Protein supplementation of human milk for promoting growth in preterm infants.

Systematic review of controlled trials in hospitalized preterm infants, including very low birth weight infants. The review pooled four small studies of protein-fortified human milk versus unsupplemented human milk.

Protein was added to human milk for preterm infants in several forms, including lyophilized human milk protein at approximately 1.5 g/kg/day or 0.8 to 1.0 g per 100 mL milk, and casein hydrolysate at 1 g per 100 mL milk. The supplemented milk was compared with unsupplemented maternal or donor human milk in hospitalized preterm infants.

Protein supplementation of human milk improved short-term growth in relatively well preterm infants. Pooled effects favored supplementation for weight gain (MD 3.64 g/kg/day, 95% CI 2.43 to 4.85), linear growth (MD 0.28 cm/week, 95% CI 0.18 to 0.38), and head growth (MD 0.14 cm/week, 95% CI 0.06 to 0.23). Blood urea was higher with supplementation (MD 1.02 mmol/L, 95% CI 0.83 to 1.21) but remained within the normal range. Evidence for serum albumin and feeding intolerance was imprecise, and there were no data on long-term growth or neurodevelopmental outcomes; one trial reported feeding intolerance in 1/9 treated infants versus 0/8 controls and no necrotizing enterocolitis.

The evidence base was small, with only a few short trials and small active-arm sample sizes. Outcomes on long-term growth, neurodevelopment, and safety were sparse, and the protein preparations and dosing strategies varied across studies. Findings are most applicable to relatively well preterm infants receiving human milk in hospital settings.