Total parenteral nutrition in sick preterm infants: effects of cysteine supplementation with nitrogen intakes of 240 and 400 mg/kg/day. Cysteine supplementation to cysteine-free intravenous feeding regimens in newborn infants. Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial. A randomised controlled trial of glutamine-enriched neonatal parenteral nutrition in Malaysia. Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants. Randomised clinical trial of parenteral selenium supplementation in preterm infants. Nutritional efficacy of preterm formula with a partially hydrolyzed protein source: a randomized pilot study. A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates. The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.
The effects of supplementing total parenteral nutrition (TPN) solutions with cysteine were assessed at two different levels of nitrogen intake by determining nitrogen retention, sulfate excretion, and sulfur-containing amino acid concentrations. Ten infants received 72 mg/kg/day of cysteine-HCl in a TPN solution for a period of 6 days. Five of these infants received 251 +/- 48 (mean +/- SD) mg/kg/day of nitrogen, and five received 403 +/- 45 mg/kg/day of nitrogen. Two other groups of five infants each received unsupplemented TPN at nitrogen intakes of 235 +/- 48 and 412 +/- 54 mg/kg/day, respectively. Fluid and nonprotein caloric intakes were similar for all four groups. Cysteine supplementation increased plasma and urine free cyst(e)ine concentrations and enhanced total sulfur retention, but did not enhance nitrogen retention. [Cyst(e)ine refers to the mixture in any proportion of the sulfhydryl (cysteine) and the disulfide (cystine) forms of this compound.] Nitrogen retention, sulfate excretion, cyst(e)ine excretion, and plasma taurine concentrations increased as the result of the increase in nitrogen intake. To determine if cysteine is an essential amino acid for the intravenously fed newborn infant, growth parameters, nitrogen balance, plasma sulfur amino acid levels, and urinary amino acid excretion of premature and term infants were measured in the presence or absence of infused cysteine. Control intravenous formulations provided amino acids, including adequate methionine, carbohydrate, lipid, minerals, vitamins, and trace elements to all infants. Group and pair-matched comparisons showed that nitrogen retention, weight change, and growth in length and head circumference were not affected by cysteine supplementation of 77 mg/kg/24 h. The failure of cysteine supplementation to alter nitrogen retention was independent of postnatal age or gestational age. Plasma 1/2 cystine concentration was increased by 60% in the supplemented group with a concomitant 3-fold increase in urinary excretion of 1/2 cystine and taurine, but not of urinary methionine or cystathionine. Cysteine-supplemented infants exhibited a small increase in 3-methylhistidine excretion compared to pair-matched controls, suggesting that either an increase in muscle protein catabolism or an increase in muscle mass may have occurred. To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery.
                Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results.
                Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources.
                Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects.
                In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise. The addition of glutamine to parenteral nutrition (PN) in neonates has not shown significant benefits as compared to adults thus far. This study aimed to determine the potential benefits of the addition of glutamine to neonatal PN in a tertiary hospital in a middle-income country.
                This was a double-blinded randomised controlled trial. Babies who were admitted to the neonatal intensive care unit (NICU) and who required PN were eligible for inclusion in the study. The subjects were randomised to receive either glutamine-added PN (intervention) or standard PN (control). The most important outcomes included time to full enteral nutrition, incidence of sepsis and necrotising enterocolitis (NEC), clinical or culture-proven sepsis.
                Out of 270 subjects, 132 were randomised to the intervention group and 138, to the control group. Baseline data were comparable in both groups. The median time taken to reach full enteral nutrition was similar for both intervention and control groups (six days in each group, p-value is 0.52). The incidences of NEC, clinical sepsis and culture-proven sepsis did not differ significantly in the intervention and control groups (5.8 vs. 7.1 percent, p-value is 0.68; 15.7 percent vs. 10.2 percent, p-value is 0.21 and 16.5 percent vs. 15.7 percent, p-value is 0.38, respectively). Other outcomes such as duration of ventilation, duration of NICU stay and a subgroup analysis for preterm and term babies also showed no statistically significant differences.
                Addition of glutamine to neonatal PN was not shown to improve outcome. Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known.
                We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis.
                Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation.
                Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population. To determine whether selenium supplementation of parenteral nutrition with 3 micrograms/kg/day of selenious acid is safe and effective in improving the selenium status of preterm infants.
                Thirty eight preterm infants with mean (SEM) birthweight of 1171 (38) g and gestational age 29 (0.3) weeks were randomly allocated to a non-supplemented (PN-selenium, n = 19) or supplemented (PN+selenium, n = 19) group. The study began at 2.8 (0.2) (range 1-5) days of age. Term breastfed (n = 23) and formula fed (n = 8) infants were used as a reference group.
                Initially there was no difference between the preterm groups in plasma or erythrocyte selenium or glutathione peroxidase activity. Plasma selenium declined by a mean (SEM) of -13.3 (3.2) micrograms/l from 28 (4) to 16 (3) micrograms/l over the first three weeks in the PN-selenium group, but there was no fall in the supplemented infants and no net change in either group over six weeks. Over six weeks, there was a net decline in erythrocyte selenium of -106 (27) ng/g haemoglobin in the PN-selenium group, but no change in the PN+selenium group, such that at week 6 erythrocyte selenium was lower in the PN-selenium group (401 (17) ng/g haemoglobin) than the PN+selenium group (493 (25) ng/g haemoglobin). Urinary selenium was substantially higher in the PN+selenium group at each week. Initially term and preterm plasma selenium concentrations were similar, but they increased in term breastfed infants (+17 (2) micrograms/l), with both groups of preterm infants having lower plasma selenium concentrations at week 6 compared with term breastfed infants (PN-selenium 22 (3) micrograms/l; PN+selenium 23 (4) micrograms/l and term breastfed 49 (2) micrograms/l).
                Selenium supplementation of PN at 3 g/kg/day prevented depletion in newborns, but was inadequate to achieve selenium concentrations equivalent to those of breastfed term infants. Whether higher doses are more effective remains to be determined, particularly in light of the high urinary selenium secretion in supplemented infants. Selenium supplementation of both parenteral nutrition and formulas is recommended, but the optimal form and dose remain unclear. Decreased nitrogen levels, calcium intestinal absorption rates, and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas. In this pilot study, we evaluated a new formula with modified nitrogen and calcium sources.
                During their second week of life, 16 preterm infants were randomly assigned to one of two groups: 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula. Nutrient balance was performed at the end of the first month of life. Amino acid concentrations and anthropometric parameters were measured at theoretical term.
                Birth weight and gestational age (mean +/- SD) were similar in the two groups (28.9 +/- 7.0 weeks and 1183 +/- 242 g vs. 27.7 +/- 1.0 weeks and 1139 +/- 162 g). Median nitrogen absorption rates (85% vs. 89%; P = 0.03) and biological values (59% vs. 69%; P = 0.13) were lower for infants who were fed the new formula than for those fed the conventional formula. After correction for difference in nitrogen intake, there was no significant difference in nitrogen retained between the two groups (P = 0.11). Plasma amino acid concentrations were also similar in the two groups. Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group (54% vs. 45%, P = 0.19). At theoretical term, infants fed the conventional formula were heavier than infants fed the new formula (3559 +/- 362 g vs. 3193 +/- 384 g, P = 0.04).
                Because nitrogen content is 10% higher in hydrolyzed-protein formula than in entire-protein formula, appropriate nitrogen retention, plasma amino acid profile, and mineral use can be achieved with the new partially hydrolyzed formula. Further studies with larger groups are needed to evaluate the effect on growth. The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates.
                Randomized controlled trial.
                Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18).
                There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups.
                Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN. Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease.
                A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency.
                No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity.
                Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.
Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance. However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants.