Does amount of protein in formula matter for low-birthweight infants? A Cochrane systematic review

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>or=3.0 g/kg/d in their initial hospital stay, without adverse consequences.

Randomized controlled trials contrasting levels of protein intakes as low (<3.0 g/kg/d), high (>or=3.0 g/kg/d but <4.0 g/kg/d), or very high protein intake (>or=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.

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 (>or=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 (>or=4.0 g/kg/d). No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea.

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.