Cheryl A. Karn

Proteolysis and phenylalanine hydroxylation in response to parenteral nutrition in extremely premature and normal newborns.

To determine to what extent intravenous nutrition can reduce proteolysis in very immature and normal newborns, and to assess the capacity of preterm and normal newborns to convert phenylalanine to tyrosine, phenylalanine and leucine kinetics were measured under basal conditions and during parenteral nutrition in clinically stable, extremely premature (approximately 26 wk of gestation) infants and in normal term newborns. In response to parenteral nutrition, there was significantly less suppression (P < 0.001) of endogenous leucine and phenylalanine rate of appearance in extremely premature infants compared with term infants. Phenylalanine utilization for protein synthesis during parenteral nutrition increased significantly (P < 0.01) and by the same magnitude (approximately 15%) in both extremely premature and term infants. Phenylalanine was converted to tyrosine at substantial rates in both extremely premature and term infants; however, this conversion rate was significantly higher (P < 0.05) in extremely premature infants during both the basal and parenteral nutrition periods. These data provide clear evidence that there is no immaturity in the phenylalanine hydroxylation pathway. Furthermore, although parenteral nutrition appears to produce similar increases in protein synthesis in extremely premature and term infants, proteolysis is suppressed much less in extremely premature newborns. The factors responsible for this apparent resistance to suppression of proteolysis in the very immature newborn remain to be elucidated.

Total But Not Resting Energy Expenditure Is Increased in Infants With Ventricular Septal Defects

Objective. The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. Methods. Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. Results. No significant differences were found in REE (VSD, 42.2 ± 8.7 kcal/kg/d; control, 43.9 ± 14.1 kcal/kg/d) or energy intake (VSD, 90.8 ± 19.9 kcal/kg/d; control, 87.1 ± 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 ± 10.8 kcal/kg/d; control, 61.9 ± 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. Conclusions. REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.

Increased energy expenditure in infants with cyanotic congenital heart disease.

Infants with cyanotic congenital heart disease (CCHD) often have reduced weight gain compared with infants in control groups. Our purpose was to conduct a longitudinal study of energy intake, resting energy expenditure (REE), and total energy expenditure (TEE) of a group of infants with CCHD. We hypothesized that increased REE and TEE and decreased energy intake in these infants would lead to reduced growth. Ten infants with uncorrected CCHD and 12 infants in a control group were studied at 2 weeks of age and again at 3 months. Indirect calorimetry was used to determine REE; the doubly labeled water method was used to determine TEE and intake. At 2 weeks and 3 months of age, infants with CCHD weighed significantly less than infants in the control group. No significant difference was seen in energy intake or REE between groups during either period. TEE was slightly but not statistically increased in the CCHD group at 2 weeks (72.6 +/- 17.4 vs 59.8 +/- 10.9 kcal/kg/d) and significantly increased at 3 months (93.6 +/- 23.3 vs 72.2 +/- 13.2 kcal/kg/d, P </=.03). We conclude that increased TEE but not increased REE is a primary factor in the reduced growth in infants with CCHD.

Energy expenditure and energy intake during dexamethasone therapy for chronic lung disease.

Dexamethasone is commonly administered to ventilator-dependent preterm infants with chronic lung disease. Infants receiving dexamethasone therapy frequency exhibit decreased rates of weight gain. The purpose of this investigation was to determine whether decreased growth in infants receiving dexamethasone therapy is caused by increased energy expenditure. Twelve infants were studied: 6 received dexamethasone treatment at 2 wk of age and crossed over to receive placebo treatment at 4 wk; the treatment order was reversed in the other 6 infants. The doubly labeled water method was used to determine energy expenditure for a 1-wk period during each treatment phase. The rate of weight gain during dexamethasone treatment was 6.5 ± 10.6 and 20.0 ± 5.7 g/kg/d during placebo treatment. Energy expenditure was 93.1 ± 34.6 kcal/kg/d during dexamethasone treatment and 88.3 ± 37.1 kcal/kg/d during placebo treatment. Energy intake was 119.2 ± 29.0 kcal/kg/d during dexamethasone treatment and 113.8 ± 23.7 kcal/kg/d during placebo treatment. The difference between intake and expenditure, or the energy available for growth, was 26.2 ± 36.8 kcal/kg/d during dexamethasone treatment and 25.5 ± 37.4 kcal/kg/d during placebo treatment. No significant differences were found in energy expenditure or energy intake between the treatment phases. The reduced growth seen in infants receiving dexamethasone treatment cannot be explained by increased energy expenditure or decreased energy intake, but may be due to differences in the composition of newly accreted tissue.

Acute changes in leucine and phenylalanine kinetics produced by parenteral nutrition in premature infants

To determine the effect of parenteral nutrition on the balance and catabolism of leucine (by oxidation) and phenylalanine (by hydroxylation) and to assess any acute changes in proteolysis and/or protein synthesis, leucine and phenylalanine kinetics were measured by stable isotope tracer infusions in nine 32-wk gestation premature infants under both basal conditions and in response to an i.v. infusion of glucose, lipid, and amino acids. Leucine and phenylalanine balance both changed from negative to positive during parenteral nutrition. However, leucine and phenylalanine catabolism were differently affected by parenteral nutrition; the rate of leucine oxidation increased 2-fold, whereas the rate of phenylalanine hydroxylation was unchanged from basal values. Phenylalanine utilization for protein synthesis and leucine utilization for protein synthesis (based on both plasma leucine andα-ketoisocaproic acid enrichments) increased significantly during parenteral nutrition. The endogenous rates of release of leucine (based on plasma leucine enrichment) and phenylalanine (both reflecting proteolysis) were significantly reduced during parenteral nutrition. The endogenous rate of release of leucine (based on α-ketoisocaproic acid enrichment) was slightly but not significantly lower during parenteral nutrition. The substantial increase in leucine oxidation without changes in phenylalanine hydroxylation suggests a possible limitation in the phenylalanine/tyrosine supply during parenteral nutrition. In addition, these results suggest that premature infants respond to parenteral nutrition with acute increases in whole body protein synthesis as well as a probable reduction in proteolysis.

Effect of enteral versus parenteral feeding on leucine kinetics and fuel utilization in premature newborns

ABSTRACT: To determine whether the route of nutrient delivery affects whole-body protein kinetics and fuel utilization, eight premature newborns were studied during both a 4-h period of enteral intake and a 4-h period of parenteral nutrition. The kinetics of the essential amino acid leucine were measured using a constant tracer infusion of 1–13C-leucine, and fuel utilization and energy expenditure were assessed by respiratory calorimetry. All leucine kinetic parameters were similar during enteral or parenteral nutrition (in mean ± SD μmol/kg/h, flux = 233 ± 51 enteral versus 258 ± 42 parenteral, leucine from protein breakdown = 177 ± 50 enteral versus 200 ± 41 parenteral, leucine oxidation = 57 ± 26 enteral versus 63 ± 20 parenteral, and leucine used for protein synthesis = 176 ± 63 enteral versus 196 ± 50 parenteral). In addition, overall rates of energy expenditure (∼52 kcal/kg/d) and pattern of fuel utilization (∼70% carbohydrate, 13% fat, 17% protein) were unaltered by the route of feeding. Thus, as reflected by leucine kinetics, overall rates of protein turnover, synthesis, oxidation, and breakdown as well as energy expenditure and fuel utilization are similar when nutrition is provided to premature newborns by either the enteral or parenteral route. These results suggest that short-term provision of parenteral nutrition may be able to substitute appropriately for enteral intake, at least with regard to the utilization of one essential amino acid and the overall pattern of fuel utilization.

Measurement of nutrient intake by deuterium dilution in premature infants

To assess whether a simple nonrestrictive method of determining nutrient intake could be applied to premature infants, we compared actual measured formula intake during a 7-day period with intake calculated from deuterium dilution in 13 hospitalized, growing, premature newborn infants. An oral dose of deuterium oxide (D2O) was administered, and urine samples were analyzed by deuterium nuclear magnetic resonance spectrometry for D2O concentration. Using an exponential model, we calculated formula intake from the decline in D2O concentration during the 7-day study period. Intake as assessed by the deuterium model correlated well with actual intake (r = 0.93; p < 0.001). However, because the deuterium dilution model measures both dietary and nondietary water intake (metabolic and cutaneous water influx), deuterium dilution-derived intake exceeded actual intake by 25 +/- 18 ml/kg per day (16% +/- 11%). When corrections were applied to account for nondietary water intake, deuterium dilution-derived nutrient intake (160 +/- 30 ml/kg per day) closely approximated actual intake (155 +/- 17 ml/kg per day). If corrections are made for nondietary water intake, the deuterium dilution method may be a useful nonrestrictive method of measuring nutrient intake in a variety of neonatal populations.

The Effect of Increased Nonprotein Energy on Protein Kinetics during Parenteral Nutrition in ELBW Infants • 1564

Adequate amino acid availability is crucial in achieving positive protein balance in parenterally fed ELBW infants; maximal accretion of protein may additionally depend on a critical level of energy intake. We hypothesized that additional nonprotein energy intake would promote protein accretion in these infants. To assess this, we measured the endogenous rates of appearance (Endog Ra) of the essential amino acids leucine (LEU) and phenylalanine (PHE) (each reflecting proteolysis), utilization of PHE for protein synthesis (PS), PHE hydroxylation (OH) (reflecting irreversible loss of PHE), and the rate of urea production in seven clinically stable, ventilated ELBW infants in the first few days of life (27±0.8 wks gestation, 1006±81 gms birth wt, 980±70 gms study wt, 2±0.3 days of age) during a graded increase in nonprotein substrate (70 and 90 kcal/kg/d). Protein intake was held constant at 3.5 gm/kg/d (Aminosyn PF) and a balanced ratio of caloric intake from glucose and lipid was maintained throughout the 5.5 hour study. Kinetics are shown below in mean±SE in μmol/kg/h; *p≤0.05.

GROWTH REDUCTION DURING DEXAMETHASONE THERAPY IS NOT CAUSED BY INCREASED ENERGY EXPENDITURE. |[utrif]| 1869

In order to investigate the effect of dexamethasone (DEX) therapy on energy expenditure and growth of preterm infants with bronchopulmonary dysplasia, we studied 12 infants (26.2±1.4 wks gestation, 916±190 gm birthweight, mean±sd) enrolled in a multicenter blinded trial of the optimum timing of DEX therapy. The 12 infants were randomly assigned to one of two groups. Group 1 infants (n=6, 25.8±1.5 wks gestation, 932±220 gm birthweight) received a 2 week course of DEX followed by two weeks of placebo. Group 2 infants (n=6, 26.6±1.2 wks gestation, 901±175 gm birthweight) had the treatment order reversed. We measured total energy expenditure (TEE) and total body water (TBW) using the doubly labeled water technique (DLW, 2H and 18O labeled water) for 7 days during each of the treatment phases. Daily energy intake (EI) and weight were recorded throughout the study. All infants required intermittent mechanical ventilation during some portion of the study and had Respiratory Index Scores (MAP × FiO2) of 3.4±2.1 at the start of the first DLW period. Results are summarized below (mean ± sd, *p<0.05, DEX vs. placebo). Table

Total Energy Expenditure in Critically Ill and Normal Term Newborns in Early Postnatal Life |[dagger]| 1504

The energy requirements of critically ill newborns in the early neonatal period are not established. We hypothesized that the total energy expenditure(TEE) of critically ill newborns is greater than that of normal, healthy, term newborns. TEE was measured in critically ill and normal newborns over a 7d period using the doubly labeled water method (DLW). At study entry, critically ill infants (n=6) had respiratory disease requiring high frequency oscillatory ventilation (used as rescue therapy at our institution) and a respiratory index score (RIS; Paw x%FiO2) of ≥ 2.5. Normal newborns (n=4) were healthy and without medical complications. Infants received an enteral dose of2 H218O; urine was collected daily over one week. Samples were analyzed using Isotope Ratio Mass Spectrometry. Total body water (TBW) at the beginning and end of the study and TEE were then determined. Results are shown below as mean (SD), *p≤ 0.05.