Introduction of gluten, HLA status, and the risk of celiac disease in children

Elena Lionetti, Stefania Castellaneta, Ruggiero Francavilla, Alfredo Pulvirenti, Elio Tonutti, Sergio Arnarri, Maria Barbato, Cristiana Barbera, Graziano Barera, Antonelia Bellantoni, Emanuela Castellano, Graziella Guariso, Maria Giovanna Limongelli, Salvatore Pellegrino, Carlo Polloni, Claudio Ughi, Giovanna Zuin, Alessio Fasano, Carlo Catassi

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P = 0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P = 0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.)

Original languageEnglish
Pages (from-to)1295-1303
Number of pages9
JournalNew England Journal of Medicine
Volume371
Issue number14
DOIs
Publication statusPublished - Oct 2 2014

ASJC Scopus subject areas

  • Medicine(all)

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