Abstract
BACKGROUND: Partially hydrolyzed cow's milk protein (PHP) formulas are nutritionally complete and have a high-quality protein composition, and extensive history of safe use. The current study evaluated growth and safety in healthy term infants receiving a new PHP formula with an added prebiotic blend. METHODS: In this multi-center, double-blind, controlled, parallel, prospective study, healthy term infants were randomized to receive one of two formulas through 365 days of age: previously marketed intact cow's milk protein formula (Control, n = 122) or investigational PHP formula (INV-PHP, n = 122). Both formulas had an added prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) (1:1, 4 g/L). The primary outcome was rate of weight gain (g/day) from 14 to 120 days of age. To establish equivalence between study formulas, the 90% two-sided confidence interval (CI) of the mean group difference in body weight growth rate from 14 to 120 days of age needed to be contained within a predefined equivalence interval (± 3 g/day). Growth rates through Day 120 and achieved anthropometrics through Day 365 were analyzed by ANOVA. Parent-reported tolerance outcomes were also collected. Medically confirmed adverse events were collected throughout the study period. RESULTS: Of 244 infants enrolled and randomized (Control, n = 122; INV-PHP, n = 122); 175 completed study feeding through Day 120 (Control, n = 91; INV-PHP, n = 84). Equivalence in rate of weight gain from 14 to 120 days of age was demonstrated with the difference in means of 0.5 g/day and 90% CI [- 1.10, 2.08 g/day] within the predefined equivalence interval (± 3 g/day). Mean achieved weight remained between 25th -75th reference percentiles of the WHO growth standard through Day 180 by sex and subsequently tracked between 50th -90th percentiles through Day 365. Formula acceptance and tolerance were good. Stool consistency remained soft in both groups throughout the study. No significant group differences in mean fussiness and gassiness scores, or medically confirmed adverse events were detected. A total of 159 participants completed the Day 365 visit (Control, n = 82; INV-PHP, n = 77). CONCLUSIONS: Overall, partially hydrolyzed cow's milk protein infant formula with an added prebiotic was safe, well-tolerated, and associated with adequate growth for healthy term infants receiving formula through one year of age. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier NCT05047978. Registered 28 August 2021, https://clinicaltrials.gov/study/NCT05047978.