title: The role of gluten consumption at an early age in celiac disease development: a further analysis of the prospective PreventCD cohort study.
abstract: Background:We previously found that the introduction of small quantities of gluten at 4-6 mo of age did not reduce the risk of celiac disease (CD) in a group of high-risk children. However, the consumption of high amounts of gluten early in life has been suggested to increase CD risk.Objective:The aim of this study was to evaluate this hypothesis by using data from the previous study of the PreventCD trial (www.preventcd.com).Design:Gluten intake was prospectively quantified by using specific food records between 11 and 36 mo of age in 715 children positive for the human leukocyte antigen (HLA)-DQ2and/orHLA-DQ8from 5 European countries. According to the PreventCD protocol, infants received 100 mg immunologically active gluten/d or placebo from 4 to 6 mo of age, with a stepwise and fixed gluten increase until age 10 mo and unrestricted intake thereafter. The primary outcome of the present study was the impact of the amount of gluten consumed from age 10 mo onward on CD development.Results:Mean daily gluten intakes from 10 mo onward were significantly different between countries for children at all ages (P< 0.001) but not between children who developed CD and those who did not within the same country (P> 0.05). The variables country, sex, intervention group, and gluten consumption pattern did not show significant associations with CD development risk (HRs not significant). In addition, the interaction betweenHLArisk group and gluten consumption pattern showed no significant risk on CD development, except for the DQ2.2/DQ7 haplotype (HR: 5.81; 95% CI: 1.18, 28.74;P= 0.031).Conclusions:Gluten consumption patterns as well as the amount of gluten consumed at 11-36 mo of age do not influence CD development for most relatedHLAgenotypes in children with a genetic risk. This study reports the gluten consumption pattern in children at risk of CD from different European countries. This trial was registered at www.controlled-trials.com as ISRCTN74582487.
authors.affiliation: Departments of Celiac Disease and Digestive Immunopathology and paula_crespo@iislafe.es.
authors.forename: Paula
authors.identifier: 0000-0003-3180-9024
authors.initials: P
authors.lastname: Crespo-Escobar
authors.affiliation: Departments of Pediatrics and.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mearin
authors.affiliation: Biostatistics, Medical Research Institute La Fe, Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Hervás
authors.affiliation: Department of Medical Translational Sciences and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Auricchio
authors.affiliation: Department of Pediatrics, Hospital Universitari Sant Joan, Reus/Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castillejo
authors.affiliation: Celiac Disease Center, Heim Pál Children's Hospital, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Gyimesi
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martinez-Ojinaga
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Werkstetter
authors.affiliation: Departments of Pediatrics and.
authors.forename: Sabine Lisa
authors.initials: SL
authors.lastname: Vriezinga
authors.affiliation: Celiac Disease Center, Heim Pál Children's Hospital, Budapest, Hungary.
authors.forename: Ilma Rita
authors.initials: IR
authors.lastname: Korponay-Szabo
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Polanco
authors.affiliation: Department of Medical Translational Sciences and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.affiliation: Medical Statistics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: Stoopman
authors.affiliation: Referral Center for Pediatric Gastroenterology and Nutrition, University Children's Hospital Zagreb, Zagreb, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Kolaček
authors.affiliation: Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Shamir
authors.affiliation: Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland; and.
authors.forename: Hania
authors.initials: H
authors.lastname: Szajewska
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Koletzko
authors.affiliation: Pediatric Gastroenterology, University Hospital La Fe, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ribes-Koninckx
mesh_terms: D001323:Autoantibodies / Q000097:blood; D002446:Celiac Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology; D002664:Child Nutritional Physiological Phenomena; D002675:Child, Preschool; D004032:Diet; D015930:Diet Records; D005060:Europe; D005247:Feeding Behavior; D005260:Female; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D006683:HLA-DQ Antigens / Q000097:blood; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C069546:HLA-DQ7 antigen; C109756:HLA-DQ8 antigen; D005983:Glutens
keywords: European cohort; HLA; celiac disease; children; gluten