Feeding advancement and tolerance in preterm infants receiving an extensively hydrolyzed protein infant formula versus an intact protein premature infant formula: A triple-blind randomized clinical trial

Objectives: To evaluate enteral feeding advancement and tolerance in preterm infants randomly assigned to receive one of two marketed preterm formulas, intact protein (IP) or extensively hydrolysed (EH) formula for the first 14 feeding days. Methods: In this triple-blind, randomized, controlled, prospective, clinical trial, eligible infants (28–33 weeks’ gestational age, birth weight 700–1750 g, adequate for gestational age) were enrolled within 24 h of first enteral feeding. Mothers were encouraged to provide their own breast milk. The primary outcome was days to full enteral feeding (≥140 mL/kg/day). Tolerance measures, adverse events (AEs), sepsis and necrotizing enterocolitis (NEC) were collected. Populations for analysis included participants who completed the study per protocol and who received ≥75% study formula intake (mL/kg/day). Results: Of 65 enrolled newborns (IP: n = 32; EH: n = 33), 60 completed the study per protocol (IP: 30; EH: 30); 54 (90%) received some breast milk; 23 received ≥75% study formula intake (IP: 11; EH: 12). No group differences were detected in tolerance measures or sepsis. No AEs or NEC were reported. Median time to achievement full enteral feeding was significantly shorter for the IP vs EH group (day 10 vs day 14, p < 0.05) for newborns receiving ≥75% study formula intake. A significant increase emerged by study end for the IP vs EH group (p < 0.05) in patients receiving ≥75% study formula intake. Conclusion: In preterm infants supplementation with an intact protein premature formula, compared to extensively hydrolysed formula, resulted in shorter time to full enteral feeding and higher feeding volume achieved by study end.