Incidence of Pediatric Celiac Disease Varies by Region: Celiac Disease Varies by Region

The Environmental Determinants of Diabetes in the Young (TEDDY) 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 celiac disease autoimmunity (CDA) and CD cumulative incidence for children born between 2004 and 2010.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 (tTGA) 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.Individual haplogenotype risks for CDA 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 US, the incidence by age 10 in Colorado was 2.4%. In the HLA, sex, and family history-adjusted model, 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 to Finland and Germany, respectively.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.