Abstract / Summary
Background: Cow's milk protein-based fortifiers are the standard for human milk fortification in very low birth weight (VLBW) infants but have been associated with a higher risk of necrotizing enterocolitis. LioNeo is produced by lyophilization of donor human milk. This study assessed whether LioNeo is non-inferior to the bovine fortifier for growth in VLBW infants. Methods: This phase 2, randomized, double-blind, non-inferiority trial was conducted at a university hospital. Hemodynamically stable VLBW infants who were small or appropriate for gestational age and exclusively fed human milk ([≥]100 mL/kg/day) were randomized 1:1 to LioNeo or human milk with a bovine fortifier (HMCA) for 21 days. The primary outcomes were length and head circumference z-scores. Secondary outcomes were weight gain, adverse events, and serum copper and zinc concentrations. Results: In total, 129 infants were randomized and analyzed by intention to treat (LioNeo, 67; HMCA, 62). At day 21, the adjusted difference in length z-score was 0.07 (95% CI -0.13 to 0.27), with the lower limit above the non-inferiority margin (-0.27). There was no difference in head circumference or weight. Late-onset neonatal sepsis occurred in six HMCA participants and none in the LioNeo group (P = 0.01). Serum zinc decreased in both groups; copper was higher with LioNeo at day 21. Conclusions: LioNeo was non-inferior to the bovine fortifier for linear growth in VLBW infants, with no difference in head circumference or weight and no increase in adverse events. Multicenter phase 3 trials are needed. Trial registration: Brazilian Registry of Clinical Trials (ReBEC), RBR-8nnpfm (UTN U1111-1220-0550). Keywords: Freeze Drying; Infant, Premature; Milk Banks; Milk, Human; Randomized Controlled Trial.