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

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.).

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    From the Departments of Pediatrics (E.L.) and Clinical and Molecular Biomedicine (A.P.), University of Catania, the Department of Pediatrics, San Paolo Hospital (S.C.), and the Department of Developmental Biomedicine, University of Bari (R.F.), Bari, the Department of Immunopathology and Allergology, Udine Hospital, Udine (E.T.), the Department of Pediatrics, Azienda Ospedaliera IRCCS Santa Maria Nuova Hospital, Reggio Emilia (S.A.), the Department of Pediatrics, Sapienza University of Rome, Rome (M.B.), the Department of Pediatrics, University of Turin, Turin (C.B.), the Department of Pediatrics, San Raffaele Hospital (G.B.), and the Department of Pediatrics, Vittore Buzzi Children's Hospital, Milan (G.Z.), the Department of Pediatrics, Bianchi Melacrino Morelli Hospital, Reggio Calabria (A.B.), Pediatric Gastroenterology Unit, Giannina Gaslini Institute, Genoa (E.C.), the Department of Pediatrics, University of Padua, Padua (G.G.), the Department of Pediatrics, Federico II University of Naples, Naples (M.G.L.), Pediatric Gastroenterology and Cystic Fibrosis Unit, University Hospital Gaetano Martino, Messina (S.P.), the Department of Pediatrics, Rovereto Hospital, Rovereto (Trento) (C.P.), the Department of Pediatrics, University of Pisa, Pisa (C.U.), and the Department of Pediatrics, Marche Polytechnic University, Ancona (C.C.) - all in Italy; and the Division of Pediatric Gastroenterology and Nutrition and Center for Celiac Research, MassGeneral Hospital for Children (A.F.), and the Celiac Program, Harvard Medical School (A.F., C.C.) - both in Boston.

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    Source

    The New England journal of medicine 371:14 2014 Oct 02 pg 1295-303

    MeSH

    Age Factors
    Age of Onset
    Autoantibodies
    Breast Feeding
    Celiac Disease
    Child
    Child, Preschool
    Diet
    Dietary Proteins
    Female
    GTP-Binding Proteins
    Genotype
    Gliadin
    Glutens
    HLA Antigens
    Humans
    Infant
    Infant, Newborn
    Intestine, Small
    Kaplan-Meier Estimate
    Male
    Prospective Studies
    Risk
    Transglutaminases

    Pub Type(s)

    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25271602

    Citation

    Lionetti, Elena, et al. "Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children." The New England Journal of Medicine, vol. 371, no. 14, 2014, pp. 1295-303.
    Lionetti E, Castellaneta S, Francavilla R, et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371(14):1295-303.
    Lionetti, E., Castellaneta, S., Francavilla, R., Pulvirenti, A., Tonutti, E., Amarri, S., ... Catassi, C. (2014). Introduction of gluten, HLA status, and the risk of celiac disease in children. The New England Journal of Medicine, 371(14), pp. 1295-303. doi:10.1056/NEJMoa1400697.
    Lionetti E, et al. Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children. N Engl J Med. 2014 Oct 2;371(14):1295-303. PubMed PMID: 25271602.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR 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 - Amarri,Sergio, AU - Barbato,Maria, AU - Barbera,Cristiana, AU - Barera,Graziano, AU - Bellantoni,Antonella, 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, AU - ,, PY - 2014/10/2/entrez PY - 2014/10/2/pubmed PY - 2014/10/15/medline SP - 1295 EP - 303 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 371 IS - 14 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.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/25271602/full_citation L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1400697?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -