Early High-Dose Amino Acid Supplementation Shows No Long-Term Neurocognitive Benefit in ELBW Infants: Study
New Zealand: A new randomized controlled trial has found that providing additional parenteral amino acids during the first 5 days of life to extremely low-birth-weight (ELBW) infants does not improve neurocognitive outcomes at school age. Researchers also observed potential negative effects on muscle strength and psychosocial functioning, raising questions about the long-term benefits of higher early protein intake in this vulnerable population.
The findings were published in Pediatrics by David A. Nyakotey and colleagues, who examined whether increasing amino acid delivery shortly after birth could enhance long-term neurodevelopment, body composition, and physical health outcomes in ELBW infants.
Extremely low birth weight infants, weighing less than 1000 grams at birth, often require intensive nutritional support, but the long-term effects of higher amino acid intake remain unclear. To investigate this, researchers conducted a multicenter, double-blind, randomized controlled trial in which newborns received either an additional 1 g/day of parenteral amino acids for the first five days after birth or a placebo.
Of the 309 eligible participants, 280 children, including 153 girls, were assessed at 6 to 7 years of corrected age. The primary outcome was survival without neurocognitive impairment, measured using standardized cognitive and motor assessments.
The trial revealed the following findings:
- Survival without neurocognitive impairment at school age was similar between the amino acid and placebo groups (21% vs 23%), indicating no significant benefit of additional amino acid supplementation.
- Providing an extra 1 g/day of parenteral amino acids for the first five days after birth did not improve long-term neurodevelopmental outcomes.
- Most secondary outcomes, including motor function, body composition, blood pressure, emotional well-being, and psychosocial health, were comparable between the two groups.
- Children who received additional amino acid supplementation had lower muscle strength at school age, as reflected by reduced relative handgrip strength scores.
- The amino acid group showed a possible increased risk of poorer psychosocial functioning compared with the placebo group.
The findings suggest that early high-dose amino acid supplementation may not provide long-term developmental benefits and could be associated with adverse effects on strength and psychosocial outcomes.
The study's strengths included a high follow-up rate and comprehensive assessment of developmental and health outcomes. However, the researchers noted that the sample size may have been insufficient to detect small neurocognitive differences, and multiple outcome analyses increased the risk of chance findings. Generalizability may also be limited because follow-up was restricted to New Zealand participants and the intervention required an umbilical artery catheter.
The researchers concluded that providing an additional 1 g/day of parenteral amino acids during the first five days after birth offers little to no long-term neurocognitive benefit in ELBW infants and may negatively affect muscle strength and psychosocial functioning. The findings suggest that amino acid intake above current recommendations is unlikely to provide overall long-term benefit.
Reference: https://doi.org/10.1542/peds.2025-074043
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