Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.

PMID- 29297078
OWN - NLM
STAT- In-Process
LR  - 20180103
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 319
IP  - 1
DP  - 2018 Jan 2
TI  - Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1
      Diabetes: The TRIGR Randomized Clinical Trial.
PG  - 38-48
LID - 10.1001/jama.2017.19826 [doi]
AB  - 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.
CN  - Writing Group for the TRIGR Study Group
FAU - Knip, Mikael
AU  - Knip M
AD  - University of Helsinki, Helsinki, Finland.
AD  - Helsinki University Hospital, Helsinki, Finland.
FAU - Akerblom, Hans K
AU  - Akerblom HK
AD  - University of Helsinki, Helsinki, Finland.
FAU - Al Taji, Eva
AU  - Al Taji E
AD  - Charles University, 3rd Faculty of Medicine, Prague, Czech Republic.
FAU - Becker, Dorothy
AU  - Becker D
AD  - University of Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Bruining, Jan
AU  - Bruining J
AD  - Sophia Children's Hospital, Rotterdam, the Netherlands.
FAU - Castano, Luis
AU  - Castano L
AD  - Cruces University Hospital-UPV/EHU-CIBERDEM/CIBERER, Barakaldo, Spain.
FAU - Danne, Thomas
AU  - Danne T
AD  - Kinder-und Jugendkrankenhaus Auf Der Bult, Hannover, Germany.
FAU - de Beaufort, Carine
AU  - de Beaufort C
AD  - Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.
FAU - Dosch, Hans-Michael
AU  - Dosch HM
AD  - University of Toronto, Toronto, Ontario, Canada.
FAU - Dupre, John
AU  - Dupre J
AD  - University of Western Ontario, London, Ontario, Canada.
FAU - Fraser, William D
AU  - Fraser WD
AD  - Universite de Sherbrooke, Sherbrooke, Quebec, Canada.
FAU - Howard, Neville
AU  - Howard N
AD  - Children's Hospital of Westmead, Sydney, Australia.
FAU - Ilonen, Jorma
AU  - Ilonen J
AD  - University of Turku and Turku University Hospital, Turku, Finland.
FAU - Konrad, Daniel
AU  - Konrad D
AD  - University Children's Hospital Zurich, Zurich, Switzerland.
FAU - Kordonouri, Olga
AU  - Kordonouri O
AD  - Kinder-und Jugendkrankenhaus Auf Der Bult, Hannover, Germany.
FAU - Krischer, Jeffrey P
AU  - Krischer JP
AD  - University of South Florida, Tampa.
FAU - Lawson, Margaret L
AU  - Lawson ML
AD  - Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
FAU - Ludvigsson, Johnny
AU  - Ludvigsson J
AD  - Linkoping University, Linkoping, Sweden.
FAU - Madacsy, Laszlo
AU  - Madacsy L
AD  - Semmelweis Medical University, Budapest, Hungary.
FAU - Mahon, Jeffrey L
AU  - Mahon JL
AD  - University of Western Ontario, London, Ontario, Canada.
FAU - Ormisson, Anne
AU  - Ormisson A
AD  - Tartu University, Tartu, Estonia.
FAU - Palmer, Jerry P
AU  - Palmer JP
AD  - University of Washington, Seattle.
FAU - Pozzilli, Paolo
AU  - Pozzilli P
AD  - University Campus Bio-Medico of Rome, Rome, Italy.
FAU - Savilahti, Erkki
AU  - Savilahti E
AD  - University of Helsinki, Helsinki, Finland.
FAU - Serrano-Rios, Manuel
AU  - Serrano-Rios M
AD  - Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders
      (CIBERDEM), Madrid, Spain.
FAU - Songini, Marco
AU  - Songini M
AD  - St Michelle Hospital /Azienda Ospedaliera Brotzu-Diabetes Unit, Cagliari, Italy.
FAU - Taback, Shayne
AU  - Taback S
AD  - University of Manitoba, Winnipeg, Manitoba, Canada.
FAU - Vaarala, Outi
AU  - Vaarala O
AD  - University of Helsinki, Helsinki, Finland.
AD  - Respiratory, Inflammation and Autoimmunity, Innovative Medicine, AstraZeneca,
      Gothenburg, Sweden.
FAU - White, Neil H
AU  - White NH
AD  - Washington University School of Medicine, St Louis, Missouri.
FAU - Virtanen, Suvi M
AU  - Virtanen SM
AD  - National Institute of Health and Welfare, Helsinki, Finland.
FAU - Wasikowa, Renata
AU  - Wasikowa R
AD  - Medical University of Wroclaw, Wroclaw, Poland.
LA  - eng
SI  - ClinicalTrials.gov/NCT00179777
GR  - U01 HD040364/HD/NICHD NIH HHS/United States
GR  - U01 HD042444/HD/NICHD NIH HHS/United States
GR  - R01 HD051997/HD/NICHD NIH HHS/United States
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
EDAT- 2018/01/04 06:00
MHDA- 2018/01/04 06:00
CRDT- 2018/01/04 06:00
PHST- 2018/01/04 06:00 [entrez]
PHST- 2018/01/04 06:00 [pubmed]
PHST- 2018/01/04 06:00 [medline]
AID - 2667723 [pii]
AID - 10.1001/jama.2017.19826 [doi]
PST - ppublish
SO  - JAMA. 2018 Jan 2;319(1):38-48. doi: 10.1001/jama.2017.19826.