Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Non-Inferiority Trial

OBJECTIVE:A high protein content of non-hydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate non-inferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. PATIENTS AND METHODS:In an European multi-centre, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groupsLP-formulas (1.9 g protein/100 kcal) as pHF (i) with or (ii) without synbiotics, (iii) LP-eHF-formula with synbiotics, or (iv) regular protein eHF (2.3 g protein/100 kcal). 101 breastfed infants served as observational reference group. As primary endpoint, non-inferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group (i) to a regular protein eHF group (iv). RESULTS:A comparison of daily weight gain in infants receiving LPpHF (2.15 g/d (CI [−0.18,inf.[) with infants receiving regular protein eHF showed non-inferior weight gain (- 3.5 g/d margin) (PP population). Non-inferiority was also confirmed for the other tested LP-formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF+synbiotics compared to LPpHF+synbiotics. CONCLUSION:All tested hydrolyzed LP-formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.