Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial

J Allergy Clin Immunol. 2017 Jun;139(6):1906-1913.e4. doi: 10.1016/j.jaci.2016.10.050. Epub 2016 Dec 30.

Abstract

Background: Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs).

Objective: We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA.

Methods: Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months.

Results: A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0-8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was -0.23 (95% CI, -0.36 to -0.10; P < .001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08-0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11-0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children.

Conclusions: EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.

Keywords: Eczema; asthma; atopic march; food allergy; gut microbiota; probiotics; rhinoconjunctivitis; urticaria.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Asthma / immunology
  • Asthma / therapy
  • Caseins / therapeutic use*
  • Conjunctivitis / immunology
  • Conjunctivitis / therapy
  • Double-Blind Method
  • Eczema / immunology
  • Eczema / therapy
  • Female
  • Food, Formulated*
  • Humans
  • Hydrolysis
  • Immune Tolerance
  • Immunoglobulin E / immunology
  • Infant
  • Lacticaseibacillus rhamnosus*
  • Male
  • Milk Hypersensitivity / immunology
  • Milk Hypersensitivity / therapy*
  • Probiotics / therapeutic use*
  • Rhinitis, Allergic / immunology
  • Rhinitis, Allergic / therapy
  • Skin Tests
  • Urticaria / immunology
  • Urticaria / therapy

Substances

  • Caseins
  • Immunoglobulin E