Age at gluten introduction and risk of celiac disease

doi:10.1542/peds.2014-1787

Comparative Study

. 2015 Feb;135(2):239-45.

doi: 10.1542/peds.2014-1787. Epub 2015 Jan 19.

Age at gluten introduction and risk of celiac disease

Carin Andrén Aronsson¹, Hye-Seung Lee², Edwin Liu³, Ulla Uusitalo², Sandra Hummel⁴, Jimin Yang², Michael Hummel⁴, Marian Rewers⁵, Jin-Xiong She⁶, Olli Simell⁷, Jorma Toppari⁸, Anette-G Ziegler⁴, Jeffrey Krischer², Suvi M Virtanen⁹, Jill M Norris¹⁰, Daniel Agardh¹¹; TEDDY STUDY GROUP

Collaborators, Affiliations

Collaborators

TEDDY STUDY GROUP:
Marian Rewers, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Kathleen Waugh, Adela Samper, Andrea Steck, Barbara Davis, Jin-Xiong She, Desmond Schatz, Diane Hopkins, Leigh Steed, Jamie Thomas, Katherine Silvis, Michael Haller, Meena Shankar, Eleni Sheehan, Melissa Gardiner, Richard McIndoe, Haitao Liu, John Nechtman, Ashok Sharma, Joshua Williams, Gabriela Foghis, Stephen W Anderson, Anette G Ziegler, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Olli G Simell, Jorma Toppari, Heikki Hyöty, Jorma Ilonen, Miia Kähönen, Mikael Knip, Annika Koivu, Mirva Koreasalo, Kalle Kurppa, Maria Lönnrot, Elina Mäntymäki, Katja Multasuo, Juha Mykkänen, Tiina Niininen, Mia Nyblom, Jenna Rautanen, Anne Riikonen, Minna Romo, Aaro Simell, Barbara Simell, Satu Simell, Tuula Simell, Ville Simell, Maija Sjöberg, Aino Stenius, Eeva Varjonen, Riitta Veijola, Suvi M Virtanen, Mari Åkerlund, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, Maria Ask, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Camilla Ekstrand, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Rasmus Håkansson, Monica Hansen, Gertie Hansson, Susanne Hyberg, Fredrik Johansen, Berglind Jonasdottir, Linda Jonsson, Helena Larsson, Barbro Lernmark, Maria Månsson-Martinez, Maria Markan, Theodosia Massadakis, Jessica Melin, Zeliha Mestan, Kobra Rahmati, Anita Ramelius, Monica Sedig Järvirova, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Erika Trulsson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A Hagopian, Xiang Yan, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Stephen Ayres, Kayleen Dunson, Diana Heaney, Rachel Hervey, Renee Kindschi, Arlene Meyer, Denise Mulenga, Elizabeth Scott, Joshua Stabbert, Nancy Williams, John Willis, Dorothy Becker, Margaret Franciscus, Mary Ellen Smith, Ashi Daftary, Mary Beth Klein, Jeffrey P Krischer, Michael Abbondondolo, Sarah Austin-Gonzalez, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Veena Gowda, David Hadley, Hye-Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Ulla Uusitalo, Kendra Vehik, Earnest Washington, Jimin Yang, Beena Akolkar, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Steve Oberste, Eric Triplett, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Saba Rokni, Joanna Boldison, Jacob Butterly, Jessica Broadhurst, Gabriella Carreno, Claire Caygill, Rachel Curnock, Peter Easton, Ivey Geoghan, Julia Goode, Anna Long, Molly Payne, James Pearson, Charles Reed, Sophie Ridewood, Rebecca Wyatt, Elisabeth Aardal Eriksson, Ewa Lönn Karlsson, Iris Erlund, Irma Salminen, Jouko Sundvall, Jaana Leiviskä, Mari Lehtonen, Randie R Little, Alethea L Tennill, Henry Erlich, Steven J Mack, Anna Lisa Fear, Oliver Fiehn, Bill Wikoff, Tobias Kind, Mine Palazoglu, Joyce Wong, Joseph F Petrosino, Santica M Marcovina, Vinod P Gaur, Heather Higgins, Sandra Ke, Jin-Xiong She, Richard McIndoe, Haitao Liu, John Nechtman, Yansheng Zhao, Na Jiang, Stephen S Rich, Wei-Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jordan Davis, Dan Gallo

Affiliations

¹ Department of Clinical Sciences, Lund University, Malmö, Sweden; carin.andren_aronsson@med.lu.se.
² Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
³ Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Denver, Colorado;
⁴ Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany;
⁵ Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado;
⁶ Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
⁷ Department of Pediatrics, Turku University Hospital, Turku, Finland;
⁸ Department of Physiology and Pediatrics, University of Turku, Turku, Finland;
⁹ National Institutes for Health and Welfare, Nutrition Unit, Helsinki, Finland; School of Health Sciences, University of Tampere, Tampere, Finland; Research Center for Child Health, Tampere University and University Hospital and the Science Center of Pirkanmaa Hospital District, Tampere, Finland; and.
¹⁰ Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Aurora, Colorado.
¹¹ Department of Clinical Sciences, Lund University, Malmö, Sweden;

PMID: 25601977
PMCID: PMC4306795
DOI: 10.1542/peds.2014-1787

Comparative Study

Age at gluten introduction and risk of celiac disease

Carin Andrén Aronsson et al. Pediatrics. 2015 Feb.

. 2015 Feb;135(2):239-45.

doi: 10.1542/peds.2014-1787. Epub 2015 Jan 19.

Authors

Collaborators

TEDDY STUDY GROUP:
Marian Rewers, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Kathleen Waugh, Adela Samper, Andrea Steck, Barbara Davis, Jin-Xiong She, Desmond Schatz, Diane Hopkins, Leigh Steed, Jamie Thomas, Katherine Silvis, Michael Haller, Meena Shankar, Eleni Sheehan, Melissa Gardiner, Richard McIndoe, Haitao Liu, John Nechtman, Ashok Sharma, Joshua Williams, Gabriela Foghis, Stephen W Anderson, Anette G Ziegler, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Olli G Simell, Jorma Toppari, Heikki Hyöty, Jorma Ilonen, Miia Kähönen, Mikael Knip, Annika Koivu, Mirva Koreasalo, Kalle Kurppa, Maria Lönnrot, Elina Mäntymäki, Katja Multasuo, Juha Mykkänen, Tiina Niininen, Mia Nyblom, Jenna Rautanen, Anne Riikonen, Minna Romo, Aaro Simell, Barbara Simell, Satu Simell, Tuula Simell, Ville Simell, Maija Sjöberg, Aino Stenius, Eeva Varjonen, Riitta Veijola, Suvi M Virtanen, Mari Åkerlund, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, Maria Ask, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Camilla Ekstrand, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Rasmus Håkansson, Monica Hansen, Gertie Hansson, Susanne Hyberg, Fredrik Johansen, Berglind Jonasdottir, Linda Jonsson, Helena Larsson, Barbro Lernmark, Maria Månsson-Martinez, Maria Markan, Theodosia Massadakis, Jessica Melin, Zeliha Mestan, Kobra Rahmati, Anita Ramelius, Monica Sedig Järvirova, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Erika Trulsson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A Hagopian, Xiang Yan, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Stephen Ayres, Kayleen Dunson, Diana Heaney, Rachel Hervey, Renee Kindschi, Arlene Meyer, Denise Mulenga, Elizabeth Scott, Joshua Stabbert, Nancy Williams, John Willis, Dorothy Becker, Margaret Franciscus, Mary Ellen Smith, Ashi Daftary, Mary Beth Klein, Jeffrey P Krischer, Michael Abbondondolo, Sarah Austin-Gonzalez, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Veena Gowda, David Hadley, Hye-Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Ulla Uusitalo, Kendra Vehik, Earnest Washington, Jimin Yang, Beena Akolkar, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Steve Oberste, Eric Triplett, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Saba Rokni, Joanna Boldison, Jacob Butterly, Jessica Broadhurst, Gabriella Carreno, Claire Caygill, Rachel Curnock, Peter Easton, Ivey Geoghan, Julia Goode, Anna Long, Molly Payne, James Pearson, Charles Reed, Sophie Ridewood, Rebecca Wyatt, Elisabeth Aardal Eriksson, Ewa Lönn Karlsson, Iris Erlund, Irma Salminen, Jouko Sundvall, Jaana Leiviskä, Mari Lehtonen, Randie R Little, Alethea L Tennill, Henry Erlich, Steven J Mack, Anna Lisa Fear, Oliver Fiehn, Bill Wikoff, Tobias Kind, Mine Palazoglu, Joyce Wong, Joseph F Petrosino, Santica M Marcovina, Vinod P Gaur, Heather Higgins, Sandra Ke, Jin-Xiong She, Richard McIndoe, Haitao Liu, John Nechtman, Yansheng Zhao, Na Jiang, Stephen S Rich, Wei-Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jordan Davis, Dan Gallo

Affiliations

¹ Department of Clinical Sciences, Lund University, Malmö, Sweden; carin.andren_aronsson@med.lu.se.
² Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
³ Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Denver, Colorado;
⁴ Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany;
⁵ Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado;
⁶ Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
⁷ Department of Pediatrics, Turku University Hospital, Turku, Finland;
⁸ Department of Physiology and Pediatrics, University of Turku, Turku, Finland;
⁹ National Institutes for Health and Welfare, Nutrition Unit, Helsinki, Finland; School of Health Sciences, University of Tampere, Tampere, Finland; Research Center for Child Health, Tampere University and University Hospital and the Science Center of Pirkanmaa Hospital District, Tampere, Finland; and.
¹⁰ Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Aurora, Colorado.
¹¹ Department of Clinical Sciences, Lund University, Malmö, Sweden;

PMID: 25601977
PMCID: PMC4306795
DOI: 10.1542/peds.2014-1787

Abstract

Objectives: The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.

Methods: TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA.

Results: Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison.

Conclusions: In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.

Keywords: breastfeeding; celiac disease; gluten; infant feeding.

PubMed Disclaimer

Figures

**FIGURE 1**
Flowchart describing the TEDDY study population

See this image and copyright information in PMC

Cited by

Looking back at the TEDDY study: lessons and future directions.
Lernmark Å, Agardh D, Akolkar B, Gesualdo P, Hagopian WA, Haller MJ, Hyöty H, Johnson SB, Larsson HE, Liu E, Lynch KF, McKinney EF, McIndoe R, Melin J, Norris JM, Rewers M, Rich SS, Toppari J, Triplett E, Vehik K, Virtanen SM, Ziegler AG, Schatz DA, Krischer J. Lernmark Å, et al. Nat Rev Endocrinol. 2024 Nov 4. doi: 10.1038/s41574-024-01045-0. Online ahead of print. Nat Rev Endocrinol. 2024. PMID: 39496810 Review.
Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.
Eurén A, Lynch K, Lindfors K, Parikh H, Koletzko S, Liu E, Akolkar B, Hagopian W, Krischer J, Rewers M, Toppari J, Ziegler A, Agardh D, Kurppa K; TEDDY Study Group. Eurén A, et al. Sci Rep. 2024 Oct 26;14(1):25463. doi: 10.1038/s41598-024-75496-w. Sci Rep. 2024. PMID: 39462122 Free PMC article.
Why are western diet and western lifestyle pro-inflammatory risk factors of celiac disease?
Skoracka K, Hryhorowicz S, Rychter AM, Ratajczak AE, Szymczak-Tomczak A, Zawada A, Słomski R, Dobrowolska A, Krela-Kaźmierczak I. Skoracka K, et al. Front Nutr. 2023 Jan 20;9:1054089. doi: 10.3389/fnut.2022.1054089. eCollection 2022. Front Nutr. 2023. PMID: 36742009 Free PMC article. Review.
A Comprehensive Review of the Neurological Manifestations of Celiac Disease and Its Treatment.
Gala D, Scharf S, Kudlak M, Green C, Khowaja F, Shah M, Kumar V, Ullal G. Gala D, et al. Diseases. 2022 Nov 21;10(4):111. doi: 10.3390/diseases10040111. Diseases. 2022. PMID: 36412605 Free PMC article. Review.
Celiac Disease Revisited.
Calado J, Verdelho Machado M. Calado J, et al. GE Port J Gastroenterol. 2021 Mar 17;29(2):111-124. doi: 10.1159/000514716. eCollection 2022 Mar. GE Port J Gastroenterol. 2021. PMID: 35497669 Free PMC article. Review.

See all "Cited by" articles

References

1. Ludvigsson JF, Leffler DA, Bai JC, et al. . The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43–52 - PMC - PubMed
1. Rewers M. Epidemiology of celiac disease: what are the prevalence, incidence, and progression of celiac disease? Gastroenterology. 2005;128(4 suppl 1):S47–S51 - PubMed
1. Hoffenberg EJ, MacKenzie T, Barriga KJ, et al. . A prospective study of the incidence of childhood celiac disease. J Pediatr. 2003;143(3):308–314 - PubMed
1. Steens RF, Csizmadia CG, George EK, Ninaber MK, Hira Sing RA, Mearin ML. A national prospective study on childhood celiac disease in the Netherlands 1993-2000: an increasing recognition and a changing clinical picture. J Pediatr. 2005;147(2):239–243 - PubMed
1. Ivarsson A. The Swedish epidemic of coeliac disease explored using an epidemiological approach—some lessons to be learnt. Best Pract Res Clin Gastroenterol. 2005;19(3):425–440 - PubMed

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Ludvigsson JF, Leffler DA, Bai JC, et al. . The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43–52 - PMC - PubMed

[2] Ludvigsson JF, Leffler DA, Bai JC, et al. . The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43–52 - PMC - PubMed

[3] Rewers M. Epidemiology of celiac disease: what are the prevalence, incidence, and progression of celiac disease? Gastroenterology. 2005;128(4 suppl 1):S47–S51 - PubMed

[4] Rewers M. Epidemiology of celiac disease: what are the prevalence, incidence, and progression of celiac disease? Gastroenterology. 2005;128(4 suppl 1):S47–S51 - PubMed

[5] Hoffenberg EJ, MacKenzie T, Barriga KJ, et al. . A prospective study of the incidence of childhood celiac disease. J Pediatr. 2003;143(3):308–314 - PubMed

[6] Hoffenberg EJ, MacKenzie T, Barriga KJ, et al. . A prospective study of the incidence of childhood celiac disease. J Pediatr. 2003;143(3):308–314 - PubMed

[7] Steens RF, Csizmadia CG, George EK, Ninaber MK, Hira Sing RA, Mearin ML. A national prospective study on childhood celiac disease in the Netherlands 1993-2000: an increasing recognition and a changing clinical picture. J Pediatr. 2005;147(2):239–243 - PubMed

[8] Steens RF, Csizmadia CG, George EK, Ninaber MK, Hira Sing RA, Mearin ML. A national prospective study on childhood celiac disease in the Netherlands 1993-2000: an increasing recognition and a changing clinical picture. J Pediatr. 2005;147(2):239–243 - PubMed

[9] Ivarsson A. The Swedish epidemic of coeliac disease explored using an epidemiological approach—some lessons to be learnt. Best Pract Res Clin Gastroenterol. 2005;19(3):425–440 - PubMed

[10] Ivarsson A. The Swedish epidemic of coeliac disease explored using an epidemiological approach—some lessons to be learnt. Best Pract Res Clin Gastroenterol. 2005;19(3):425–440 - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Age at gluten introduction and risk of celiac disease

Collaborators

Affiliations

Age at gluten introduction and risk of celiac disease

Authors

Collaborators

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials