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Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial.
JAMA 2014; 311(22):2279-87JAMA

Abstract

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.

Authors+Show Affiliations

University of Helsinki, Helsinki, Finland.University of Helsinki, Helsinki, Finland.University of Pittsburgh, Pittsburgh, Pennsylvania.University of Toronto, Toronto, Ontario, Canada.University of Western Ontario, London, Canada.University of Montréal, Montréal, Québec, Canada.Children's Hospital of Westmead, Sydney, Australia.University of Turku, Turku, Finland.University of South Florida, Tampa.Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.University of Washington, Seattle.University of Helsinki, Helsinki, Finland.National Institute for Health and Welfare, Helsinki, Finland.National Institute for Health and Welfare, Helsinki, Finland.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24915259

Citation

Knip, Mikael, et al. "Hydrolyzed Infant Formula and Early Β-cell Autoimmunity: a Randomized Clinical Trial." JAMA, vol. 311, no. 22, 2014, pp. 2279-87.
Knip M, Åkerblom HK, Becker D, et al. Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. JAMA. 2014;311(22):2279-87.
Knip, M., Åkerblom, H. K., Becker, D., Dosch, H. M., Dupre, J., Fraser, W., ... Virtanen, S. M. (2014). Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. JAMA, 311(22), pp. 2279-87. doi:10.1001/jama.2014.5610.
Knip M, et al. Hydrolyzed Infant Formula and Early Β-cell Autoimmunity: a Randomized Clinical Trial. JAMA. 2014 Jun 11;311(22):2279-87. PubMed PMID: 24915259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. AU - Knip,Mikael, AU - Åkerblom,Hans K, AU - Becker,Dorothy, AU - Dosch,Hans-Michael, AU - Dupre,John, AU - Fraser,William, AU - Howard,Neville, AU - Ilonen,Jorma, AU - Krischer,Jeffrey P, AU - Kordonouri,Olga, AU - Lawson,Margaret L, AU - Palmer,Jerry P, AU - Savilahti,Erkki, AU - Vaarala,Outi, AU - Virtanen,Suvi M, AU - ,, PY - 2014/6/11/entrez PY - 2014/6/11/pubmed PY - 2014/6/24/medline SP - 2279 EP - 87 JF - JAMA JO - JAMA VL - 311 IS - 22 N2 - 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/24915259/Hydrolyzed_infant_formula_and_early_β_cell_autoimmunity:_a_randomized_clinical_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2014.5610 DB - PRIME DP - Unbound Medicine ER -