A Randomized Controlled Trial of a Partially Hydrolyzed Formula on Comfort Measures in Fussy Infants

Objective This study evaluated the nutritive effects of a partially hydrolyzed cow's milk protein (PHP) formula with an added prebiotic blend on parent/caregiver-reported fussiness and other measures of comfort in infants with perceived fussiness. Methods Infants (15-75 days of age) exclusively receiving a commercial intact protein infant formula and rated moderately, very, or extremely fussy were randomized to receive: intact cow's milk protein formula (Control, n=73) or investigational PHP formula (INV-PHP, n=76). Both formulas had a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) (1:1, 4 g/L). Parent-reported outcomes at baseline (D0), end of study feeding day one (D1), and daily over the 28-day study feeding were analyzed using repeated measures ANOVA. Results Of 149 infants randomized, 127 completed study feeding (Control, n=65; INV-PHP, n=62). The primary outcome of parent-reported fussiness was not different between groups. Among secondary outcomes, there was a significant decrease in crying throughout the study (Weeks 1-4, p=0.01) and significantly fewer infants who experienced excessive crying during the study (Weeks 1, 2, and 4, p≤0.045) for INV-PHP vs Control. Formula intake was not different between groups. Incidences of adverse events were low with no significant group differences. On post-hoc analysis, within each group, fussiness, gassiness, and spit-up significantly decreased from D0 to D1 (P<0.001) and was maintained through study end (P<0.001). Conclusions In infants with parent-perceived fussiness, a partially hydrolyzed cow's milk protein formula with an added prebiotic blend, INV-PHP, did not decrease fussiness, but did reduce crying and excessive crying versus Control formula. Clinical Trial Registry The study was registered at clinicaltrials.gov (Registration # NCT05245422).