A Systematic Review of Controlled Trials of Lower-Protein or Energy-Containing Infant Formulas for Use by Healthy Full-Term Infants

Infant formulas have historically been developed based on providing macronutrients at intake concentrations approximately matching the composition of human milk. In most countries, targets of 1.4-1.5 g of protein/dL and 20 kcal/oz (67-68 kcal/dL) have been set as the protein and energy concentrations for formulas during the first year of life, although this may be an overestimation of these contents. Recent introduction of lower-protein and -energy formulas in full-term infants led us to systematically review the literature for its effects on growth. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, our inclusion criteria were studies that enrolled healthy full-term infants and evaluated lower-protein or lower-energy formula, reported anthropometric outcomes including weight and length, and followed infants for at least 6 mo. Six studies were eligible for inclusion. These studies varied in the content of nutrients provided in the intervention and control groups, by additional dietary components in the study groups, and the timing and length of the intervention, which limit their usefulness for interpreting newly introduced lower-protein and -energy formulas in the United States. These studies suggest adequate growth during infancy and early childhood with infant formulas with concentrations of protein and energy slightly below historical standards in the United States. Further long-term research is needed to assess the impact of the use of lower-protein and/or lower-energy products, especially for nutritionally at-risk populations such as preterm infants and infants who are born small for gestational age.