An Infant Formula with Partially Hydrolyzed Whey Protein Supports Adequate Growth and Is Safe and Well-Tolerated in Healthy, Term Infants: A Randomized, Double-Blind, Equivalence Trial

Abstract

The current study evaluates the safety and tolerance of a partially hydrolyzed whey protein-based infant formula (PHF) versus an in intact cow's milk protein formula (IPF). Breastfed infants were included as a reference group. In a multi-country, multicenter, randomized, double-blinded, controlled clinical trial, infants whose mothers intended to fully formula feed were randomized to PHF (n = 134) or IPF (n = 134) from ≤14 days to 17 weeks of age. The equivalence analysis of weight gain per day within margins of +/-3 g/d (primary outcome), the recorded adverse events, growth and gastro-intestinal tolerance parameters were considered for the safety evaluation. Equivalence of weight gain per day from enrolment until 17 weeks of age was demonstrated in the PHF group compared to the IPF group (difference in means -1.2 g/d; 90% CI (-2.42; 0.02)), with estimated means (SE) of 30.2 (0.5) g/d and 31.4 (0.5) g/d, respectively. No significant differences in growth outcomes, the number, severity or type of (serious) adverse events and tolerance outcomes, were observed between the two formula groups. A partially hydrolyzed whey protein-based infant formula supports adequate infant growth, with a daily weight gain equivalent to a standard intact protein-based formula; it is also safe for use and well-tolerated in healthy term infants.

Keywords: infant growth; partially hydrolyzed formula; prebiotic; safety; tolerance.

Figure 1

Flow chart of progression of infants during the study. PHF = partially hydrolyzed formula; IPF = intact protein-based formula; BF = breastfed; ASR = all subjects randomized; AST = all subjects treated; PP = per-protocol population assessed per visit (V2 at 4 weeks, V3 at 8 weeks, V4 at 13 weeks and V5 at 17 weeks).^A non-randomized part of a twin assigned to the same study product as their sibling (excluded from ASR but included in AST). ^B includes three randomized twin subjects; ^C n = 134 individual subjects minus one subject without study product intake; ^D n = 134 individual subjects (including three twins, minus three subjects without study product intake).

Figure 2

Mean (±95% CI) weight-for-age, length-for-age, head circumference-for-age and BMI-for-age WHO growth standard z-scores per visit for PHF and IPF groups as well as breastfed reference group. V1 before 14 days, V2 at 4 weeks, V3 at 8 weeks, V4 at 13 weeks and V5 at 17 weeks. WHO Z-scores for PHF and IPF are based on arbitrary means model with two groups. Model with (1) fixed effect terms for: group, time (=visit), sex, birth weight and country; (2) interactions for: group by time and sex by time (for a subject) with an unstructured covariance matrix. No statistical differences were observed between the intervention groups. WHO Z-scores for BF reference groups are the non-modeled actual values.

Figure 3

Forest plot with the estimated means as well as the difference in mean (95%) occurrence of (serious) adverse events for each system organ class per/between intervention group(s) of the AST population.