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Original Investigation |

A Nationwide Study of the Association Between Celiac Disease and the Risk of Autistic Spectrum Disorders

Jonas F. Ludvigsson, MD, PhD1,2,3,4; Abraham Reichenberg, PhD5,6; Christina M. Hultman, PhD2; Joseph A. Murray, MD4
[+] Author Affiliations
1Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden
2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
3Department of Pediatrics, Orebro University Hospital, Orebro University, Orebro, Sweden
4Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
5Department of Psychosis Studies, Institute of Psychiatry, King’s College, London, United Kingdom
6Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
JAMA Psychiatry. 2013;70(11):1224-1230. doi:10.1001/jamapsychiatry.2013.2048.
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Importance  Most case reports suggest an association between autistic spectrum disorders (ASDs) and celiac disease (CD) or positive CD serologic test results, but larger studies are contradictory.

Objective  To examine the association between ASDs and CD according to small intestinal histopathologic findings.

Design and Setting  Nationwide case-control study in Sweden.

Main Outcomes and Measures  Through 28 Swedish biopsy registers, we collected data about 26 995 individuals with CD (equal to villous atrophy, Marsh stage 3), 12 304 individuals with inflammation (Marsh stages 1-2), and 3719 individuals with normal mucosa (Marsh stage 0) but positive CD serologic test results (IgA/IgG gliadin, endomysium, or tissue transglutaminase) and compared them with 213 208 age- and sex-matched controls. Conditional logistic regression estimated odds ratios (ORs) for having a prior diagnosis of an ASD according to the Swedish National Patient Register. In another analysis, we used the Cox proportional hazards regression model to estimate hazard ratios (HRs) for future ASDs in individuals undergoing small intestinal biopsy.

Results  A prior ASD was not associated with CD (OR, 0.93; 95% CI, 0.51-1.68) or inflammation (OR 1.03; 95% CI, 0.40-2.64) but was associated with a markedly increased risk of having a normal mucosa but a positive CD serologic test result (OR, 4.57; 95% CI, 1.58-13.22). Restricting our data to individuals without a diagnosis of an ASD at the time of biopsy, CD (HR, 1.39; 95% CI, 1.13-1.71) and inflammation (HR, 2.01; 95% CI, 1.29-3.13) were both associated with moderate excess risks of later ASDs, whereas the HR for later ASDs in individuals with normal mucosa but positive CD serologic test results was 3.09 (95% CI, 1.99-4.80).

Conclusions and Relevance  Although this study found no association between CD or inflammation and earlier ASDs, there was a markedly increased risk of ASDs in individuals with normal mucosa but a positive CD serologic test result.

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Figure.
Flowchart of Study Participants

CD indicates celiac disease.aThe subgroup of 3736 is part of this 46 330 individuals.

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