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 language | English (US) |
|---|---|
| Pages (from-to) | 1217-1225 |
| Number of pages | 9 |
| Journal | JAMA Pediatrics |
| Volume | 171 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2017 |
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
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Association between early-life antibiotic use and the risk of islet or celiac disease autoimmunity. / 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, Åke; Hagopian, William A.; She, Jin-Xiong; Akolkar, Beena; Schatz, Desmond A.; Atkinson, Mark A.; Blaser, Martin J.; Krischer, Jeffrey P.; Hyöty, Heikki; Agardh, Daniel; Triplett, Eric W.; Bautista, Kimberly; Baxter, Judith; Bedoy, Ruth; Felipe-Morales, Daniel; Driscoll, Kimberly; Frohnert, Brigitte I.; Gesualdo, Patricia; Hoffman, Michelle; Karban, Rachel; Norris, Jill; Samper-Imaz, Adela; Steck, Andrea; Waugh, Kathleen; Wright, Hali; Adamsson, Annika; Ahonen, Suvi; Ilonen, Jorma; Jokipuu, Sanna; Kallio, Tiina; Karlsson, Leena; Kähönen, Miia; Knip, Mikael; Kovanen, Lea; Koreasalo, Mirva; Kurppa, Kalle; Latva-Aho, Tiina; Lönnrot, Maria; Mäntymäki, Elina; Multasuo, Katja; Mykkänen, Juha; Niininen, Tiina; Niinistö, Sari; Nyblom, Mia; Rajala, Petra; Rautanen, Jenna; Riikonen, Anne; Riikonen, Mika; Rouhiainen, Jenni; Romo, Minna; Simell, Tuula; Sjöberg, Maija; Stenius, Aino; Leppänen, Maria; Vainionpää, Sini; Varjonen, Eeva; Veijola, Riitta; Virtanen, Suvi M.; Vähä-Mäkilä, Mari; Åkerlund, Mari; Lindfors, Katri; Schatz, Desmond; Hopkins, Diane; Steed, Leigh; Thomas, Jamie; Adams, Janey; Silvis, Katherine; Haller, Michael; Gardiner, Melissa; McIndoe, Richard A; Sharma, Ashok Kumar; William, Joshua; Young, Gabriela; Anderson, Stephen W.; Jacobsen, Laura; Beyerlein, Andreas; Bonifacio, Ezio; Hummel, Michael; Hummel, Sandra; Foterek, Kristina; Janz, Nicole; Kersting, Mathilde; Knopff, Annette; Peplow, Claudia; Roth, Roswith; Scholz, Marlon; Stock, Joanna; Warncke, Katharina; Wendel, Lorena; Winkler, Christiane; Aronsson, Carin Andrén; Ask, Maria; Bremer, Jenny; Carlsson, Ulla Marie; Cilio, Corrado; Ericson-Hallström, Emelie; Fransson, Lina; Gard, Thomas; Gerardsson, Joanna; Bennet, Rasmus; Hansen, Monica; Hansson, Gertie; Hyberg, Susanne; Johansen, Fredrik; Jonsdottir, Berglind; Lindström, Marielle; Lundgren, Markus; Månsson-Martinez, Maria; Markan, Maria; Melin, Jessica; Mestan, Zeliha; Ottosson, Karin; Rahmati, Kobra; Ramelius, Anita; Salami, Falastin; Sibthorpe, Sara; Sjöberg, Birgitta; Swartling, Ulrica; Amboh, Evelyn Tekum; Törn, Carina; Wallin, Anne; Wimar, Åsa; Åberg, Sofie; Killian, Michael; Crouch, Claire Cowen; Skidmore, Jennifer; Carson, Josephine; Dalzell, Maria; Dunson, Kayleen; Hervey, Rachel; Johnson, Corbin; Lyons, Rachel; Meyer, Arlene; Mulenga, Denise; Tarr, Alexander; Uland, Morgan; Willis, John; Becker, Dorothy; Franciscus, Margaret; Smith, Mary Ellen Dalmagro Elias; Daftary, Ashi; Klein, Mary Beth; Yates, Chrystal; Abbondondolo, Michael; Austin-Gonzalez, Sarah; Avendano, Maryouri; Baethke, Sandra; Brown, Rasheedah; Burkhardt, Brant; Butterworth, Martha; Clasen, Joanna; Cuthbertson, David; Eberhard, Christopher; Fiske, Steven; Garcia, Dena; Garmeson, Jennifer; Gowda, Veena; Heyman, Kathleen; Laras, Francisco Perez; Lee, Hye Seung; Liu, Shu; Liu, Xiang; Lynch, Kristian; Malloy, Jamie; McCarthy, Cristina; Meulemans, Steven; Parikh, Hemang; Shaffer, Chris; Smith, Laura; Smith, Susan; Sulman, Noah; Tamura, Roy; Uusitalo, Ulla; Vijayakandipan, Ponni; Wood, Keith; Yang, Jimin; Ballard, Lori; Hadley, David; McLeod, Wendy; Bourcier, Kasia; Briese, Thomas; Johnson, Suzanne Bennett; Yu, Liping; Miao, Dongmei; Bingley, Polly; William's, Alistair; Chandler, Kyla; Rokni, Saba; Willia, Claire; Wyatt, Rebecca; George, Gifty; Grace, Sian; Mulholland, Niveen.
In: JAMA Pediatrics, Vol. 171, No. 12, 12.2017, p. 1217-1225.Research output: Contribution to journal › Article › peer-review
}
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 - Bautista, Kimberly
AU - Baxter, Judith
AU - Bedoy, Ruth
AU - Felipe-Morales, Daniel
AU - Driscoll, Kimberly
AU - Frohnert, Brigitte I.
AU - Gesualdo, Patricia
AU - Hoffman, Michelle
AU - Karban, Rachel
AU - Norris, Jill
AU - Samper-Imaz, Adela
AU - Steck, Andrea
AU - Waugh, Kathleen
AU - Wright, Hali
AU - Adamsson, Annika
AU - Ahonen, Suvi
AU - Ilonen, Jorma
AU - Jokipuu, Sanna
AU - Kallio, Tiina
AU - Karlsson, Leena
AU - Kähönen, Miia
AU - Knip, Mikael
AU - Kovanen, Lea
AU - Koreasalo, Mirva
AU - Kurppa, Kalle
AU - Latva-Aho, Tiina
AU - Lönnrot, Maria
AU - Mäntymäki, Elina
AU - Multasuo, Katja
AU - Mykkänen, Juha
AU - Niininen, Tiina
AU - Niinistö, Sari
AU - Nyblom, Mia
AU - Rajala, Petra
AU - Rautanen, Jenna
AU - Riikonen, Anne
AU - Riikonen, Mika
AU - Rouhiainen, Jenni
AU - Romo, Minna
AU - Simell, Tuula
AU - Sjöberg, Maija
AU - Stenius, Aino
AU - Leppänen, Maria
AU - Vainionpää, Sini
AU - Varjonen, Eeva
AU - Veijola, Riitta
AU - Virtanen, Suvi M.
AU - Vähä-Mäkilä, Mari
AU - Åkerlund, Mari
AU - Lindfors, Katri
AU - Schatz, Desmond
AU - Hopkins, Diane
AU - Steed, Leigh
AU - Thomas, Jamie
AU - Adams, Janey
AU - Silvis, Katherine
AU - Haller, Michael
AU - Gardiner, Melissa
AU - McIndoe, Richard A
AU - Sharma, Ashok Kumar
AU - William, Joshua
AU - Young, Gabriela
AU - Anderson, Stephen W.
AU - Jacobsen, Laura
AU - Beyerlein, Andreas
AU - Bonifacio, Ezio
AU - Hummel, Michael
AU - Hummel, Sandra
AU - Foterek, Kristina
AU - Janz, Nicole
AU - Kersting, Mathilde
AU - Knopff, Annette
AU - Peplow, Claudia
AU - Roth, Roswith
AU - Scholz, Marlon
AU - Stock, Joanna
AU - Warncke, Katharina
AU - Wendel, Lorena
AU - Winkler, Christiane
AU - Aronsson, Carin Andrén
AU - Ask, Maria
AU - Bremer, Jenny
AU - Carlsson, Ulla Marie
AU - Cilio, Corrado
AU - Ericson-Hallström, Emelie
AU - Fransson, Lina
AU - Gard, Thomas
AU - Gerardsson, Joanna
AU - Bennet, Rasmus
AU - Hansen, Monica
AU - Hansson, Gertie
AU - Hyberg, Susanne
AU - Johansen, Fredrik
AU - Jonsdottir, Berglind
AU - Lindström, Marielle
AU - Lundgren, Markus
AU - Månsson-Martinez, Maria
AU - Markan, Maria
AU - Melin, Jessica
AU - Mestan, Zeliha
AU - Ottosson, Karin
AU - Rahmati, Kobra
AU - Ramelius, Anita
AU - Salami, Falastin
AU - Sibthorpe, Sara
AU - Sjöberg, Birgitta
AU - Swartling, Ulrica
AU - Amboh, Evelyn Tekum
AU - Törn, Carina
AU - Wallin, Anne
AU - Wimar, Åsa
AU - Åberg, Sofie
AU - Killian, Michael
AU - Crouch, Claire Cowen
AU - Skidmore, Jennifer
AU - Carson, Josephine
AU - Dalzell, Maria
AU - Dunson, Kayleen
AU - Hervey, Rachel
AU - Johnson, Corbin
AU - Lyons, Rachel
AU - Meyer, Arlene
AU - Mulenga, Denise
AU - Tarr, Alexander
AU - Uland, Morgan
AU - Willis, John
AU - Becker, Dorothy
AU - Franciscus, Margaret
AU - Smith, Mary Ellen Dalmagro Elias
AU - Daftary, Ashi
AU - Klein, Mary Beth
AU - Yates, Chrystal
AU - Abbondondolo, Michael
AU - Austin-Gonzalez, Sarah
AU - Avendano, Maryouri
AU - Baethke, Sandra
AU - Brown, Rasheedah
AU - Burkhardt, Brant
AU - Butterworth, Martha
AU - Clasen, Joanna
AU - Cuthbertson, David
AU - Eberhard, Christopher
AU - Fiske, Steven
AU - Garcia, Dena
AU - Garmeson, Jennifer
AU - Gowda, Veena
AU - Heyman, Kathleen
AU - Laras, Francisco Perez
AU - Lee, Hye Seung
AU - Liu, Shu
AU - Liu, Xiang
AU - Lynch, Kristian
AU - Malloy, Jamie
AU - McCarthy, Cristina
AU - Meulemans, Steven
AU - Parikh, Hemang
AU - Shaffer, Chris
AU - Smith, Laura
AU - Smith, Susan
AU - Sulman, Noah
AU - Tamura, Roy
AU - Uusitalo, Ulla
AU - Vijayakandipan, Ponni
AU - Wood, Keith
AU - Yang, Jimin
AU - Ballard, Lori
AU - Hadley, David
AU - McLeod, Wendy
AU - Bourcier, Kasia
AU - Briese, Thomas
AU - Johnson, Suzanne Bennett
AU - Yu, Liping
AU - Miao, Dongmei
AU - Bingley, Polly
AU - William's, Alistair
AU - Chandler, Kyla
AU - Rokni, Saba
AU - Willia, Claire
AU - Wyatt, Rebecca
AU - George, Gifty
AU - Grace, Sian
AU - Mulholland, Niveen
N1 - Funding Information: Funding/Support: This study was funded by grants U01 DK63829, U01 6 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, 7 U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 8 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, and UC4 DK106955 and by contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases. The TEDDY study is also funded by grants from the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the Juvenile Diabetes Research Foundation, and the Centers for Disease Control and Prevention. Publisher Copyright: © 2017 American Medical Association. All rights reserved.
PY - 2017/12
Y1 - 2017/12
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 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85038220552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038220552&partnerID=8YFLogxK
U2 - 10.1001/jamapediatrics.2017.2905
DO - 10.1001/jamapediatrics.2017.2905
M3 - Article
C2 - 29052687
AN - SCOPUS:85038220552
VL - 171
SP - 1217
EP - 1225
JO - A.M.A. American journal of diseases of children
JF - A.M.A. American journal of diseases of children
SN - 2168-6203
IS - 12
ER -