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Published on: November 20, 2015
Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years
Frank H Bloomfield1, Yannan Jiang1, Jane E Harding1
1From the Liggins Institute (F.H.B., Y.J., J.E.H., C.A.C., B.E.C.) and the Department of Statistics, (Y.J.), University of Auckland, and Newborn Services, Auckland City Hospital (F.H.B., B.E.C.) - all in Auckland, New Zealand.
Insights
Extra parenteral amino acids for extremely low birth weight infants did not improve survival free from neurodisability. This study found no significant benefit in neurodevelopmental outcomes at two years for these vulnerable infants.
Area of Science:
- Neonatal Medicine
- Pediatric Nutrition
- Clinical Trials
Background:
- The benefits of increased parenteral amino acid intake for extremely low birth weight (ELBW) infants remain uncertain.
- Optimizing nutritional support is critical for improving outcomes in ELBW infants.
Purpose of the Study:
- To investigate whether supplemental parenteral amino acids improve survival free from neurodisability in ELBW infants.
- To assess the impact of early amino acid supplementation on neurodevelopmental outcomes at two years corrected age.
Main Methods:
- A multicenter, double-blind, randomized, placebo-controlled trial involving 434 infants with birth weights under 1000 g.
- Infants received either 1 g/day of amino acids or placebo for the first 5 days of life, alongside usual nutrition.
- The primary outcome was survival free from neurodisability assessed at 2 years using the Bayley Scales and neurologic examination.
Main Results:
- Survival free from neurodisability was similar between groups: 47.8% in the amino acid group versus 49.8% in the placebo group (aRR, 0.95; 95% CI, 0.79-1.14).
- Moderate to severe neurodisability was more frequent in the amino acid group (16.5% vs 8.6%).
- Increased rates of patent ductus arteriosus and refeeding syndrome were observed in the intervention group.
Conclusions:
- Early parenteral amino acid supplementation at 1 g/day for 5 days did not improve survival free from neurodisability in ELBW infants.
- The findings suggest potential risks associated with early high-dose amino acid administration in this population.
Background:
Whether higher parenteral amino acid intake improves outcomes in infants with extremely low birth weight is unclear.
Methods:
In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned infants with birth weights of less than 1000 g at 8 neonatal intensive care units to receive amino acids at a dose of 1 g per day (intervention group) or placebo in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability as assessed with the Bayley Scales of Infant and Toddler Development and neurologic examination at 2 years, corrected for gestational age at birth. Secondary outcomes were the components of the primary outcome as well as the presence or absence of neonatal disorders, the rate of growth, and nutritional intake.
Results:
We enrolled 434 infants (217 per group) in this trial. Survival free from neurodisability was observed in 97 of 203 children (47.8%) in the intervention group and in 102 of 205 (49.8%) in the placebo group (adjusted relative risk, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P = 0.56). Death before the age of 2 years occurred in 39 of 217 children (18.0%) in the intervention group and 42 of 217 (19.4%) in the placebo group (adjusted relative risk, 0.93; 95% CI, 0.63 to 1.36); neurodisability occurred in 67 of 164 children (40.9%) in the intervention group and 61 of 163 (37.4%) in the placebo group (adjusted relative risk, 1.16; 95% CI, 0.90 to 1.50). Neurodisability was moderate to severe in 27 children (16.5%) in the intervention group and 14 (8.6%) in the placebo group (adjusted relative risk, 1.95; 95% CI, 1.09 to 3.48). More children in the intervention group than in the placebo group had patent ductus arteriosus (adjusted relative risk, 1.65; 95% CI, 1.11 to 2.46). In a post hoc analysis, refeeding syndrome occurred in 42 of 172 children in the intervention group and 26 of 166 in the placebo group (adjusted relative risk, 1.64; 95% CI, 1.09 to 2.47). Eight serious adverse events occurred.
Conclusions:
In infants with extremely low birth weight, extra parenteral amino acids at a dose of 1 g per day for 5 days after birth did not increase the number who survived free from neurodisability at 2 years. (Funded by the New Zealand Health Research Council and others; ProVIDe Australian New Zealand Clinical Trials Registry number, ACTRN12612001084875.).
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