OBJECTIVE: To determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease. DESIGN: Case-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016. SETTING: Norwegian population. PARTICIPANTS: Children carrying the HLA genotype DR4-DQ8/DR3-DQ2 conferring increased risk of coeliac disease. EXPOSURES: Enterovirus and adenovirus detected using real time polymerase chain reaction in monthly stool samples from age 3 to 36 months. MAIN OUTCOME MEASURE: Coeliac disease diagnosed according to standard criteria. Coeliac disease antibodies were tested in blood samples taken at age 3, 6, 9, and 12 months and then annually. Adjusted odds ratios from mixed effects logistic regression model were used to assess the relation between viral infections before development of coeliac disease antibodies and coeliac disease. RESULTS: Among 220 children, and after a mean of 9.9 (SD 1.6) years, 25 children were diagnosed as having coeliac disease after screening and were matched to two controls each. Enterovirus was found in 370 (17%) of 2135 samples and was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls (adjusted odds ratio 1.49, 95% confidence interval 1.07 to 2.06; P=0.02). The association was restricted to infections after introduction of gluten. High quantity samples (>100 000 copies/μL) (adjusted odds ratio 2.11, 1.24 to 3.60; P=0.01) and long lasting infections (>2 months) (2.16, 1.16 to 4.04; P=0.02) gave higher risk estimates. Both the commonly detected enterovirus species Enterovirus A and Enterovirus B were significantly associated with coeliac disease. The association was not found for infections during or after development of coeliac disease antibodies. Adenovirus was not associated with coeliac disease. CONCLUSIONS: In this longitudinal study, a higher frequency of enterovirus, but not adenovirus, during early childhood was associated with later coeliac disease. The finding adds new information on the role of viral infections in the aetiology of coeliac disease.

Department of Gastroenterology Oslo University Hospital Rikshospitalet Oslo Norway

Department of IT and e health Division of Institute Resources Norwegian Institute of Public Health Oslo Norway

Department of Paediatrics 2nd Faculty of Medicine Charles University Prague and University Hospital Motol Prague Czech Republic

Department of Pediatric Research Oslo University Hospital Oslo Norway

Department of Pediatrics Institute of Clinical Sciences The Sahlgrenska Academy at University of Gothenburg and Queen Silvia Children's Hospital Gothenburg Sweden

Department of Pediatrics Østfold Hospital Trust Grålum Norway

Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

K G Jebsen Coeliac Disease Research Centre University of Oslo Oslo Norway

Norwegian Institute of Public Health Oslo Norway

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