Observational outcome results following a randomized controlled trial of early amino acid administration in preterm infants.

OBJECTIVE: Several reports have investigated amino acid administration in premature infants during the early postnatal phase. Most of these previous studies, however, have only evaluated short-term in-hospital outcomes. Our aim was to describe long-term outcomes in premature infants previously subjected to different nutritional regimens in a randomized controlled trial. The primary outcome was survival without major disabilities, and the secondary outcomes included anthropometry and mental development. METHODS: Infants born <32 weeks' gestation and <1500 g were randomized to receive glucose (n = 69) or glucose with 2.4 g · kg(-1) · day(-1 amino acids) (n = 63) from birth. From postnatal day 3 onward, the nutritional intake was similar. At 2 years of corrected age, the surviving infants were assessed for neurodevelopmental outcome and anthropometry. RESULTS: Ninety-seven percent of the surviving infants were examined at follow-up, with no overall effect on survival without major disabilities. Boys, however, had a normal outcome significantly more often if amino acids were administered from birth onward (crude odds ratio 3.8, 95% confidence interval 1.3-11.4) and following adjustment for confounders (odds ratio 6.2, 95% confidence interval 1.0-38.0). The secondary outcomes exhibited no differences in anthropometric data. The mental developmental index was lower in the small number of girls who survived without major disabilities following the early administration of amino acids. CONCLUSIONS: In this hypothesis-generating outcome study, premature boys, but not girls, benefited from amino acid administration directly following birth. The observed lower mental developmental index in a subgroup of girls, however, warrants further studies.

High-dose cysteine administration does not increase synthesis of the antioxidant glutathione preterm infants.

OBJECTIVE: Our aim was to evaluate whether administration of additional cysteine is safe and stimulates glutathione synthesis in preterm infants in early life. METHODS: We conducted a prospective, randomized, clinical trial with infants with birth weights of <1500 g (N = 20). The infants were assigned randomly to receive either a standard dose (45 mg/kg per day) or a high dose (81 mg/kg per day) of cysteine. Intakes of other amino acids were similar, providing a total protein intake of 2.4 g/kg per day in both groups. We recorded base requirements in the first 6 days of life. On postnatal day 2, we conducted a stable isotope study to determine glutathione concentrations and synthesis rates in erythrocytes. RESULTS: Base requirements were higher in the high-dose cysteine group on days 3, 4, and 5. Despite an 80% increase in cysteine intake, plasma cystine concentrations did not increase. Glutathione concentrations and synthesis rates did not increase with additional cysteine administration. CONCLUSIONS: Administration of a high dose of cysteine (81 mg/kg per day) to preterm infants seems clinically safe but does not stimulate glutathione synthesis, compared with a lower dose (45 mg/kg per day). Further research is required to determine whether there is significant benefit associated with cysteine supplementation.

Glutathione synthesis rates after amino acid administration directly after birth in preterm infants.

BACKGROUND: The availability of glutathione, the main intracellular antioxidant, is compromised in preterm neonates. A possible explanation is the low availability of substrate for synthesis, because many neonatologists are reluctant to administer amino acids in the direct postnatal period for fear of intolerance. OBJECTIVE: The objective of the study was to determine the effects of amino acid administration directly after birth on glutathione synthesis rates and markers of oxidative stress. DESIGN: Premature infants (<1500 g) received from birth onward either dextrose (control group; n = 10) or dextrose plus 2.4 g amino acids . kg (- 1) . d(-1) (intervention group; n = 10). On postnatal day 2, [1-(13)C]glycine was administered to determine glutathione fractional synthesis rates (FSR(GSH)) and absolute synthesis rates (ASR(GSH)) in erythrocytes. In plasma, advanced oxidized protein products and dityrosine, both markers of oxidative stress, were measured. The results are expressed as means +/- SDs. RESULTS: The FSR(GSH) was not different between groups: 44 +/- 6 and 48 +/- 9%/d in the control and intervention groups, respectively (P = 0.28). The concentration of erythrocyte glutathione was higher (P < 0.001) in the intervention group (2.28 +/- 0.35 mmol/L) than in the control group (1.73 +/- 0.37 mmol/L). ASR(GSH) values were 6.5 +/- 1.5 and 11.3 +/- 1.9 mg . kg(-1) . d(-1) in the control and intervention groups, respectively (P < 0.001). Advanced oxidized protein products and dityrosine concentrations were not significantly different between groups. CONCLUSIONS: Amino acid administration directly after birth increases ASR(GSH) in preterm infants. Our data are consistent, however, with higher glutathione concentrations rather than a higher FSR(GSH). Greater availability of glutathione, nevertheless, did not decrease markers of oxidative stress.

Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life.

BACKGROUND: We recently showed that parenteral administration of amino acids to premature infants immediately after birth is safe and results in a positive nitrogen balance and increased whole-body protein synthesis. However, we did not determine organ-specific effects; albumin, produced by the liver, is an important protein, but its concentration is often low in premature neonates during the first few days after birth. OBJECTIVE: The objective of the study was to test the hypothesis that the fractional and absolute albumin synthesis rates would increase with the administration of amino acids after birth, even at low nonprotein energy intake. DESIGN: Premature infants (<1500 g birth weight), who were on ventilation, received from birth onward either glucose only (control group, n = 7) or glucose and 2.4 g amino acid kg(-1) d(-1) (intervention group, n = 8). On postnatal day 2, all infants received a primed continuous infusion of [1-(13)C]leucine, and mass spectrometry techniques were used to determine the incorporation of the leucine into albumin. Results are expressed as medians and 25th and 75th percentiles. RESULTS: Albumin fractional synthesis rates in the intervention group were significantly higher than those in the control group [22.9% (17.6-28.0%)/d and 12.6% (11.0-19.4%)/d, respectively; P = 0.029]. Likewise, the albumin absolute synthesis rates in the intervention group were significantly higher than those in the control group [228 (187-289) mg kg(-1) d(-1) and 168 (118-203) mg kg(-1) d(-1), respectively; P = 0.030]. CONCLUSION: Amino acid administration increases albumin synthesis rates in premature neonates even at a low energy intake.

Amino acid administration to premature infants directly after birth.

OBJECTIVES: To test the hypothesis that the administration of 2.4 g amino acids (AA)/(kg.d) to very low birth weight infants is safe and results in a positive nitrogen balance. STUDY DESIGN: We conducted a randomized, clinical trial. Preterm infants with birth weights <1500 g received either glucose and 2.4 g AA/(kg.d) from birth onward (n=66) or solely glucose during the first day with a stepwise increase in AA intake to 2.4 g AA/(kg.d) on day 3 (n=69). Blood gas analysis was performed daily during the first 6 postnatal days; blood urea nitrogen levels were determined on days 2, 4, and 6; AA plasma concentrations and nitrogen balances were determined on days 2 and 4. Student t tests, Mann-Whitney tests, and chi2 tests were performed to compare groups. RESULTS: Infants supplemented with AA had no major adverse side effects. Their blood urea nitrogen levels were higher, nitrogen balance turned positive upon AA administration, and more AA concentrations were within reference ranges. CONCLUSIONS: High-dose AA administration to very low birth weight infants can be introduced safely from birth onward and results in an anabolic state.