Background: The role of infant feeding practices, particularly the timing of gluten introduction, in the development of celiac disease (CD) autoimmunity remains a critical question, especially for infants with a familial risk. This study aimed to investigate the association between the age at gluten introduction and the risk of developing CD autoimmunity in at-risk infants. Methods: A prospective observational cohort study was conducted from 2010 to 2015. We enrolled 350 infants with a first-degree relative (parent or sibling) with biopsy-proven CD. Parents maintained detailed feeding diaries. Infants were categorized based on age of gluten introduction: Early (≤6 months), Standard (>6 to 8 months), and Late (>8 months). The primary outcome was the development of CD autoimmunity, defined as persistently positive tissue transglutaminase (tTG-IgA) antibodies on two consecutive visits after 12 months of age. Children were followed with annual serological screening until age 3. Cox proportional hazards regression was used to assess the association, adjusting for HLA genotype (DQ2/DQ8), breastfeeding status at introduction, and sex. Results: Of the 320 children who completed follow-up, 42 (13.1%) developed CD autoimmunity. The median age of gluten introduction was 6.5 months (IQR 5.8-7.4). The cumulative incidence of CD autoimmunity was: Early group: 20.0% (n=16/80), Standard group: 10.2% (n=18/176), Late group: 12.5% (n=8/64) (Log-rank p=0.038). In adjusted analysis, early gluten introduction (≤6 months) was associated with a significantly increased hazard of CD autoimmunity compared to the Standard group (aHR 2.15, 95% CI 1.10-4.20). Conclusion: In this 2015 cohort of infants at familial risk for CD, introduction of gluten at or before 6 months of age was associated with a greater than two-fold increased risk of developing CD autoimmunity by age 3, compared to introduction between 6 and 8 months.

Celiac Disease, Gluten, Infant Nutrition, Autoimmunity, Paediatrics, Cohort Study.