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

Design: parallel randomised controlled trials; participants: preterm infants (<37 weeks gestation) hospitalized and fed human milk; included very low birth weight (VLBW) or low birth weight infants in some studies; donor and maternal milk used across arms; micronutrient supplements allowed in both groups.

Protein fortification of expressed breast milk in preterm infants may improve short-term growth during hospitalization: weight gain around 3.82 g/kg/day, length around 0.12 cm/week, and head circumference around 0.06 cm/week (low-quality evidence). Higher blood urea nitrogen observed with fortification; no clear differences in weight at term or end of study; one small trial reported longer hospital stay. No clear effect on necrotising enterocolitis or feeding intolerance; long-term growth, BMI, body composition, neurodevelopmental or cardio-metabolic outcomes are not reported. Authors suggest fortification could be considered where risk of poor postnatal growth is high and multi-nutrient fortification is unavailable; overall evidence is of low quality and uncertain.

Small number of trials with limited sample sizes; risk of bias mostly unclear; substantial heterogeneity across studies; lack of data on long-term outcomes; limited generalizability to settings outside developed countries; potential selective reporting.