Adaptive regulation of amino acid metabolism on early parenteral lipid and high-dose amino acid administration in VLBW infants - a randomized, controlled trial.
OBJECTIVE
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.
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Hester
H
Vlaardingerbroek
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Jorine A
JA
Roelants
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Denise
D
Rook
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Kristien
K
Dorst
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Pediatrics, Emma Children's Hospital - AMC, c/o Room H7-282, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands; Department of Pediatrics, VU University Medical Center, c/o Room ZH 9D11, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Henk
H
Schierbeek
Hospital Pharmacy, Erasmus MC, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Andras
A
Vermes
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Marijn J
MJ
Vermeulen
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Pediatrics, Emma Children's Hospital - AMC, c/o Room H7-282, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands; Department of Pediatrics, VU University Medical Center, c/o Room ZH 9D11, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: h.vangoudoever@amc.uva.nl.
Johannes B
JB
van Goudoever
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, c/o Room SP3433, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Chris H P
CH
van den Akker
D000596:Amino Acids / Q000008:administration & dosage* / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D002149:Energy Intake; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development; D019102:Infant, Very Low Birth Weight / Q000254:growth & development*; D007651:Keto Acids / Q000008:administration & dosage; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D000069463:Olive Oil; D010288:Parenteral Nutrition; D010649:Phenylalanine / Q000008:administration & dosage / Q000378:metabolism; D010938:Plant Oils / Q000008:administration & dosage; D013024:Soybean Oil / Q000008:administration & dosage; D014443:Tyrosine / Q000008:administration & dosage / Q000378:metabolism
D000596:Amino Acids; D004041:Dietary Fats; D004655:Emulsions; D005395:Fish Oils; D007651:Keto Acids; D000069463:Olive Oil; D010938:Plant Oils; D014443:Tyrosine; D010649:Phenylalanine; D013024:Soybean Oil; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose
Growth; Metabolism; Parenteral nutrition; Preterm infant; Stable isotopes