Clinical Response to Two Formulas in Infants with Parent-Reported Signs of Formula Intolerance: A Multi-Country, Double-Blind, Randomized Trial

Abstract

Background: Signs of feeding intolerance are common in formula-fed infants. We evaluated the clinical response to a partially hydrolyzed 100% whey protein formula with high sn-2 palmitate and reduced lactose (FA) and to an alpha-lactalbumin-enriched whey-predominant intact protein formula with full lactose (FB) in healthy full-term infants with parent-reported signs of feeding intolerance. Methods: In a double-blind, parallel-group trial in 6 Asian study centers, exclusively formula-fed infants aged 30 to 90 days, whose parents reported fussiness-crying for ≥2 hours/day plus gassiness and/or stooling difficulty, and intended to switch formula, were randomly assigned to FA (n = 130) or FB (n = 129) for 14 days. Primary endpoint was daily duration of fussiness-crying. Secondary endpoints included gassiness, spitting-up, vomiting, sleep pattern, Infant Gastrointestinal Symptom Questionnaire (IGSQ) Index, infant temperament and maternal anxiety. Results: Mean ± SE minutes/day of fussiness-crying in the 256 analyzed infants (FA, n = 127 and FB, n = 129) substantially decreased from baseline to study end in FA (291 ± 14 to 140 ± 8; –52%, P < .001), and FB (313 ± 14 to 153 ± 11, –51%, P < .001) with no difference between groups. Similarly, gassiness, spitting-up, vomiting and sleep pattern significantly improved by study end for both formulas. Mean ± SE IGSQ index scores significantly decreased from baseline to study end (FA: 44.5 ± 0.9 to 28.6 ± 0.7; FB: 44.5 ± 0.8 to 29.0 ± 0.7; P < .001) with no differences between groups. Infant temperament and maternal anxiety also improved significantly in both groups by study end. Conclusion: Switching from standard, full-lactose, intact whey/casein infant formulas to either study formula resulted in an improvement of gastrointestinal symptoms and associated behaviors in infants with signs of feeding intolerance. Trial Registration: https://clinicaltrials.gov , NCT02021058

Effects of a Novel High-Quality Protein Infant Formula on Energetic Efficiency and Tolerance: A Randomized Trial

“…Alpha-lactalbumin improves formula digestion tolerability (29,31). Hydrolyzed proteins and alpha-lactalbumin reduce regurgitation in infants (29,31,(38)(39)(40)(41). The whey predominance of the SF likely further contributes, as gastric emptying of whey protein is faster than casein (42).…”

Growth and gut comfort of healthy term infants exclusively fed with a partially hydrolysed protein-based infant formula: a randomized controlled double-blind trial

“…Comparable results were found in the study by Wu and colleagues that showed no significant gastrointestinal tolerance difference among healthy infants who consumed either a formula based on hydrolysed whey protein combined with intact casein protein-or intact protein-based formula or were breastfed (21). Vivatvakin et al who studied 256 healthy infants also found no difference in the mean scores of IGSQ between infants fed with a pHF or an IPF, while lower mean total scores were observed with increasing age of the infants (26). As the control groups of the abovementioned studies showed similar findings as the test products, this might indicate that the improvement shown over time is not related to the formulas, but that other factors played a role.…”

Gastrointestinal Tolerance of Formula-Fed Infants During the Immediate Postnatal Period in Saudi Arabia: An Observational Study

“…The results of our study align with those from a recently published, prospective, randomized trial that reported the safety and tolerability of an extensively hydrolyzed, whey-protein infant formula derived from non-porcine enzymes in infants with CMA 16 and other studies of partially hydrolyzed whey-based formulas in older infants. 17 - 20 …”