Journal article
Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.
- Knip M University of Helsinki, Helsinki, Finland.
- Åkerblom HK Charles University, 3rd Faculty of Medicine, Prague, Czech Republic.
- Al Taji E University of Pittsburgh, Pittsburgh, Pennsylvania.
- Becker D Sophia Children's Hospital, Rotterdam, the Netherlands.
- Bruining J Cruces University Hospital-UPV/EHU-CIBERDEM/CIBERER, Barakaldo, Spain.
- Castano L Kinder-und Jugendkrankenhaus Auf Der Bult, Hannover, Germany.
- Danne T Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.
- de Beaufort C University of Toronto, Toronto, Ontario, Canada.
- Dosch HM University of Western Ontario, London, Ontario, Canada.
- Dupre J Université de Sherbrooke, Sherbrooke, Quebec, Canada.
- Fraser WD Children's Hospital of Westmead, Sydney, Australia.
- Howard N University of Turku and Turku University Hospital, Turku, Finland.
- Ilonen J University Children's Hospital Zürich, Zürich, Switzerland.
- Konrad D Kinder-und Jugendkrankenhaus Auf Der Bult, Hannover, Germany.
- Kordonouri O University of South Florida, Tampa.
- Krischer JP Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
- Lawson ML Linköping University, Linköping, Sweden.
- Ludvigsson J Semmelweis Medical University, Budapest, Hungary.
- Madacsy L University of Western Ontario, London, Ontario, Canada.
- Mahon JL Tartu University, Tartu, Estonia.
- Ormisson A University of Washington, Seattle.
- Palmer JP University Campus Bio-Medico of Rome, Rome, Italy.
- Pozzilli P University of Helsinki, Helsinki, Finland.
- Savilahti E Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
- Serrano-Rios M St Michelle Hospital /Azienda Ospedaliera Brotzu-Diabetes Unit, Cagliari, Italy.
- Songini M University of Manitoba, Winnipeg, Manitoba, Canada.
- Taback S University of Helsinki, Helsinki, Finland.
- Vaarala O Washington University School of Medicine, St Louis, Missouri.
- White NH National Institute of Health and Welfare, Helsinki, Finland.
- Virtanen SM Medical University of Wroclaw, Wroclaw, Poland.
- Wasikowa R
- 2018-01-04
Published in:
- JAMA. - 2018
Caseins
Child
Diabetes Mellitus, Type 1
Disease-Free Survival
Double-Blind Method
Female
Follow-Up Studies
Humans
Infant Formula
Infant Nutritional Physiological Phenomena
Infant, Newborn
Male
Nutrition Policy
Risk
English
Importance
Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas.
Objective
To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children.
Design, Setting, and Participants
An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017.
Interventions
The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age.
Main Outcomes and Measures
Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events).
Results
Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group).
Conclusions and Relevance
Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
Trial Registration
clinicaltrials.gov Identifier: NCT00179777.
Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas.
Objective
To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children.
Design, Setting, and Participants
An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017.
Interventions
The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age.
Main Outcomes and Measures
Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events).
Results
Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group).
Conclusions and Relevance
Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
Trial Registration
clinicaltrials.gov Identifier: NCT00179777.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1001/jama.2017.19826
- PMID 29297078
- Persistent URL
- https://susi.usi.ch/global/documents/215550
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