Table 1C

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

Author
Country
Design		Age diagnosis* or study endpoint‡Cases/controls or cohortCases exposed
Time exposure
Recording details		Confounders for which correctedSignificant associationQuality score
Bittker and Bell
USA
Case–control42		6.1 years*332/241237 (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%)/6558Unknown
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*373/58197 (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.