Higher versus lower protein intake in formula-fed low birth weight infants.

The Cochrane database of systematic reviews

Apr 2014

DOI: 10.1002/14651858.CD003959.pub3

Citations:20

Influential Citations:0

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized controlled trials; formula-fed neonates weighing <2.5 kg at birth; includes both AGA and SGA; exclusively formula-fed; no parenteral nutrition during the study.

Intervention

Protein intake in formula during the initial hospital stay, categorized as: low < 3.0 g/kg/d; high ≥ 3.0 g/kg/d but < 4.0 g/kg/d; very high ≥ 4.0 g/kg/d. Delivered via standard formula feeds; duration: initial hospitalization.

Results

Higher protein intake (3.0–<4.0 g/kg/d) accelerates weight gain and nitrogen accretion. Weight gain difference: +2.36 g/kg/d (95% CI 1.31–3.40). Nitrogen accretion: +143.7 mg/kg/d (95% CI 128.7–158.8). No significant differences in necrotizing enterocolitis, sepsis, or diarrhea. Very high protein intake (≥4.0 g/kg/d) showed some growth benefits but was associated with uremia in some infants and uncertain long-term neurodevelopment; the evidence is not adequate to recommend routine very high protein intake. Overall, protein intake of 3–4 g/kg/d promotes growth with limited short-term risks; very high intake >4 g/kg/d should be considered experimental, and monitoring for blood urea nitrogen and acid-base status is advised.

Limitations

Heterogeneity across trials; small sample sizes; variation in formulas beyond protein content; duration of interventions ranged from 8 days to 2 years; some trials had risk of bias due to incomplete allocation concealment or blinding; long-term neurodevelopmental outcomes were limited; differences in participant maturity and health status across studies.

Abstract

BACKGROUND The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate. Protein intake must be sufficient to achieve normal growth without negative effects such as acidosis, uremia, and elevated levels of circulating amino acids. OBJECTIVES To determine whether higher (≥ 3.0 g/kg/d) versus lower (< 3.0 g/kg/d) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants (< 2.5 kilograms) results in improved growth and neurodevelopmental outcomes without evidence of short- and long-term morbidity.To examine the following distinctions in protein intake. 1. Low protein intake if the amount was less than 3.0 g/kg/d. 2. High protein intake if the amount was equal to or greater than 3.0 g/kg/d but less than 4.0 g/kg/d. 3. Very high protein intake if the amount was equal to or greater than 4.0 g/kg/d.If the reviewed studies combined alterations of protein and energy, subgroup analyses were to be carried out for the planned categories of protein intake according to the following predefined energy intake categories. 1. Low energy intake: less than 105 kcal/kg/d. 2. Medium energy intake: greater than or equal to 105 kcal/kg/d and less than or equal to 135 kcal/kg/d. 3. High energy intake: greater than 135 kcal/kg/d.As the Ziegler-Fomon reference fetus estimates different protein requirements for infants based on birth weight, subgroup analyses were to be undertaken for the following birth weight categories. 1. < 800 grams. 2. 800 to 1199 grams. 3. 1200 to 1799 grams. 4. 1800 to 2499 grams. SEARCH METHODS The standard search methods of the Cochrane Neonatal Review Group were used. MEDLINE, CINAHL, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library) were searched. SELECTION CRITERIA Randomized controlled trials contrasting levels of formula protein intake as low (< 3.0 g/kg/d), high (≥ 3.0 g/kg/d but < 4.0 g/kg/d), or very high (≥ 4.0 g/kg/d) in formula-fed hospitalized neonates weighing less than 2.5 kilograms were included. Studies were excluded if infants received partial parenteral nutrition during the study period or were fed formula as a supplement to human milk. Studies in which nutrients other than protein also varied were added in a post-facto analysis. DATA COLLECTION AND ANALYSIS The standard methods of the Cochrane Neonatal Review Group were used. MAIN RESULTS Five studies compared low versus high protein intake. Improved weight gain and higher nitrogen accretion were demonstrated 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 versus very high protein intake during and after an initial hospital stay. Very high protein intake promoted improved gain in length at term, but differences did not remain significant at 12 weeks corrected age. Three of the 24 infants receiving very high protein intake developed uremia.A post-facto analysis revealed further improvement in all growth parameters in infants receiving formula with higher protein content. No significant difference in the concentration of plasma phenylalanine was noted between high and low protein intake groups. However, one study (Goldman 1969) documented a significantly increased incidence of low intelligence quotient (IQ) scores among infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg). AUTHORS' CONCLUSIONS Higher protein intake (≥ 3.0 g/kg/d but < 4.0 g/kg/d) from formula accelerates weight gain. However, limited information is available regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopmental abnormalities. Available evidence is not adequate to permit specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/d) from formula during the initial hospital stay or after discharge. show less