title: Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort.
abstract: BACKGROUND
  Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria.
  
  
  METHODS
  Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge.
  
  
  RESULTS
  Across Europe, 12 049 children were enrolled, and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA.
  
  
  CONCLUSIONS
  This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon.
authors: Department of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors: A A
authors: AA
authors: Schoemaker
authors: Department of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors: A B
authors: AB
authors: Sprikkelman
authors: Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors: K E
authors: http://orcid.org/0000-0003-3649-7963
authors: KE
authors: Grimshaw
authors: Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors: G
authors: G
authors: Roberts
authors: Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Centre, Berlin, Germany.
authors: L
authors: L
authors: Grabenhenrich
authors: Department of Paediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany.
authors: L
authors: L
authors: Rosenfeld
authors: Department of Paediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany.|German Agency for Quality in Medicine, Berlin, Germany.
authors: S
authors: S
authors: Siegert
authors: Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
authors: R
authors: R
authors: Dubakiene
authors: Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
authors: O
authors: O
authors: Rudzeviciene
authors: Sofia Children's University Hospital, Madrid, Spain.
authors: M
authors: M
authors: Reche
authors: University Hospital La Paz, Madrid, Spain.
authors: A
authors: A
authors: Fiandor
authors: Department of Allergy, Second Paediatric Clinic, University of Athens, Athens, Greece.
authors: N G
authors: NG
authors: Papadopoulos
authors: Neonatal Division, Second Department of Obstetrics and Gynaecology, University of Athens, Athens, Greece.
authors: A
authors: A
authors: Malamitsi-Puchner
authors: Division of Allergy, Department of Pediatrics, Pediatric Hospital Bambino Gesù, Rome, Italy.
authors: A
authors: A
authors: Fiocchi
authors: Division of Allergy, Department of Pediatrics, Pediatric Hospital Bambino Gesù, Rome, Italy.
authors: L
authors: L
authors: Dahdah
authors: Department of Immunology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
authors: S Th
authors: ST
authors: Sigurdardottir
authors: Children's Hospital, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
authors: M
authors: M
authors: Clausen
authors: Department of Pediatrics, Preventive Cardiology and Immunology, Medical University of Łódź, Łódź, Poland.
authors: A
authors: A
authors: Stańczyk-Przyłuska
authors: Department of Pediatrics, Preventive Cardiology and Immunology, Medical University of Łódź, Łódź, Poland.|Department of Pediatrics, Immunology and Nephrology, Department of Pediatrics, Clinical Immunology and Cardiology, Polish Mother's Health Centre Research Institute Łódź, Medical University of Łódź, Łódź, Poland.
authors: K
authors: K
authors: Zeman
authors: Institute of Inflammation and Repair, Manchester Academic Health Science Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.
authors: E N C
authors: EN
authors: Mills
authors: Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Centre, Berlin, Germany.
authors: D
authors: D
authors: McBride
authors: Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Centre, Berlin, Germany.|Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
authors: T
authors: T
authors: Keil
authors: Department of Paediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany.
authors: K
authors: K
authors: Beyer
mesh_terms: D017677:Age Distribution; D000485:Allergens / Q000276:immunology; D000818:Animals; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D015994:Incidence; D007223:Infant; D008297:Male; D016269:Milk Hypersensitivity / Q000175:diagnosis* / Q000453:epidemiology*; D008894:Milk Proteins / Q000009:adverse effects* / Q000276:immunology; D012720:Severity of Illness Index; D017678:Sex Distribution; D012882:Skin Tests / Q000379:methods
chemical_list: D000485:Allergens; D008894:Milk Proteins; D007073:Immunoglobulin E
keywords: EuroPrevall; birth cohort study; cow's milk allergy; food allergy; incidence