Parenteral glycerol enhances gluconeogenesis in very premature infants

We have previously demonstrated that very premature infants receiving total parenteral nutrition maintain normoglycemia primarily by glucose produced via gluconeogenesis and that the lipid emulsion is most important in supporting gluconeogenesis. It is, however, not clear whether this is a result of the glycerol or the fatty acid constituent. The purpose of the present study was to determine the effect of intravenous supplemental glycerol alone on glucose production and gluconeogenesis. Twenty infants (birth weight, 1014 +/- 32 g; gestational age, 27 +/- 1 wk) were studied on d 4 +/- 1 (mean +/- SE). All infants received glucose at 17 micromol/kg x min for 9 h (after an initial study hour with 33 micromol/kg x min). Eight infants received no additional substrate during the study, and 12 infants received supplemental glycerol at 5 (n = 6) or 10 micromol/kg x min (n = 6) over the last 5 h of study. In infants receiving glucose alone, between period 1 (study hours 4-5) and period 2 (study hours 9-10), rates of glucose production ([U-13C]glucose) decreased from 12.9 +/- 1.2 to 7.4 +/- 0.9 micromol/kg x min (p < 0.01). This was the result of decreased glycogenolysis but no change in gluconeogenesis ([U-13C]glucose mass isotopomer distribution analysis) (5.1 +/- 0.6 versus 5.7 +/- 0.4 micromol/kg x min) (ns). Glycerol infusion at 5 and 10 micromol/kg x min, respectively, maintained glucose production (despite comparable decrease in glycogenolysis) by increasing gluconeogenesis from 4.3 +/- 0.2 to 6.3 +/- 0.5 (p < 0.03), and 6.0 +/- 0.7 to 8.8 +/- 0.8 micromol/kg/min (p < 0.01). In very premature infants, parenteral glycerol enhances gluconeogenesis and attenuates time dependent decrease in glucose production.     

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.     

Insulin infusion with parenteral nutrition in extremely low birth weight infants with hyperglycemia

From Nov. 7, 1983, to Nov. 6, 1986, all infants with birth weight less than or equal to 1000 gm admitted to Oregon Health Sciences University who had persistent hyperglycemia and glycosuria were treated with graded insulin infusion while energy intake was increased to at least 100 kcal/kg/day (419 kilojoules/kg/day). The records of these infants were reviewed to define the clinical characteristics of infants likely to develop hyperglycemia and to see whether insulin administration would allow goals for energy intake to be met. There were 76 surviving infants; 34 received insulin and 42 did not. Treated infants were smaller (767 +/- 161 vs 872 +/- 98 gm; p = 0.0004), were more immature (26.8 +/- 1.4 vs 27.7 +/- 2.0 weeks; p = 0.0115), and required mechanical ventilation longer (28 +/- 19 vs 17 +/- 15 days; p = 0.0196). There were no significant differences between the groups at 3, 7, 10, or 14 days for intravenously administered glucose or for total nonprotein energy intake at 3, 7, 10, 14, 28, or 56 days. Treated infants achieved an intake of 100 kcal/kg/day (419 kilojoules/kg/day) at 15 +/- 8 vs 17 +/- 11 days and regained birth weight at 12 +/- 6 vs 13 +/- 6 days (NS). There was no difference in percent change from birth weight at 7, 14, 28, or 56 days. Treated infants had a glucose concentration of 195 +/- 60 mg/dl (10.8 +/- 3.3 mmol/L) while receiving 7.9 +/- 3.0 mg/kg/min (43 +/- 17 mumol/kg/min) of glucose at the start of insulin infusion on days 1 to 14. Insulin was given for 1 to 58 days. The initial dose was 40 to 100 mU/gm of dextrose infused (57 to 142 nmol/mol) and then gradually decreased. Less than 0.5% of blood glucose values were 25 to 40 mg/dl (1.4 to 2.2 mmol/L). We conclude that insulin infusion improves glucose tolerance in extremely low birth weight infants and allows hyperglycemic infants to achieve adequate energy intake similar to that of infants who do not become hyperglycemic.     

Splanchnic uptake and release of energy substrates in the fasting baboon infant

Estimates of splanchnic energy substrate exchange in the primate infant have been obtained using a baboon model. The splanchnic bed of the fasting baboon newborn released glucose at an estimated rate of 14.5 +/- 5.0 mumol/min X kg body weight. Splanchnic glucose release in the fasting 5-7 wk old baboon infant proceeded similarly at an estimated rate of 15.5 +/- 4.5 mumol/min X kg body weight. The principal precursors taken up by the splanchnic bed were lactate, glycerol, and alanine. Uptake of alanine correlated in a linear fashion with glucose release. Lactate was the most important precursor in both age groups. Glucose recycling through lactate is an active mechanism in the primate fetus as well as in the young of other species.     

Protein requirements in preterm infants: effect of different levels of protein intake on growth and body composition

This study compares growth and body composition in preterm infants (< or =1750 g birth weight, < or =34 wk gestation) fed three iso-caloric formulas (80 kcal/100 mL) with different protein concentrations (A = 3.3 g/100 kcal, B = 3.0 g/100 kcal, C = 2.7 g/100 kcal). The study began when full enteral feeding (150 mL/kg/d) was established and lasted until term plus 12 wk corrected age (T + 12 wca). Nutrient intake was closely monitored throughout the study; daily during initial hospital stay and following discharge averaged between each clinic visit. Anthropometry and serum biochemistries were determined weekly during initial stay and at each clinic visit. Body composition was measured after hospital discharge and at T + 12 wca. Seventy-seven infants were recruited. No differences were detected in birth/enrollment characteristics between the groups. Protein intake was closely paralleled by changes in serum urea nitrogen and differed between the groups. Infants in group A were heavier and longer and had greater head circumference at discharge, but this was confounded by a slightly older corrected age in this group. There were no significant anthropometric differences at term or T + 12 wca. No differences were detected in body composition between the groups following discharge or at T + 12 wca. An intake of 3.3 g/100 kcal appears safe and may promote increased growth before initial hospital discharge. After discharge, intakes greater than 2.7 g/100 kcal do not appear to offer clear advantage. Further studies are needed to more precisely define protein requirements in these nutritionally at-risk infants.     

Whole body protein turnover measured with 13C-leucine and energy expenditure in preterm infants

Our study was undertaken in preterm infants to examine the relationship of whole body protein kinetics with protein intake and energy expenditure. Leucine kinetics were determined in seven low birth wt preterm infants fed human milk or human milk enriched with protein (2.5 to 4.3 g protein/kg.d). The infants received a short (4-h) constant infusion of L-[1-13C]leucine and leucine turnover and oxidation were calculated from 13C-plasma leucine and expired 13CO2 enrichments measured by mass spectrometry. Energy expenditure was measured by indirect calorimetry. Nonoxidative leucine disposal (an estimate of protein synthesis) and leucine derived from protein (an estimate of protein breakdown) were, respectively, 2.98 +/- 0.82 and 2.06 +/- 0.74 mumol/kg.min. Whole body protein turnover and deposition, derived from leucine kinetics, were 8.22 +/- 2.31 and 2.17 +/- 0.50 g/kg.d, whereas energy expenditure was 56.3 kcal/kg.day. Protein turnover was correlated with protein intake but not with protein deposition. Energy expenditure was correlated with protein turnover, synthesis, and breakdown but not with protein deposition. These data are in agreement with the fact that protein deposition depends upon protein intake, but they also suggest that an elevated protein deposition is not necessarily the result of a rapid protein turnover or associated with an elevated energy expenditure.     

The influence of NaCl supplementation on the postnatal development of urinary excretion of noradrenaline, dopamine, and serotonin in premature infants

The present study was designed to investigate the role of noradrenaline (NA), dopamine (DA), and serotonin (5-HT) in the adaptation of premature infants to alterations of sodium balance. Urinary excretion of NA, DA, and 5-HT was measured spectrofluorimetrically in a group of low birth weight premature infants with (group S) and without (group NS) NaCl supplementation. Group NS consisted of 10 infants with a birth weight of 1200-1750 g (mean, 1493 g) and gestational age of 28-31 wk (mean, 30.1 wk). Group S included 10 infants with mean birth weight of 1414 g (range, 1150-1600 g) and mean gestational age of 30.5 wk (range, 27-32 wk). Measurements were made on the 7th day and weekly thereafter until the 5th wk of life. NaCl supplementation was given in a dose of 3-5 and 1.5-2.5 mEq/kg/day for 8-21 and 22-35 days, respectively. In group NS, mean urinary excretion of NA and DA increased from 8.6 +/- 1.5 and 15.8 +/- 2.4 micrograms/day to maximum values of 21.4 +/- 5.5 (p less than 0.05) and 33.4 +/- 6.0 micrograms/day (p less than 0.01) in weeks 2-3, respectively. 5-HT excretion averaged about 60 micrograms/day and showed no consistent change during the course of the study. NaCl supplementation prevented the rise of NA and DA excretion above the initial baseline values. The postnatal course of 5-HT excretion, however, remained unaffected by NaCl supplementation. Urinary excretion of NA in weeks 2-3 (p less than 0.05) and DA in weeks 2-4 (p less than 0.05) were significantly lower in group NS.     

Energy substrate production in infants born small for gestational age

AIM: To investigate energy substrate production and its hormonal regulation in infants born small for gestational age. METHODS: Eleven infants, aged 24.4 +/- 5.3 hour, were studied following a fast of 4.0 +/- 0.6 hour. Gestational age was 35.4 +/- 2.8 weeks and birth weight 1804 +/- 472 g (<-2 SD). Rates of glucose production and lipolysis were analyzed using [6,6-(2)H(2)]-glucose and [2-(13)C]-glycerol. RESULTS: Plasma levels of glucose and glycerol were 4.1 +/- 1.1 mmol x L(-1) and 224 +/- 79 micromol x L(-1), respectively. Glucose appearance averaged 30.3 +/- 8.2 and glucose production rate 21.1 +/- 6.1 micromol x kg(-1) x minutes(-1). Glycerol production rate was 5.6 +/- 1.6 micromol x kg(-1) x minutes(-1), correlating strongly to birth weight (r = 0.904, p < 0.001). Of the glycerol produced, 55 +/- 22% was converted to glucose, corresponding to 8 +/- 3% of the glucose production. CONCLUSIONS: Even though the infants could produce energy substrates, lipolysis was reduced and the glucose production was in the low end of the normal range compared with infants born appropriate for gestational age. The correlation between glycerol production and birth weight indicates that lipolysis depends on the amount of stored fat. Data on insulin and insulin-like growth factor binding protein 1 support the view that insulin sensitivity in these infants is reduced in the liver but increased peripherally.     

Energy expenditure and deposition of breast-fed and formula-fed infants during early infancy

The energy intake, expenditure, and deposition of 40 breast-fed and formula-fed infants were investigated at 1 and 4 mo of age to explore possible differences in energy utilization between feeding groups. Energy intake was calculated from 5-d test-weighing records or pre- and postweighing of formula bottles, in combination with bomb calorimetry of the milks. Total daily energy expenditure (TDEE) was determined by the doubly labeled water method. Sleeping metabolic rate (SMR) and minimal observable energy expenditure were measured by indirect calorimetry. Activity was estimated as the difference between TDEE and SMR. Energy deposition was estimated from dietary intake and TDEE. Energy intakes were significantly higher for the formula-fed than breast-fed infants at 1 mo (118 +/- 17 versus 101 +/- 16 kcal/kg/d) and 4 mo (87 +/- 11 versus 72 +/- 9 kcal/kg/d) (p less than 0.001). TDEE averaged 67 +/- 8 and 64 +/- 7 kcal/kg/d at 1 mo and 73 +/- 9 and 64 +/- 8 kcal/kg/d at 4 mo for the formula-fed and breast-fed infants, respectively, and differed between feeding groups (p less than 0.04). SMR and minimal observable energy expenditure (kcal/min) were higher among the formula-fed infants at 1 and 4 mo (p less than 0.005). The energy available for activity and the thermic effect of feeding did not differ between feeding groups. Rates of weight gain (g/d) and energy deposition (kcal/kg/d) tended to be greater among the formula-fed infants at 1 and 4 mo (p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)     

Total energy expenditure, body composition and weight gain in moderately preterm and full-term infants at term postconceptional age

AIM: To assess total energy expenditure (TEE) and body composition, i.e. total body water (TBW) and adipose tissue volume (ATV), at term age in 8 healthy preterm infants, born between gestational weeks 30 and 33, and in 9 healthy full-term newborns. METHODS: Total and subcutaneous ATVs were assessed using magnetic resonance imaging, while TEE and TBW were estimated using doubly labelled water. RESULTS: Total ATV was 272 +/- 21 and 261 +/- 56 ml/kg body weight, while subcutaneous ATV was 88.9 +/- 1.6 and 89.7 +/- 2.0% of total ATV for preterm and full-term infants, respectively. The corresponding figures for TBW (as percentage of body weight) were 67.4 +/- 2.5 and 68.1 +/- 4.1, respectively. A significant correlation between ATV/kg body weight and body weight was found for full-term (p < 0.0001) but not for preterm infants. TEE for preterm infants was 315 +/- 20 kJ/kg body weight/24 h, which was significantly higher (p < 0.05) than TEE for full-term infants (254 +/- 45 kJ/kg body weight/24 h). At the time of investigation preterm infants weighed significantly (p < 0.05) less (540 g) than full-term infants. After the time of investigation, weight gains of preterm and full-term infants were 38 +/- 12 and 24 +/- 14 g/24 h, respectively. CONCLUSION: When compared to full-term newborns, predominantly breastfed healthy preterm infants at term postconceptional age were significantly smaller, had a similar average proportion of body fat and showed catch-up growth. Their higher TEE/kg body weight can be explained by a higher growth rate and possibly also by higher physical activity.     

Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn: effect of maternal diabetes and intrauterine growth retardation.

Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin-dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7- to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 +/- 0.39, SGA 0.35 +/- 0.09, IDM 0.33 +/- 0.21 mmol/L; mean +/- SD). The rate of appearance of glycerol was significantly elevated (p less than 0.05) in SGA infants (AGA 9.47 +/- 2.11, IDM 9.55 +/- 2.14, SGA 12.15 +/- 3.87 mumol/kg.min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2 carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptation of glucose production and gluconeogenesis to diminishing glucose infusion in preterm infants at varying gestational ages

In preterm infants low plasma glucose concentrations are frequently observed. We hypothesized that the infants' ability to adapt endogenous glucose production to diminishing exogenous supply is disturbed, but will improve with increasing gestational age. Glucose production rate and gluconeogenesis were measured using stable isotope techniques with [6,6-2H2]glucose and [2-13C]glycerol in 19 preterm infants (10 < or = 30 wk and nine >30 wk gestational age) on d 5.0 +/- 1.4 of life. Exogenous glucose was administered at a rate of 33 micromol x kg-1 x min-1 followed by 22 micromol x kg-1 x min-1. In the first 2 h after the decrease in exogenous supply, plasma glucose concentration declined comparably in both groups: < or =30 wk, from 4.3 +/- 1.2 to 3.2 +/- 0.9 mM; >30 wk, from 3.7 +/- 0.7 to 3.0 +/- 0.6 mM. Thereafter, only in infants >30 wk an increase was observed, to 3.4 +/- 0.8 mM. Glucose production rate increased comparably in both groups: < or =30 wk, from 6.0 +/- 4.1 to 8.8 +/- 3.4 micromol x kg-1 x min-1; >30 wk, from 7.8 +/- 4.6 to 11.6 +/- 5.2 micromol x kg-1 x min-1. This increase was equivalent to approximately 30% of the decline in exogenous glucose. Gluconeogenesis increased comparably in both groups: <30 wk, from 3.2 +/- 1.2 to 4.5 +/- 1.3 micromol x kg-1 x min-1; >30 wk, from 4.3 +/- 1.9 to 6.8 +/- 2.9 micromol x kg-1 x min-1. We conclude that preterm infants can only partly compensate a decline in exogenous glucose supply by increasing endogenous glucose production rate, probably because of limitations in the final common pathway of intracellular glucose metabolism (i.e. glucose-6-phosphatase). The ability to maintain the plasma glucose concentration after a decrease in exogenous supply is better preserved in infants >30 wk owing to more efficient adaptation of peripheral glucose utilization.     

Increased energy expenditure and fecal fat excretion do not impair weight gain in small-for-gestational-age preterm infants.

In order to optimize the nutrition of high-risk premature infants beyond the early postnatal period, a more precise knowledge of individual nutritional requirements is needed. We therefore studied the influence of intrauterine growth retardation on energy expenditure and nutrient utilization determined by indirect calorimetry and fecal fat excretion (steatocrit) in nineteen premature infants who were appropriate-for-gestational-age (AGA; mean gestational age 29.9+/-0.3 weeks, mean birth weight 1.30+/-0.05 kg) and thirteen small-for-gestational-age (SGA) premature infants [mean gestational age 32.4+/-0.5 weeks, mean birth weight 1.024+/-0.07 kg (i.e., below the 10th percentile)] during the first and second month of life. All infants were clinically stable during the study period. In nine SGA infants we observed a significantly higher steatocrit compared to twelve AGA infants (29+/-1 vs. 17+/-1% p = 0.0001). SGA infants (n = 12) also showed a slightly (albeit statistically not significantly) higher energy expenditure than AGA infants (n = 15) (58.7+/-1.9 vs. 53.6+/-1.5 kcal/kg per day, p = 0.054). Despite the increased fat excretion and higher energy expenditure, SGA infants gained weight more rapidly during the study period than AGA infants (20+/-1 vs. 17+/-1 g/kg per day, p = 0.026). We conclude that influences of intrauterine growth retardation on energy expenditure and nutrient utilization persist during the first weeks of extrauterine life. However, these metabolic changes do not impair the capability of SGA infants for extrauterine catch-up growth if adequate nutrition is provided.     

Energy balance, physical activity, and thermogenic effect of feeding in premature infants

In order to assess the contribution of the thermogenic effect of feeding and muscular activity to total energy expenditure, nine premature infants were studied for 2 consecutive days during which time repeated measurements of energy expenditure by indirect calorimetry were performed throughout the day, combined with a visual activity score based on body movement. The infants were growing at 16.6 +/- 4.0 g/kg/day (mean +/- SD) and received 110 +/- 8 kcal/kg/day metabolizable energy (milk formula) and 522 +/- 40 mgN/kg/day. Their total energy expenditure was 68 +/- 4 kcal/kg/day indicating that 41 +/- 7 kcal/kg/day was retained for growth. Based on the combination of energy + N balances it was estimated that 80% of the weight gain was fat-free tissue and 20% was fat tissue. The rate of energy expenditure measured minute-by-minute was significantly and linearly correlated with the activity score in both the premeal (r = 0.75;p less than 0.001) and the postmeal periods (r = 0.74; p less than 0.001) with no difference in the regression slope, but with a significant difference in intercept. In preset feeding schedules the latter allowed an estimation of the thermogenic effect without the confounding effect of activity. This was found to be 3.1 +/- 1.8% when expressed as a percentage of metabolizable energy intake. However when the "classical" approach was used as a comparison (integration of extra energy expenditure induced by the meal), the thermogenic effect was found to be greater, i.e. 9.5 +/- 3.8% of the meal's metabolizable energy, due to the superimposed effect of physical activity in the postprandial state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose production and oxidation in preterm infants during total parenteral nutrition

During total parenteral nutrition in preterm infants, glucose may be infused at high rates, but it is not known if the endogenous glucose production is fully suppressed under these circumstances. Eight preterm appropriate for gestational age (AGA) (birth wt: 1613 +/- 151 g, gestational age: 31.1 +/- 1.5 wk) and eight preterm small for gestational age (SGA) newborn infants (1185 +/- 241 g, 32.9 +/- 2.6 wk) receiving a glucose infusion rate of 7.55 +/- 0.56 and 8.16 +/- 0.65 mg/kg.min, respectively, were studied during continuous total parenteral nutrition at postnatal d 8. Glucose oxidation rate was determined with a primed constant infusion of [U-13C] glucose, measuring the 13CO2 production in breath gas by isotope ratio mass spectrometry and the glucose production rate in plasma by gas chromatography mass spectrometry. In breath gas of AGA and SGA infants, 60 and 65%, respectively, of the infused tracer appeared as 13CO2. The glucose production rates were 7.97 +/- 1.61 and 8.12 +/- 1.84 mg/kg.min in AGA and SGA infants, respectively, indicating that no significant endogenous glucose production occurred. The glucose oxidation calculated from the glucose production and 13CO2 production was 4.74 +/- 0.99 mg/kg.min in AGA infants and was significantly different from the carbohydrate oxidation rate of 6.62 +/- 1.23 mg/kg.min measured by simultaneous indirect calorimetry. In SGA infants, however, the glucose and carbohydrate oxidation rates were not significantly different at 5.33 +/- 1.56 and 6.16 +/- 2.45 mg/kg.min. It is concluded that 1-wk-old AGA or SGA preterm infants receiving total parenteral nutrition of 80 kcal/kg.d produce no endogenous glucose and their glucose oxidation rates are similar at 63-65% of the glucose infused. It is suggested that the significant difference between glucose and carbohydrate oxidation rates observed in AGA but not in SGA infants is due either to a higher rate of lipogenesis from carbohydrates, or, less likely, to a higher rate of glycogen oxidation.     

Energy expenditure in infants with congenital heart disease,including a meta-analysis

AIM: To assess energy requirements and body composition in preoperative children with congenital heart disease (CHD). METHODS: In 11 infants with CHD (2-8 mo), total daily energy expenditure (TDEE) and total body water (TBW) were measured with doubly labelled water and compared with historic data from healthy controls. Within the patient group, energy expenditure of infants with versus those without congestive heart failure was compared. Subsequently, the data were pooled with literature data in meta-analyses. RESULTS: CHD patients showed increased TBW (mean +/- SD 66 +/- 3 vs 58 +/- 5% of body weight, p < 0.05) and energy expenditure (381 +/- 42 vs 298 +/- 36 kJ kg(-1) d(-1), p < 0.001). Meta-analyses showed that CHD infants have 35% increased TDEE (376 vs 278 kJ kg(-1) d(-1) , p < 0.00001) and 7% higher TBW (p < 0.0001). Coexistent congestive heart failure (treated with diuretics) had no influence on TDEE (mean difference 14 kJ kg(-1) d(-1) , not significant). In patients with heart failure and growth retardation, an energy balance study showed an average 12% loss of initially ingested energy due to vomiting, increased TDEE and low faecal energy loss, resulting in low energy available for growth, compared with controls (42 +/- 30 vs 96 +/- 61 kJ kg(-1) d(-1) , p < 0.05). CONCLUSION: Many infants with CHD require substantially higher energy intake (at least 100 kJ kg(-1) d(-1) extra) owing to increased TDEE, which is not explained by a higher percentage of body water. Coexistent heart failure does not appear to have an additional influence on TDEE. In infants with CHD and growth failure factors other than elevated TDEE, including vomiting, may explain the disturbed energy balance.     

A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance

To determine whether a continuous insulin infusion improves glucose tolerance in extremely low birth weight infants, we conducted a prospective, randomized trial in 24 neonates 4 to 14 days old (mean birth weight 772.9 +/- 128 gm; mean gestational age 26.3 +/- 1.6 weeks). Infants who had glucose intolerance were randomly assigned to receive either intravenous glucose and total parenteral nutrition with insulin through a microliter-sensitive pump or standard intravenous therapy alone. One infant assigned to receive insulin never required it. The groups were similar in birth weight, gestational age, race, gender, medical condition, and energy intake before the study. The mean duration of therapy was 14.6 days (range 7 to 21 days). During the study, the 11 insulin-treated infants tolerated higher glucose infusion rates (20.1 +/- 2.5 vs 13.2 +/- 3.2 mg/kg/min (1.1 +/- 0.1 vs 0.7 +/- 0.2 mmol/L); p less than 0.01), had greater nonprotein energy intake (124.7 +/- 18 vs 86.0 +/- 6 kcal/kg/day; p less than 0.01), and had better weight gain (20.1 +/- 12.1 vs 7.8 +/- 5.1 gm/kg/day; p less than 0.01) than the 12 control infants. The incidence of hypoglycemia, electrolyte imbalance, chronic lung disease, and death did not differ between groups. We conclude that a controlled insulin infusion improves and sustains glucose tolerance, facilitates provision of calories, and enhances weight gain in glucose-intolerant premature infants.     

Nutritional rehabilitation increases resting energy expenditure without affecting protein turnover in patients with cystic fibrosis.

The effect of nutritional rehabilitation on several nutritional parameters was studied in eight malnourished patients with cystic fibrosis during the first year after gastrostomy tube insertion. Body composition was studied by fat skinfold measurements and by total body potassium count, resting energy expenditure (REE) by indirect calorimeter, and protein turnover by a single dose administration of [15N]glycine. Weight gain was accompanied by a significant increase in the various body compartments: weight 41.4 +/- 7.5 to 46.1 +/- 8.4 kg (p less than 0.0002), fat body mass 5.6 +/- 2.8 to 7.7 +/- 3.4 kg (p less than 0.005) and fat-free body mass (FFBM) 35.7 +/- 6.3 to 38.3 +/- 6.9 kg (p less than 0.0003). REE increased significantly per kg of body weight as well as per kg of FFBM. No significant differences were found in protein turnover during refeeding nor in pulmonary function. We conclude that nutritional support restores body composition, but is accompanied by an increase in energy expenditure. This increase could not be attributed to increased protein turnover.     

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 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.     

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.