Tolerance development in cow's milk-allergic infants receiving amino acid-based formula: A randomized controlled trial

J Allergy Clin Immunol. 2022 Feb;149(2):650-658.e5. doi: 10.1016/j.jaci.2021.06.025. Epub 2021 Jul 2.

Abstract

Background: Tolerance development is an important clinical outcome for infants with cow's milk allergy.

Objective: This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid-based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy.

Methods: Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n = 80) or AAF (n = 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set.

Results: At baseline, mean ± SD age was 9.36 ± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036).

Conclusions: After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

Keywords: Cow’s milk allergy; amino acid–based formula; infection; oral tolerance; prebiotics; probiotics; synbiotics.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / administration & dosage*
  • Double-Blind Method
  • Female
  • Humans
  • Immune Tolerance*
  • Infant
  • Infant Formula* / adverse effects
  • Infant, Newborn
  • Male
  • Milk Hypersensitivity / immunology*
  • Prospective Studies
  • Synbiotics / administration & dosage

Substances

  • Amino Acids