E J Sulkers

Structural position and amount of palmitic acid in infant formulas: Effects on fat, fatty acid, and mineral balance

The structure of the triglycerides (TG) in human milk (HM) differs from those of vegetable oils used in infant formulas. In HM, palmitic acid is predominantly esterified to the center or beta-position of the TG, in vegetable oil, it is mainly at the external or alpha-positions. These differences in configuration affect intestinal fat absorption. Fat and mineral balances were investigated in three groups of 9 healthy term infants aged 5 weeks. Infants were randomly assigned to receive one of the three study formulas from birth: (a) formula beta, resembling the structure of HM fat most closely (24% palmitic acid, 66% esterified to beta-position), (b) formula intermediate (24% palmitic acid, 39% esterified to the beta-position), and (c) regular formula (20% palmitic acid; 13% esterified to the beta-position). Fat absorption was highest in infants fed the beta formula (97.6 +/- 0.9%), intermediate in those fed with the intermediate formula (93.0 +/- 1.8%), and lowest in infants receiving the regular formula (90.4 +/- 4.6%). Fecal calcium excretion was significantly lower in the beta group than in the other two groups (43.3 +/- 18.1 vs. 59.9 +/- 15.1 vs. 68.4 +/- 22.3 mg.kg-1.day-1 for beta, intermediate, and regular respectively). Dietary TG containing palmitic acid predominantly at the beta-position, as in HM, have significant beneficial effects on the intestinal absorption of fat and calcium in healthy term infants.

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.

Quantitation of oxidation of medium-chain triglycerides in preterm infants.

ABSTRACT: Medium-chain triglycerides, with a chain length of eight and 10 carbon atoms, form up to 50% of the total fat content in some preterm infant formulas. In 20 small preterm infants (birthwt: 1153 ± 227 g; mean ± SD) fed a special formula containing 40% MCT, a primed constant oral infusion study of l-13C-potassium octanoate was conducted to quantify the oxidation of MCT. A plateau in 13C enrichment in breath CO2 was reached in all patients within 1-3 h. Simultaneously, substrate utilization was measured using a closed system indirect calorimeter. No significant difference was found between appropriate for gestational age (»=8) and small for gestational age (»=12) infants in the percentage of the administered tracer that was oxidized (44.9 ± 9.1% versus 48.5 ± 11.0%). In all patients, the recovery was calculated to be 47.1 ± 10.2%, which is less than previously estimated and corresponds to a mean MCT oxidation of 1.26 ± 0.27 g/kg/d. With indirect calorimetry, a total fat oxidation of 1.42 ± 0.84 g/kg/d in appropriate for gestational age and 2.00 ± 0.85 g/kg/d in small for gestational age infants was found, indicating that MCT accounted for around 85% of the total fat oxidation in appropriate for gestational age versus 65% in small for gestational age 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.

Comparison of Short Term Indirect Calorimetry and Doubly Labeled Water Method for the Assessment of Energy Expenditure in Preterm Infants

The accuracy of 8-hour indirect calorimetry (IDC) as an estimate of energy expenditure was investigated in 8 healthy preterm infants (birth weight 1,270 +/- 193 g, gestational age 32 +/- 3 weeks, mean +/- SD) in comparison with an analysis over 5 days using the doubly-labeled water (2H2(18)O) method (DLW). The infants that were fed continuously by nasogastric drip with 120 kcal/kg/day of special infant formula were measured twice under thermoneutral conditions in a closed system indirect calorimeter during 8 h with a 4-day interval; simultaneously isotope decay was measured by isotope ratio mass spectrometry in urine samples collected daily during 5 days from 6 h after an oral dose of 2H2(18)O on the first day of IDC, all during the 4th postnatal week. The mean differences between carbon dioxide production rate (rCO2) measured either by single 8-hour IDC or by duplicate 8-hour IDC and the 5-day DLW method, using the two-point analysis or the multipoint analysis were not significantly different from zero. The rCO2 calculated from the DLW method using the two-point analysis differed -1.4 +/- 1.7% from that measured by the multipoint analysis. The mean differences between the metabolic rate estimated from 8 h of IDC and from the 5-day DLW method based on a measured RQ of 0.90 was -6.7 +/- 6.2% and based on the RQ of the feeding -4.5 +/- 6.0%. These differences were not significantly different from zero. We conclude that IDC over 8 h and two-point DLW measurement over 5 days, both methods that can be applied with relative ease in practice, offer an adequate average estimate of energy expenditure in continuously fed preterm infants under thermoneutral conditions.

Decreased Glucose Oxidation in Preterm Infants Fed a Formula Containing Medium-Chain Triglycerides

ABSTRACT: Several formulas for preterm infants contain medium-chain triglycerides (MCT) to enhance fat absorption. Although fat absorption with MCT was slightly higher in several studies in preterm infants, a beneficial effect on growth has only been reported in one publication. We hypothesized that when part of the fat blend of preterm formula is substituted by MCT oil, this might lead to a different metabolic pattern in which, due to the preferential oxidation of MCT, an increase in lipogenesis from glucose could lead to an increase in metabolic rate. To study the impact of MCT on glucose metabolism, 18 preterm infants were randomized to receive either an MCT or an LCT formula containing 38- and 6%-by-weight medium-chain fatty acids, respectively, in their fat blend. At 4 wk of age, the metabolic rate, substrate utilization, glucose kinetics, and oxidation were measured by indirect respiratory calorimetry in combination with a constant-rate oral infusion of [U-13C]glucose. The “true” rate of appearance of glucose (Ra “true”) was measured from the dilution of the uniformly labeled (m + 6) species of infused tracer, whereas “apparent” rate of appearance of glucose (Ra “apparent”) was measured from the dilution of infused tracer C (carbon). The latter was measured by an on-line combustion method using a gas chromatograph-isotope ratio mass spectrometer. At a carbohydrate intake of 8.4 mg·kg−1·min−1, total utilization of carbohydrate was equal in both groups at 7.6 mg·kg−1·-min−1. However, glucose oxidation, as measured by the appearance of 13C in breath CO2 was significantly lower in the MCT group (4.5 ± 0.83 versus 5.7 ± 0.67 mg·kg−1· min−1, MCT versus LCT). Therefore, it can be assumed that a larger proportion of the glucose intake in the MCT group was used in the nonoxidative pathway, e.g. synthesis of fat as compared with the LCT group. There was no difference in the rate of endogenous glucose production and glucose C recycling between the two groups. In addition, the metabolic rate calculated from the rate of oxygen consumption was also similar (59 ± 5 versus 62 ± 4 kcal·kg−1·d−1 MCT versus LCT). We conclude that, in preterm infants fed a formula containing 38% MCT in their fat blend, glucose oxidation is significantly decreased whereas lipogenesis is probably increased. These findings may provide a mechanism for the so-called metabolic inefficiency of MCT.

Glucose metabolism in a term infant with transient hyperinsulinism and high carbohydrate intake

Transient hyperinsulinaemia is a well-known cause of hypoglycaemia in newborn infants. The hypoglycaemia may be caused by a decreased glucose production and/or an increased glucose uptake. Whether the increased uptake is caused by increased glucose oxidation or increased non-oxidative disposal is not known. The aim of this study was to investigate the fate of the large amount of glucose infused in a term infant who developed hypoglycaemia due to transient hyperinsulinaemia shortly after birth and was treated with high glucose infusions. On day 6 an indirect calorimetry study was performed, together with a glucose turnover study. Carbohydrate intake was 13.6 mg/kg per minute (19.6 g/kg per day). Both studies were repeated on day 11, when carbohydrate intake was normalised to 7.8 mg/kg per minute (11.2 g/kg per day). Glucose oxidation was 28% higher and non-oxidative glucose disposal was 257% higher on day 6 as compared to day 11. Our results indicate that hypoglycaemia during hyperinsulinism is the result of increased non-oxidative disposal of glucose and not increased glucose oxidation. The results indicate a remarkable capacity of the newborn for lipogenesis during high carbohydrate intake.