Age at Gluten Introduction and Risk of Celiac Disease: a Prospective, Multicentre, Nutritional Intervention Study on Infants at Family Risk (The Italian Baby-Study on Weaning and CD Risk)

Principal Investigator: Professor Catassi C., Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy.


Objectives: The primary aim of the study was to evaluate in a large cohort of infants at increased risk for celiac disease (CD) the role of age at gluten introduction on the risk of CD-autoimmunity and of CD.

Methods: This is an ongoing not recruiting prospective, multicenter, nationwide intervention trial. 730 infants at increased risk for CD (first-degree relatives of patients with CD) were enrolled. Infants were blindly assigned to introduce gluten at 4th-6th month (group A) or after the 12th month (group B); diet (duration of breastfeeding, adherence to the protocol, amount of gluten administered) was evaluated at 4, 7, 9, and 12 months; CD serology was tested at 15 (plus HLA), 24, 36 and 60 months.

Results: 395 infants were enrolled in group A (F 49.9%) and 335 in group B (F 50%). The current median age of the cohort is 5,1 and the percentage of children older than 3 years is 95%. The type of kinship was: 58.2% one sibling, 39.5% mother, 8% father (two relatives 8.1%). The mean duration of breastfeeding was 4 months. The average gluten consumption was >6 gr/day in 95.1%, 3-6 gr/d in 4.1%, and <3 gr/d in 0.8%. HLA genotyping showed: DR3 or DR3/DR7 in 7.5%, DR5/DR7 in 15.8%, DR3/DR5 or DR3/DR4 or DR3/DRX in 28.7%, DR7/DR7 in 15.8%, DR7/DR4 or DR4/DR4 in 7.5%, others in 24.7%. Overall, at 24 months the incidence of CD-autoimmunity and of CD was higher in group A (CD-autoimmunity: group A 11.1% vs group B 5.7%; p=0.01. CD: group A 8.1% vs group B 4.2%; p=0.03).

Conclusion: Introducing gluten after 12 months of age may prevent the developing of CD in the first two years of life. A prolonged follow-up is required.


Publications Related to the FC Grant:

  1. Lionetti E, Castellaneta S, Pulvirenti A, Tonutti E, Francavilla R, Fasano A, Catassi C, and “the Italian Working Group of Weaning and CD risk. Prevalence and natural history of potential celiac disease in at-family-risk infants prospectively investigated from birth. J Ped 2012; 161:908-14.
  2.  Sellitto M, Bai G, Serena G, et al Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS One. 2012;7(3):e33387.
  3. Fasano A, Catassi C. Early feeding practices and their impact on development of celiac disease. Nestle Nutr Workshop Ser Pediatr Program. 2011;68:201-9; discussion 210-3. Epub 2011 Oct 3. Review.
  4. Lionetti E, Catassi C. New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment. Int Rev Immunol. 2011 Aug;30(4):219-31. Review.