TY - JOUR
T1 - Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial
AU - TRIGR Study Group Members
AU - Knip, Mikael
AU - Åkerblom, Hans K.
AU - Altaji, Eva
AU - Becker, Dorothy
AU - Bruining, Jan
AU - Castano, Luis
AU - Danne, Thomas
AU - De Beaufort, Carine
AU - Dosch, Hans Michael
AU - Dupre, John
AU - Fraser, William D.
AU - Howard, Neville
AU - Ilonen, Jorma
AU - Konrad, Daniel
AU - Kordonouri, Olga
AU - Krischer, Jeffrey P.
AU - Lawson, Margaret L.
AU - Ludvigsson, Johnny
AU - Madacsy, Laszlo
AU - Mahon, Jeffrey L.
AU - Ormisson, Anne
AU - Palmer, Jerry P.
AU - Pozzilli, Paolo
AU - Savilahti, Erkki
AU - Serrano-Rios, Manuel
AU - Songini, Marco
AU - Taback, Shayne
AU - Vaarala, Outi
AU - White, Neil H.
AU - Virtanen, Suvi M.
AU - Wasikowa, Renata
AU - Mandrup-Poulsen, Thomas
AU - Arjas, Elja
AU - Lernmark, Åke
AU - Läärä, Esa
AU - Schmidt, Barbara
AU - Hyytinen, Mila
AU - Koski, Katriina
AU - Koski, Matti
AU - Merentie, Kristiina
AU - Pajakkala, Eeva
AU - Reunanen, Antti
AU - Salonen, Marja
AU - Terhonen, Tuija
AU - Virkkunen, Seija
AU - Cuthbertson, David
AU - Gainer, Bruce
AU - Hadley, David
AU - Malloy, Jamie
AU - Nallamshetty, Lavanya
N1 - Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/1/2
Y1 - 2018/1/2
N2 - IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 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 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. 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 ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 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 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). 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 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes.
AB - IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 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 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. 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 ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 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 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). 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 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85040226123&partnerID=8YFLogxK
U2 - 10.1001/jama.2017.19826
DO - 10.1001/jama.2017.19826
M3 - Article
C2 - 29297078
AN - SCOPUS:85040226123
SN - 0098-7484
VL - 319
SP - 38
EP - 48
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 1
ER -