Powdered human milk-derived versus bovine milk-derived breastmilk fortification: A multi-centre preterm randomised controlled trial.

Objective: To compare faecal calprotectin, plasma amino acids and clinical outcomes in preterm infants receiving powdered human milk-based fortifier (PHMF) compared to powdered bovine milk-based fortifier (PBMF) in preterm infants on an otherwise exclusive human milk diet.

Methods: A randomised controlled trial in infants <32 weeks of gestation or <1500 g who only received human milk and had reached full enteral feeds (150 mL/kg/day), without pre-existing gastrointestinal morbidity. Primary outcome was faecal calprotectin within 21 days of starting fortification; secondary outcomes were calprotectin at discharge, plasma amino acids and clinical outcomes, including growth and neonatal morbidities.

Results: The trial stopped early after the manufacturer's withdrawal of PHMF. Thirty-one infants were enroled, three without informative sampling, leaving 14 per group. No statistical differences were seen in faecal calprotectin on Day 7 (236 mcg/g PHMF vs. 303 mcg/g PBMF, p = 0.90) or 21 (135 mcg/g PHMF vs. 315 mcg/g PBMF, p = 0.21). Adjusting for gestation and day of life, and including all time points after enrolment to discharge, fortifier type did not impact faecal calprotectin (coefficient estimate -7.13, 95% confidence interval = -172 to 158, p = 0.93). Rates of key neonatal morbidities did not differ. PHMF infants grew more slowly reaching statistical significance in change in weight standard deviation score at discharge compared to PBMF infants (mean (standard deviation) -0.94 (0.7) PHMF vs. -0.24 (0.8) PBMF, p = 0.02).

Conclusions: We did not detect reduced gut inflammation as measured by faecal calprotectin in PHMF compared to PBMF but weight gain was slower, of potential clinical importance.