Review question

We reviewed the evidence to see whether the addition of extra protein to human milk, compared with no additional protein, fed to preterm infants, improved growth, body fat, obesity, heart problems, high blood sugar, and brain development, without significant side effects.

Background

Lack of adequate protein intake during the early stages of the preterm infant’s life can result in poor growth and development. Preterm infants need more protein than full term babies. Breast milk has numerous benefits for babies born preterm (before 37 weeks), but its protein content is variable, and may not meet the nutritional needs of the rapidly growing preterm infant. Therefore, to meet their higher protein needs, and to promote optimum health and long-term development, additional protein, in the form of a fortifier, may be added to expressed breast milk for preterm babies.

Study characteristics

We found six randomised trials (trials in which each infant had an equal chance of being chosen to receive either treatment), involving 204 preterm infants. The search is up to date to February 2018.

Key results

Low-quality evidence showed that the addition of extra protein to breast milk increased short-term rates of weight gain (five trials), length gain (four trials), and head growth (four trials). Low-quality evidence from one trial did not show a clear difference in the rate of growth of skin fold thickness (measure of fat under the skin) between the supplemented and unsupplemented groups. Very low-quality evidence from one trial reported that infants who received additional protein stayed in hospital longer, while very low-quality evidence from four trials observed higher blood urea nitrogen concentrations (measure of kidney function and protein breakdown) in these infants, compared to those who received no additional protein. Very low-quality evidence from one trial suggested that adding extra protein to expressed breast milk did not clearly increase the risk of necrotising enterocolitis (inflammation of the intestine) or feeding intolerance, or clearly alter serum albumin concentrations (a measure of blood protein levels). No data were available on the effects of adding extra protein to human milk on long-term growth, body fat, obesity, high blood sugar, or brain development.

Conclusions

Adding extra protein to human milk for preterm infants may increase short-term growth. However, its effect on length of hospital stay, feeding intolerance, and necrotizing enterocolitis is uncertain, due to data limitations and very low-quality evidence. There were no data about effects on later health and development, or effects in low resource settings.

Since protein supplementation of human milk is now usually done as a component of multi-nutrient fortifiers, future studies should compare different amounts of protein in multi-component fortifiers, and be designed to determine the effects on length of hospital stay, safety, long-term growth, body fat, obesity, high blood sugar, and brain development.