Incidence of Pediatric Celiac Disease Varies by Region

Marisa Stahl¹, Qian Li², Kristian Lynch³, Sibylle Koletzko^{4

5}, Pooja Mehta¹, Loren Gragert⁶, Jill M Norris⁷, Carin Andrén Aronsson⁸, Katri Lindfors⁹, Kalle Kurppa^{9

10}, Jorma Ilonen¹¹, Jeffrey Krischer³, Beena Alkolkar^{12

13}, Anette-G Ziegler¹⁴, Jorma Toppari¹⁵, Marian J Rewers¹⁶, Daniel Agardh¹⁷, William Hagopian¹⁸, Edwin Liu¹; TEDDY Study Group

Affiliations

¹ Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
² Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
³ Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
⁴ Department of Pediatrics, Dr von Hauner Kinderspital, LMU Klinikum, Munich, Germany.
⁵ Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.
⁶ Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁷ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁸ Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
⁹ Celiac Disease Research Center, Tampere University and Tampere University Hospital, Tampere, Finland.
¹⁰ Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
¹¹ Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
¹² Department of Pediatrics, Turku University Hospital, Turku, Finland.
¹³ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States.
¹⁴ Forschergruppe Diabetes e.V. and Institute of Diabetes Research, Helmholtz Zentrum, Munich, Germany.
¹⁵ Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, Univeristy of Turku, Turku, Finland.
¹⁶ Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹⁷ Diabetes and Celiac Disease, Lund University, Malmö, Sweden.
¹⁸ Department of Diabetes, Pacific Northwest Research Institute, Seattle, Washington, USA.

PMID: 36219178
PMCID: PMC9991947
DOI: 10.14309/ajg.0000000000002056

Incidence of Pediatric Celiac Disease Varies by Region

Marisa Stahl et al. Am J Gastroenterol. 2023.

. 2023 Mar 1;118(3):539-545.

doi: 10.14309/ajg.0000000000002056. Epub 2022 Oct 11.

Authors

Affiliations

¹ Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
² Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
³ Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
⁴ Department of Pediatrics, Dr von Hauner Kinderspital, LMU Klinikum, Munich, Germany.
⁵ Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.
⁶ Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁷ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁸ Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
⁹ Celiac Disease Research Center, Tampere University and Tampere University Hospital, Tampere, Finland.
¹⁰ Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
¹¹ Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
¹² Department of Pediatrics, Turku University Hospital, Turku, Finland.
¹³ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States.
¹⁴ Forschergruppe Diabetes e.V. and Institute of Diabetes Research, Helmholtz Zentrum, Munich, Germany.
¹⁵ Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, Univeristy of Turku, Turku, Finland.
¹⁶ Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹⁷ Diabetes and Celiac Disease, Lund University, Malmö, Sweden.
¹⁸ Department of Diabetes, Pacific Northwest Research Institute, Seattle, Washington, USA.

PMID: 36219178
PMCID: PMC9991947
DOI: 10.14309/ajg.0000000000002056

Abstract

Introduction: The Environmental Determinants of Diabetes in the Young study follows an HLA risk selected birth cohort for celiac disease (CD) development using a uniform protocol. Children under investigation come from 6 different regions within Europe and the United States. Our aim was to identify regional differences in CD autoimmunity and CD cumulative incidence for children born between 2004 and 2010.

Methods: Children (n = 6,628) with DQ2.5 and/or DQ8.1 were enrolled prospectively from birth in Georgia, Washington, Colorado, Finland, Germany, and Sweden. Children underwent periodic study screening for tissue transglutaminase antibodies and then CD evaluation per clinical care. Population-specific estimates were calculated by weighting the study-specific cumulative incidence with the population-specific haplogenotype frequencies obtained from large stem cell registries from each site.

Results: Individual haplogenotype risks for CD autoimmunity and CD varied by region and affected the cumulative incidence within that region. The CD incidence by age 10 years was highest in Swedish children at 3%. Within the United States, the incidence by age 10 years in Colorado was 2.4%. In the model adjusted for HLA, sex, and family history, Colorado children had a 2.5-fold higher risk of CD compared to Washington. Likewise, Swedish children had a 1.4-fold and 1.8-fold higher risk of CD compared with those in Finland and Germany, respectively.

Discussion: There is high regional variability in cumulative incidence of CD, which suggests differential environmental, genetic, and epigenetic influences even within the United States. The overall high incidence warrants a low threshold for screening and further research on region-specific CD triggers.

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Figures

**Figure 1:. TEDDY Population Cumulative Risk of CDA and CD among DQ2.5/2.5, DQ2.5/8.1, DQ8.1/8.1 by site**
The cumulative risk of CDA and CD stratified by site and HLA-DQ haplogenotype. The y-axis shows the cumulative risk (%) and the x-axis shows the age (months). The figure legend is ordered from highest to lowest cumulative risk. The y-axis scales were adjusted for each panel based on the range of data.

**Figure 2:. Estimated General Population Cumulative Incidence of CDA and CD by Site**
The cumulative incidence of CDA and CD stratified by TEDDY site. Observed incidences were weighted with the HLA-DQ haplogenotype frequencies from regional stem cell donor registries to obtain regional estimates.

See this image and copyright information in PMC

References

1. King JA, et al., Incidence of Celiac Disease Is Increasing Over Time: A Systematic Review and Meta-analysis. Am J Gastroenterol, 2020. 115(4): p. 507–525. - PubMed
1. Agardh D, et al., Clinical features of celiac disease: a prospective birth cohort. Pediatrics, 2015. 135(4): p. 627–34. - PMC - PubMed
1. Stahl MG, et al., Mass Screening for Celiac Disease: The Autoimmunity Screening for Kids Study. Am J Gastroenterol, 2021. 116(1): p. 180–187. - PMC - PubMed
1. Liu E, et al., High Incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes. Gastroenterology, 2017. 152(6): p. 1329–1336 e1. - PMC - PubMed
1. Liu E, et al., Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med, 2014. 371(1): p. 42–9. - PMC - PubMed

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Incidence of Pediatric Celiac Disease Varies by Region

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Incidence of Pediatric Celiac Disease Varies by Region

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