Albumin synthesis in very low birth weight infants is enhanced by early parenteral lipid and high-dose amino acid administration.

BACKGROUND & AIMS: Albumin is one of the most important plasma proteins and plays a key role in many physiologic processes, such as preserving colloid osmotic pressure, scavenging radicals, and binding and transporting bilirubin, hormones, and drugs. However, albumin concentrations are often low in preterm infants during the first days of life. We hypothesized that early parenteral lipid and high-dose amino acid (AA) administration to very low birth weight (VLBW) infants from birth onwards increases hepatic albumin synthesis rates. METHODS: Inborn VLBW infants were randomized to receive from birth onwards either 2.4 g amino acids/(kg(·)d) (control group), 2.4 g amino acids/(kg(·)d) plus 2 g lipids/(kg(·)d) (AA + lipid group), or 3.6 g amino acids/(kg(·)d) plus 2 g lipids/(kg(·)d) (high AA + lipid group). On postnatal day 2, infants received a primed continuous infusion of [U-(13)C6,(15)N]leucine. Mass spectrometry was used to determine the fractional and absolute albumin synthesis rates (FSR and ASR, respectively). RESULTS: In total, 28 infants (median gestational age 27 weeks (IQR 25-28), median birth weight 810 g (IQR 679-998) were studied. The median FSR was 6.5%/d in the control group, 10.6%/d in the AA group, and 12.3%/d in the high AA + lipid group, while the median was 84 mg/(kg(·)d) in the control group, 138 mg/(kg(·)d) in the AA group, and 160 mg/(kg(·)d) in the high AA + lipid group. CONCLUSION: A group of VLBW infants given parenteral nutrition containing lipids and high-dose amino acids showed a higher rate of albumin synthesis compared to infants receiving no lipids and standard amounts of amino acids during the first two days of life.

Adaptive regulation of amino acid metabolism on early parenteral lipid and high-dose amino acid administration in VLBW infants - a randomized, controlled trial.

BACKGROUND & AIMS: An anabolic state can be achieved upon intravenous amino acid administration during the immediate postnatal phase despite a low energy intake. The optimal dosing of amino acid and energy intake has yet to be established. The aim was to quantify the efficacy of early initiation of parenteral lipids and increased amounts of amino acids on metabolism and protein accretion in very low birth weight infants. METHODS: 28 very low birth weight infants were randomized to receive parenteral nutrition with glucose and either 2.4 g amino acids/(kg·d) (control group), 2.4 g amino acids/(kg·d) plus 2-3 g lipid/(kg·d) (AA + lipid group), or 3.6 g amino acids/(kg·d) plus 2-3 g lipid/(kg·d) (high AA + lipid group) from birth onward. On postnatal day 2, we performed a stable isotope study with [1-(13)C]phenylalanine, [ring-D4]tyrosine, [U-(13)C6,(15)N]leucine, and [methyl-D3]α-ketoisocaproic acid to quantify intermediate amino acid metabolism. RESULTS: The addition of lipids only had no effect on phenylalanine metabolism, whereas the addition of both lipids and additional amino acids increased the amount of phenylalanine used for protein synthesis. In addition, high amino acid intake significantly increased the rate of hydroxylation of phenylalanine to tyrosine, increasing the availability of tyrosine for protein synthesis. However, it also increased urea concentrations. Increasing energy intake from 40 to 60 kcal/(kg·d) did not increase protein efficiency as measured by phenylalanine kinetics. The leucine data were difficult to interpret due to the wide range of results and inconsistency in the data between the phenylalanine and leucine models. CONCLUSIONS: High amino acid and energy intakes from birth onwards result in a more anabolic state in very low birth weight infants, but at the expense of higher urea concentrations, which reflects a higher amino acid oxidation. Long-term outcome data should reveal whether this policy deserves routine implementation. This trial was registered at www.trialregister.nl, trial number NTR1445, name Nutritional Intervention for Preterm Infants-2.

Safety and efficacy of early parenteral lipid and high-dose amino acid administration to very low birth weight infants.

OBJECTIVE: To assess the efficacy and safety of early parenteral lipid and high-dose amino acid (AA) administration from birth onwards in very low birth weight (VLBW, birth weight <1500 g) infants. STUDY DESIGN: VLBW infants (n = 144; birth weight 862 ± 218 g; gestational age 27.4 ± 2.2 weeks) were randomized to receive 2.4 g of AA kg(-1) · d(-1) (control group), or 2.4 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (AA + lipid group), or 3.6 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (high AA + lipid group) from birth onwards. The primary outcome was nitrogen balance. The secondary outcomes were biochemical variables, urea rate of appearance, growth rates, and clinical outcome. RESULTS: The nitrogen balance on day 2 was significantly greater in both intervention groups compared with the control group. Greater amounts of AA administration did not further improve nitrogen balance compared with standard AA dose plus lipids and was associated with high plasma urea concentrations and high rates of urea appearance. No differences in other biochemical variables, growth, or clinical outcomes were observed. CONCLUSIONS: In VLBW infants, the administration of parenteral AA combined with lipids from birth onwards improved conditions for anabolism and growth, as shown by improved nitrogen balance. Greater levels of AA administration did not further improve the nitrogen balance but led to increased AA oxidation. Early lipid initiation and high-dose AA were well tolerated.