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Gastroenterology. 2017 Oct;153(4):961-970.e3. doi: 10.1053/j.gastro.2017.06.049. Epub 2017 Jul 5.

Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial.

Author information

1
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
2
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
3
Nutrition Unit, National Institute for Health and Welfare, Helsinki, Finland; University of Tampere, School of Health Sciences, Tampere, Finland; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; The Science Center of Pirkanmaa Hospital District, Tampere, Finland.
4
Immunogenetics Laboratory, University of Turku and Turku University Hospital, Turku, Finland.
5
Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
6
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Respiratory, Inflammation and Autoimmunity, Innovative Medicine, AstraZeneca, Molndal, Sweden.
7
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland. Electronic address: mikael.knip@helsinki.fi.

Abstract

BACKGROUND & AIMS:

Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease.

METHODS:

We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life.

RESULTS:

Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease.

CONCLUSIONS:

In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.

KEYWORDS:

Diet; Immune System Development; Pediatric; TRIGR Study

PMID:
28687275
DOI:
10.1053/j.gastro.2017.06.049
[Indexed for MEDLINE]

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