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Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk

Educational Objective
To understand the relationship of gluten intake with celiac disease in genetically at-risk children.
1 Credit CME
Key Points

Question  Is the amount of gluten intake during the first 5 years of life associated with the risk of celiac disease autoimmunity and celiac disease in at-risk children?

Findings  In this multinational prospective birth cohort consisting of 6605 genetically predisposed children, higher gluten intake was associated with a statistically significant increase in celiac disease autoimmunity (absolute risk difference, 6.1%) and celiac disease (absolute risk difference, 7.2%) for every gram increase of gluten intake per day.

Meaning  Increased intake of gluten during the first 5 years of life was an independent risk factor for celiac disease autoimmunity and celiac disease in genetically predisposed children.

Abstract

Importance  High gluten intake during childhood may confer risk of celiac disease.

Objectives  To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children.

Design, Setting, and Participants  The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017.

Exposures  Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years.

Main Outcomes and Measures  The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels.

Results  Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]).

Conclusions and Relevance  Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

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Article Information

Corresponding Author: Daniel Agardh, MD, PhD, Clinical Research Centre, Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Lund University, Jan Waldenströms Gata 35, 20502 Malmö, Sweden (daniel.agardh@med.lu.se).

Author Contributions: Dr Lee had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Lee, Liu, Kurppa, Ziegler, She, Hagopian, Rewers, Akolkar, Virtanen, Agardh.

Acquisition, analysis, or interpretation of data: Andrén Aronsson, Lee, Hård af Segerstad, Uusitalo, Yang, Koletzko, Kurppa, Bingley, Toppari, Ziegler, She, Hagopian, Rewers, Krischer, Virtanen, Norris, Agardh.

Drafting of the manuscript: Andrén Aronsson, Lee, Hård af Segerstad, Bingley, Agardh.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Andrén Aronsson, Lee, Yang, Krischer, Virtanen.

Obtained funding: Toppari, Ziegler, She, Hagopian, Rewers.

Administrative, technical, or material support: Yang, Koletzko, Kurppa, Toppari, Hagopian, Rewers, Krischer, Norris.

Supervision: Yang, Kurppa, Toppari, Ziegler, She, Hagopian, Rewers, Akolkar, Virtanen, Norris, Agardh.

Conflict of Interest Disclosures: Dr Koletzko reported being a member of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guideline group for celiac disease and a member of the PreventCD consortium. No other disclosures were reported.

Funding/Support: This study was funded by grants U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, and UC4 DK117483 and contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and JDRF. This work was supported in part by the clinical and translational science awards given to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082) from the National Institutes of Health and the National Center for Advancing Translational Sciences.

Role of the Funder/Sponsor: The sponsors were represented in The Environmental Determinants of Diabetes in the Young (TEDDY) steering committee. The sponsors had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and review and approval to submit the manuscript for publication. The sponsors did not have the right to veto submission to any particular journal, but did participate in the writing group’s discussion when selecting an appropriate journal for submission. The corresponding author had the final say in submitting the manuscript for publication.

Group Information: The TEDDY Study Group clinical sites and members are located in Finland: Jorma Toppari, MD, PhD, primary investigator (University of Turku, Turku University Hospital, Hospital District of Southwest Finland), Olli G. Simell, MD, PhD (University of Turku), Annika Adamsson, PhD (Turku University Hospital, Hospital District of Southwest Finland), Suvi Ahonen (University of Tampere, Tampere University Hospital, and National Institute for Health and Welfare, Finland), Mari Åkerlund (University of Tampere, Tampere University Hospital, and National Institute for Health and Welfare, Finland), Anne Hekkala, MD (University of Oulu, Oulu University Hospital), Henna Holappa (University of Oulu, Oulu University Hospital), Heikki Hyöty, MD, PhD (University of Tampere, Tampere University Hospital), Anni Ikonen (University of Oulu, Oulu University Hospital), Jorma Ilonen, MD, PhD (University of Turku and University of Kuopio), Sinikka Jäminki (University of Tampere, Tampere University Hospital), Sanna Jokipuu (Turku University Hospital, Hospital District of Southwest Finland), Leena Karlsson (Turku University Hospital, Hospital District of Southwest Finland), Miia Kähönen (University of Oulu, Oulu University Hospital), Mikael Knip, MD, PhD (University of Tampere, Tampere University Hospital), Minna-Liisa Koivikko (University of Oulu, Oulu University Hospital), Mirva Koreasalo (University of Tampere, Tampere University Hospital, and National Institute for Health and Welfare, Finland), Kalle Kurppa, MD, PhD (University of Tampere, Tampere University Hospital), Jarita Kytölä (University of Tampere, Tampere University Hospital), Tiina Latva-aho (University of Oulu, Oulu University Hospital), Katri Lindfors, PhD (University of Tampere), Maria Lönnrot, MD, PhD (University of Tampere, Tampere University Hospital), Elina Mäntymäki (Turku University Hospital, Hospital District of Southwest Finland), Markus Mattila (University of Tampere), Katja Multasuo (University of Oulu, Oulu University Hospital), Teija Mykkänen (University of Oulu, Oulu University Hospital), Tiina Niininen (Tampere University Hospital, University of Tampere), Sari Niinistö (Tampere University Hospital and National Institute for Health and Welfare, Finland), Mia Nyblom (University of Tampere, Tampere University Hospital), Sami Oikarinen, PhD (University of Tampere, Tampere University Hospital), Paula Ollikainen (University of Oulu, Oulu University Hospital), Sirpa Pohjola (University of Oulu, Oulu University Hospital), Petra Rajala (Turku University Hospital, Hospital District of Southwest Finland), Jenna Rautanen (Tampere University Hospital and National Institute for Health and Welfare, Finland), Anne Riikonen (University of Tampere, Tampere University Hospital, and National Institute for Health and Welfare, Finland), Minna Romo (Turku University Hospital, Hospital District of Southwest Finland), Suvi Ruohonen (Turku University Hospital, Hospital District of Southwest Finland), Satu Simell, MD, PhD (University of Turku), Maija Sjöberg (University of Turku, Turku University Hospital, Hospital District of Southwest Finland), Aino Stenius (University of Oulu, Oulu University Hospital), Päivi Tossavainen, MD (University of Oulu, Oulu University Hospital), Mari Vähä-Mäkilä (Turku University Hospital, Hospital District of Southwest Finland), Sini Vainionpää (Turku University Hospital, Hospital District of Southwest Finland), Eeva Varjonen (University of Turku, Turku University Hospital, Hospital District of Southwest Finland), Riitta Veijola, MD, PhD (University of Oulu, Oulu University Hospital), Irene Viinikangas (University of Oulu, Oulu University Hospital), and Suvi M. Virtanen, MD, PhD (University of Tampere, Tampere University Hospital, National Institute for Health and Welfare, Finland); Germany: Anette G. Ziegler, MD, primary investigator (all investigators affiliated with Forschergruppe Diabetes eV, Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes eV, Neuherberg, unless otherwise noted), Ezio Bonifacio, PhD (Center for Regenerative Therapies, TU Dresden), Miryam D'Angelo, Anita Gavrisan, Cigdem Gezginci, Anja Heublein, Verena Hoffmann, PhD, Sandra Hummel, PhD, Andrea Keimer (University of Bonn, Department of Nutritional Epidemiology), Annette Knopff, Charlotte Koch, Sibylle Koletzko, MD (Dr von Hauner Children’s Hospital, Department of Gastroenterology, Ludwig Maximillians University Munich), Claudia Ramminger, Roswith Roth, PhD, Marlon Scholz, Joanna Stock, Katharina Warncke, MD, Lorena Wendel, and Christiane Winkler, PhD; Sweden: Åke Lernmark, PhD, primary investigator (all investigators affiliated with Lund University), Daniel Agardh, MD, PhD, Carin Andrén Aronsson, PhD, Maria Ask, Jenny Bremer, Corrado Cilio, PhD, MD, Emelie Ericson-Hallström, Annika Fors, Lina Fransson, Thomas Gard, Rasmus Bennet, Monika Hansen, Hanna Jisser, Fredrik Johansen, Berglind Jonsdottir, MD, PhD, Silvija Jovic, Helena Elding Larsson, MD, PhD, Marielle Lindström, Markus Lundgren, MD, PhD, Maria Månsson-Martinez, Maria Markan, Jessica Melin, Zeliha Mestan, Caroline Nilsson, Karin Ottosson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Anette Sjöberg, Birgitta Sjöberg, Carina Törn, PhD, Anne Wallin, Åsa Wimar, and Sofie Åberg; United States: Colorado: Marian Rewers, MD, PhD, primary investigator (all investigators affiliated with the University of Colorado, Anschutz Medical Campus, Barbara Davis Center for Childhood Diabetes), Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Kimberly Driscoll, PhD, Brigitte I. Frohnert, MD, Marisa Gallant, MD, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, MD, Jill Norris, PhD, Andrea Steck, MD, and Kathleen Waugh; Georgia and Florida: Jin-Xiong She, PhD, primary investigator (Center for Biotechnology and Genomic Medicine, Augusta University), Desmond Schatz, MD (University of Florida), Diane Hopkins (Center for Biotechnology and Genomic Medicine, Augusta University), Leigh Steed (Center for Biotechnology and Genomic Medicine, Augusta University), Jennifer Bryant (Center for Biotechnology and Genomic Medicine, Augusta University), Katherine Silvis (Center for Biotechnology and Genomic Medicine, Augusta University), Michael Haller, MD (University of Florida), Melissa Gardiner (Center for Biotechnology and Genomic Medicine, Augusta University), Richard McIndoe, PhD (Center for Biotechnology and Genomic Medicine, Augusta University), Ashok Sharma (Center for Biotechnology and Genomic Medicine, Augusta University), Stephen W. Anderson, MD (Pediatric Endocrine Associates, Atlanta), Laura Jacobsen, MD (University of Florida), John Marks, DHSc (University of Florida), and P. D. Towe (University of Florida); Pennsylvania Satellite Center: Dorothy Becker, MD (all investigators affiliated with Children’s Hospital of Pittsburgh of UPMC), Margaret Franciscus, MaryEllen Dalmagro-Elias Smith, Ashi Daftary, MD, Mary Beth Klein, and Chrystal Yates; Washington: William A. Hagopian, MD, PhD, primary investigator (all investigators affiliated with Pacific Northwest Research Institute), Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Ashley Akramoff, Masumeh Chavoshi, Kayleen Dunson, Rachel Hervey, Rachel Lyons, Arlene Meyer, Denise Mulenga, Jared Radtke, Matei Romancik, Davey Schmitt, Julie Schwabe, and Sarah Zink; Data Coordinating Center: Jeffrey P. Krischer, PhD, primary investigator (all investigators affiliated with the University of South Florida unless otherwise noted), Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Rasheedah Brown, Brant Burkhardt, PhD, Martha Butterworth, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske, Jennifer Garmeson, Veena Gowda, Kathleen Heyman, Belinda Hsiao, Christina Karges, Francisco Perez Laras, Hye-Seung Lee, PhD, Qian Li, Shu Liu, Xiang Liu, PhD, Kristian Lynch, PhD, Colleen Maguire, Jamie Malloy, Cristina McCarthy, Aubrie Merrell, Steven Meulemans, Hemang Parikh, PhD, Ryan Quigley, Cassandra Remedios, Chris Shaffer, Laura Smith, PhD, Susan Smith, Noah Sulman, PhD, Roy Tamura, PhD, Dena Tewey, Michael Toth, Ulla Uusitalo, PhD, Kendra Vehik, PhD, Ponni Vijayakandipan, Keith Wood, and Jimin Yang, PhD, RD (former staff members: Michael Abbondondolo, Lori Ballard, David Hadley, PhD, and Wendy McLeod); Autoantibody Reference Laboratories: Liping Yu, MD (Barbara Davis Center for Childhood Diabetes, University of Colorado Denver), Dongmei Miao, MD (Barbara Davis Center for Childhood Diabetes, University of Colorado Denver), Polly Bingley, MD, FRCP (Bristol Medical School, University of Bristol UK), Alistair Williams (Bristol Medical School, University of Bristol UK), Kyla Chandler (Bristol Medical School, University of Bristol UK), Olivia Ball (Bristol Medical School, University of Bristol UK), Ilana Kelland (Bristol Medical School, University of Bristol UK), Sian Grace (Bristol Medical School, University of Bristol UK), and Ben Gillard (Bristol Medical School, University of Bristol UK); HLA Reference Laboratory: William Hagopian, MD, PhD (all investigators affiliated with Pacific Northwest Research Institute unless otherwise noted), Masumeh Chavoshi, Jared Radtke, and Julie Schwabe (former staff members: Henry Erlich, PhD, Steven J. Mack, PhD, and Anna Lisa Fear); Repository: Sandra Ke and Niveen Mulholland, PhD (both with the National Institutes of Diabetes and Digestive and Kidney Diseases biosample repository at Fisher BioServices); Project Scientist: Beena Akolkar, PhD (National Institutes of Diabetes and Digestive and Kidney Diseases); and Other Contributors: Kasia Bourcier, PhD (National Institutes of Allergy and Infectious Diseases), Thomas Briese, PhD (Columbia University), Suzanne Bennett Johnson, PhD (Florida State University), and Eric Triplett, PhD (University of Florida).

References
1.
Biesiekierski  JR.  What is gluten?  J Gastroenterol Hepatol. 2017;32(suppl 1):78-81. doi:10.1111/jgh.13703PubMedGoogle ScholarCrossref
2.
Lebwohl  B, Sanders  DS, Green  PHR.  Coeliac disease.  Lancet. 2018;391(10115):70-81. doi:10.1016/S0140-6736(17)31796-8PubMedGoogle ScholarCrossref
3.
Tjon  JM, van Bergen  J, Koning  F.  Celiac disease: how complicated can it get?  Immunogenetics. 2010;62(10):641-651. doi:10.1007/s00251-010-0465-9PubMedGoogle ScholarCrossref
4.
Bouziat  R, Hinterleitner  R, Brown  JJ,  et al.  Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease.  Science. 2017;356(6333):44-50. doi:10.1126/science.aah5298PubMedGoogle ScholarCrossref
5.
Kemppainen  KM, Lynch  KF, Liu  E,  et al; TEDDY Study Group.  Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life.  Clin Gastroenterol Hepatol. 2017;15(5):694-702.e5, e5. doi:10.1016/j.cgh.2016.10.033PubMedGoogle ScholarCrossref
6.
Hagopian  W, Lee  HS, Liu  E,  et al; TEDDY Study Group.  Co-occurrence of type 1 diabetes and celiac disease autoimmunity.  Pediatrics. 2017;140(5):e20171305. doi:10.1542/peds.2017-1305PubMedGoogle ScholarCrossref
7.
Agardh  D, Lee  HS, Kurppa  K,  et al; TEDDY Study Group.  Clinical features of celiac disease: a prospective birth cohort.  Pediatrics. 2015;135(4):627-634. doi:10.1542/peds.2014-3675PubMedGoogle ScholarCrossref
8.
Norris  JM, Barriga  K, Hoffenberg  EJ,  et al.  Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease.  JAMA. 2005;293(19):2343-2351. doi:10.1001/jama.293.19.2343PubMedGoogle ScholarCrossref
9.
Størdal  K, White  RA, Eggesbø  M.  Early feeding and risk of celiac disease in a prospective birth cohort.  Pediatrics. 2013;132(5):e1202-e1209. doi:10.1542/peds.2013-1752PubMedGoogle ScholarCrossref
10.
Lionetti  E, Castellaneta  S, Francavilla  R,  et al; SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk.  Introduction of gluten, HLA status, and the risk of celiac disease in children.  N Engl J Med. 2014;371(14):1295-1303. doi:10.1056/NEJMoa1400697PubMedGoogle ScholarCrossref
11.
Vriezinga  SL, Auricchio  R, Bravi  E,  et al.  Randomized feeding intervention in infants at high risk for celiac disease.  N Engl J Med. 2014;371(14):1304-1315. doi:10.1056/NEJMoa1404172PubMedGoogle ScholarCrossref
12.
Szajewska  H, Shamir  R, Mearin  L,  et al.  Gluten introduction and the risk of coeliac disease: a position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.  J Pediatr Gastroenterol Nutr. 2016;62(3):507-513. doi:10.1097/MPG.0000000000001105PubMedGoogle ScholarCrossref
13.
Ivarsson  A, Hernell  O, Stenlund  H, Persson  LA.  Breast-feeding protects against celiac disease.  Am J Clin Nutr. 2002;75(5):914-921. doi:10.1093/ajcn/75.5.914PubMedGoogle ScholarCrossref
14.
Crespo-Escobar  P, Mearin  ML, Hervás  D,  et al.  The role of gluten consumption at an early age in celiac disease development: a further analysis of the prospective PreventCD cohort study.  Am J Clin Nutr. 2017;105(4):890-896. doi:10.3945/ajcn.116.144352PubMedGoogle ScholarCrossref
15.
Andrén Aronsson  C, Lee  HS, Koletzko  S,  et al; TEDDY Study Group.  Effects of gluten intake on risk of celiac disease: a case-control study on a Swedish birth cohort.  Clin Gastroenterol Hepatol. 2016;14(3):403-409.e3, e3. doi:10.1016/j.cgh.2015.09.030PubMedGoogle ScholarCrossref
16.
TEDDY Study Group.  The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design.  Pediatr Diabetes. 2007;8(5):286-298. doi:10.1111/j.1399-5448.2007.00269.xPubMedGoogle ScholarCrossref
17.
Hagopian  WA, Erlich  H, Lernmark  A,  et al; TEDDY Study Group.  The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.  Pediatr Diabetes. 2011;12(8):733-743. doi:10.1111/j.1399-5448.2011.00774.xPubMedGoogle ScholarCrossref
18.
TEDDY Study Group.  The Environmental Determinants of Diabetes in the Young (TEDDY) study.  Ann N Y Acad Sci. 2008;1150:1-13. doi:10.1196/annals.1447.062PubMedGoogle ScholarCrossref
19.
Vehik  K, Fiske  SW, Logan  CA,  et al; TEDDY Study Group.  Methods, quality control and specimen management in an international multicentre investigation of type 1 diabetes: TEDDY.  Diabetes Metab Res Rev. 2013;29(7):557-567.PubMedGoogle Scholar
20.
Rewers  M, Hyöty  H, Lernmark  Å,  et al; TEDDY Study Group.  The Environmental Determinants of Diabetes in the Young (TEDDY) study: 2018 update.  Curr Diab Rep. 2018;18(12):136. doi:10.1007/s11892-018-1113-2PubMedGoogle ScholarCrossref
21.
Yang  J, Lynch  KF, Uusitalo  UM,  et al; TEDDY Study Group.  Factors associated with longitudinal food record compliance in a paediatric cohort study.  Public Health Nutr. 2016;19(5):804-813. doi:10.1017/S1368980015001883PubMedGoogle ScholarCrossref
22.
Joslowski  G, Yang  J, Aronsson  CA,  et al; TEDDY Study Group.  Development of a harmonized food grouping system for between-country comparisons in the TEDDY study.  J Food Compost Anal. 2017;63:79-88. doi:10.1016/j.jfca.2017.07.037PubMedGoogle ScholarCrossref
23.
van Overbeek  FM, Uil-Dieterman  IG, Mol  IW, Köhler-Brands  L, Heymans  HS, Mulder  CJ.  The daily gluten intake in relatives of patients with coeliac disease compared with that of the general Dutch population.  Eur J Gastroenterol Hepatol. 1997;9(11):1097-1099. doi:10.1097/00042737-199711000-00013PubMedGoogle ScholarCrossref
24.
Bao  F, Yu  L, Babu  S,  et al.  One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies.  J Autoimmun. 1999;13(1):143-148. doi:10.1006/jaut.1999.0303PubMedGoogle ScholarCrossref
25.
Bingley  PJ, Williams  AJ, Norcross  AJ,  et al; Avon Longitudinal Study of Parents and Children Study Team.  Undiagnosed coeliac disease at age seven: population based prospective birth cohort study.  BMJ. 2004;328(7435):322-323. doi:10.1136/bmj.328.7435.322PubMedGoogle ScholarCrossref
26.
Liu  E, Lee  HS, Aronsson  CA,  et al; TEDDY Study Group.  Risk of pediatric celiac disease according to HLA haplotype and country.  N Engl J Med. 2014;371(1):42-49. doi:10.1056/NEJMoa1313977PubMedGoogle ScholarCrossref
27.
Willett  WC, Howe  GR, Kushi  LH.  Adjustment for total energy intake in epidemiologic studies.  Am J Clin Nutr. 1997;65(4)(suppl):1220S-1228S. doi:10.1093/ajcn/65.4.1220SPubMedGoogle ScholarCrossref
28.
Asar  Ö, Ritchie  J, Kalra  PA, Diggle  PJ.  Joint modelling of repeated measurement and time-to-event data: an introductory tutorial.  Int J Epidemiol. 2015;44(1):334-344. doi:10.1093/ije/dyu262PubMedGoogle ScholarCrossref
29.
Tsiatis  A, Davidian  M.  Joint modeling of longitudinal and time-to-event data: an overview.  Stat Sin. 2004;14(3):809-834.Google Scholar
30.
Zhang  D, Chen  MH, Ibrahim  JG, Boye  ME, Wang  P, Shen  W.  Assessing model fit in joint models of longitudinal and survival data with applications to cancer clinical trials.  Stat Med. 2014;33(27):4715-4733. doi:10.1002/sim.6269PubMedGoogle ScholarCrossref
31.
Zhang  D, Chen  MH, Ibrahim  JG, Boye  ME, Shen  W.  JMFit: a SAS macro for joint models of longitudinal and survival data.  J Stat Softw. 2016;71(3). doi:10.18637/jss.v071.i03PubMedGoogle Scholar
32.
Contal  C, O’Quigley  J.  An application of changepoint methods in studying the effect of age on survival in breast cancer.  Comput Stat Data Anal. 1999;30:253-270. doi:10.1016/S0167-9473(98)00096-6Google ScholarCrossref
33.
Lernmark  B, Johnson  SB, Vehik  K,  et al.  Enrollment experiences in a pediatric longitudinal observational study: The Environmental Determinants of Diabetes in the Young (TEDDY) study.  Contemp Clin Trials. 2011;32(4):517-523. doi:10.1016/j.cct.2011.03.009PubMedGoogle ScholarCrossref
34.
Aronsson  CA, Lee  HS, Liu  E,  et al; TEDDY Study Group.  Age at gluten introduction and risk of celiac disease.  Pediatrics. 2015;135(2):239-245. doi:10.1542/peds.2014-1787PubMedGoogle ScholarCrossref
35.
Hopman  EG, Pruijn  R, Tabben  EH, le Cessie  S, Mearin  ML.  Food questionnaire for the assessment of gluten intake by children 1 to 4 years old.  J Pediatr Gastroenterol Nutr. 2012;54(6):791-796. doi:10.1097/MPG.0b013e31825144fePubMedGoogle ScholarCrossref
36.
Hoppe  C, Trolle  E, Gondolf  UH, Husby  S.  Gluten intake in 6-36-month-old Danish infants and children based on a national survey.  J Nutr Sci. 2013;2:e7. doi:10.1017/jns.2013.1PubMedGoogle ScholarCrossref
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