P J J Sauer

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infants own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

Immediate commencement of amino acid supplementation in preterm infants: Effect on serum amino acid concentrations and protein kinetics on the first day of life

To determine whether the general reluctance to begin amino acid administration to preterm infants from birth onward might lead to loss of lean body mass and impairment of growth, we measured amino acid levels and protein kinetics in 18 preterm infants. Nine infants received amino acids (1.15 +/- 0.06 gm.kg-1.day-1) and glucose (6.05 +/- 1.58 gm.kg-1.day-1), whereas the other nine infants received only glucose (6.48 +/- 1.30 gm.kg-1.day-1) from birth onward. Protein kinetics on the first postnatal day were measured with a stable isotope dilution technique with [1-13C]leucine as a tracer. No statistically significant differences were noted in blood pH, base excess, urea concentration, or glucose levels. Both total amino acid concentration and total essential amino acid concentration were significantly lower and were below the reference range in the nonsupplemented group. Plasma amino acid levels of five essential amino acids (methionine, cystine, isoleucine, leucine, arginine) were below the reference range in the nonsupplemented group, whereas only cystine was below the reference range in the supplemented group. Nitrogen retention was improved significantly by the administration of amino acids (-110 +/- 44 mg nitrogen per kilogram per day in the glucose-only group vs +10 +/- 127 mg nitrogen per kilogram per day in the group given glucose and amino acids; p = 0.001); leucine oxidation was not significantly increased in the supplemented group (41 +/- 13 mumol.kg-1.hr-1 vs 46 +/- 16 mumol.kg-1.hr-1). Leucine balance also improved significantly (-41 +/- 13 mumol.kg-1.hr-1 vs -8 +/- 16 mumol.kg-1.hr-1; p = 0.01) because of a combination of an increased amount of leucine being used for protein synthesis and a lower amount of leucine coming from protein breakdown. Plasma cystine concentration, the only amino acid below the reference range in the supplemented group, was highly predictive for protein synthesis in that group. We conclude that the administration of amino acids to preterm infants from birth onward seems safe and prevents the loss of protein mass.

Effect of dexamethasone on protein metabolism in infants with bronchopulmonary dysplasia.

Corticosteroids result in protein wasting in human adults and rats. To determine to what extent this therapy affects protein metabolism in preterm infants, we studied 10 very low birth weight infants before a gradually tapered dexamethasone regimen was started and at day 4 of treatment (dexamethasone dosage 0.35 +/- 0.09 mg.kg-1.day-1), and seven infants at day 19 of treatment (dexamethasone dosage, 0.10 +/- 0.01 mg.kg-1.day-1). Protein breakdown and turnover rates were increased at day 4 of treatment but not any more at day 19 of treatment. Protein synthesis rate was not significantly affected during dexamethasone therapy. Weight gain was severely diminished during the first week of treatment but not during the next 2 weeks. We conclude that nitrogen balance during high dosages of dexamethasone is significantly lower because of an increase in proteolysis and not because of a suppression of synthesis.

Amino acid solutions for premature neonates during the first week of life : the role of N-acetyl-L-cysteine and N-acetyl-L-tyrosine

Tyrosine and cyst(e)ine are amino acids that are thought to be essential for preterm neonates. These amino acids have low stability (cyst(e)ine) or low solubility (tyrosine) and are therefore usually present only in small amounts in amino acid solutions. Acetylation improves the stability and solubility of amino acids, facilitating a higher concentration in the solution. We compared three commercially available amino acid solutions, Aminovenös-N-päd 10%, Vaminolact 6.5%, and Primène 10%, administered to 20 low-birth-weight neonates on total parenteral nutrition from postnatal day 2 onward. Aminovenös-N-päd 10% contains acetylated tyrosine and acetylated cysteine; the other solutions do not contain acetylated amino acids and differ in the amount of tyrosine and cysteine added. On postnatal day 7, plasma amino acids were measured together with urinary excretion of amino acids and the total nitrogen excretion; 38% of the intake of N-acetyl-L-tyrosine and 53% of the intake of N-acetyl-L-cysteine were excreted in urine. Plasma levels of N-acetyl-L-tyrosine (331 +/- 74 mumol/L) and N-acetyl-L-cysteine (18 +/- 29 mumol/L) were higher than those of tyrosine (105 +/- 108 mumol/L) and cystine (11 +/- 9 mumol/L), respectively. Plasma tyrosine levels in the groups receiving small amounts of tyrosine remained just below the reference range. We show a linear correlation of plasma cystine with the intake of cysteine (r = .75, p = 0.01), but not with N-acetyl-L-cysteine. The estimated intake of cysteine should be 500 mumol.kg-1.d-1 in order to obtain levels comparable with those shown in normal term, breast-fed neonates. Nitrogen retention did not differ among the three groups (247 to 273 mg.kg-1.d-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Whole-body protein turnover in preterm appropriate for gestational age and small for gestational age infants: comparison of [15N]glycine and [1-(13)C]leucine administered simultaneously.

ABSTRACT: Measurements of whole-body protein turnover in preterm infants have been made using different stable isotope methods. Large variation in results has been found, which could be due to different clinical conditions and/or the use of different tracers. We studied 14 appropriate for gestational age and nine small for gestational age orally fed preterm infants using [15N]glycine and [1-13C]leucine simultaneously, which allowed us to make a comparison of commonly used methods to calculate whole-body protein turnover. Whole-body protein turnover was calculated from 15N enrichment in urinary ammonia and urea after [15N]-glycine administration and from the 13C enrichment in expired CO2 after administration of [1-13C]leucine. Enrichment of α-ketoisocaproic acid after [1-13C]leucine constant infusion was measured as a direct parameter of whole-body protein turnover. Group means for whole-body protein turnover using [15N]glycine or [1-13C]leucine ranged from 10 to 14 g.kg-1.d-1, except when using the end product method that assumes a correlation between leucine oxidation and total nitrogen excretion. We found very low 15N enrichment of urinary urea in the majority of small for gestational age infants. These infants also had a lower nitrogen excretion in urine and oxidized less leucine. Nitrogen balance was higher in small for gestational age infants (416 pm 25 mg±kg-1d-1) compared with appropriate for gestational age infants (374 pm 41 mg±kg-1d-1, p= 0.003). [15N]Glycine does not seem to exchange its label with the body nitrogen pool to a significant degree and is therefore not always suitable as a carrier for 15N in protein turnover studies in premature infants.

Glucose kinetics and glucoregulatory hormone levels in ventilated preterm infants on the first day of life.

ABSTRACT: Glucose production and oxidation were measured in ventilated preterm appropriate-for-gestational-age and small-for-gestational-age infants on the first day of life. Using a new technique of NaH13CO3 infusion followed by a [U-13C]glucose infusion, we measured glucose oxidation rates without measuring the CO2 production rate. Infants were studied at 18 ± 4 h (mean ± 1 SD) of life and received parenterally administered glucose only (4.2 ± 0.5 mg·kg−1 · min−1). In 13 of 16 patients, the glucose production rate exceeded 1.0 mg·kg−1·min−1. Infants born from mothers who had been receiving steroids antenatally had higher glucose production rates (2.3 ± 1.1 mg·kg−1·min−1) compared with infants from mothers who had not (1.1 ± 0.8 mg · kg−1 · min−1, p = 0.036). The glucose oxidized (2.9 ±1.0 mg · kg−1 · min−1) was lower than the amount of glucose infused (p = 0.005) and was not different for appropriate-for-gestational-age and small-for-gestational-age infants. Plasma levels of glucose, insulin, glucagon, and total IGF-I were not correlated with glucose metabolism on the first day of life. Total IGF-II levels were negatively correlated with the rate of glucose appearance. We conclude that preterm infants on the first day of life receiving a glucose infusion of 4.2 mg · kg−1 · min−1 continue to produce glucose. The glucose oxidation rate is lower than the glucose infusion rate and the contribution of glucose oxidation to the total energy expenditure is limited.

Treatment with exogenous surfactant stimulates endogenous surfactant synthesis in premature infants with respiratory distress syndrome

ObjectiveTreatment of preterm infants with respiratory distress syndrome (RDS) with exogenous surfactant has greatly improved clinical outcome. Some infants require multiple doses, and it has not been studied whether these large amounts of exogenous surfactant disturb endogenous surfactant metabolism in humans. We studied endogenous surfactant metabolism in relation to different amounts of exogenous surfactant, administered as rescue therapy for RDS. DesignProspective clinical study. SettingNeonatal intensive care unit in a university hospital. PatientsA total of 27 preterm infants intubated and mechanically ventilated for respiratory insufficiency. InterventionsInfants received a 24-hr infusion with the stable isotope [U-13C]glucose starting 5.3 ± 0.5 hrs after birth. The 13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Infants received either zero (n = 5), one (n = 4), two (n = 15), or three (n = 3) doses of Survanta (100 mg/kg) when clinically indicated. Measurements and Main ResultsUsing multiple regression analysis, the absolute synthesis rate (ASR) of surfactant PC from plasma glucose increased with 1.3 ± 0.4 mg/kg/day per dose of Survanta (p = .007) (mean ± sem). The ASR of surfactant PC from glucose was increased by prenatal corticosteroid treatment with 1.3 ± 0.4 mg/kg/day per dose corticosteroid (p = .004), and by the presence of a patent ductus arteriosus with 2.1 ± 0.7 mg/kg/day (p = .01). ConclusionThese data are reassuring and show for the first time in preterm infants that multiple doses of exogenous surfactant for RDS are tolerated well by the developing lung and stimulate endogenous surfactant synthesis.

Lysine kinetics in preterm infants: the importance of enteral feeding

Introduction: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. Patients and methods: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (nu200a=u200a6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) μmol/(kg×h); and period B (nu200a=u200a4): 100% enteral feeding; lysine intake 100 (3) μmol/(kg×h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. Results: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) μmol/(kg×h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) μmol/(kg×h); p<0.05). Conclusions: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.

Comparison of two preterm formulas with or without addition of medium-chain triglycerides (MCTs). II: Effects on mineral balance.

Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on calcium (Ca), phosphorus (P), and magnesium (Mg) balances and plasma levels and on plasma levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There was a higher absorption of Ca in the MCT group (73% vs. 60%. p < 0.005), and an equal absorption of P (both 92%). The excretion of Ca correlated with the excretion of fat (p < 0.00005). The LCT group showed a higher median PTH level (MCT: 2.1 pmol/L, LCT: 4.7 pmol/L, p < 0.01) and a higher urinary P excretion (p < 0.001). Mg absorption was also lower with LCT, but retention of Mg exceeded intrauterine values in both groups. Mineral plasma levels were in the normal range in both groups. AP was not different between groups and in the upper part of the reference range, whereas 1,25-(OH)2D levels were above the normal range and also not different between groups. We conclude that with the LCT formula, Ca absorption is slightly lower than with the MCT formula, whereas P absorption is unaffected. The resulting imbalance in absorption is compensated for by an increased urinary excretion of P. We conclude that current recommendations for the maximum Ca/P ratio in preterm formulas (2:1) might be too low in formulas containing only LCT.

Leucine kinetics during simultaneously administered insulin and dexamethasone in preterm infants with severe lung disease

The objective of this study was to determine whether insulin administration would prevent the well-documented catabolic effect of dexamethasone given to preterm infants with chronic lung disease. We studied leucine metabolism in 11 very-low-birth-weight infants before dexamethasone treatment and on d 2, 4, and 7 thereafter. During the first 4 d of dexamethasone, insulin was administered i.v. at a dose of 0.5 (n = 7) or 1.0 (n = 5) IU/kg/d. Leucine turnover was not significantly different between d 0 (337 ± 41.3 μmol leucine/kg/h), d 2 (288 ± 27.2 μmol leucine/kg/h), d 4 (302 ± 22.1 μmol leucine/kg/h), and d 7 (321 ± 21.2 μmol leucine/kg/h), and neither was leucine breakdown (272 ± 21.9 μmol leucine/kg/h on d 0, 225 ± 21.5 μmol leucine/kg/h on d 2, 231 ± 21 μmol leucine/kg/h on d 4, and 242 ± 17.6 μmol leucine/kg/h on d 7). Weight gain rates were significantly lower during the first week of dexamethasone treatment compared with the week before treatment or the second and third week. We conclude that during insulin and corticosteroid administration in very-low-birth-weight infants, no changes were observed in leucine kinetics in contrast to previous studies. The decrease in weight gain was not reversed.