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The purpose of this study was to determine whether the ovine fetus is capable of increased disposal of an amino acid load; if so, would it respond by increased protein synthesis, amino acid catabolism or both? A further purpose of the study was to determine whether the pathways of aromatic amino acid catabolism are functional in the fetus. Late gestation ovine fetuses of well-nourished ewes received an infusion of Aminosyn PF alone (APF), and Aminosyn PF + glycyl-L-tyrosine (APF+GT) at rates estimated to double the intake of these amino acids. The initial study, using APF, was performed at 126 +/- 1.4 d; the APF+GT study was performed at 132 +/- 1.7 d (term = 150 d). Phenylalanine and tyrosine kinetics were determined using both stable and radioactive isotopes. Plasma concentrations of most amino acids, but not tyrosine, increased during both studies; tyrosine concentration increased only during the APF+GT study. Phenylalanine rate of appearance and phenylalanine hydroxylation increased during both studies. Tyrosine rate of appearance increased only during the APF+GT study; tyrosine oxidation did not increase during either study. Fetal protein synthesis increased significantly during both studies, producing a significant increase in fetal protein accretion. Fetal proteolysis was unchanged in response to either amino acid infusion. These results indicate that the fetus responds to an acute increase in amino acid supply primarily by increasing protein synthesis and accretion, with a smaller but significant increase in amino acid catabolism also. Both phenylalanine hydroxylation and tyrosine oxidation are active in the fetus, and the fetus is able to increase phenylalanine hydroxylation rapidly in response to increased supply. [ABSTRACT FROM AUTHOR]

Insulin is regarded as the primary fetal growth-promoting hormone, but direct in vivo experimental data supporting this conjecture are sparse. Data obtained from studies in in vivo, chronically catheterized fetal lambs under a variety of experimental circumstances demonstrate that glucose availability is the primary modulator of fetal protein accretion, via its ability to diminish amino acid catabolism. The ovine fetus is shown to be resistant to insulin-induced suppression of proteolysis, relative to the adult. Data from studies in the human premature infant show that the findings in the ovine fetus are similar to those in the ex utero premature human. [ABSTRACT FROM AUTHOR]

The observed growth failure in infants with pulmonary insufficiency is postulated to be a consequence of elevated rates of energy expenditure. Assessment of energy expenditure by the classical technique of indirect calorimetry has yielded conflicting results. The adoption of the newer, doubly labeled water technique has provided evidence to support increased rates of energy expenditure in infants with chronic lung disease, congenital heart disease and in minimally ill, extremely low birth weight infants. The doubly labeled water technique holds great promise for the detailed study of energy expenditure in a variety of clinical conditions, including very ill as well as free-living subjects. [ABSTRACT FROM AUTHOR]

Although protein and energy requirements in healthy growing and enterally fed infants are relatively well established, the nutritional requirements of extremely low birth weight infants are considerably less certain. New and emerging data in ELBW infants suggest high rates of energy expenditure and protein losses, which results in significant nutritional deficits and high rates of growth failure. Based on the limited and incomplete available data, energy intakes of 125-130 kcal/kg/d and protein intakes of 3.5-4 g/kg/d appear to be necessary to produce normal growth in ELBW infants. Although these intakes may be difficult to achieve in clinical practice, there is clear evidence that aggressive early nutrition can improve growth outcomes in these infants., (Copyright 2002 Elsevier Science Ltd.)

To determine whether increased amino acid availability can reduce proteolysis in premature neonates and to assess the capacity of infants born prematurely to acutely increase the irreversible catabolism of the essential amino acids leucine (via oxidation) and phenylalanine (via hydroxylation to form tyrosine), leucine and phenylalanine kinetics were measured under basal conditions and in response to a graded infusion of intravenous amino acids (1.2 and 2.4 g. kg(-1). day(-1)) in clinically stable premature (approximately 32 wk gestation) infants in the 1st wk of life. In contrast to the dose-dependent suppression of proteolysis seen in healthy full-term neonates, the endogenous rates of appearance of leucine and phenylalanine (reflecting proteolysis) were unchanged in response to amino acids (297 +/- 21, 283 +/- 19, and 284 +/- 31 micromol. kg(-1). h(-1) for leucine and 92 +/- 6, 92 +/- 4, and 84 +/- 7 micromol. kg(-1). h(-1) for phenylalanine). Similar to full-term neonates, leucine oxidation (40 +/- 5, 65 +/- 6, and 99 +/- 7 micromol. kg(-1). h(-1)) and phenylalanine hydroxylation (12 +/- 1, 16 +/- 1, and 20 +/- 2 micromol. kg(-1). h(-1)) increased in a stepwise fashion in response to graded amino acids. This capacity to increase phenylalanine hydroxylation may be crucial to meet tyrosine needs when exogenous supply is limited. Finally, to determine whether amino acids stimulate glucose production in premature neonates, glucose rate of appearance was measured during each study period. In response to amino acid infusion, rates of endogenous glucose production were unchanged (and near zero).

Objective: Infants with cyanotic congenital heart disease (CCHD) have previously been shown to have similar resting energy expenditures (REEs) and elevated total energy expenditures (TEEs) compared with age-matched healthy infants. The purpose of this investigation was to re-examine the REE and TEE of the same individuals at 5 years of age, after surgical repair of the heart defect was done, to determine whether metabolic differences persist., Study Design: Seven children were studied approximately 2.6 years after they underwent surgical repair of CCHD along with 10 age-matched healthy children. Indirect calorimetry was used to determine REE, and the doubly labeled water method was used to determine TEE and body composition., Results: Results were compared with single-factor repeated measures analysis of variance. No significant differences were found between groups in weight or body composition. No significant differences were found between groups in REE, TEE, or the energy expended in physical activity., Conclusion: We conclude that differences in TEE observed during infancy are no longer present in 5-year-old children after they undergo surgical repair of CCHD. Furthermore, the individual components of energy expenditure of children with CCHD after repair are indistinguishable from those of healthy age-matched children.

Information about energy requirements of extremely low-birth weight infants is sparse, despite the rapidly improving survival rates of this population. Metabolizable energy intake can be estimated from energy balance studies and the percentage of caloric intake that is actually absorbed by these infants is approximately 87%. Data on energy expenditure in extremely premature infants is limited; however, energy expenditure has been shown to increase with postnatal age. Because both intake and expenditure are affected by multiple factors, there is significant variability in estimates of the energy requirements in extremely low-birth weight infants. At present, no valid recommendations can be made regarding optimal energy requirements for the extremely low-birth weight infant, except that their requirements probably exceed those of stable, growing very low-birth weight infants, currently estimated at 105 to 135 kcal.kg-1d-1.

Insulin-like growth factor I (IGF-I) has anabolic effects and is thought to be important in fetal development. The present study was designed to determine the dose response of recombinant human (rh) IGF-I on ovine fetal glucose and amino acid kinetics. Chronically catheterized fetal lambs were studied at 122-127 days gestation. The kinetics of leucine, phenylalanine, and glucose were measured before and during the infusion of rhIGF-I. rhIGF-I was infused into the fetal inferior vena cava at low, medium, or high rates (9.9, 20.1, or 40.2 nmol/h, respectively). A stepwise increase in serum IGF-I was achieved (164 +/- 3, 222 +/- 7, and 275 +/- 5 ng/ml). Insulin concentrations were decreased at the medium and high rhIGF doses. The rate of appearance (Ra) of leucine and phenylalanine and leucine oxidation decreased. Phenylalanine appearance from protein breakdown was decreased, with a maximal suppression of 30% observed at the highest rate of infusion. Glucose Ra was increased at the medium and high doses; other aspects of glucose metabolism were unchanged. The change in both glucose Ra and suppression of proteolysis was significantly correlated to the rhIGF-I infusion rate. It is concluded that rhIGF-I exerts dose-related effects in the ovine fetus, increasing fetoplacental glucose turnover and causing significant suppression of both proteolysis and amino acid oxidation.

Dexamethasone is commonly administered to ventilator-dependent preterm infants with chronic lung disease. Infants receiving dexamethasone therapy frequently 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.

Interpretation of tracer studies of amino acid kinetics in the fed state is dependent on knowledge of splanchnic uptake of diet-derived amino acids. We studied five healthy control children and five children with cystic fibrosis (CF). After an overnight fast, the children ingested, hourly, a formula diet for 11 h. 5,5,5-[2H3]Leucine was added to the feedings during the last 6 h, and an i.v. infusion of 1-[13C]leucine was administered during the last 2 h of the formula feeding. The mean rate of splanchnic uptake of leucine was similar in the CF and control group, 23.8 +/- 24.0 and 21.5 +/- 21.2 mumol.kg-1.h-1, respectively. Fractional splanchnic uptake of leucine was not significantly different in the patients with CF (0.16 +/- 0.112 mean +/- SD) compared with the control children (0.244 +/- 0.256(-1)). The rate of whole body protein breakdown was not significantly different between the groups (CF versus control) with (159 +/- 18 versus 135 +/- 28 mumol.kg-1.h-1) or without (135 +/- 14 versus 114 +/- 20 mumol.kg-1.h-1) correction for splanchnic leucine uptake. However, for the 10 cases combined, protein breakdown corrected for splanchnic leucine uptake (147 +/- 26 mumol.kg-1.h-1) was 18% greater than uncorrected protein breakdown (124 +/- 20 mumol.kg-1.h-1) (p = 0.009). The data suggest that companion studies of splanchnic uptake might enhance the interpretation of leucine kinetics in the fed state.

Insulin-like growth factor I (IGF-I) has been shown to have significant anabolic effects in the regulation of fetal protein metabolism. To investigate the tissue-specific effects of IGF-I on fetal skeletal muscle metabolism, we infused recombinant human (rh) IGF-I directly into the hindlimb of nine chronically catheterized, late-gestation fetal sheep. Substrate balance and amino acid kinetics were measured across the hindlimb and were compared with the effects at the whole body level before and during a 3-h infusion of rhIGF-I into the external iliac artery at 150 microgram/h. Infusion of rhIGF-I resulted in increases in IGF-I concentrations by 2- to 5. 75-fold in the ipsilateral iliac vein and by nearly 3-fold in the abdominal aorta. In the study limb, IGF-I had no effect on protein synthesis (phenylalanine rate of disposal 0.88 +/- 0.13 before vs. 0. 73 +/- 0.19 micromol/min during IGF-I) or breakdown (phenylalanine rate of appearance 0.67 +/- 0.13 before vs. 0.60 +/- 0.17 micromol/min during IGF-I) and did not alter net phenylalanine balance. IGF-I also did not affect hindlimb oxygen or glucose uptake. In contrast, at the whole body level, the rate of appearance of leucine, indicative of fetal protein breakdown, decreased during IGF-I infusion (rate of appearance of leucine 41.1 +/- 3.3 to 37.6 +/- 2.7 micromol/min) as did fetal leucine oxidation (8.4 +/- 0.8 to 6.8 +/- 0.6 micromol/min). There was no change in the umbilical uptake of leucine, and although not statistically significant, fetal leucine accretion increased 2.4-fold. These results provide further evidence that IGF-I promotes fetal protein accretion; however, its site of action is in tissues other than skeletal muscle.

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

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.

Objective: To determine the effect of a continuous insulin infusion on protein and glucose metabolism in extremely low birth weight (ELBW) infants., Study Design: We measured the rate of appearance (Ra) of the essential amino acids leucine and phenylalanine (reflecting proteolysis), utilization of phenylalanine for protein synthesis, and glucose Ra using stable isotope tracers during a basal infusion of glucose (6 mg/kg/min) and in response to a continuous infusion of insulin (0.05 U/kg/hr) by means of the euglycemic hyperinsulinemic clamp technique. Four clinically stable, euglycemic ELBW infants (26 +/- 0 weeks' gestation, 894 +/- 44 gm birth weight, 2.8 +/- 0.8 days of age) were studied., Results: In response to a greater than tenfold increase in insulin concentration (from 7 +/- 2 to 79 +/- 13 microU/ml), there was a 20% decrease in leucine Ra (Basal: 272 +/- 27 mumol/kg/hr; Insulin: 226 +/- 29 mumol/kg/hr; p < 0.01) and in phenylalanine Ra (Basal: 91 +/- 5 mumol/kg/hr; Insulin: 72 +/- 2 mumol/kg/hr; p < 0.05). Use of phenylalanine for protein synthesis also decreased by a similar magnitude (Basal: 77 +/- 4 mumol/kg/hr; Insulin: 62 +/- 1 mumol/kg/hr; p < 0.05). Glucose utilization doubled (from 8 +/- 0.9 to 15.7 +/- 1.1 mg/kg/min; p = 0.0003) and plasma lactate concentrations tripled (from 2.1 +/- 0.5 to 5.7 +/- 1.0 mmol/L; p < 0.05) during the insulin infusion., Conclusions: During an infusion of glucose alone, pharmacologic concentrations of insulin in ELBW infants produced no net protein anabolic effect. Furthermore, euglycemic hyperinsulinemia was accompanied by development of significant metabolic acidosis.

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 and alpha-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 alpha-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.

We hypothesized that there is less suppression of whole-body protein breakdown with feeding in patients with cystic fibrosis (CF) who exhibit decreased insulin secretion after a single meal. Using [1-13C]leucine, we measured rates of nonoxidative leucine disappearance (whole-body protein synthesis) and protein breakdown in nine CF patients (6-11 y of age) and five healthy control subjects (8-10 y of age) during feeding and fasting. In the CF patients, synthesis and breakdown (x +/- SD) were 172 +/- 61 and 157 +/- 67 mumol.kg-1.h-1 during feeding and 140 +/- 24 and 178 +/- 26 mumol.kg-1.h-1 during fasting. The respective control values were 129 +/- 27 and 114 +/- 20 mumol.kg-1.h-1 during feeding and 136 +/- 13 and 173 +/- 18 mumol.kg-1.h-1 during fasting. Leucine balance was nearly identical in the two groups. By analysis of variance, there was a significant effect of feeding on protein breakdown but no difference between the groups. However, when each group was analyzed separately, feeding resulted in a 34% decrease in breakdown in the control subjects (P = 0.001) and a 23% increase in synthesis in the CF group (P = 0.058). Plasma insulin concentrations did not differ in the two groups. Thus, feeding may affect protein turnover differently in children with CF than in control children independently of plasma insulin concentration.

This study was undertaken to assess the incidence of culture-proved sepsis in term infants without symptoms born to mothers receiving intrapartum antibiotics and to determine the usefulness of the immature neutrophil: total neutrophil (I:T) ratio in the initial evaluation of these infants. A retrospective chart review was made of 103 infants born during a 3-year period. There was one positive blood culture and two positive cerebrospinal fluid cultures in three different patients; all three isolates were considered contaminants and all patients remained without symptoms. In spite of the lack of culture-proved sepsis and clinical illness, more than 50% of the initial I:T ratios were greater than the usually accepted upper limit of normal (that is, 0.16). We conclude that the incidence of sepsis in this population is very low and the initial I:T ratio is not useful as a predictive tool in term newborns without symptoms.

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 mumol/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 (approximately 52 kcal/kg/d) and pattern of fuel utilization (approximately 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.

The effect of diabetes in pregnancy on leucine turnover and oxidation was examined in 12 insulin-dependent diabetic (IDDM) subjects and 12 gestationally diabetic (GDM) subjects during the third trimester of pregnancy. The data were compared with those in normal pregnant women studied during the same time period and reported previously. Eight of the IDDM subjects were on continuous subcutaneous insulin infusion (insulin pump), and four were on conventional twice-daily insulin treatment. Of the GDM group, seven were on insulin therapy and five were on dietary management. Leucine kinetics were quantified using [1-13C]leucine tracer in combination with respiratory calorimetry and measurement of lean body mass using the H2[18O] dilution method. In addition, glucose kinetics were measured in insulin-treated subjects using [6,6(2)H2]glucose tracer. Despite rigorous metabolic control, fasting plasma glucose (IDDM 5.5 +/- 1.9 mmol/L [P < .05], GDM 4.7 +/- 1.3 [P < .01], controls 3.6 +/- .6, mean +/- SD) and hemoglobin A1 ([HbA1] IDDM 7.9 +/- 1.9%, GDM 7.5% +/- 2.1%) levels were higher in diabetic subjects. Although total insulin levels were higher in insulin-treated diabetic subjects, free-insulin concentrations were similar in all groups. Rates of excretion of urinary urea nitrogen and respiratory quotients were also similar. The rate of glucose turnover was lower in insulin-treated subjects compared with normals. Leucine flux, a measure of the rate of protein breakdown, and leucine oxidation were higher in IDDM and insulin-treated GDM subjects. The rate of leucine oxidation was increased in conventionally managed IDDM and insulin-treated GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

To examine how feeding affects changes in leucine and protein metabolism, leucine kinetics were determined in nine preterm infants (32 +/- 2 wk gestation; mean +/- SD) after a brief fast and again during hourly feedings. Rates of leucine oxidation were similar during the fasting and feeding periods (31 +/- 4 vs 37 +/- 6 mumol.kg-1.h-1; mean +/- SE). The nonoxidative disposal rates of leucine (a reflection of protein synthesis) were also similar during both periods (228 +/- 20 vs 205 +/- 10 mumol.kg-1.h-1; mean +/- SE). In contrast, the rates of leucine release from endogenous protein (an indication of protein breakdown) were significantly reduced by feeding (259 +/- 23 vs 185 +/- 11 mumol.kg-1.h-1; mean +/- SE, P = 0.02). A significant positive correlation was demonstrated between the fasting rate of leucine release from endogenous protein and the degree of suppression produced by feeding (r2 = 0.796, P = 0.001). Conversely, a significant inverse correlation was shown between the nonoxidative disposal rate of leucine during fasting and the increase in response to feeding (r2 = 0.848, P < 0.001). These data suggest that premature infants respond to feeding after a brief fast by suppressing protein breakdown, rather than by increasing protein synthesis, and changes in protein metabolism produced by feeding in premature newborns may be influenced by the prevailing rates of protein breakdown and synthesis during fasting.

To examine proteolysis, protein and leucine oxidation, and fuel utilization during a brief fast (approximately 17 hours) in human pregnancy, we determined leucine kinetics, urea nitrogen excretion, and respiratory quotient (RQ) in 11 pregnant subjects during the second half of gestation, and in 11 normal nonpregnant controls. The total rate of appearance (Ra) of leucine was similar in the pregnant and control groups (pregnant 4.99 +/- 0.60 v control 5.25 +/- 1.60 mmol/h [mean +/- SD]). However, leucine Ra per kilogram was significantly lower in pregnant subjects (pregnant 68 +/- 7 v control 82 +/- 13 mumol/kg/h, P less than .01). In addition, urinary urea nitrogen excretion was also significantly less in pregnant subjects (pregnant 3.74 +/- 1.09 v control 5.58 +/- 1.6 mg/kg/h, P less than .01). The RQ measured in the pregnant group was significantly higher than controls (0.82 +/- 0.05 v 0.76 +/- 0.04, P = .01), resulting in higher calculated carbohydrate oxidation rates during fasting in pregnancy. These data suggest that total rates of proteolysis (reflected by leucine flux) are similar in pregnant and nonpregnant subjects after an overnight fast. When normalized to body weight, proteolysis is lower in pregnant subjects. Urea excretion rates are also lower in pregnancy. These findings support the hypothesis that there is a pregnancy-induced adaptation to conserve maternal protein stores during a brief fast. The higher rate of carbohydrate oxidation during fasting in pregnancy may be a reflection of the fetal-placental unit's use of glucose as its predominant oxidative substrate.

During fasting of the ewe, the rate of amino acid oxidation by the ovine fetus increases substantially. We hypothesized that the increase in amino acid oxidation derived mainly from reduced protein synthesis. We further hypothesized that fetal glucose supplementation would result in diminished amino acid oxidation. To test these hypotheses, nine ovine fetuses were infused with [15N,1-13C]leucine to determine the rates of leucine appearance and disposal. Simultaneously, the fetal uptake of leucine was determined. Animals were studied in the fed and fasted state. After baseline measurements, glucose was infused into the fetal inferior vena cava at a rate estimated to match the fetal glucose uptake. Results of these studies indicate that leucine nitrogen flux, leucine carbon flux and fetal leucine uptake were constant. Leucine oxidation was increased by 50% in the fasted state (6.3 versus 13.4 mumol/min); glucose infusion resulted in a 25% decline in oxidation (to 10.4 mumol/min) in the fasted state, but had no effect in the fed state. Mean leucine umbilical uptake during fasting was 9.3 mumol/min, 4.1 mumol/min less than leucine oxidation. These data suggest that leucine (and potentially other amino acids) may be in negative balance during maternal fasting, and can be spared by supplementation of the fetus with exogenous glucose.

To examine how leucine and protein metabolism is affected by feeding, leucine kinetics were determined in 11 normal term newborns during feeding using a prime constant tracer infusion of 1-13C leucine combined with respiratory calorimetry. Fed newborns were compared with previously studied fasting newborns. Feeding and fasting newborns had similar rates of leucine oxidation (34 +/- 3 mumol/kg/h versus 31 +/- 4 mumol/kg/h) and leucine release from existing protein (156 +/- 16 mumol/kg/h versus 164 +/- 8 mumol/kg/h). In contrast, nonoxidative disposal rates of leucine (a reflection of protein synthesis) were significantly greater in feeding newborns (170 +/- 13 mumol/kg/h versus 129 +/- 9 mumol/kg/h). A significant positive correlation between birth weight and leucine flux was demonstrated in both feeding and fasting newborns. These results suggest that 1) newborns may accomplish protein accretion primarily by increases in protein synthesis rather than suppression of protein breakdown; 2) an estimate can be made of the minimal leucine intake required to replace irreversible leucine oxidative losses (816 mumol/kg/d, 107 mg/kg/d); and 3) the positive correlation between birth weight and leucine flux in both feeding and fasting newborns may be a result of differences in previous protein and energy supplies.

The purpose of this study was to examine whether premature infants have higher rates of energy expenditure and diet-induced thermogenesis during intermittent feeding compared with continuous feeding. Using open-circuit respiratory calorimetry, we measured energy expenditure in 11 premature newborn infants on 2 successive days for 5 to 7 hours during and after either intermittent or continuous feeding. Infants were fed the same quantity of formula each day, either for 5 minutes or by continuous drip for 2 to 3 hours. The order of feeding type was randomized. No response of diet-induced thermogenesis to continuous feeding was found, whereas a peak increase of 15% over baseline was observed after intermittent feeding. Overall energy expenditure during the study period was significantly greater after intermittent compared with continuous feeding (2.18 +/- 0.07 kcal/kg per hour vs 2.09 +/- 0.05 kcal/kg per hour; p less than 0.05). Thus there was a mean 4% difference (range up to 17%) in energy expenditure between the two feeding modes. These results are similar to those obtained with adults and support the concept of the increased energy efficiency of continuous feeding. Further study will be necessary to document whether the increased energy efficiency provided by continuous feeding may be clinically significant.

The H2[18O] tracer dilution method was applied to quantify total body water in 6 normal nonpregnant women, 8 normal pregnant women (gestation 29.3 +/- 6.0 weeks, range 21-37 weeks), and 8 insulin-dependent diabetic pregnant subjects (gestation 29.4 +/- 6.1 weeks, range 20-37 weeks). Plateau or equilibrium enrichment of 18O in the breath CO2 was achieved at approximately 2 h in nonpregnant normal subjects. In contrast, in pregnant subjects equilibrium plateau was reached later, at approximately 3 h. In order to examine whether the amniotic fluid/fetal compartment had also reached equilibrium with the maternal water compartment, amniotic fluid samples were obtained from 5 women undergoing elective cesarean section, approximately 5 h after the administration of tracer H2[18O]. The 18O enrichment of amniotic fluid was similar to that of the mother. Total body water was similar in normal and diabetic pregnant subjects (40.4 +/- 4.4 vs. 40.1 +/- 5.8 kg) and represented 55.8 +/- 5.4 and 58.7 +/- 5.5% of body weight, respectively. These data demonstrate the usefulness of the H2[18O] tracer method to measure total body water in pregnancy and emphasize the importance of an adequate equilibrium period 4-5 h in order to measure the dilution of administered tracer. The measurements by H2[18O] tracer are similar to those previously reported with deuterium oxide. Insofar as total body water reflects lean body mass, the data suggest that body compositional changes in normal and diabetic pregnancy are qualitatively similar.

Phototherapy results in the conversion of native bilirubin to more water-soluble configurational and structural isomers. The serum half-life for the configurational isomer, the principal photoproduct in vivo, was determined by high pressure liquid chromatography in six premature infants following cessation of phototherapy. The mean half-life for this isomer was 15 h. The excretion of this isomer, calculated from the measured half-life, is less than half of daily bilirubin production, and therefore cannot account for the total bilirubin elimination observed during phototherapy. The serum concentration of the structural isomer, lumirubin, is lower than that of the configurational isomer; however, excretion is more rapid (serum half-life less than 2 h). Because of its rapid excretion, lumirubin may be an important pathway for bilirubin elimination during phototherapy.

Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 +/- 17.1 vs. 138.3 +/- 20.4 mumoles per liter, mean +/- S.D., p less than 0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 +/- 19.0 vs. 87.8 +/- 19.0 mumoles per kg X hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 +/- 2.5 vs. 12.7 +/- 3.1 mumoles per kg X hr, p less than 0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)