title: Introduction of gluten, HLA status, and the risk of celiac disease in children.
abstract: BACKGROUND
  The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear.
  
  
  METHODS
  We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age.
  
  
  RESULTS
  Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease.
  
  
  CONCLUSIONS
  Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).
authors.affiliation: From the Departments of Pediatrics (E.L.) and Clinical and Molecular Biomedicine (A.P.), University of Catania, the Department of Pediatrics, San Paolo Hospital (S.C.), and the Department of Developmental Biomedicine, University of Bari (R.F.), Bari, the Department of Immunopathology and Allergology, Udine Hospital, Udine (E.T.), the Department of Pediatrics, Azienda Ospedaliera IRCCS Santa Maria Nuova Hospital, Reggio Emilia (S.A.), the Department of Pediatrics, Sapienza University of Rome, Rome (M.B.), the Department of Pediatrics, University of Turin, Turin (C.B.), the Department of Pediatrics, San Raffaele Hospital (G.B.), and the Department of Pediatrics, Vittore Buzzi Children's Hospital, Milan (G.Z.), the Department of Pediatrics, Bianchi Melacrino Morelli Hospital, Reggio Calabria (A.B.), Pediatric Gastroenterology Unit, Giannina Gaslini Institute, Genoa (E.C.), the Department of Pediatrics, University of Padua, Padua (G.G.), the Department of Pediatrics, Federico II University of Naples, Naples (M.G.L.), Pediatric Gastroenterology and Cystic Fibrosis Unit, University Hospital Gaetano Martino, Messina (S.P.), the Department of Pediatrics, Rovereto Hospital, Rovereto (Trento) (C.P.), the Department of Pediatrics, University of Pisa, Pisa (C.U.), and the Department of Pediatrics, Marche Polytechnic University, Ancona (C.C.) - all in Italy; and the Division of Pediatric Gastroenterology and Nutrition and Center for Celiac Research, MassGeneral Hospital for Children (A.F.), and the Celiac Program, Harvard Medical School (A.F., C.C.) - both in Boston.
authors.forename: Elena
authors.initials: E
authors.lastname: Lionetti
authors.forename: Stefania
authors.initials: S
authors.lastname: Castellaneta
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Francavilla
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pulvirenti
authors.forename: Elio
authors.initials: E
authors.lastname: Tonutti
authors.forename: Sergio
authors.initials: S
authors.lastname: Amarri
authors.forename: Maria
authors.initials: M
authors.lastname: Barbato
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbera
authors.forename: Graziano
authors.initials: G
authors.lastname: Barera
authors.forename: Antonella
authors.initials: A
authors.lastname: Bellantoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Castellano
authors.forename: Graziella
authors.initials: G
authors.lastname: Guariso
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Limongelli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pellegrino
authors.forename: Carlo
authors.initials: C
authors.lastname: Polloni
authors.forename: Claudio
authors.initials: C
authors.lastname: Ughi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zuin
authors.forename: Alessio
authors.initials: A
authors.lastname: Fasano
authors.forename: Carlo
authors.initials: C
authors.lastname: Catassi
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D001942:Breast Feeding; D002446:Celiac Disease / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D005838:Genotype; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007421:Intestine, Small / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012306:Risk; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D004044:Dietary Proteins; D006680:HLA Antigens; D005983:Glutens; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins