Phenylalanine requirements of enterally fed term and preterm neonates.
BACKGROUND
Phenylalanine, which is an essential aromatic amino acid, is either used for protein synthesis or irreversibly hydroxylated to tyrosine. The provision of optimal amounts of dietary phenylalanine is not only important for growth and development but might also influence catecholamine synthesis and release rates. The current recommended aromatic amino acid requirement for infants aged 0-6 mo is based on the amino acid content of human milk.


OBJECTIVE
We quantified the requirements for phenylalanine in the presence of excess tyrosine (166 or 177 mg/kg per day for term and preterm infants, respectively) for term and preterm neonates by using the indicator amino acid oxidation method with l-[1-(13)C]lysine 2HCl as an indicator. Hence, we determined the minimum obligatory phenylalanine requirement.


METHODS
Fully enterally fed term and preterm infants received randomly graded amounts of phenylalanine (5-177 mg/kg per day) as part of an elemental formula. Data are expressed as means ± SDs.


RESULTS
Twenty term (birth weight: 3.19 ± 0.34 kg; gestational age: 38.9 ± 1 wk) and 16 preterm (birth weight: 1.75 ± 0.17 kg; gestational age: 32.5 ± 0.6 wk) Asian infants participated at a postnatal age of 17 ± 8 d. In total, 44 studies were performed. The minimum obligatory phenylalanine requirement was 58 mg/kg per day (95% CI: 38-78 mg/kg per day) and 80 mg/kg per day (95% CI: 40-119 mg/kg per day) for term and preterm infants, respectively.


CONCLUSIONS
The determined mean phenylalanine-requirement estimates are lower than the contents of term and preterm formulas currently on the market. This trial was registered at www.trialregister.nl as NTR1610.
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Jacomine E
JE
Hogewind-Schoonenboom
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Li
L
Zhu
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Lin
L
Zhu
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Eveline Cam
EC
Ackermans
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Renske
R
Mulders
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Bart
B
Te Boekhorst
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Mandy
M
Wijnen
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Lianne
L
Bijnevelt
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Gardi J
GJ
Voortman
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Henk
H
Schierbeek
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Lisha
L
Huang
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Femke
F
de Groof
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Andras
A
Vermes
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Chao
C
Chen
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG).
Ying
Y
Huang
From the Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands (JEH-S, HS, Li Zhu, and JBvG); the Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, China (Li Zhu, CC, and YH), Department of Pediatrics, Sophia Children's Hospital (JEH-S, Lin Zhu, MW, GJV, LH, FdG, and JBvG), and the Hospital Pharmacy (AV), Erasmus Medical Centre, Rotterdam, The Netherlands; The Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (ECAMA, RM, BtB, and LB); and the Department of Pediatrics, VU University Medical Centre, Amsterdam, The Netherlands (JBvG). h.vangoudoever@amc.uva.nl.
Johannes B
JB
van Goudoever
D018592:Cross-Over Studies; D004750:Enteral Nutrition / Q000379:methods*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development; D016014:Linear Models; D008297:Male; D008895:Milk, Human / Q000737:chemistry; D009751:Nutritional Requirements; D010649:Phenylalanine / Q000008:administration & dosage*; D047929:Term Birth; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D010649:Phenylalanine
amino acids; formula; indicator amino acid oxidation; nutrition; protein