1. Among infants with extremely low birth weights, additional amino acids given parenterally did not reduce the risk of neurodisability at two-year follow-up.

2. Supplementation of amino acids may be associated with an increased risk of refeeding syndrome in these infants.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Adequate amino acid intake (3 to 4g/kg) is necessary to support fetal growth and neurodevelopment. For preterm infants with extremely low birth weights (less than 1000g), the postpartum intake needed to maintain this growth and reduce the risk of neurodisability later in life is unknown. Observational and trial results thus far have been equivocal about the benefits and harm of increased parenteral amino acids in critically ill children. The present study reported results from a randomized controlled trial investigating the impact of parenteral amino acids at 1g/day in addition to usual nutrition for the first five days after birth in infants with birth weights less than 1000g. At two years, the addition of parenteral amino acids did not reduce the risk of neurodisability in surviving infants. Furthermore, this intervention was associated with an increased risk of developing refeeding syndrome. The main study limitation was its focus on infants with an umbilicated arterial catheter, who often are the smallest and most ill patients, without employing an illness severity scale for stratification. Although, it demonstrated that in infants with extremely low birth weights, additional parenteral amino acid supplementation did not improve the rate of survival without neurodisability at two years of age.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: The current study was a double-blind, randomized, controlled trial to investigate the efficacy of additional parenteral amino acids in reducing the risk of neurodisability in infants with extremely low birth weights. Infants with a birth weight of less than 1000g and an umbilical arterial catheter were eligible. Exclusion criteria included admission to the neonatal intensive care unit (NICU) more than 24 hours after birth, genetic or congenital condition affecting growth, and risk of imminent death. Overall, 434 infants were randomized to receive either amino acids at a dose of 1g/day (intervention group) or placebo (placebo group) for the first five days after birth. The primary outcome was survival without neurodisability at two years of corrected age. Survival free from neurodisability was observed in 47.8% of infants who received additional amino acids and 49.8% of those who received placebo (Adjusted Relative Risk [ARR], 0.95; 95% Confidence Interval [CI], 0.79 to 1.14; p=0.56). Mortality rates were 18.0% and 19.4% in the intervention and placebo groups, respectively (ARR, 0.93; 95% CI, 0.63 to 1.36). The incidence of neurodisability was 40.9% and 37.4% in the intervention and placebo groups, respectively (ARR, 1.16; 95% CI, 0.90 to 1.50). The length of NICU stay was similar among the two groups. However, the risk of developing refeeding syndrome was higher in the intervention group (ARR, 1.64; 95% CI, 1.09 to 2.47).  In summary, this study demonstrated that among patients with extremely low birth weights, parenteral amino acid supplementation in the first five days of life did not increase the rate of survival without neurodisability at two years of age.

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