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Background Preterm neonates often require glucocorticoids to manage refractory hypotension, prevent, and treat bronchopulmonary dysplasia. We have investigated the effect of cumulative dose and duration of glucocorticoids on blood pressure and renal function in VLBW infants. Methods In this retrospective cohort study, medical records of infants (GA ≤ 35 weeks) born January 2015 to December 2019 were reviewed to extract demographic and clinical characteristics, dose and duration of steroids, blood pressure (BP), and creatinine at the time of discharge from the neonatal intensive care unit. Results Two hundred and eighty-three neonates with average GA (28 ± 3 weeks) and birthweight (1060±381 g). Twenty-eight percent (33/116) of infants who received postnatal steroids developed hypertension versus 16% (27/167) of controls (OR = 2.0, p = 0.011). There was a correlation between the cumulative dosage of postnatal steroids and systolic BP (R2 = 0.06, p

A 231/7-week-old and 560-g-weighing premature male infant was evaluated on day of life 33 for increased frequency of bradycardias, bilious residual, and an increase in abdominal girth. Physical examination was notable for distended and mild tender abdomen. Investigations revealed pneumoperitoneum with dilated bowel loops and a normal acid–base balance. An urgent exploratory laparotomy demonstrated isolated jejunal perforation with an adhesive band extending from the omentum to the base of the mesentery. A segmental jejunal resection followed by an end-to-end anastomosis was performed. The diagnosis of intestinal perforation was inconsistent with focal spontaneous intestinal perforation and necrotizing enterocolitis. Decision to perform exploratory laparotomy led to diagnosis of congenital adhesion band, a rare clinical condition, and the patient had a favorable outcome. This premature infant made an excellent recovery and the upper gastrointestinal (GI) study demonstrated that the anastomotic site was intact. He is currently tolerating advancing enteral feeds.

BackgroundUp to 90% of all drugs used in neonatal intensive care units (NICUs) have not been clinically tested for safety and efficacy. To promote drug development for neonates, the pharmaceutical industry is moving toward rigorous testing, necessitating the need to development, and validating biomarkers in neonates to predict their response. The objective of this review is to evaluate the quality of the response biomarker reporting in neonatal clinical trials.MethodsA validated literature search strategy was applied. Prospective neonatal intervention studies reporting response biomarkers published in 2014 were included. The data were extracted independently and in duplicate using a data-extraction form.ResultsFollowing the full-text review, 167 published prospective neonatal trials were included; 35% (59/167) reported the use of response biomarkers. In these 59 trials, we identified 275 biomarkers used to measure the response (pharmacodynamics and safety) reported as primary or secondary outcomes. Heart rate and oxygen saturation were the most commonly reported. Measurement and instrumentation data were often not provided.ConclusionWe identified a huge variability in the selection, measurement, and reporting of neonatal response biomarkers in prospective intervention studies. Reporting initiatives are needed to reduce research waste and improve the reproducibility of biomarker use in neonatal intervention studies.

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking versus delayed cord clamping among infants

This study was conducted to survey US pediatric specialists about administration of respiratory syncytial virus (RSV) immunoprophylaxis, communication patterns among physicians and parents, and barriers to access. Separate surveys were sent to neonatologists, pediatricians, pediatric pulmonologists, and pediatric cardiologists. Most physicians (≥93.5%) routinely recommended immunoprophylaxis to high-risk children. Most respondents (≥71.8%) reported that >50.0% of eligible infants and young children received each monthly dose throughout the RSV season, with the first dose most commonly administered before discharge from the birth hospitalization. To ensure receipt of subsequent doses, specialists frequently scheduled a follow-up visit at the end of the current appointment. All specialists reported insurance denials as the biggest obstacle to the administration of immunoprophylaxis to high-risk children. These findings may be used to improve adherence to immunoprophylaxis by enhancing education and physician-parent communications about severe RSV disease prevention, and by reducing known barriers to use of this preventive therapy.

Background In premature infants, donor breast milk (DBM) is assumed to provide reduced nutrients vs. mother's own milk (MOM). This study examined calorie and protein delivery when very low birth weight infants were fed fortified MOM or DBM, with a known nutrient composition, relative to established nutrition recommendations and to determine if there were differences between the groups. Methods A retrospective medical record review was conducted in 29 very low birth weight infants receiving MOM or DBM. Nutrient content of human milk was measured using the Calais Analyzer. Added fortifiers feeding volume, and weight were collected to determine total daily calorie and protein intake. Results 145 days of enteral feedings among 29 infants were included, 78 (53.8%) from DBM and 67 (46.2%) from MOM. Mean daily fluid intake among infants receiving DBM was significantly higher when compared with MOM, 150.6 ± 7.6 mL/kg vs 146.8 ± 11.3 mL/kg (P = .016). DBM feedings provided 110.1 ± 9.0 kcals/kg/d vs 113.0 ± 21.0 kcals/kg/d from MOM feedings (P = .275). Mean protein intake was similar, 4.1 ± 0.5 g /kg/d on DBM days vs 4.0 ± 0.5 g kg/d on MOM days (P = .162). A total of 46 of 78 DBM days (59.0%) and 30 of 67 MOM days (44.8%) were below the minimum established calorie needs of 110 kcals/kg/day. Conclusions DBM provides comparable nutrient intake to MOM at a higher enteral feeding volume. However, both types of human milk failed to meet energy needs with standard fortification regimens.

We have examined hepatic, genomic, and metabolic responses to dietary protein restriction in the non-pregnant Sprague-Dawley rat. Animals were pair-fed either a 6 or 24% casein-based diet for 7–10 days. At the end of the dietary period, a microarray analysis of the liver was performed, followed by validation of the genes of interest. The rates of appearance of phenylalanine, methionine, serine, and glucose and the contribution of pyruvate to serine and glucose were quantified using tracer methods. Plasma and tissue amino acid levels, enzyme activities, and metabolic intermediates were measured. Protein restriction resulted in significant differential expression of a number of genes involved in cell cycle, cell differentiation, transport, transcription, and metabolic processes. RT-PCR showed that the expression of genes involved in serine biosynthesis and fatty acid oxidation was higher, and those involved in fatty acid synthesis and urea synthesis were lower in the liver of protein-restricted animals. Free serine and glycine levels were higher and taurine levels lower in all tissues examined. Tracer isotope studies showed an ∼50% increase in serine de novo synthesis. Pyruvate was the primary (∼90%) source of serine in both groups. Transmethylation of methionine was significantly higher in the protein-restricted group. This was associated with a higher S-adenosylmethionine/S-adenosylhomocysteine ratio and lower cystathione β-synthase and cystathionine γ-lyase activity. Dietary isocaloric protein restriction results in profound changes in hepatic one-carbon metabolism within a short period. These may be related to high methylation demands placed on the organism and caused by possible changes in cellular osmolarity as a result of the efflux of the intracellular taurine.

Glutamine is a non-essential amino acid that can be synthesized de novo from glutamate. This synthesis can be increased by intravenous infusion of carbon precursors (alpha-ketoglutarate or amino acids) in adults and in infants. The metabolism of glutamine is highly compartmentalized between the splanchnic tissues and the periphery, so that orally administered glutamine is completely metabolized in the splanchnic compartment. Data from studies in adults and children show that plasma levels of glutamine decline during acute stress and illness. Because of its importance in several physiological functions (the demonstrated benefits of supplemental glutamine in adult burns and trauma patients and the inhibitory effect on proteolysis in the skeletal muscle in vitro), it has been suggested that during 'acute stress' the demands of glutamine outweigh its de novo synthesis, resulting in a fall in plasma glutamine levels. As a consequence, glutamine has been considered a 'conditionally essential' amino acid. Because of its instability in solution, glutamine is not routinely added to the parenteral amino acid mixtures. A number of clinical trials of parenteral and enteral supplementation of glutamine have been performed. The outcome measures examined have varied between acute effects and long-term complex clinical events such as mortality and risk of infections. Although acute studies in LBW babies have shown some beneficial effects such as changes in protein metabolism and activation of immune system, these have not been translated into prolonged advantages such as reduction in mortality or in nosocomial infection. The reasons for these differences are discussed.

Glutamine may be a conditionally essential amino acid in low-birth-weight (LBW) preterm neonates. Exogenously administered amino acids, by providing anaplerotic carbon into the tricarboxylic acid cycle, could result in greater cataplerotic efflux and glutamine de novo synthesis. The effect of dose and duration of amino acid infusion on glutamine and nitrogen (N) kinetics was examined in LBW infants in the period immediately after birth. Preterm neonates (−1·h−1 of an intravenous amino acid solution for 19–24 hours, followed by a higher or lower amino acid load for either 5 h or 24 h. Glutamine de novo synthesis, leucine N, phenylalanine, and urea kinetics were determined using stable isotopic tracers. An increase in amino acid infusion from 480 to 960 μmol·kg−1·h−1 for 5 h resulted in decreased glutamine de novo synthesis in every neonate (384.4 ± 38.0 to 368.9 ± 38.2 μmol·kg−1·h−1, P < 0.01) and a lower whole body rate of proteolysis ( P < 0.001) and urea synthesis ( P < 0.001). However, when the increased amino acid infusion was extended for 24 h, glutamine de novo synthesis increased (369.7 ± 92.6 to 483.4 ± 97.5 μmol·kg−1·h−1, P < 0.001), whole body rate of proteolysis did not change, and urea production increased. Decreasing the amino acid load resulted in a decrease in glutamine rate of appearance (Ra) and leucine N Ra, but had no effect on phenylalanine Ra. Acutely stressed LBW infants responded to an increase in amino acid load by transiently suppressing whole body rate of glutamine synthesis, proteolysis, and oxidation of protein. The mechanisms of this transient effect on whole body protein/nitrogen metabolism remain unknown.

Kinetics of leucine and its oxidation were determined in human pregnancy and in the newborn infant, using stable isotopic tracers, to quantify the dynamic aspects of protein metabolism. These data show that in human pregnancy there is a decrease in whole-body rate of leucine turnover compared with nonpregnant women. In addition, data in newborn infants show that leucine turnover expressed as per kg body weight is higher compared with adults. The administering of nutrients resulted in a suppression of the whole-body rate of proteolysis. Because nonessential amino nitrogen is an important component of nutritional nitrogen and can be limiting for growth under certain circumstances, and because BCAA are an important source of nonessential amino nitrogen, we have examined the relations among the transamination of leucine, leucine N kinetics, and urea synthesis and glutamine kinetics in human pregnancy and newborn infants. In human pregnancy, early in gestation, there is a significant decrease in urea synthesis in association with a decrease in the rate of transamination of leucine. A linear correlation was evident between the rate of leucine reamination and urea synthesis during fasting in pregnant and nonpregnant women. In healthy-term newborn and growing infants, although the reamination of leucine was positively related to glutamine flux, leucine reamination was negatively related to urea synthesis, suggesting a redirection of amino N toward protein accretion. The regulatory mechanism involved in this redirection of nitrogen from irreversible loss to accretion remains under investigation.

Threonine kinetics, threonine oxidative pathway, and the relationship between threonine and whole body protein turnover were quantified in 10 healthy term infants during the first 48 h after birth. The kinetic data were obtained 6 h after the last feed (fasting) and in response to formula feeding, using [U-13C4,15N]threonine, [2H5]phenylalanine, and [15N]glycine tracers. The rate of carbon dioxide production (V̇co2) and13C enrichment of the expired CO2were measured to quantify the rate of oxidation of threonine. The rate of appearance (Ra) of threonine (136 ± 37 μmol·kg−1·h−1) was higher in newborn infants than that reported in adults. Formula feeding resulted in a significant decrease in threonine Ra( P < 0.05). A significant positive correlation was seen between phenylalanine Raand threonine Ra, both during fasting and after formula feeding ( r2= 0.65). In contrast to a 1:1 ratio of threonine and phenylalanine in mixed muscle protein, threonine Rarelative to phenylalanine Rawas 2.2 ± 0.4. The fractional rate of threonine flux oxidized was 20% during fasting and 26% ( P < 0.05) in response to nutrient administration. There was a significant correlation between plasma threonine concentration and threonine oxidation ( r2= 0.75). No measurable incorporation of threonine in plasma glycine was seen. These data suggest that threonine is exclusively degraded by the glycine-independent serine/threonine dehydratase pathway. A higher flux of threonine relative to phenylalanine indicates higher turnover of threonine enriched proteins.

Objectives To examine the effect of supplemental glutamine (0.6 g.kg −1 .d −1 ) on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW) infants receiving parenteral nutrition in the immediate neonatal period. Study design Premature infants ≤32 weeks gestation with a birth weight from 694 to 1590 g were randomly assigned to either a glutamine-supplemented group (n=10) or to a control group (n=10). Tracer isotope studies were performed when the infants were 6 to 7 days old and had been receiving an amino acid intake of approximately 3.0 g.kg −1 .d −1 for at least 3 days. Whole body glutamine and nitrogen kinetics were measured with [5- 15 N]glutamine, [ 2 H 5 ]phenylalanine, [1- 13 C, 15 N]leucine, [ 15 N 2 ]urea, and GC-mass spectrometry. Results Supplemental glutamine was associated with a lower rate of appearance of glutamine ( P =.003), phenylalanine ( P =.001), and leucine C ( P =.003). There was no significant difference in leucine N turnover, urea turnover and plasma cortisol, and C-reactive protein levels in the 2 groups. Conclusion Parenteral glutamine supplement in LBW infants was associated with lower whole-body protein breakdown. Because the decrease in whole body proteolysis is associated with protein accretion, parenteral glutamine supplement may be beneficial in selected populations of LBW infants.

A low-protein diet during pregnancy in the rat results in intrauterine growth restricted (IUGR) fetuses. The adaptive responses of the mother to low-protein diet and the mechanisms of IUGR in this model are not understood. In the present study, we report the maternal metabolic responses to protein restriction and their impact on growth, carcass composition, and translation initiation in the fetus. Pregnant Sprague-Dawley rats were pair-fed either a 6% protein (LP, n = 7) or a 24% protein (NP, n = 7) diet from conception until delivery. Plasma amino acids and urea levels and rate of oxygen consumption were measured sequentially through pregnancy. Translation initiation factors eIF2alpha, Ser51 phosphorylated eIF2alpha, eIF4E, phosphorylated eIF4E, and 4E-BP1 were quantified in the maternal and fetal muscle and liver. Protein restriction resulted in higher rate of oxygen consumption (p0.01), lower plasma branched chain amino acid (p0.05) in the mother, and lower plasma histidine levels (p0.05) in the fetus. Plasma urea nitrogen was lower in the LP group throughout gestation. The phosphorylated 4E-BP1 (gamma form) in the maternal liver was 4-fold higher in the LP group. The phosphorylated eIF2alpha was higher in the livers of IUGR fetuses. We speculate that the lower plasma branched chain amino acids in the mother during early pregnancy may be due to a lower rate of protein turnover in the LP group. The mechanism of increased energy consumption due to protein restriction remains unclear. The data on translation initiation factors suggest a higher rate of protein synthesis in the maternal liver and a lower rate in the fetal liver in response to protein restriction.

Background: Glutamine is a critical amino acid for the metabolism of enterocytes, lymphocytes, and other proliferating cells. Although supplementation with glutamine has been suggested for growing infants, its effect on protein metabolism has not been examined. Objective: The objective was to examine the effect of enteral glutamine or glycine on whole-body kinetics of glutamine, phenylalanine, leucine, and urea in preterm infants. Design: Infants at 32 wk of gestation were given formula supplemented with either glutamine (0. 6g·k g 1 ·d 1 ; n 9) or isonitrogenous amounts of glycine (n 9) for 5 d. Eight infants fed unsupplemented formula served as control subjects. Glutamine, phenylalanine, leucine nitrogen flux, leucine carbon flux, and urea kinetics were quantified during a basal fasting period and in response to nutrient intake. Results: Growing preterm infants had a high weight-specific rate of appearance of glutamine, phenylalanine, and leucine nitrogen flux. When compared with the control treatment, enteral glutamine resulted in a high rate of urea synthesis, no change in the plasma glutamine concentration, and no change in the rate of appearance of glutamine. Glycine supplementation resulted in similar changes in nitrogen metabolism, but the magnitude of change was less than that in the glutamine group. In the nonsupplemented infants, the rate of appearance of leucine nitrogen flux was negatively correlated ( 0.72) with urea synthesis. In contrast, the correlation ( 0.75) was positive in the glutamine group. Conclusion: Enterally administered glutamine in growing preterm infants is entirely metabolized in the gut and does not have a discernable effect on whole-body protein and nitrogen kinetics. Am J Clin Nutr 2004;79:402–9.

Perturbations in glucose metabolism in the fetus and in the neonate are a consistent finding in several different animal models of intrauterine growth retardation (IUGR) as well as in humans. Studies in rats who have undergone IUGR have shown decreased hepatic glycogen stores in the fetus and delayed induction of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) at birth. Hepatic transcription factors CCAAT enhancer binding protein (C/EBP)alpha and C/EBPbeta and the increase in cyclic AMP at birth have been implicated in the initial appearance of PEPCK-C. We have examined the effect of IUGR induced by reduced maternal inspired oxygen (fractional inspired oxygen concentration 0.14) on a) the expression of genes for hepatic C/EBPalpha, C/EBPbeta, PEPCK-C and glycogen synthase; and b) transcription of the genes for C/EBPbeta and PEPCK-C by dibutyryl cyclic AMP in the fetus. Three days (d 18-21) of decrease in maternal inspired oxygen resulted in lower maternal arterial PO(2) and a lower birth weight of the pups (p < 0.01). Fetuses that underwent IUGR had significantly lower concentrations of plasma glucose, hepatic glycogen, and glycogen synthase mRNA and a higher hepatic lactate:pyruvate ratio. They also had lower levels of hepatic PEPCK-C mRNA at birth. The concentration of hepatic mRNA for C/EBPalpha and C/EBPbeta as well as the transcription factors themselves were not affected by the decreased maternal inspired oxygen. Fetal injection of dibutyryl cyclic AMP after 24 h of decreased maternal inspired oxygen (d 18-19) had no effect on the expression of C/EBPbeta. However, it resulted in an attenuated induction of PEPCK-C in the fetuses with IUGR. We speculate that a decrease in maternal inspired oxygen induced certain mediators, either in the mother or in the placenta, that caused lower fetal glucose concentration and affected the transcription of genes involved in fetal hepatic glucose metabolism. IUGR, as a result of decreased fractional inspired oxygen concentration may also be the consequence of pH-mediated changes in uterine blood flow. However, these remain to be examined in this experimental model.

OBJECTIVE: To determine whether dexamethasone use increases the risk for Candida sepsis (CS) in very low birth weight premature infants (

Glutamine kinetics and its relation to transamination of leucine and urea synthesis were quantified in 16 appropriate-for-gestational-age infants, four small-for-gestational-age infants, and seven infants of diabetic mothers. Kinetics were measured between 4 and 5 h after the last feed (fasting) and in response to formula feeding using [5-15N]glutamine, [1-13C,15N]leucine, [2H5]phenylalanine, and [15N2]urea tracers. Leucine nitrogen and glutamine kinetics during fasting were significantly higher than those reported in adults. De novo synthesis accounted for ∼85% of glutamine turnover. In response to formula feeding, a significant increase ( P = 0.04) in leucine nitrogen turnover was observed, whereas a significant decrease ( P = 0.002) in glutamine and urea rate of appearance was seen. The rate of appearance of leucine nitrogen was positively correlated ( r2= 0.59, P = 0.001) with glutamine turnover. Glutamine flux was negatively correlated ( r2= 0.39, P = 0.02) with the rate of urea synthesis. These data suggest that, in the human newborn, glutamine turnover is related to a high anaplerotic flux into the tricarboxylic acid cycle as a consequence of a high rate of protein turnover. The negative relationship between glutamine turnover and the irreversible oxidation of protein (urea synthesis) suggests an important role of glutamine as a nitrogen source for other synthetic processes and accretion of body proteins.

The rate of glucose turnover (Ra) and gluconeogenesis (GNG) via pyruvate were quantified in seven full-term healthy babies between 24 and 48 h after birth and in twelve low-birth-weight infants on days 3 and 4 by use of [13C6]glucose and2H2O. The preterm babies were receiving parenteral alimentation of either glucose or glucose plus amino acid with or without lipids. The contribution of GNG to glucose production was measured by the appearance of 2H on C-6 of glucose. Glucose Ra in full-term babies was 30 ± 1.7 (SD) μmol · kg−1 · min−1. GNG via pyruvate contributed ∼31% to glucose Ra. In preterm babies, the contribution of GNG to endogenous glucose Rawas variable (range 6–60%). The highest contribution was in infants receiving low rates of exogenous glucose infusion. In an additional group of infants of normal and diabetic mothers, lactate turnover and its incorporation into glucose were measured within 4–24 h of birth by use of [13C3]lactate tracer. The rate of lactate turnover was 38 μmol · kg−1 · min−1, and lactate C, not corrected for loss of tracer in the tricarboxylic acid cycle, contributed ∼18% to glucose C. Lactate and glucose kinetics were similar in infants that were small for their gestational age and in normal infants or infants of diabetic mothers. These data show that gluconeogenesis is evident soon after birth in the newborn infant and that, even after a brief fast (5 h), GNG via pyruvate makes a significant contribution to glucose production in healthy full-term infants. These data may have important implications for the nutritional support of the healthy and sick newborn infant.

Gluconeogenesis (GNG), a key metabolic process, involves the formation of glucose and glycogen from non-glucose precursors via pyruvate. In the strict sense, it also includes the contribution of glycerol as well as recycled glucose carbon (Cori's cycle). The developmental expression of GNG in the fetus and newborn and the quantitative contribution of GNG to glucose has been extensively investigated in humans and other mammalian species. Data from studies in rodents, rabbits, and sheep fetuses show that the development of GNG is a well-orchestrated process that is regulated by the expression of specific factors involved in the transcription of the genes for specific regulating enzymes, which catalyze GNG. These transcription factors and the genes for gluconeogenic enzymes are expressed at specific time periods during development. Although the fetus has the potential for GNG, the actual formation of glucose from pyruvate is not apparent until after birth because the rate limiting enzyme phosphoenolpyruvate carboxykinase appears only after birth in the immediate newborn period. Several tracer isotope methods have been employed to quantify the contribution of GNG to glucose. Of these, the recently developed stable isotope techniques with deuterium labeled water and the mass isotopomer distribution analysis appear to be the most precise and easily applicable in human studies. The available data show that in the human newborn, GNG appears soon after birth and contributes 30% to 70% to glucose produced. Application of new molecular biology techniques, in combination with sensitive tracer isotopic methods, will allow us to identify and examine metabolic disorders that impact GNG and help develop intervention strategies.

This study was designed to determine the effect of dexamethasone treatment on peripheral blood lymphocyte counts and subpopulations in premature infants with bronchopulmonary dysplasia (BPD).Peripheral blood lymphocyte subpopulations in 12 premature infants with BPD were analyzed before treatment with a 6-week course of dexamethasone (day 0), on days 3 and 10 of treatment, and 2 weeks after discontinuing dexamethasone therapy (day 56). Lymphocyte immunophenotypes were determined using direct two-color immunofluorescent staining followed by flow cytometry.The percentage of lymphocytes was significantly lower on days 3 (17.55 +/- 2.55) and 10 (20 +/- 11.8) of dexamethasone therapy compared with before (30.36 +/- 6.41) or after treatment. The percentage of T cells was significantly lower on days 3 and 10 of dexamethasone therapy (mean +/- SEM; 58.09 +/- 1.93 and 60.09 +/- 2.47, respectively) compared with before (67.09 +/- 4.24) or after treatment. The absolute number of T cells was significantly lower on day 10 of therapy. The percentage of CD4+ cells was significantly lower on days 3 (38.91 +/- 2.49) and 10 (40.45 +/- 2.24) of therapy, and this decrease persisted after dexamethasone was stopped (36.73 +/- 3.41). The absolute number of CD4 cells was significantly lower on day 10 (1328 +/- 216) of therapy and reached a nadir on day 56 (1143 +/- 106). Similarly, the CD4/CD8 ratio was also significantly lower on days 3 and 10 of treatment (1.56 +/- 0.18 and 1.64 +/- 0.14, respectively) and reached a nadir on day 56 (1.04 +/- 0.13).Dexamethasone significantly reduced the percentage and absolute number of lymphocytes, T cells, and CD4 cells, as well as the CD4/CD8 ratio. A reduction in CD4 cells and in the CD4/CD8 ratio persisted 2 weeks after dexamethasone therapy was stopped. In contrast, the absolute number of B cells increased transiently, and CD8 cells were unaffected by dexamethasone. This alteration in lymphocyte subpopulations may help account for the clinically beneficial anti-inflammatory effect of dexamethasone in the treatment of BPD complicated by respiratory failure. The dexamethasone-induced decrease in CD4 cells may also increase the susceptibility of these infants to infection.

We present a case report of a term neonate with congenital human immunodeficiency virus (HIV) infection born with nonimmune hydrops fetalis who developed hepatitis shortly after birth. Maternal HIV infection was diagnosed after delivery. An extensive evaluation for known causes of nonimmune hydrops, both infectious and noninfectious, was negative. After beginning highly active antiretroviral therapy, hepatitis resolved and the HIV viral load became undetectable. We believe this is the first report of nonimmune hydrops fetalis and hepatitis in an infant with congenital HIV infection.

Background: Hyperhomocysteinemia during pregnancy, which is a consequence of perturbations in methionine and/or folate metabolism, has been implicated in adverse outcomes such as neural tube defects, preeclampsia, spontaneous abortion, and premature delivery. The adaptive changes in methionine metabolism during pregnancy in humans have not been determined. Objective: Our objective was to examine the kinetics of methionine and its rate of transsulfuration and transmethylation in healthy women with advancing gestation. Design: The whole-body rate of appearance (Ra) of methionine and phenylalanine was measured in healthy pregnant women during the first (n ¼ 10), second (n ¼ 5), and third (n ¼ 10) trimesters of pregnancy. These data were compared with those for nonpregnant women (n ¼ 8). Tracers [1- 13 C]methionine, [C 2 H3]methionine, and [ 2 H5]phenylalanine were administered as prime-constant rate infusions. The effect of enteral high-protein, mixed-nutrient load on tracer-determined variables was also examined. Results: In pregnant women, the Ra of phenylalanine was significantly (P , 0.05) lower in the first trimester than in the second and third trimesters and was significantly lower than that in nonpregnant women. A linear positive correlation was evident between gestational age and phenylalanine Ra. The fractional rate and total rate of transsulfuration of methionine was significantly (P , 0.05) higher during the first trimester, whereas the rate of transmethylation was higher during the third trimester. Plasma concentrations of total cysteine and homocysteine were lower during pregnancy. Conclusions: Uncomplicated pregnancy in humans is associated with a higher rate of transsulfuration early in gestation and a higher rate of transmethylation of methionine in late gestation. These data may have implications for understanding the role of methionine and homocysteine in complications of pregnancy and for the nutritional care of pregnant women. Am J Clin Nutr 2010;91:357‐65.

The rates of transmethylation and transsulfuration of methionine were quantified using [1-(13)C]methionine and [C2H3]methionine tracers in newborn infants born at term gestation and in prematurely born low birth weight infants. Whole body rate of protein breakdown was also measured using [2H5]phenylalanine. The response to enteral formula feeding and parenteral nutrition was examined in full term and prematurely born babies, respectively. The relative rates of appearance of methionine and phenylalanine were comparable to the amino acid composition of mixed body proteins. Rates of transmethylation were high, both in full term infants (fast 32 +/- 14 micromol kg(-1) x h(-1); fed 21.7 +/- 3.2) and in preterm infants (57.2 +/- 14.8). Significant flux through the transsulfuration pathway was evident (full term: fast 6.0 +/- 4.4, fed 4.1 +/- 2.1; preterm: 24.9 +/- 9.9 micromol kg(-1) x h(-1)). Transsulfuration of methionine is evident in the human newborn in the immediate neonatal period, suggesting that cysteine may not be considered a "conditionally" essential amino acid for the neonate. The high rate of transmethylation may reflect the high methylation demand, whereas high rates of transsulfuration in premature babies may be related to high demands for glutathione and to the amounts of methionine in parenteral amino acid mixtures.

Aggressive parenteral nutrition (PN) including amino acids is recommended for low-birth-weight infants to prevent energy and protein deficit. Their impact on acid-base homeostasis has not been examined.We investigated the impact of dose and duration of parenteral amino acids, with cysteine, on acid-base parameters in 122 low-birth-weight infants. Premature infantsor=32 weeks,or=1850 g, and receiving parenteral amino acids at 1.5 g/kg/d for an extended period (24 hours), or 3 g/kg/d for a short (5 hour), extended (24 hour), or prolonged (3-5 days) duration were included in the study. Data were obtained at age 0-3 days (n = 43) or, when clinically stable, age 3-5 days (n = 49). Data from 30 infants, matched for birth weight and gestational age, receiving PN during the first 5 days after birth were also obtained. Acidosis was defined as pH7.25.Acidosis was evident in all infants between 2 and 5 days after birth. Infants with large patent ductus arteriosus (PDA) exhibited significantly (p.05) lower pH early, had higher blood urea nitrogen levels (26 +/- 9 vs 18 + 8 mg/dL; p.05), and had greater weight loss ( approximately 17% of birth weight) when compared with infants without PDA. Gestational age, weight loss, and patent ductus arteriosus accounted for 65% of variance in acidosis.Low-birth-weight infants develop metabolic acidosis between 2 and 5 days after birth, irrespective of dose and duration of parenteral amino acid administration. Careful management of parenteral fluids and comorbidities may lower the incidence of acidosis and promote protein accretion.

Glutamine has been proposed to be conditionally essential for premature infants, and the currently used parenteral nutrient mixtures do not contain glutamine. De novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of parenteral amino acids by increasing the influx of amino acid carbon into the TCA cycle will enhance the rate of DGln. Very low birth weight infants were randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5-(15)N]glutamine, [2H5]phenylalanine, [1-(13)C,15N]leucine, and [15N2]urea tracers. An acute increase in parenteral amino acid infusion for 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an acute increase in parenteral amino acid-suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis.

Serine plays an important role in intermediary metabolism as a source of one carbon pool for nucleotide biosynthesis, as a precursor for glycine and glucose, and as a contributor to cysteine biosynthesis. A unique serine-glycine cycling between the liver and the placenta has been demonstrated in the sheep fetus. We hypothesized that, because of serine's role in growth and development, significant changes in serine metabolism will occur in pregnancy with advancing gestation. The rate of appearance (Ra) of serine and its metabolism were quantified in healthy women longitudinally through pregnancy with a [2-15N13C]serine tracer. The contribution of serine N to urea and the rate of oxidation of serine were measured using the precursor-product relation. Plasma serine concentrations and serine Ra were lower in pregnant (P) women, in both early and late gestation, compared with nonpregnant (NP) women [plasma serine: NP, 113 ± 24.5; P early, 71.9 ± 6.2; P late, 68.5 ± 9.6 μmol/l; serine Ra: NP ( n = 7), 152.9 ± 42.8; P early ( n = 12), 123.7 ± 21.5; P late ( n = 8), 102.8 ± 18.2 μmol · kg−1 · h−1]. Serine contributed ∼6% to urea N and 15–20% to the plasma glycine pool, and oxidation of serine represented ∼8% of Ra. There was no significant difference between P and NP subjects. Glucose infusion, at 3 mg · kg−1 · min−1in P subjects, resulted in a decrease in serine Ra and an increase in oxidation. The decrease in serine turnover in pregnancy may represent a decrease in α-amino nitrogen turnover related to a decreased rate of branched-chain amino acid transamination and caused by pregnancy-related hormones aimed at nitrogen conservation and accretion.

Early administration of parenteral nutrition to LBW infants has been advocated in order to (a) meet the nutrient needs and (b) achieve intrauterine growth velocity. We have examined the impact of high parenteral amino acids on whole body protein/nitrogen turnover in low birth weight infants (

Ventilatory Indices and Ureaplasma urealyticum during the First Week of Life Are Very Strongly Associated with Severe Bronchopulmonary Dysplasia in Very-Low Birth weight Infants

Vaginal Delivery Increases the Risk of Candida Sepsis in Very Low Birth Weight Infants (≤1250g)

Objective: Reliance on abdominal radiographs to diagnose intestinal perforation secondary to necrotizing enterocolitis in premature infants may delay operative intervention and increase the short and longterm complications. The objective of the study was to determine whether clinical and hematological alterations predict impending perforation in neonates with necrotizing enterocolitis.