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Published on: March 23, 2018
Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial
Mikael Knip1, Hans K Åkerblom1, Dorothy Becker2
1University of Helsinki, Helsinki, Finland.
Insights
Weaning high-risk infants to hydrolyzed formula did not decrease diabetes-associated autoantibodies. This study found no benefit of hydrolyzed formula in preventing type 1 diabetes autoimmunity.
Area of Science:
- Immunology
- Pediatrics
- Endocrinology
Background:
- Type 1 diabetes autoimmunity often begins in early childhood.
- Early exposure to dietary proteins may increase type 1 diabetes risk in genetically susceptible children.
- Extensively hydrolyzed formulas lack intact proteins, potentially altering immune responses.
Purpose of the Study:
- To determine if weaning infants at risk for type 1 diabetes to an extensively hydrolyzed formula reduces the incidence of diabetes-associated autoantibodies.
- To test the hypothesis that hydrolyzed formula use mitigates the development of beta-cell autoimmunity.
Main Methods:
- A double-blind randomized clinical trial involving 2159 high-risk infants.
- Infants were randomized to receive either an extensively hydrolyzed casein formula or a conventional cow's milk-based formula.
- Participants were monitored for a median of 7 years for the development of diabetes-associated autoantibodies.
Main Results:
- The cumulative incidence of at least two diabetes-associated autoantibodies was 13.4% in the hydrolyzed formula group versus 11.4% in the conventional formula group.
- The adjusted hazard ratio for developing autoantibodies was 1.23 (95% CI, 0.96-1.58) for the hydrolyzed formula group, indicating no significant reduction.
- No significant differences in adverse events were observed between the two feeding groups.
Conclusions:
- Use of extensively hydrolyzed formula did not decrease the incidence of diabetes-associated autoantibodies in infants genetically at risk for type 1 diabetes.
- These findings do not support the use of hydrolyzed formula to prevent the development of type 1 diabetes autoimmunity.
- Further research may be needed to explore alternative early-life interventions for type 1 diabetes prevention.
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 β-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.
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