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Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity.
JAMA Pediatr 2017; 171(12):1217-1225JP

Abstract

Importance

Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases.

Objective

To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD.

Design, Setting, and Participants

HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D.

Exposures

Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively.

Main Outcomes and Measures

Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity.

Results

Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02).

Conclusions and Relevance

The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD.

Authors+Show Affiliations

Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville.Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmö, Sweden.Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville.MediCity Laboratory, University of Turku, Turku, Finland.Division of Paediatric Gastroenterology and Hepatology, Dr von Hauner Children's Hospital, Ludwig Maximilian University, München, Germany.Digestive Health Institute, Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado Denver, Aurora.Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.Department of Pediatrics, University of Turku, Turku University Hospital, Turku, Finland. Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.Institute of Diabetes Research, Helmholtz Zentrum München, München, Germany. Klinikum Rechts der Isar, Technische Universität München, München, Germany. Forschergruppe Diabetes e.V., Neuherberg, Germany.Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora.Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmö, Sweden.Pacific Northwest Diabetes Research Institute, Seattle, Washington.Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta.National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.Department of Pediatrics, College of Medicine, University of Florida, Gainesville.Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville.Department of Medicine and Microbiology, New York School of Medicine, New York.Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.Department of Virology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmö, Sweden.Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

29052687

Citation

Kemppainen, Kaisa M., et al. "Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity." JAMA Pediatrics, vol. 171, no. 12, 2017, pp. 1217-1225.
Kemppainen KM, Vehik K, Lynch KF, et al. Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity. JAMA Pediatr. 2017;171(12):1217-1225.
Kemppainen, K. M., Vehik, K., Lynch, K. F., Larsson, H. E., Canepa, R. J., Simell, V., ... Triplett, E. W. (2017). Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity. JAMA Pediatrics, 171(12), pp. 1217-1225. doi:10.1001/jamapediatrics.2017.2905.
Kemppainen KM, et al. Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity. JAMA Pediatr. 2017 12 1;171(12):1217-1225. PubMed PMID: 29052687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity. AU - Kemppainen,Kaisa M, AU - Vehik,Kendra, AU - Lynch,Kristian F, AU - Larsson,Helena Elding, AU - Canepa,Ronald J, AU - Simell,Ville, AU - Koletzko,Sibylle, AU - Liu,Edwin, AU - Simell,Olli G, AU - Toppari,Jorma, AU - Ziegler,Anette G, AU - Rewers,Marian J, AU - Lernmark,Åke, AU - Hagopian,William A, AU - She,Jin-Xiong, AU - Akolkar,Beena, AU - Schatz,Desmond A, AU - Atkinson,Mark A, AU - Blaser,Martin J, AU - Krischer,Jeffrey P, AU - Hyöty,Heikki, AU - Agardh,Daniel, AU - Triplett,Eric W, AU - ,, PY - 2017/10/21/pubmed PY - 2017/12/13/medline PY - 2017/10/21/entrez SP - 1217 EP - 1225 JF - JAMA pediatrics JO - JAMA Pediatr VL - 171 IS - 12 N2 - Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases. Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD. Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D. Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively. Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity. Results: Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02). Conclusions and Relevance: The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD. SN - 2168-6211 UR - https://www.unboundmedicine.com/medline/citation/29052687/Association_Between_Early_Life_Antibiotic_Use_and_the_Risk_of_Islet_or_Celiac_Disease_Autoimmunity_ L2 - https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2017.2905 DB - PRIME DP - Unbound Medicine ER -