Infections and risk of celiac disease in childhood: a prospective nationwide cohort study.
OBJECTIVE
Studies on early life infections and risk of later celiac disease (CD) are inconsistent but have mostly been limited to retrospective designs, inpatient data, or insufficient statistical power. We aimed to test whether early life infections are associated with increased risk of later CD using prospective population-based data.


METHODS
This study, based on the Norwegian Mother and Child Cohort Study, includes prospective, repeated assessments of parent-reported infectious disease data up to 18 months of age for 72,921 children born between 2000 and 2009. CD was identified through parental questionnaires and the Norwegian Patient Registry. Logistic regression was used to estimate odds ratios adjusted for child's age and sex (aOR).


RESULTS
During a median follow-up period of 8.5 years (range, 4.5-14.5), 581 children (0.8%) were diagnosed with CD. Children with ≥10 infections (≥fourth quartile) up to age 18 months had a significantly higher risk of later CD, as compared with children with ≤4 infections (≤first quartile; aOR=1.32; 95% confidence interval (CI)=1.06-1.65; per increase in infectious episodes, aOR=1.03; 95% CI=1.02-1.05). The aORs per increase in specific types of infections were as follows: upper respiratory tract infections: 1.03 (95% CI=1.02-1.05); lower respiratory tract infections: 1.12 (95% CI=1.01-1.23); and gastroenteritis: 1.05 (95% CI=0.99-1.11). Additional adjustments for maternal CD, education level, smoking, birth weight, prematurity, infant feeding practices, birth season, and antibiotic treatment yielded largely unchanged results.


CONCLUSIONS
This is the first large-scale population-based cohort study of this association. Our results are in line with immunological data suggesting that early life infections may have a role in CD development. However, non-causal explanations for this association due to surveillance bias and reverse causation cannot be excluded.
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.|Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Karl
K
Mårild
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.|Department of Pediatrics, Østfold Hospital Trust, Fredrikstad, Norway.
Christian R
CR
Kahrs
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
German
G
Tapia
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
Lars C
LC
Stene
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.|Department of Pediatrics, Østfold Hospital Trust, Fredrikstad, Norway.
Ketil
K
Størdal
D002446:Celiac Disease / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D011014:Pneumonia / Q000453:epidemiology*; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000453:epidemiology*; D012307:Risk Factors; D011795:Surveys and Questionnaires