, lipids play a primary role in supporting gluconeogenesis.     

Whole body protein metabolism in children with cancer.

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Effect of two different doses of parenteral amino acid supplementation on postnatal growth of very low birth weight neonates — A randomized controlled trial

Objectives

To evaluate the effects of two different doses of parenteral aminoacid supplementation on postnatal growth in Very Low Birth Weight (VLBW) infants receiving partial parenteral nutrition (PPN).

Design

Double blinded randomized controlled trial.

Settings

Level 3 NICU between February 2008 to February 2010.

Participants

150 inborn babies with birthweight between 900–1250 g, irrespective of gestational age, were randomized to either of the two interventions of amino acid supplementation.

Intervention

Two different initial doses of parenteral amino acids (AA) in the PPN solutions- Low AA group: 1 g/kg/d versus High AA group: 3 g/kg/d from day 1 of life with increment by 1 g/kg every day till a maximum of 4 g/kg/d, until babies tolerated 75% enteral feeds.

Main outcome

Average postnatal weight gain (in g/kg/d)) by 28 days of life.

Results

Both groups had similar baseline characteristics. The gain in weight, length and head circumference at 28 days were significantly lower in the High AA group. The average weight gain at 28 days was 8.67g/kg/d in the High AA group and 13.15g/kg/d in the Low AA group (mean difference 123.12, 95% CI 46.67 to 199.37, P<0.001). The incidences of neonatal morbidities associated with prematurity were similar in both groups.

Conclusion

Higher initial parenteral aminoacid supplementation, in settings where partial parenteral nutrition is administered, results in poor growth in VLBW infants due to inadequate non-protein calorie intake.     

Parenteral amino acids increase albumin and skeletal muscle protein fractional synthetic rates in premature newborn minipigs

OBJECTIVES: Early administration of parenteral amino acids increases whole body nitrogen retention in premature infants. Tracer kinetic studies suggest an increase in whole body protein synthesis as a possible mechanism for this increase in nitrogen retention. However, the effect of early parenteral amino acids on synthesis of specific proteins remains uncertain. Using premature newborn minipigs as a model for human premature newborns, we investigated the effects of parenterally administered amino acids on albumin and skeletal muscle protein fractional synthetic rates. METHODS: Fifteen Yucatan minipigs were delivered by cesarean section 6 days before the mean expected delivery date (day 106 of gestation; expected gestation, 111-113 days) and randomized to two groups immediately after birth: 7 piglets received a mixture of amino acids (0.4 g. kg. h ) and glucose (0.8 g. kg. h ) for 5 hours, and 8 piglets (control group) received glucose only. All piglets received a continuous primed infusion of 1-[ C]valine. Arterial plasma free C-valine enrichment was measured by gas chromatography/mass spectrometry, and protein synthetic rates were determined by measuring incorporation of C-valine into albumin and skeletal muscle protein using gas chromatography/combustion/isotope ratio mass spectrometry. RESULTS: Administration of amino acids increased albumin (87.0% +/- 42.1% [mean +/- SD] vs. 37.6% +/- 6.8% per 24 hours; < 0.05) and skeletal muscle fractional synthetic rates (11.60% +/- 6.9% vs. 6.5% +/- 1.5% per 24 hours; < 0.05). CONCLUSION: We conclude that parenteral amino acids increase albumin and skeletal muscle fractional synthetic rates in premature piglets on the first day of life.     

Increased parenteral amino acid administration to extremely low-birth-weight infants during early postnatal life

BACKGROUND: Early administration of parenteral amino acids to infants with extremely low birth weight (birth weight < or = 1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit. METHODS: The peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g . kg -1 . d -1 in the standard group and 4 g . kg -1 . d -1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid-base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome. RESULTS: The corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 +/- 0.83 g . kg -1 . d -1; mean, +/-1 SD) and 18% greater (3.86 +/- 0.94 g . kg -1 . d -1 ) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 +/- 1.8 mEq/dL at week 1 and 23.9 +/- 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 +/- 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 ( P < 0.03) in both groups. CONCLUSIONS: Infants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g . kg -1 . d -1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.     

静脉补充谷氨酰胺对外科手术新生儿喂养耐受的影响

目的 评价含丙氨酰谷氨酰胺(Ala-Gin)肠外营养(PN)对接受外科手术新生儿喂养耐受的影响.方法 对两家儿童医疗中心2006年1月至2007年1月收治的40例接受外科手术的新生儿进行研究,采用平行、随机、双盲、对照实验,随机分为常规PN组(对照组)和常规PN+Ala-Gln组(研究组),二组各20例,对照组氨基酸的剂量为2～3g·kg-1·d-1;研究组添加0.3g·kg-1·d-1 Ala-Gln双肽,其中Ala-Gln双肽取代了处方中相应氨基酸的量.首要终点指标为术后开始喂养时间,术后达到全肠内喂养天数(标准配方摄入量≥120 ml·kg-1·d-1)、完全脱离肠外营养时间和病死率.结果 研究组和对照组比较,患儿术后开始喂养时间[研究组(8±4)d,对照组(8±5)d]、术后达到全肠内喂养天数[研究组(14±8)次,对照组(15±7)次]以及完全脱离肠外营养时间[研究组(15±8)d,对照组(16±7)d]差异均无统计学意义.对照组有3例死亡,研究组患儿无死亡,病死率通过非意向性分析,二组比较差异有统计学意义,OR值为0.789,95%CI为0.626～0.996.但是通过意向性分析,OR值为0.706,95%CI为0.136～3.658,病死率比较差异没有统计学意义.结论 本研究显示,静脉补充谷氨酰胺未能使接受外科手术的新生儿减少术后开始喂养时间和术后达到全肠内喂养天数,缩短全肠外营养应用时间;但关于是否能够降低患儿病死率,通过意向性分析和非意向性分析的结果有差异,尚需进一步研究.     

积极肠外营养支持方案在胎龄<34周早产儿中的应用

目的 探讨积极肠外营养支持方案(高初始剂量氨基酸和脂肪乳)在胎龄<34周早产儿肠外营养中的近期疗效及耐受情况.方法 根据早期应用氨基酸和脂肪乳剂量不同,将2019年5月至2019年12月收治,生后24小时内入院、胎龄<34周138例早产儿随机分2组.积极肠外营养组69例,氨基酸自2.5 g/(kg·d)始,逐日增加1....     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

营养支持在严重脓毒症患儿中的应用研究

目的 探讨严重脓毒症患儿营养支持治疗方法。方法 198例严重脓毒症患儿进行生化指标、营养指标、血气分析、血常规以及入院后24 h尿尿素氮等检测,根据患儿机体状况给予相应的营养支持,选择肠内营养或肠外营养,或同时给予肠内营养和肠外营养,肠外营养组又分谷氨酰胺（glutamine,Gln）组和非Gln组.监测严重脓毒症存活患儿及死亡患儿的营养指标及代谢指标,包括血糖、C反应蛋白、血红蛋白（Hb）、pH值、血钠、血钾、谷丙转氨酶、血尿素氮、血肌酐、血乳酸,乳酸清除率、血甘油三酯、血总胆固醇、血清前白蛋白（pre-albumin,PA）、视黄醇结合蛋白（retinal-binding protein,RBP）、血清白蛋白（albumin,ALB）、24h尿尿素氮.对存活及死亡患儿营养支持前0d及营养支持第3天、第7天的摄入热卡进行比较。对Gln组和非Gln组患儿的免疫球蛋白指标进行比较。结果 存活组患儿营养指标均较死亡组高[PA（130.0±30.0）mg/L vs （50.8±20.5）mg/L,RBP（22.3±10.3） mg/L vs （15.7±6.7） mg/L,ALB（35.3 ±8.1） g/L vs （28.7 ±6.2）g/L,Hb（113.2±27.7） g/L vs （95.3±10.6） g/L,IgA（0.40±0.03） g/Lvs （0.40±0.03）g/L,IgM（0.52±0.18） g/L vs （0.49±0.03） g/L] （P ＜0.05）。存活组患儿营养支持第3天和第7天的热卡分别为（50.32 ±2.76） kcal/（kg·d）和（65.70±3.25） kcal/（kg·d）,明显高于死亡组（32.54±1.72） kcal/（kg·d）和（46.12±1.08） kcal/（kg·d） （P ＜0.05）。存活组患儿Gln组免疫球蛋白明显高于非Gln组[IgG（4.93 ±2.1）g/L vs（4.01±1.03） g/L,IgA（0.31±0.07） g/L vs（0.19 ±0.03） g/L,IgM（0.52±0.08） g/L vs （0.32 ±0.10） g/L] （P ＜0.05）,负氮平衡状况也好于非Gln组[（-2.5±1.4）g/d vs（-5.3±1.3）g/d],差异有统计学意义（P＜0.05）。结论 严重脓毒症患儿疾病早期表现为代谢率明显升高,能量消耗明显增加,蛋白分解利用大于合成,呈现明显负氮平衡,病情越重,机体代谢指标、营养指标、免疫球蛋白等越低.对患儿进行PN时加用Gln很有必要。     

Pediatric parenteral amino acid mixture in low birth weight infants

A mixture of amino acids designed to maintain normal plasma amino acid concentrations in infants and children requiring parenteral nutrition was evaluated in 28 low birth weight (LBW) infants (birth weight, 750 to 1750 g; postnatal age, 1 to 4 weeks) who required parenteral nutrients for optimal nutritional management. Sixteen babies received only parenteral nutrients for five to 21 days. Ten of these received a typical regimen by peripheral vein (1.91 +/- 0.16 g/kg/d of amino acids and 44.7 +/- 4.4 kcal/kg/d) and six received a typical regimen through a central vein (2.39 +/- 0.11 g/kg/d of amino acids and 95.9 +/- 14.5 kcal/kg/d). Mean weight gain of the peripheral vein subgroup was 10.3 +/- 10.6 g/kg/d; mean nitrogen balance was 230 +/- 66 mg/kg/d. Both the mean rate of weight gain (17.2 +/- 5.1 g/kg/d) and the mean rate of nitrogen retention (267 +/- 49 g/kg/d) of the central vein subgroup were similar to intrauterine rates. In these two subgroups as well as the total population, plasma concentrations of all amino acids except phenylalanine were within the 95% confidence limits of the plasma concentrations observed in LBW infants fed sufficient amounts of human milk to result in a rate of weight gain similar to the intrauterine rate. However, although plasma tyrosine and cyst(e)ine concentrations were within the 95% confidence limits of the plasma concentrations goals, the LBW infant's ability to use N-acetyl-L-tyrosine and cysteine HCl appears to be even less than that of the term infant and older child. In toto, these data support the efficacy of the amino acid mixture evaluated for LBW infants. Of equal importance, they suggest that the LBW infant's ability to use parenterally delivered amino acids is not as limited as commonly thought.     

Amino acid administration to premature infants directly after birth

OBJECTIVES: To test the hypothesis that the administration of 2.4 g amino acids (AA)/(kg.d) to very low birth weight infants is safe and results in a positive nitrogen balance. STUDY DESIGN: We conducted a randomized, clinical trial. Preterm infants with birth weights <1500 g received either glucose and 2.4 g AA/(kg.d) from birth onward (n=66) or solely glucose during the first day with a stepwise increase in AA intake to 2.4 g AA/(kg.d) on day 3 (n=69). Blood gas analysis was performed daily during the first 6 postnatal days; blood urea nitrogen levels were determined on days 2, 4, and 6; AA plasma concentrations and nitrogen balances were determined on days 2 and 4. Student t tests, Mann-Whitney tests, and chi2 tests were performed to compare groups. RESULTS: Infants supplemented with AA had no major adverse side effects. Their blood urea nitrogen levels were higher, nitrogen balance turned positive upon AA administration, and more AA concentrations were within reference ranges. CONCLUSIONS: High-dose AA administration to very low birth weight infants can be introduced safely from birth onward and results in an anabolic state.     

Minimum protein intake for the preterm neonate determined by protein and amino acid kinetics

Lower limits of protein needs in prematurely born neonates have not been adequately studied, yet providing protein in amounts maximizing accretion without excess is a goal in these infants' nutritional care. We hypothesized that with the use of amino acid oxidation methodology, it would be possible to define minimum protein requirement. Our objective was to investigate protein kinetics during short-term changes in protein intake by measurement of nitrogen balance and amino acid flux and oxidation using [(15)N]glycine, [(13)C]phenylalanine, and [(13)C]leucine tracers. Protein kinetics were examined in 21 preterm infants (gestational age: 29 +/- 3 wk; birth weight: 1091 +/- 324 g) at five protein intakes (1.0, 1.5, 2.0, 2.5, and 3.0 g x kg(-1) x d(-1)) with 1 d of adaptation to the test intakes. From nitrogen balance data, a protein need of 0.74 g x kg(-1 x -1) was estimated to achieve zero balance. For all three amino acids, flux and oxidation estimates were not different across protein intakes. Whole-body protein synthesis and breakdown estimates from [(15)N]ammonia data were 14.6 +/- 3.4 and 14.4 +/- 4.1 g x kg(-1) x d(-1), respectively. Glycine flux (680 +/- 168 micromol x kg(-1) x h(-1)) was greater than leucine flux (323 +/- 115 micromol x kg(-1) x h(-1)), which was greater than phenylalanine flux (84.3 +/- 35.2 micromol x kg(-1) x h(-1)). Leucine oxidation (36.7 +/- 15.6 micromol x kg(-1) x h(-1)) was also greater than phenylalanine oxidation (6.64 +/- 4.41 micromol x kg(-1) x h(-1)). Infants in our study were able to adapt to short-term changes in protein intake with little consequence to the overall whole-body protein economy, as measured by the three test amino acids.     

A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates

OBJECTIVE: The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates. DESIGN: Randomized controlled trial. METHODS: Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18). RESULTS: There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups. CONCLUSIONS: Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN.     

Effect of low versus high intravenous amino acid intake on very low birth weight infants in the early neonatal period

Greater protein intakes are required than have been commonly used to achieve fetal in utero protein accretion rates in preterm neonates. To study the efficacy and safety of more aggressive amino acid intake, we performed a prospective randomized study in 28 infants [mean wt, 946 +/- 40 g (SEM)] of 1 (low amino acid intake, LAA) versus 3 g.kg(-1).d(-1) (high amino acid intake, HAA) at 52.0 +/- 3.0 h of life. After a minimum of 12 h of parenteral nutrition, efficacy was determined by protein balance and was significantly lower in the LAA versus HAA groups by both nitrogen balance (-0.26 +/- 0.11 versus 1.16 +/- 0.15 g.kg(-1).d(-1), p < 0.00005) and leucine stable isotope (0.184 +/- 0.17 versus 1.63 +/- 0.20 g.kg(-1).d(-1), p < 0.0005) methods. Leucine flux and oxidation and nonoxidative leucine disposal rates were all significantly higher in the HAA versus LAA groups (249 +/- 13 versus 164 +/- 8, 69 +/- 5 versus 32 +/- 3, and 180 +/- 10 versus 132 +/- 8 micro mol.kg(-1).h(-1), respectively, p < 0.005), but leucine appearance from protein breakdown was not (140 +/- 15 in HAA versus 128 +/- 8 micro mol.kg(-1).h(-1)). In terms of possible toxicity with HAA, there were no significant differences between groups in the amount of sodium bicarbonate administered, degree of acidosis as determined by base deficit, or blood urea nitrogen concentration. Parenteral HAA versus LAA intake resulted in increased protein accretion, primarily by increasing protein synthesis versus suppressing protein breakdown, and appeared to be well tolerated by very preterm infants in the first days of life.     

Evidence that phenylalanine may not provide the full needs for aromatic amino acids in children

Phenylalanine is nutritionally classified as an indispensable amino acid and can be converted to tyrosine by phenylalanine hydroxylation. The initial goal of the present study was to determine the aromatic amino acid (phenylalanine plus tyrosine) requirements in healthy children fed a diet without tyrosine by using the indicator amino acid oxidation (IAAO) method using lysine as the indicator amino acid. Healthy school-age children (n = 5) were fed in random order a diet with eight graded intakes of phenylalanine without tyrosine. The requirement was determined by the rate of recovery of CO2 from L-[1-C]lysine oxidation (FCO2). Phenylalanine (total aromatic amino acid) requirement, in the absence of tyrosine, for children was determined to be 28 mg/kg/d, which was only 64% of the adult requirement, which is biologically absurd. A possible reason for the lower estimate of phenylalanine requirement could be lower phenylalanine hydroxylation rate in children, which is supported by the finding of lower urinary tyrosine/phenylalanine ratios in children compared with adults. In conclusion, this study indicates that phenylalanine may not provide the total needs for aromatic amino acids in children fed an amino acid-based diet without tyrosine.     

A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations

OBJECTIVE: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short-term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants. METHODS: In a double-blind placebo-controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. RESULTS: Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non-essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30). CONCLUSIONS: Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.     

Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition

A mixture of amino acids designed to maintain normal plasma amino acid concentrations of infants and children requiring parenteral nutrition was evaluated in 40 infants and children receiving only parenteral nutrients (2.39 +/- 0.26 g/kg/d of amino acids and 110.3 +/- 10.4 kcal/kg/d) for five to 21 days. The children ranged in weight from 2.0 to 12.6 kg (median weight, 3.83 kg; fifth to 95th percentile, 2.06 to 11.1 kg) and in age from 1 week to 43.6 months (median age, 2.7 months; fifth to 95th percentile, 0.2 to 25.3 months). Mean weight gain was 11.0 +/- 5.0 g/kg/d; mean nitrogen balance was 242 +/- 70 mg/kg/d. Plasma concentrations of all amino acids except tyrosine were within the normal range (ie, within the 95% confidence limits of the two-hour postprandial plasma concentrations observed in 30-day-old, healthy, normally growing, breast-fed, term infants) throughout the period of study. Mean prestudy and poststudy serum total protein, albumin, and transthyretin (prealbumin) concentrations were not significantly different. However, plasma transthyretin concentration increased in all children with low prestudy concentrations. Mean poststudy serum total bilirubin concentration of the total population was not different from the mean prestudy concentration. This was true also for the 31 children who received the parenteral amino acid mixture for more than ten days. In contrast to the expected 30% to 50% incidence of cholestasis, only one of these 31 experienced an unexplained increase in serum total bilirubin concentration during study, suggesting that normalizing plasma amino acid concentrations and/or providing taurine during parenteral nutrition may decrease the incidence of cholestasis associated with this therapy.