title: Infant feeding and anti-tissue transglutaminase antibody concentrations in the Generation R Study.
abstract: BACKGROUND
  Celiac disease (CD) has emerged as a common, but largely undiagnosed health problem. Numerous studies examined the influence of infant nutrition on the development of diagnosed CD. However, results are still inconsistent. In addition, the effect of infant feeding practices on the development of potential forms of CD might be different.
  
  
  OBJECTIVE
  The objective was to examine whether the timing of gluten introduction and breastfeeding duration are associated with CD autoimmunity (CDA) in children at the age of 6 y.
  
  
  METHODS
  This study was embedded in the Generation R Study, a population-based prospective cohort study. Participants included 1679 Dutch children who were positive for human leukocyte antigen (HLA) DQ2/DQ8. Data on the timing of gluten introduction (<6 mo compared with ≥6 mo) and duration of breastfeeding (<6 mo compared with ≥6 mo) were obtained by questionnaire. Serum samples were analyzed for anti-tissue transglutaminase (anti-tTG) concentrations at age 6 y. Anti-tTG concentrations were categorized into negative (<7 U/mL) and positive (≥7 U/mL) values. Positive anti-tTG concentrations were further categorized based on ≥10 times the upper limit of normal (ULN) values of the test kit (≥7-70 and ≥70 U/mL). Multivariable logistic regression analyses were performed.
  
  
  RESULTS
  Positive anti-tTG concentrations were found in 43 children, 26 of whom had concentrations ≥10 times the ULN (≥70 IU/mL). The introduction of gluten from the age of 6 mo onward and breastfeeding for ≥6 mo were not significantly associated with positive anti-tTG concentrations. In addition, the timing of gluten introduction and duration of breastfeeding were not significantly associated with positive anti-tTG concentrations below or above 10 times the ULN.
  
  
  CONCLUSIONS
  Delayed introduction of gluten beyond the age of 6 mo does not increase the risk of CDA. In addition, breastfeeding for ≥6 mo does not decrease the risk of CDA in children at 6 y of age.
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Michelle A E
authors.initials: MA
authors.lastname: Jansen
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Ilse I M
authors.initials: II
authors.lastname: Tromp
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Escher
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Herbert
authors.initials: H
authors.lastname: Hooijkaas
authors.affiliation: From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands.
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Moll
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity / Q000276:immunology; D001942:Breast Feeding; D002446:Celiac Disease / Q000097:blood / Q000276:immunology; D002648:Child; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D005983:Glutens / Q000008:administration & dosage*; D006683:HLA-DQ Antigens / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011795:Surveys and Questionnaires; D013997:Time Factors; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000097:blood*; D014886:Weaning
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins