Although breast milk is considered the ideal food for the term infant, for the VLBW infant it provides inadequate amounts of several nutrients, especially protein, vitamin D, calcium, phosphorus, and sodium. While large volumes of human milk (180 mL/kg/d) provide the energy sufficient to enable nearly all infants with birthweights <1250 g to gain weight at intrauterine rates (approximately 15 g/kg/d), the protein content is suboptimal, and may result in lower serum albumin and transthyretin (prealbumin) levels, which are reliable indicators of protein nutrition in preterm infants. The calcium and phosphorus content is low in unsupplemented human milk regardless of large volumes in comparison with that required to achieve intrauterine accretion rates, resulting in poor bone mineralization in VLBW infants. In addition, the sodium content of human milk results in less sodium retention than intrauterine estimates and may result in hyponatremia and may be rate-limiting for appropriate weight gain

Lucas and colleagues (1984) found that infants weighing less than 1200 g at birth fed unfortified human milk were less than two standard deviations below the mean for weight for age when they reached 2.0 kg. Therefore, infants weighing less than 1.0 kg at birth who were fed unfortified human milk would be expected to take three weeks longer to reach a weight of 2.0 kg than infants receiving preterm formulas.

In a study focusing on developmental outcomes, Lucas et al. (1989) observed that infants receiving breast milk had a significantly higher intelligence quotient at eight years than formula-fed infants. These studies included infants receiving unfortified donor human milk.