Table 3 ∣.
Clinical studies evaluating antibiotic exposure and coeliac disease risk
| Study | Antibiotic exposure timing |
Date (location) | Study design | Antibiotic data source |
Coeliac disease diagnosis |
Key findingsa |
|---|---|---|---|---|---|---|
| Mårild et al.225 | Prenatal | 2014 (Sweden) | Cohort | Prospective questionnaire | Histology (Marsh 3) and either positive coeliac serologies or symptoms consistent with coeliac which resolved on GFDb | No significant difference HR 1.33 (0.69–2.56) |
| Mårild et al.226 | Prenatal | 2017 (Norway) | Cohort | Prospective questionnaire | Questionnaire or database diagnostic codes for coeliac diseasec | No significant difference aOR 1.16 (0.94–1.43) |
| Myléus et al.232 | Birth to 6 months | 2012 (Sweden) | Case–control | Parental questionnaire | Three consecutive duodenal biopsy samples (Marsh 3) | No significant difference between coeliac disease and controls OR 1.2 (0.87–1.6) |
| Canova et al.221 | Birth to 12 months | 2014 (Italy) | Cohort | Prescriber registry | Database diagnostic codes for coeliac disease | OR 1.3 (1.10–1.56) Dose–response relationship with five or more antibiotic courses OR 2.66 (1.79–3.95) |
| Dydensborg Sander et al.222 | Birth to 12 months | 2019 (Denmark and Norway) | Observational cohort | Prescriber registry | Database diagnostic codes for coeliac disease | OR 1.26 (1.16–1.36) Dose-dependent relationship for each additional antibiotic OR 1.08 (1.05–1.11) |
| Kemppainen et al.228 | Birth to 48 months | 2017 (Finland, Germany, Sweden and USA (TEDDY)) | Cohort with T1DM and permissive HLA for CD | Prospective questionnaire | Risk of coeliac disease defined as two consecutive positive serum TTG IgA at least 3 months apartd | No increased risk of positive TTG IgA and antibiotic exposure HR 1.00 (0.98–1.02) |
| Bittker and Bell223 | Birth to 48 months | 2019 (USA) | Case–control Internet-based survey | Parental report | Diagnosis from medical professional | aOR 1.13 (1.04–1.24) Dose-dependent relationship for number of antibiotic courses For four to seven, OR 1.62 (1.03–2.55) For eight or more, OR 2.48 (1.29–4.75) |
| Aversa et al.94 | Birth to 24 months | 2021 (USA) | Cohort | Prescriber registry | Database diagnostic codes for coeliac disease | Dose-dependent relationship Gender specific for girls: For one or two antibiotic prescriptions, HR 8.12 (1.03–64.10) For more than five antibiotic prescriptions, HR 12.32 (1.56–97.32) |
| Simre et al.227 | Birth to 60 months | 2016 (Estonia and Finland (DIABIMMUNE)) | Cohort with T1DM and permissive HLA for CD | Parental report of antibiotic exposure | Positive coeliac serology and duodenal biopsy sample (Marsh 3) | No significant difference (number of antibiotic courses 1.1 versus 1.0 Finland) |
| Mårild et al.224 | All ages | 2013 (Sweden) | Case–control | Prescriber registry | Histology database (Marsh 3) | OR 1.40 (1.27–1.53) Also found increased risk with inflammation (Marsh 1 and 2) and those with normal histology (Marsh 0) but positive coeliac serologies |
aOR, adjusted odds ratio; CD, coeliac disease; GFD, gluten-free diet; OR, odds ratio; T1DM, type 1 diabetes mellitus; TTG, tissue transglutaminase.
a
Value ranges in parentheses are 95% confidence intervals.
b
Data obtained from prior study published in 2004.
c
Validation study performed by authors.
d
Primary outcome was risk of coeliac disease.