Table 1C.

Study characteristics and association with antibiotics: coeliac disease (CeD)

Author Country Design	Age diagnosis* or study endpoint‡	Cases/controls or cohort	Cases exposed Time exposure Recording details	Confounders for which corrected	Significant association	Quality score
Bittker and Bell USA Case–control42	6.1 years*	332/241	237 (71%) 0–24 months Parental reported	Age. Age mother (at birth). Education mother. Ethnicity.	Antibiotic exposure is associated with subsequent CeD (aOR=1.133, 95% CI 1.037 to 1.244; p=0.007). Dose-dependent: ORs increase with number of antibiotic courses.	5/9 moderate
Canova et al Italy Cohort22	6.4 years*	1.227 CeD (0.6%) 866 confirmed‡ and 361 unconfirmed‡/203 557	336 (47%) 0–12 months ATC code	Education mother (only in sensitivity analysis with pathological confirmed villous atrophy). Sex. Year of birth.	Increased risk of developing CeD after at least 1 AB course (IRR=1.24, 95% CI 1.07 to 1.43), (IRR=1.31, 95% CI 1.10 to 1.56) for histopathologically confirmed CeD. Dose-dependent: risk increased with more AB courses (p trend <0.01). Type-dependent: cephalosporin use was strongly associated with CeD onset (IRR=1.42, 95% CI 1.18 to 1.73), (IRR=1.51, 95% CI 1.21 to 1.89) for histopathologically confirmed CeD. For first-generation and second-generation drugs: (IRR=1.39, 95% CI 1.11 to 1.76 and third-generation and fourth-generation drugs: IRR=1.49, 95% CI 1.14 to 1.95).	8/9 high
Kemppainen et al Finland, Germany, Sweden and the USA Cohort24	21.4 months*	783 (11.9%)/6558	Unknown 0–24 months Parental reported	Breastfeeding (at 90 days of age). CeD genotype with family. Delivery mode. Maternal AB use during pregnancy. Place of residence. Probiotic use before 90 days of age. Season of birth. Sex.	Exposure to AB was not associated with CeD. Dose-dependent: 2 or more doses of macrolides within the first year of life (157 of 6558 (2.4%)) had elevated CeD risk (HR=1.77, 95% CI 1.18 to 2.66; p=0.006 before but not after adjustment).	6/9 moderate
Mårild et al Sweden Case–control35	0–2 years*	132 coeliac disease/655 12 inflammation/60 17 normal mucosa/85	CeD 51 (39%) Inflammation 6 (50%) 0–24 months ATC code	Age. Education mother. Number of outpatient visits before biopsy. Sex.	Exposure to AB was associated with CeD ORs for prior AB use (CeD): cases 51/132 (38.6%) controls 189/655 (28.9%) (OR=1.58, 95% CI 1.07 to 2.34).	8/9 high
Myléus et al Sweden Case–control36	14 months*	373/581	97 (26%) 0–6 months Parental reported	Age. Place of residence. Sex.	No significantly increased risk for coeliac disease (OR=1.2, 95% CI 0.87 to 1.6; p=0.27).	7/9 moderate
Dydensborg Sander et al Denmark and Norway Cohort28	Danish: 11.6 years‡ Norwegian: 5.4 years‡	Danish: 1427 (0.12%)/1 168 656 Norwegian: 1919 (0.36%)/537 457	Danish: 622 (43.6%) Norwegian: 390 (20.3%) 0–12 months ATC code	Age mother. Associated comorbidity. Birth order. Education mother. Hospitalisation with infection. Season of birth. Sex. Type 1 diabetes child and/or mother.	Exposure to systemic AB (penicillins and extended spectrum penicillins) was positively associated with diagnosed coeliac disease in both cohorts (pooled aOR=1.26, 95% CI 1.16 to 1.36). Dose-dependent: between number of AB courses and risk of CeD (pooled aOR for each additional dispensed AB=1.08, 95% CI 1.05 to 1.11).	9/9 high

AB, antibiotic; aOR, adjusted OR; IRR, incidence rate ratio.