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Pediatrics. 2019 Oct;144(4). pii: e20183933. doi: 10.1542/peds.2018-3933. Epub 2019 Sep 6.

Celiac Disease Autoimmunity and Emotional and Behavioral Problems in Childhood.

Author information

Generation R Study Group and.
Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands.
Departments of Child and Adolescent Psychiatry and Psychology and.
Psychology, Education, and Child Studies, Erasmus University Rotterdam, Rotterdam, Netherlands; and.
Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands;
Department of Public Health and Primary Care, Campus The Hague, Leiden University Medical Center, The Hague, Netherlands.



Celiac disease (CeD) is associated with psychopathology in children. It is unknown whether this association is present in children with celiac disease autoimmunity (CDA) identified by screening. We examined the associations between subclinical CDA and emotional and behavioral problems in children without previous CeD diagnosis.


In a population-based cohort study of 3715 children (median age: 6 years), blood titers of tissue transglutaminase autoantibodies were analyzed. CDA was defined as a measurement of tissue transglutaminase autoantibodies ≥7 U/mL (n = 51). Children with previous CeD diagnosis or children on a gluten-free diet, were excluded. The Child Behavior Checklist (CBCL) was filled in by parents and was used to assess behavioral and emotional problems of children at a median age of 5.9 years. Multiple linear regression models were applied to evaluate the cross-sectional associations between CDA and CBCL scores. Sensitivity analyses were done in a subgroup of children who were seropositive carrying the HLA antigen risk alleles for CeD.


In basic models, CDA was not associated with emotional and behavioral problems on the CBCL scales. After adjustment for confounders, CDA was significantly associated with anxiety problems (β = .29; 95% confidence interval 0.02 to 0.55; P = .02). After exclusion of children who did not carry the HLA-DQ2 and/or HLA-DQ8 risk alleles (n = 4), CDA was additionally associated with oppositional defiant problems (β = .35; 95% confidence interval 0.02 to 0.69). Associations were not explained by gastrointestinal complaints.


Our results reveal that CDA, especially combined with the HLA-DQ2 and HLA-DQ8 risk alleles, is associated with anxiety problems and oppositional defiant problems. Further research should be used to establish whether behavioral problems are a reflection of subclinical CeD.


Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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