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  1. Wagner, Julie RD, LMNT, CNSC
  2. Hanson, Corrine RD, PhD
  3. Anderson-Berry, Ann MD


Preterm infants provided with sufficient nutrition to achieve intrauterine growth rates have the greatest potential for optimal neurodevelopment. Although human milk is the preferred feeding for preterm infants, unfortified human milk provides insufficient nutrition for the very low-birth-weight infant. Even after fortification with human milk fortifier, human milk often fails to meet the high protein needs of the smallest preterm infants, and additional protein supplementation must be provided. Although substantial evidence exists to support quantitative protein goals for human milk-fed preterm infants, the optimal type of protein for use in human milk fortification remains uncertain. This question was addressed through a PubMed literature search of prospective clinical trials conducted since 1990 in preterm or low-birth-weight infant populations. The following 3 different aspects of protein quality were evaluated: whey-to-casein ratio, hydrolyzed versus intact protein, and bovine milk protein versus human milk protein. Because of a scarcity of current studies conducted with fortified human milk, studies examining protein quality using preterm infant formulas were included to address certain components of the clinical question. Twenty-six studies were included in the review study. No definite advantage was found for any specific whey-to-casein ratio. Protein hydrolyzate products with appropriate formulations can support adequate growth and biochemical indicators of nutrition status and may reduce gastrointestinal transit time, gastroesophageal reflux events, and later incidence of atopic dermatitis in some infants. Plasma amino acid levels similar to those of infants fed exclusive human milk-based diets can be achieved with products composed of a mixture of bovine proteins, peptides, and amino acids formulated to replicate the amino acid composition of human milk. Growth and biochemical indicators of nutrition status are similar for infants fed human milk fortified with human milk protein and bovine milk protein.