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Kemppainen, Kaisa M.; Vehik, Kendra; Lynch, Kristian F.; Larsson, Helena Elding; Canepa, Ronald J.; Simell, Ville; Koletzko, Sibylle; Liu, Edwin; Simell, Olli G.; Toppari, Jorma; Ziegler, Anette G.; Rewers, Marian J.; Lernmark, Ake; Hagopian, William A.; She, Jin-Xiong; Akolkar, Beena; Schatz, Desmond A.; Atkinson, Mark A.; Blaser, Martin J.; Krischer, Jeffrey P.; Hyoety, Heikki; Agardh, Daniel; Triplett, Eric W. (2017): Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity. In: Jama Pediatrics, Vol. 171, No. 12: pp. 1217-1225
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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 autoimmunitywere 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.