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BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Objectives: To identify the variables that predict death/physiologic bronchopulmonary dysplasia (BPD) in preterm infants with severe respiratory failure., Study Design: The study was a secondary analysis of data from the NICHD Neonatal Research Network trial of inhaled nitric oxide (iNO) in preterm infants. Stepwise logistic regression models and Classification and Regression Tree (CART) models were developed for the outcome of death or physiologic BPD (O(2) at 36 weeks post-menstrual age)., Result: Death and/or BPD was associated with lower birth weight, higher oxygen requirement, male gender, additional surfactant doses, higher oxygenation index and outborn status, but not the magnitude of response in PaO(2) to iNO. The positive predictive value of the CART model was 82% at 95% sensitivity., Conclusions: The major factors associated with death/BPD were an increased severity of respiratory failure, lower birth weight, male gender and outborn status, but not the magnitude of initial response to iNO.

Objective: Inhaled nitric oxide (iNO) use in infants >1500 g, but <34 weeks gestation with severe respiratory failure will reduce the incidence of death and/or bronchopulmonary dysplasia (BPD)., Study Design: Infants born at <34 weeks gestation with a birth weight >1500 g with respiratory failure were randomly assigned to receive placebo or iNO., Results: Twenty-nine infants were randomized. There were no differences in baseline characteristics, but the status at randomization showed a statistically significant difference in the use of high-frequency ventilation (P=0.03). After adjustment for oxygenation index entry strata, there was no difference in death and/or BPD (adjusted relative risk (RR) 0.80, 95% confidence interval (CI) 0.43 to 1.48; P=0.50), death (adjusted RR 1.26, 95% CI 0.47 to 3.41; P=0.65) or BPD (adjusted RR 0.40, 95% CI 0.47 to 3.41; P=0.21)., Conclusions: Although sample size limits our ability to make definitive conclusions, this small pilot trial of iNO use in premature infants >1500 g and <34 weeks with severe respiratory failure suggests that iNO does not affect the rate of BPD and/or death.

Objective: To determine the differences in short term outcome of very low birthweight infants attributable to sex., Methods: Boys and girls weighing 501-1500 g admitted to the 12 centres of the National Institute of Child Health and Human Development Neonatal Research Network were compared. Maternal information and perinatal data were collected from hospital records. Infant outcome was recorded at discharge, at 120 days of age if the infant was still in hospital, or at death. Best obstetric estimate based on the last menstrual period, standard obstetric factors, and ultrasound were used to assign gestational age in completed weeks. Data were collected on a cohort that included 3356 boys and 3382 girls, representing all inborn births from 1 May 1991 to 31 December 1993., Results: Mortality for boys was 22% and that for girls 15%. The prenatal and perinatal data indicate few differences between the sex groups, except that boys were less likely to have been exposed to antenatal steroids (odds ratio (OR) = 0.80) and were less stable after birth, as reflected in a higher percentage with lower Apgar scores at one and five minutes and the need for physical and pharmacological assistance. In particular, boys were more likely to have been intubated (OR = 1.16) and to have received resuscitation medication (OR = 1.40). Boys had a higher risk (OR > 1.00) for most adverse neonatal outcomes. Although pulmonary morbidity predominated, intracranial haemorrhage and urinary tract infection were also more common., Conclusions: Relative differences in short term morbidity and mortality persist between the sexes.

During an 8-month study, 14 laboratories used automated analytical systems to measure total bilirubin concentrations in lyophilized bovine specimens containing 38, 169, and 253 micromol/L bilirubin (2.2, 9.9, and 14.8 mg/dL, respectively). The measured mean +/- SD (n, range) were: 39 +/- 7 micromol/L (n = 90, 31-53) [2.3 +/- 0.4 mg/dL (1.8-3.1)]; 176 +/- 29 micromol/L (n = 89, 146-222) [10.3 +/- 1.7 mg/dL (8.5-13.0)]; and 260 +/- 43 micromol/L (n = 103, 208-316) [15.2 +/- 2.5 mg/dL (12.1-18.5)]. In comparison with target values, measurements were consistently lower at 4, higher at 6, and within +/- 4% at 4 laboratories for each of the three concentrations. The measured values for each concentration remained fairly constant during the study at each laboratory. We conclude that bilirubin measurements differed significantly from the established target values at most of the participating laboratories.

CD4+ T cells from alpha beta-T-cell receptor transgenic mice were analyzed for coexpression of cytokine mRNAs during phenotype development using a double-label in situ hybridization technique. T cells that produced cytokines in the primary response were a fraction of the activated population, and only a minority of the cytokine-positive cells coexpressed two cytokines. In secondary responses, frequencies of double-positive cells increased, although they remained a minority of the total. Of the cytokine pairs examined, interleukin (IL)-4 and IL-5 were the most frequently coexpressed. IL-4 and interferon gamma showed the greatest tendency toward segregation of expression, being rarely coexpressed after the primary stimulation. These data indicate that there is significant heterogeneity of cytokine gene expression by individual CD4+ T cells during early antigenic responses. Coexpression of any pairs of cytokines, much less Th1 and Th2 cytokines, is generally the exception. The Th0 phenotype is a population phenotype rather than an individual cell phenotype.

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.

The guinea pig is a small animal species in which the conceptus constitutes a large proportion of maternal weight at term, thereby imposing a major metabolic demand on the mother during pregnancy. In addition the neonatal fat concentration is similar to the human making the guinea pig an interesting model for comparative physiologic study. The purpose of our study was to describe the fetal and maternal physical/chemical growth characteristics of the Hartley albino guinea pig throughout the latter half of gestation. Forty-eight pregnant adult and 122 fetal guinea pigs were sacrificed at intervals throughout gestation and the carcasses analyzed for a variety of growth parameters. The fetal growth rate during the last 8 days of gestation (5.8 g/day) was 9.7 times faster than from 30 to 40 days of gestation (0.6 g/day). The fetal mass comprised 55.4% of the maternal weight gain at term. Fetal energy increased from 403 cal/g at 30 days to 1950 cal/g at term and was paralleled by an increase in fetal fat concentration from 0.3 to 9.8% (wet weight). Nitrogen concentration increased from 0.9% wet weight at 30 days to 2.6% at term. An increasing carbon concentration and carbon:nitrogen ratio was also evident. Fetal water concentration declined from 91.6 to 67.8% during latter gestation. On a wet weight basis, the concentration of fetal sodium remained stable throughout the latter half of pregnancy; potassium, magnesium, iron, calcium, and phosphorus concentrations increased. In contrast to the changes in fetal composition, maternal energy, fat, protein, water, sodium, potassium, calcium, phosphorus, magnesium, and iron concentrations remained relatively constant throughout pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

The composition of human milk from mothers delivering prematurely (PT) and at term (T) was studied over the first weeks of lactation. Complete 24 h milk expressions were obtained by electric pump at weekly or biweekly intervals through 44 wk conceptual age (120 samples from 20 PT mothers and 28 samples from 7 T mothers). PT milk was found to contain significantly higher concentrations than T milk of the following nutrients: total nitrogen, protein nitrogen, sodium, chloride, magnesium and iron. No differences were found between T and PT milk for nonprotein nitrogen, volume, solids, total calories, lactose, fat, fatty acids, potassium or calcium. The nutrients supplied to a 33 wk preterm infant fed 200 ml/kg/day of "average" PT milk were in excess of theoretic intrauterine requirements for all substrates except calcium and phosphorus. PT human milk is theoretically more suitable for the premature infant than either mature or term human milk, but may be deficient in specific nutrients for the very low birth weight baby.

During fasting, branched-chain amino acids (BCAA) are thought to be major sources of nitrogen for myocyte synthesis of alanine (Ala) and glutamine (Gln), as well as possible sources of carbon skeleton for Gln synthesis. To study the relationships between Ala, Gln, and BCAA, we utilized the chronic fetal lamb preparation and measured arteriovenous concentration differences of Ala, Gln, BCAA, and branched-chain alpha-keto acids across the fetal hindlimb. Studies were performed when the ewe was fed and repeated after 1 and 5 days of complete maternal fasting. Ala and Gln are released from fetal hindquarters during fasting (arteriovenous -9.6 +/- 5 and -8.8 +/- 4.1 mumol/liter), while arteriovenous differences for BCAA simultaneously increase by 65% as compared to the fed state. During fasting, total nitrogen exiting fetal hindlimb as Ala and Gln equals nitrogen entering as BCAA. Branched-chain alpha-keto acids are released from fetal hindquarters during the fed state as well as after 1 day of fasting; at 5 days of fasting only keto-isovalerate had a net negative arteriovenous difference. In all cases, the release was much smaller than the entry of the corresponding amino acid, as determined by simultaneously measured arteriovenous concentration differences. These results indicate: Ala and Gln are released from fetal hindlimb, as in postnatal animals, during fasting, shuttling nitrogen and carbon to liver and/or other tissues. There is negligible movement of BCAA carbon as the branched-chain alpha-keto acids from hindlimb to other tissues in the fetus. BCAA carbon taken up is utilized within the hindquarters. It may be used for tissue synthesis, as an energy source, or possibly for Gln synthesis.

Fetal and maternal sheep were studied to determine whether changes in gluconeogenic enzyme activities could be detected in the liver and/or kidney associated with maternal nutritional deprivation. Thirteen ewes and 16 fetuses were sacrificed in the fed state, while 13 ewes with 17 fetuses were sacrificed after 5 days of fasting, all at 125 days gestation (term = 147 days). Fetal weight was decreased in the fasted versus fed group (2.86 +/- 0.56 versus 3.61 +/- 0.58 kg, p less than 0.001). Tissues were analyzed for glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase, phosphoenolpyruvate carboxykinase, glutamate oxaloacetate aminotransferase, and glutamate pyruvate aminotransferase. In maternal liver, four of the six enzymes increased significantly during fasting, whereas none of the enzymes increased in maternal kidney. In fetal hepatic tissue, five of the six enzymes (with the exception of pyruvate carboxylase) increased during maternal fasting and three of the enzymes increased in renal tissue. These data are consistent with the potential for increased rates of gluconeogenesis in the ovine fetus during periods of compromised maternal nutrition.

We prospectively examined 298 sets (298 aerobic, 299 anaerobic, and 73 resin cultures) of blood cultures from 161 critically ill newborns. The attending physicians were unaware of the study. The mean blood volume per patient (aerobic and anaerobic) was 1.05 (range, 0.11 to 3.04) ml. The mean blood volume per aerobic bottle was 0.53 (range, 0.01 to 1.90) ml. Among aerobic samples 2.7% were less than or equal to 0.1 ml, 16% were less than or equal to 0.3 ml, 33% were less than or equal to 0.4 ml, and 55% were less than or equal to 0.5 ml. For anaerobic cultures the mean blood volume was 0.52 (range, 0.01 to 1.79) ml. Among anaerobic samples 2.7% were less than or equal to 0.1 ml, 15% were less than or equal to 0.3 ml, 35% were less than or equal to 0.4 ml, and 58% were less than or equal to 0.5 ml. Blood volume did not correlate with gestational age, chronologic age, or weight. The mean volume of blood submitted in positive cultures was not significantly greater than that in negative cultures. The blood volume used for culture from ill newborns may be inadequate for detecting sepsis, and the adequacy of currently available culture methods needs to be assessed for the small samples submitted from critically ill newborns.

Branched-chain amino acid aminotransferase (BCAAT) and branched-chain 2-oxo acid dehydrogenase (BCODH) activities were determined in sheep maternal and fetal liver, kidney, skeletal muscle, adipose and placenta in the fed and 5-day-starved states at 125 days gestation (term is 147 days). BCAAT activities were quite low in maternal skeletal muscle, low in fetal and maternal liver, high in fetal muscle, and very high in placenta. No significant changes occurred with maternal starvation. The high BCAAT activity of the placenta may provide the essential branched-chain 2-oxo acids for the fetus. BCODH activity was highest in liver and kidney of both the mother and fetus; it was largely in the active (dephosphorylated) state in maternal liver and kidney, and in fetal kidney, and about 50% active in fetal liver. The enzyme was largely inactive in fetal muscle, and about 50% active in maternal muscle. Although starvation had little effect on the activity of BCODH in fetal tissues, a significant decrease in activity was observed in maternal tissues, thereby potentially sparing branched-chain amino acids or the corresponding 2-oxo acids for maintenance of the fetus during compromised maternal nutrition.

Aspiration of uncontaminated human amniotic fluid was investigated in adult and newborn rabbits and compared with three other experimental groups: 10% meconium solution, saline, and sham-injected controls. Fluids were injected into the trachea of adult animals (4 or 6 ml/kg body weight), newborn vaginally-delivered animals (a mean volume of 8 ml/kg), and cesarean-delivered animals before their first breath (a mean volume of 11 ml/kg). In adult animals aspirating amniotic fluid or saline, arterial PO2 measured over a 24-h period showed a mean difference between groups of less than 5% for both 4 and 6 ml/kg. Meconium aspiration produced a greater depression in PO2 than amniotic fluid aspiration (a mean difference of 16 and 31% for 4 and 6 ml/kg, respectively) and animals aspirating meconium showed a deteriorating trend over 24 h, whereas animals aspirating amniotic fluid improved. One of eight adult animals aspirating amniotic fluid died versus four of five aspirating meconium. All five animals aspirating saline 6 ml/kg survived. Lung weight and resting volume of adult animals aspirating amniotic fluid were not significantly different from animals aspirating saline or nothing. Lung pressure volume curves from adult animals aspirating amniotic fluid were nearly identical to controls. Histology showed significantly greater atelectasis in adult animals that received 6 ml/kg amniotic fluid than controls, but this was not different from saline. There was no association between the number of cells in amniotic fluid and arterial PO2 after aspiration or any other aspect of pulmonary function measured.(ABSTRACT TRUNCATED AT 250 WORDS)

The whole blood concentrations of 22 amino acids were measured in a chronic, unstressed fetal lamb preparations. Samples were taken daily from the umbilical artery, umbilical vein, and maternal artery over the latter quarter of gestation. 73 sets of samples (from the umbilical artery and vein and the maternal artery) from 13 animals were analyzed for amino acid levels. Oxygen contents were determined simultaneously in 48 sets (umbilical artery and vein) to relate fetal oxygen consumption to amino acid uptake via the umbilical circulation. The results indicate that there is no umbilical uptake of the acidic amino acids, glutamate and aspartate; there is, in fact, a net flux of glutamate out of the fetus into the placenta. As both of these amino acids are major constituents of body proteins, the data indicate that they are formed within the fetus. The umbilical uptake of some neutral and basic amino acids (e.g., valine, leucine, isoleucine, arginine, phenylalanine, and tyrosine) is in considerable excess of estimated growth requirements, suggesting that some amino acids undergo extensive transamination and oxidative degradation in the fetus. Finally, the net uptake of nitrogen, carbon, and calories by the growing ovine fetus in the form of amino acids, glucose, and lactate is compared to estimated requirements as determined in previous studies.