Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Writing Group for the TRIGR Study Group

PROVIDER: S-EPMC5833549 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Knip Mikael M Åkerblom Hans K HK Al Taji Eva E Becker Dorothy D Bruining Jan J Castano Luis L Danne Thomas T de Beaufort Carine C Dosch Hans-Michael HM Dupre John J Fraser William D WD Howard Neville N Ilonen Jorma J Konrad Daniel D Kordonouri Olga O Krischer Jeffrey P JP Lawson Margaret L ML Ludvigsson Johnny J Madacsy Laszlo L Mahon Jeffrey L JL Ormisson Anne A Palmer Jerry P JP Pozzilli Paolo P Savilahti Erkki E Serrano-Rios Manuel M Songini Marco M Taback Shayne S Vaarala Outi O White Neil H NH Virtanen Suvi M SM Wasikowa Renata R

JAMA 20180101 1

<h4>Importance</h4>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.<h4>Objective</h4>To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children.<h4>Design, setting, and participants</h4>An international double-blind randomized clinical trial of 2159 infants with hu ...[more]

PMID: 29297078

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Project description:IMPORTANCE:The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of ?-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins. OBJECTIVE:To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children. DESIGN, SETTING, AND PARTICIPANTS:A double-blind randomized clinical trial of 2159 infants with HLA-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; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013. INTERVENTIONS:The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate. MAIN OUTCOMES:AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years). RESULTS:The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups. CONCLUSIONS AND RELEVANCE:Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.

Project description:Background:Millions of infants are fed breast milk substitutes, and the type of infant formula can impact weight gain patterns. Objective:We conducted a randomized controlled trial to determine the direct impact of 2 types of infant formula (cow milk formula, CMF; extensively protein hydrolyzed formula, EHF) on growth and energy balance. Design:A racially diverse group of formula-fed infants (n = 113) were randomly assigned to either CMF or EHF from the age of 0.75 to 12.5 mo. At each monthly visit, anthropometric measures were obtained to determine growth z scores and weight gain velocity, and to categorize early weight gain patterns as rapid or nonrapid. Also, diet records were collected to determine energy from formula and other sources. Comprehensive assessments of energy balance (intake, expenditure, loss) were made at 0.75, 3.5, and 12.5 mo. Results:Beginning 3 wk after randomization, CMF infants had significantly higher weight, but not length, z scores than did EHF infants, and this persisted after solid foods complemented the formula diet. On average, weight gain velocity from 0.75 to 4.5 mo was within the range of typically growing infants for both groups, yet velocity was 3.9 g/d greater for CMF infants (P = 0.002), who were more likely to be classified as an early rapid weight gainer, than EHF infants (46% compared with 18%; P = 0.007). Early differences in energy intake and fecal loss, yielding greater energy available for deposition among CMF infants, contributed to the differential weight gain patterns. There were no significant differences between the formula treatment groups in total energy expenditure or sleeping energy expenditure. Conclusions:Among healthy infants, the type of formula impacted on early rapid weight gain patterns owing to energy intake and loss mechanisms. Research is needed to identify the macronutrients and other compositional constituents in EHF and breast milk that promote satiation and healthy weight gain during sensitive periods of development. This trial was registered at clinicaltrials.gov as: NCT01700205.

Dataset Information

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

Publications

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

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