title: 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.
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.
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy; European Laboratory for the Investigation of Food-Induced Diseases, University of Naples "Federico II", Naples, Italy; CEINGE Advanced Biotechnologies, University of Naples "Federico II", Naples, Italy. Electronic address: berni@unina.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Berni Canani
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Di Costanzo
authors.affiliation: CEINGE Advanced Biotechnologies, University of Naples "Federico II", Naples, Italy; Clinical Epidemiology Unit, Liver Research Center Basovizza, Trieste, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bedogni
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy; CEINGE Advanced Biotechnologies, University of Naples "Federico II", Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Cosenza
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Scala
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Granata
authors.affiliation: Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy; CEINGE Advanced Biotechnologies, University of Naples "Federico II", Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Nocerino
mesh_terms: D001249:Asthma / Q000276:immunology / Q000628:therapy; D002364:Caseins / Q000627:therapeutic use*; D003231:Conjunctivitis / Q000276:immunology / Q000628:therapy; D004311:Double-Blind Method; D004485:Eczema / Q000276:immunology / Q000628:therapy; D005260:Female; D005526:Food, Formulated; D006801:Humans; D006868:Hydrolysis; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology; D007223:Infant; D052201:Lacticaseibacillus rhamnosus; D008297:Male; D016269:Milk Hypersensitivity / Q000276:immunology / Q000628:therapy*; D019936:Probiotics / Q000627:therapeutic use*; D065631:Rhinitis, Allergic / Q000276:immunology / Q000628:therapy; D012882:Skin Tests; D014581:Urticaria / Q000276:immunology / Q000628:therapy
chemical_list: D002364:Caseins; D007073:Immunoglobulin E
keywords: Eczema; asthma; atopic march; food allergy; gut microbiota; probiotics; rhinoconjunctivitis; urticaria