Does Amount of Protein in Formula Matter for Low-Birthweight Infants? A Cochrane Systematic Review

Abstract

Background: High protein intake may be associated with negative consequences such as acidosis, uremia, and elevated levels of circulating amino acids (eg, phenylalanine levels). We performed a systematic review of randomized controlled trials to determine whether formula-fed low-birthweight infants could tolerate protein intakes ≥3.0 g/kg/d in their initial hospital stay, without adverse consequences. Methods: Randomized controlled trials contrasting levels of protein intakes as low (<3.0 g/kg/d), high (≥3.0 g/kg/d but <4.0 g/kg/d), or very high protein intake (≥4.0 g/kg/d) while other nutrients were held constant, were identified through a systematic search of the literature. Standard methods of the Cochrane Collaboration were used by 2 independent reviewers, with the third reviewer facilitating consensus decision making. Results: A meta-analysis of 5 randomized trials indicated improved weight gain (weighted mean difference [WMD] 2.36 g/kg/d; 95% confidence interval [CI] 1.31–3.40) and higher nitrogen accretion (WMD 143.7 mg/kg/d; 95% CI 128.7–158.8) with high (≥3.0 g/kg/d but <4.0 g/kg/d) compared with low (< 3.0 g/kg/d) protein intakes while other nutrients were kept constant. No data were available for IQ or Bayley scores at 18 months or later or for very high protein intakes (≥4.0 g/kg/d). No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea. Conclusions: Accelerated weight and nitrogen accretion were noted with higher protein intakes in “healthy” formula-fed low-birthweight infants. This benefit could not be weighed against the adverse consequences of elevated blood urea nitrogen levels and increased metabolic acidosis and neurodevelopmental abnormalities.

Although accelerated weight and nitrogen accretion was noted with higher protein intakes, the precise protein requirement to achieve normal growth without short- and long-term morbidities could not be determined in this Cochrane systematic review. Future research is required to determine the precise protein requirements of preterm infants.