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

Shahirose Premji, RN, PhD^*, Tanis Fenton, MHSc, RD and Reg Sauve, MD, MPH, FRCPC

From the ^* Faculty of Nursing and Paediatrics and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; and the Alberta Children's Hospital, Calgary, Alberta, Canada

Correspondence: Shahirose Premji, RN, PhD, Assistant Professor and Neonatal Nurse Practitioner, University of Calgary, Faculty of Nursing, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4. Electronic mail may be sent to premjis{at}ucalgary.ca.

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.

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