In a Cochrane review [Abstract] 1included 10 studies. Five studies compared low (< 3.0 g/kg/day) to high protein intakes (≥ 3.0 g/kg/day but < 4.0 g/kg/day). There was an improved weight gain (WMD 2.36 g/kg/day, 95% CI 1.31, 3.40) and higher nitrogen accretion (WMD 143.7 mg/kg/day, 95% CI 128.7, 158.8) in infants receiving formula with higher protein content while other nutrients were kept constant. No significant differences were seen in rates of necrotizing enterocolitis, sepsis or diarrhea. One study compared high to very high protein intakes during and after initial hospital stay. Very high protein intakes promoted improved length gain at term but differences did not remain significant at 12 weeks corrected age. Three of the 24 infants receiving very high protein intakes developed uremia. The post-facto analysis (three studies) revealed further improvement in all growth parameters in infants receiving formula with higher protein content (weight gain: WMD 2.53 g/kg/day, 95% CI 1.62, 3.45, linear growth: WMD 0.16 cm/week, 95% CI 0.03, 0.30, and head growth: WMD 0.23, 95% CI 0.12, 0.35). There was no significant difference (WMD 0.25, 95% CI -0.20, 0.70) in the concentration of plasma phenylalanine between the high and low protein intake groups. However, one study documented a significantly increased incidence of low IQ scores in infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg).
Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison).
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