Effect of hyperalimentation and insulin-treated hyperglycemia on tyrosine levels in very preterm infants receiving parenteral nutrition.

BACKGROUND: Hyperalimentation describes the increase in glucose, amino acids (AAs), and lipid intake designed to overcome postnatal growth failure in preterm infants. Preterm infants are dependent on phenylalanine metabolism to maintain tyrosine levels because of tyrosine concentration limits in parenteral nutrition (PN). We hypothesized that hyperalimentation would increase individual AA levels when compared with the control group but avoid high phenylalanine/tyrosine levels. AIM: To compare the plasma AA profiles on days 8-10 of life in preterm infants receiving a hyperalimentation vs a control regimen. METHODS: Infants <29 weeks' gestation were randomized to receive hyperalimentation (30% more PN macronutrients) or a control regimen. Data were collected to measure macronutrient (including protein) intake and PN intolerance, including hyperglycemia, insulin use, urea, and AA profile. Plasma profiles of 23 individual AA levels were measured on days 8-10 using ion exchange chromatography. RESULTS: One hundred forty-two infants were randomized with 118 AA profiles obtained on days 8-10. There were no differences in birth weight or gestation between groups. There was an increase (P < .05) in 8 of 23 median individual plasma AA levels when comparing hyperalimentation (n = 57) with controls (n = 61). Only tyrosine levels (median; interquartile range) were lower with hyperalimentation: 27 (15-52) µmol/L vs 43 (24-69) µmol/L (P < .01). Hyperalimentation resulted in more insulin-treated hyperglycemia. No difference between the groups was apparent in tyrosine levels when substratified for insulin-treated hyperglycemia. All insulin vs no insulin comparisons showed lower tyrosine levels with insulin treatment (P < .01). CONCLUSION: Hyperalimentation can result in paradoxically low plasma tyrosine levels associated with an increase in insulin-treated hyperglycemia.

Plasma arginine levels and blood glucose control in very preterm infants receiving 2 different parenteral nutrition regimens.

BACKGROUND: Improving parenteral nutrition (PN) amino acid (AA) intake in very preterm infants is associated with less hyperglycemia. AAs stimulate newborn insulin secretion with arginine, demonstrating a specific effect. We hypothesized that low arginine levels would be associated with increased insulin-treated hyperglycemia and higher mean daily blood glucose levels in very preterm infants. METHODS: We performed a secondary analysis on previous study data comparing high-protein/calorie PN (HPC-PN) and control groups in infants <29 weeks' gestation. Infants were substratified (within original groups) according to high (highARG) and low (lowARG) plasma arginine levels on days 8-10 using a reference population-derived threshold for high/low arginine (57 µmol/L). Daily protein, arginine, carbohydrate intake, mean daily blood glucose, and insulin treatment data from the first 15 days of life were collected. RESULTS: Control group infants (n = 60) were stratified into lowARG (n = 41) and highARG (n = 19) groups. There were no differences in basic demographic data or carbohydrate intake. LowARG infants had higher mean daily blood glucose levels ( P .05) and a trend to more insulin treatment on days 610. HPC-PN group infants (n = 55) were stratified into lowARG (n = 33) and highARG (n = 22) GROUPS. LowARG infants had lower gestation and birth weight and were sicker than highARG infants. There were no differences in carbohydrate intake. LowARG infants had higher mean daily blood glucose levels (p .01) and more insulin treatment (p .01) on days 15 and 610. Insulin-treated hyperglycemia was also associated with low plasma glutamine levels. CONCLUSION: Low plasma arginine levels (≤57 µmol/L) in very preterm infants are associated with poorer blood glucose control.

SCAMP: standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care.

BACKGROUND: Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake. METHODS: We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age. TRIAL REGISTRATION: Current controlled trials: ISRCTN76597892; EudraCT Number: 2008-008899-14.