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

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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.)

LanguageEnglish
Pages1295-1303
Number of pages9
JournalNew England Journal of Medicine
Volume371
Issue number14
DOIs
StatePublished - Oct 2 2014

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Glutens
Celiac Disease
Autoimmunity
Genotype
Breast Feeding
Age Groups
Newborn Infant

ASJC Scopus subject areas

  • Medicine(all)

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Lionetti, E., Castellaneta, S., Francavilla, R., Pulvirenti, A., Tonutti, E., Arnarri, S., ... Catassi, C. (2014). Introduction of gluten, HLA status, and the risk of celiac disease in children. New England Journal of Medicine, 371(14), 1295-1303. DOI: 10.1056/NEJMoa1400697

Introduction of gluten, HLA status, and the risk of celiac disease in children. / Lionetti, Elena; Castellaneta, Stefania; Francavilla, Ruggiero; Pulvirenti, Alfredo; Tonutti, Elio; Arnarri, Sergio; Barbato, Maria; Barbera, Cristiana; Barera, Graziano; Bellantoni, Antonelia; Castellano, Emanuela; Guariso, Graziella; Limongelli, Maria Giovanna; Pellegrino, Salvatore; Polloni, Carlo; Ughi, Claudio; Zuin, Giovanna; Fasano, Alessio; Catassi, Carlo.

In: New England Journal of Medicine, Vol. 371, No. 14, 02.10.2014, p. 1295-1303.

Research output: Contribution to journalArticle

Lionetti, E, Castellaneta, S, Francavilla, R, Pulvirenti, A, Tonutti, E, Arnarri, S, Barbato, M, Barbera, C, Barera, G, Bellantoni, A, Castellano, E, Guariso, G, Limongelli, MG, Pellegrino, S, Polloni, C, Ughi, C, Zuin, G, Fasano, A & Catassi, C 2014, 'Introduction of gluten, HLA status, and the risk of celiac disease in children' New England Journal of Medicine, vol. 371, no. 14, pp. 1295-1303. DOI: 10.1056/NEJMoa1400697
Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Arnarri S et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. New England Journal of Medicine. 2014 Oct 2;371(14):1295-1303. Available from, DOI: 10.1056/NEJMoa1400697
Lionetti, Elena ; Castellaneta, Stefania ; Francavilla, Ruggiero ; Pulvirenti, Alfredo ; Tonutti, Elio ; Arnarri, Sergio ; Barbato, Maria ; Barbera, Cristiana ; Barera, Graziano ; Bellantoni, Antonelia ; Castellano, Emanuela ; Guariso, Graziella ; Limongelli, Maria Giovanna ; Pellegrino, Salvatore ; Polloni, Carlo ; Ughi, Claudio ; Zuin, Giovanna ; Fasano, Alessio ; Catassi, Carlo. / Introduction of gluten, HLA status, and the risk of celiac disease in children. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 14. pp. 1295-1303
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T1 - Introduction of gluten, HLA status, and the risk of celiac disease in children

AU - Lionetti,Elena

AU - Castellaneta,Stefania

AU - Francavilla,Ruggiero

AU - Pulvirenti,Alfredo

AU - Tonutti,Elio

AU - Arnarri,Sergio

AU - Barbato,Maria

AU - Barbera,Cristiana

AU - Barera,Graziano

AU - Bellantoni,Antonelia

AU - Castellano,Emanuela

AU - Guariso,Graziella

AU - Limongelli,Maria Giovanna

AU - Pellegrino,Salvatore

AU - Polloni,Carlo

AU - Ughi,Claudio

AU - Zuin,Giovanna

AU - Fasano,Alessio

AU - Catassi,Carlo

PY - 2014/10/2

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N2 - 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.)

AB - 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.)

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