Higher versus lower protein intake in formula‐fed low birth weight infants
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 the effect of higher versus lower protein intakes of formula‐fed preterm infants on growth and neurodevelopmental outcome.
Search methods
The standard search methods of the Cochrane Neonatal Review Group were used. MEDLINE, CINAHL, PubMed, EMBASE and The Cochrane Library were searched.
Selection criteria
Randomized controlled trials contrasting levels of formula protein intakes as low (< 3.0 g/kg/day), high (≥ 3.0 g/kg/day but < 4.0 g/kg/day), or very high protein intake (≥ 4.0 g/kg/day) in formula‐fed hospitalized neonates 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 to high protein intakes. Improved weight gain and higher nitrogen accretion was 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 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.
A post‐facto analysis revealed further improvement in all growth parameters in infants receiving formula with higher protein content. There was no significant difference in the concentration of plasma phenylalanine between the high and low protein intake groups. However, one study (Goldman 1969) 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).
Authors' conclusions
Higher protein intake (≥ 3.0 g/kg/day but < 4.0 g/kg/day) from formula accelerates weight gain. However, there is limited information regarding the impact of higher formula protein intake on long‐term outcomes such as neurodevelopmental abnormalities. The available evidence is not adequate to make specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/day) from formula in the initial hospital stay or after discharge.
PICOs
Plain language summary
Higher versus lower protein intake in formula‐fed low birth weight infants
Dietary protein is needed for normal growth and development. The protein intake required for growth of the low birth weight infant has been estimated by the growth rate of the fetus to be 3.5 to 4 g/kg/day. Controlling the amount of protein given to low birth‐weight babies (less than 2.5 kg) fed with formula is important . Too much protein can raise blood urea and amino acid (phenylalanine) levels that may harm neurodevelopment. Too low protein intakes may limit the growth of these infants. The review authors searched the medical literature to identify studies that compared protein intakes: between 3 and 4 g of protein per kg of infant body weight each day versus less than 3.0 g/kg/day or greater than 4.0 g/kg/day by low birth‐weight infants fed on formula during their initial hospital stay. Increased protein intake resulted in a greater weight gain of around 2 g/kg/day. Based on increased body incorporation of nitrogen, this was associated with increased lean body mass. The present conclusion was based on five studies changing only the protein content of the formula and supported by three additional studies that also made changes in other nutrients. There was no significant difference in the concentration of plasma phenylalanine between infants fed with high or low protein content formula. The review was limited in the conclusions made since the differences in protein content among comparison groups in some of the individual trials were small and the formulas differed substantially across studies; some studies included healthier and more mature premature infants. The study periods varied from eight days to two years so there was limited information on long‐term outcomes. Existing research is not adequate to make specific recommendations regarding formula with protein content that provides more than 4.0 g/kg/day.
