Exposure to Antibiotics during infancy linked to Celiac Disease

The study cohorts consisted of children born in Denmark from 1995 to 2012 (the Danish National Birth Cohort) and followed until May 2015, and children born in Norway from 2004 to 2012 (the Norwegian Mother and Child Cohort Study) and followed until December 2013. The mothers answered questionnaires, sometimes aided by computer-assisted telephone interviews, on infectious diseases and feeding.

The final analysis in the Danish cohort included 1,168,656 children with a median age at end of follow-up of 11.6 years. A diagnosis of celiac disease was registered for 1,427 of these children (0.12%). Systemic antibiotics in the first year of life were dispensed to 451,196 participants without celiac disease (38.7%) and to 622 with celiac disease (43.6%).

The final Norwegian cohort consisted of 537,457 children, with a median age at end of follow-up of 5.4 years. Celiac disease was diagnosed in 1,919 (0.36%) of participants. Systemic antibiotics in the first year of life were dispensed to 98,538 without celiac disease (18.4%) and to 390 with celiac disease (20.3%).

Data from two large subgroups within the final cohort looked at the potentially confounding impact of adjustment for the number of children's maternally reported infections as well as the duration of breastfeeding, examined 6 and 18 months postpartum for 55,082 Danish children (100 with celiac disease) and 53,257 Norwegian children (464 with celiac disease). Neither variable had a measurable impact, nor did prescriptions for topical antifungal drugs, although these were more common in those registered for systemic antibiotics.

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Key Findings:

• Exposure to systemic antibiotics in the first year of life was positively associated with diagnosed celiac disease in the Danish and in the Norwegian cohort.


• A dose-dependent relationship was found between an increasing number of dispensed antibiotics and the risk of celiac disease.


• No specific type of antibiotic or age period within the first year of life was prominent.


• Adjustment for hospital admissions with an infectious disease in the first year of life did not change the estimates; adjustment for the number of maternally reported infections in the child in 2 large sub-cohorts reduced the association slightly.

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The authors pointed out that the intestinal microbiota is considered a player in the pathogenesis of celiac disease and one strongly influenced by systemic antibiotics, especially in early life. Early-life infections have been proposed as promoters of celiac disease development and important potential confounders. Some studies have reported associations with types of infection, as well as the number of hospital admissions for infectious diseases, medically attended infectious diseases, and parentally reported infectious diseases.

The authors concluded that the findings could have resulted from reverse causality, in which the symptoms of celiac disease can mimic infection, exaggerate infectious symptoms, or raise the risk of infectious diseases, thereby increasing the propensity for prescriptions for antibiotics.

For further reference log on to https://doi.org/10.1053/j.gastro.2019.02.039