Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial.

Background: Human milk-based fortifiers (HMBFs) are being adopted in neonatal care to enrich the nutrients in human milk for very low birth weight (VLBW) infants despite being costly and there being limited efficacy data. No randomized clinical trial has evaluated the use of HMBF compared with bovine milk-based fortifiers (BMBFs) in the absence of formula feeding. Objective: To determine if HMBF compared with BMBF for routine nutrient enrichment of human milk improves feeding tolerance, reduces morbidity, reduces fecal calprotectin (a measure of gut inflammation), and supports the growth of infants <1250 g. Design: In this blinded randomized clinical trial, infants born weighing <1250 g were recruited from neonatal units in Ontario, Canada between August 2014 and November 2015. The infants were fed mother's milk and donor milk as required. Fortification commenced at 100 mL/kg per day of HMBF (0.81 kcal/mL) or BMBF (0.72 kcal/mL) and advanced at 140 mL/kg per day to 0.88 and 0.78 kcal/mL, respectively. The primary outcome was percentage of infants with a feeding interruption for ≥12 h or a >50% reduction in feeding volume. Secondary outcomes included a dichotomous mortality and morbidity index (i.e., affirmative for any one of death, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, or severe retinopathy of prematurity), fecal calprotectin, and growth. Results: Of 232 eligible infants, 127 (54.7%) were randomized (n = 64 HMBF, n = 63 BMBF). Mean ± SD birth weight and gestational age of infants were 888 ± 201 g and 27.7 ± 2.5 wk, respectively. No statistically significant differences were identified in feeding interruptions [17/64 HMBF, 20/61 BMBF; unadjusted risk difference: -6.2% (95% CI: -22.2%, 9.8%)]. There was no statistically significant difference in the mortality and morbidity index (48.4% HMBF, 49.2% BMBF, adjusted P = 0.76), changes in fecal calprotectin, or growth z scores. Conclusions: Among infants born weighing <1250 g and exclusively fed human milk, the use of HMBF did not improve feeding tolerance or reduce mortality and morbidity compared with BMBF. This trial was registered at clinicaltrials.gov as NCT02137473.