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

2022-02
The Journal of allergy and clinical immunology 149(2)
- Pantipa Chatchatee
- Anna Nowak-Wegrzyn
- Lars Lange
- Suwat Benjaponpitak
- Kok Wee Chong
- Pasuree Sangsupawanich
- Marleen T J van Ampting
- Manon M Oude Nijhuis
- Lucien F Harthoorn
- Jane E Langford
- Jan Knol
- Karen Knipping
- Johan Garssen
- Valerie Trendelenburg
- Robert Pesek
- Carla M Davis
- Antonella Muraro
- Mich Erlewyn-Lajeunesse
- Adam T Fox
- Louise J Michaelis
- Kirsten Beyer

PubMed: 34224785
DOI: 10.1016/j.jaci.2021.06.025

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 89
Population: infants aged ≤13 months with IgE-mediated cow's milk allergy
Methods: Multicenter, prospective, randomized, double-blind, controlled clinical study; subjects randomized to receive AAF-S or AAF for 12 months; tolerance evaluated by double-blind, placebo-controlled food challenge at 12 and 24 months
Blinding: Double-blind
Duration: 12 months

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.

Research Insights

Bifidobacterium breve M-16V→Developed Cow's Milk Tolerance
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.
Effect
Neutral
Effect size
Small

Adverse Events Reported

Bifidobacterium breve M-16V→infection-related hospitalization
fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036)
Finding
Reported
Severity
Serious adverse event
Magnitude
9% vs 20%
Significant
Yes