Association between early-life antibiotic use and the risk of islet or celiac disease autoimmunity

Kaisa M. Kemppainen, Kendra Vehik, Kristian F. Lynch, Helena Elding Larsson, Ronald J. Canepa, Ville Simell, Sibylle Koletzko, Edwin Liu, Olli G. Simell, Jorma Toppari, Anette G. Ziegler, Marian J. Rewers, Åke Lernmark, William A. Hagopian, Jin-Xiong She, Beena Akolkar, Desmond A. Schatz, Mark A. Atkinson, Martin J. Blaser, Jeffrey P. KrischerHeikki Hyöty, Daniel Agardh, Eric W. Triplett, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Daniel Felipe-Morales, Kimberly Driscoll, Brigitte I. Frohnert, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Jill Norris, Adela Samper-Imaz, Andrea Steck, Kathleen Waugh, Hali Wright, Annika Adamsson, Suvi Ahonen, Jorma Ilonen, Sanna Jokipuu, Tiina Kallio, Leena Karlsson, Miia Kähönen, Mikael Knip, Lea Kovanen, Mirva Koreasalo, Kalle Kurppa, Tiina Latva-Aho, Maria Lönnrot, Elina Mäntymäki, Katja Multasuo, Juha Mykkänen, Tiina Niininen, Sari Niinistö, Mia Nyblom, Petra Rajala, Jenna Rautanen, Anne Riikonen, Mika Riikonen, Jenni Rouhiainen, Minna Romo, Tuula Simell, Maija Sjöberg, Aino Stenius, Maria Leppänen, Sini Vainionpää, Eeva Varjonen, Riitta Veijola, Suvi M. Virtanen, Mari Vähä-Mäkilä, Mari Åkerlund, Katri Lindfors, Desmond Schatz, Diane Hopkins, Leigh Steed, Jamie Thomas, Janey Adams, Katherine Silvis, Michael Haller, Melissa Gardiner, Richard A McIndoe, Ashok Kumar Sharma, Joshua William, Gabriela Young, Stephen W. Anderson, Laura Jacobsen, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Nicole Janz, Mathilde Kersting, Annette Knopff, Claudia Peplow, Roswith Roth, Marlon Scholz, Joanna Stock, Katharina Warncke, Lorena Wendel, Christiane Winkler, Carin Andrén Aronsson, Maria Ask, Jenny Bremer, Ulla Marie Carlsson, Corrado Cilio, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Rasmus Bennet, Monica Hansen, Gertie Hansson, Susanne Hyberg, Fredrik Johansen, Berglind Jonsdottir, Marielle Lindström, Markus Lundgren, Maria Månsson-Martinez, Maria Markan, Jessica Melin, Zeliha Mestan, Karin Ottosson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Evelyn Tekum Amboh, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Josephine Carson, Maria Dalzell, Kayleen Dunson, Rachel Hervey, Corbin Johnson, Rachel Lyons, Arlene Meyer, Denise Mulenga, Alexander Tarr, Morgan Uland, John Willis, Dorothy Becker, Margaret Franciscus, Mary Ellen Dalmagro Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Michael Abbondondolo, Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Jennifer Garmeson, Veena Gowda, Kathleen Heyman, Francisco Perez Laras, Hye Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Steven Meulemans, Hemang Parikh, Chris Shaffer, Laura Smith, Susan Smith, Noah Sulman, Roy Tamura, Ulla Uusitalo, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Lori Ballard, David Hadley, Wendy McLeod, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Liping Yu, Dongmei Miao, Polly Bingley, Alistair William's, Kyla Chandler, Saba Rokni, Claire Willia, Rebecca Wyatt, Gifty George, Sian Grace, Niveen Mulholland

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)1217-1225
Number of pages9
JournalJAMA Pediatrics
Volume171
Issue number12
DOIs
StatePublished - Dec 2017

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Kemppainen, K. M., Vehik, K., Lynch, K. F., Larsson, H. E., Canepa, R. J., Simell, V., Koletzko, S., Liu, E., Simell, O. G., Toppari, J., Ziegler, A. G., Rewers, M. J., Lernmark, Å., Hagopian, W. A., She, J-X., Akolkar, B., Schatz, D. A., Atkinson, M. A., Blaser, M. J., ... Mulholland, N. (2017). Association between early-life antibiotic use and the risk of islet or celiac disease autoimmunity. JAMA Pediatrics, 171(12), 1217-1225. https://doi.org/10.1001/jamapediatrics.2017.2905