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Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity

Kemppainen, Kaisa M ; Vehik, Kendra LU ; Lynch, Kristian F LU ; Larsson, Helena Elding LU orcid ; Canepa, Ronald J ; Simell, Ville ; Koletzko, Sibylle ; Liu, Edwin ; Simell, Olli G and Toppari, Jorma , et al. (2017) In JAMA Pediatrics 171(12). p.1217-1225
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... (More)

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.

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keywords
Age Factors, Anti-Bacterial Agents, Autoantibodies, Autoimmune Diseases, Celiac Disease, Child, Preschool, Diabetes Mellitus, Type 1, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Utilization, Europe, Female, Follow-Up Studies, Genetic Predisposition to Disease, HLA-DR Antigens, Histocompatibility Testing, Humans, Infant, Islets of Langerhans, Male, Prospective Studies, Risk Assessment, Sensitivity and Specificity, United States, Multicenter Study
in
JAMA Pediatrics
volume
171
issue
12
pages
9 pages
publisher
American Medical Association
external identifiers
  • scopus:85038220552
  • wos:000416971000020
  • pmid:29052687
ISSN
2168-6211
DOI
10.1001/jamapediatrics.2017.2905
language
English
LU publication?
yes
id
9d6b780f-6cb0-4264-b457-1ddf41166622
date added to LUP
2018-01-11 14:49:27
date last changed
2025-01-08 02:38:35
@article{9d6b780f-6cb0-4264-b457-1ddf41166622,
  abstract     = {{<p>Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases.</p><p>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.</p><p>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.</p><p>Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively.</p><p>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.</p><p>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).</p><p>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.</p>}},
  author       = {{Kemppainen, Kaisa M and Vehik, Kendra and Lynch, Kristian F and Larsson, Helena Elding and Canepa, Ronald J and Simell, Ville and Koletzko, Sibylle and Liu, Edwin and Simell, Olli G and Toppari, Jorma and Ziegler, Anette G and Rewers, Marian J and Lernmark, Åke and Hagopian, William A and She, Jin-Xiong and Akolkar, Beena and Schatz, Desmond A and Atkinson, Mark A and Blaser, Martin J and Krischer, Jeffrey P and Hyöty, Heikki and Agardh, Daniel and Triplett, Eric W}},
  issn         = {{2168-6211}},
  keywords     = {{Age Factors; Anti-Bacterial Agents; Autoantibodies; Autoimmune Diseases; Celiac Disease; Child, Preschool; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Utilization; Europe; Female; Follow-Up Studies; Genetic Predisposition to Disease; HLA-DR Antigens; Histocompatibility Testing; Humans; Infant; Islets of Langerhans; Male; Prospective Studies; Risk Assessment; Sensitivity and Specificity; United States; Multicenter Study}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  pages        = {{1217--1225}},
  publisher    = {{American Medical Association}},
  series       = {{JAMA Pediatrics}},
  title        = {{Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity}},
  url          = {{http://dx.doi.org/10.1001/jamapediatrics.2017.2905}},
  doi          = {{10.1001/jamapediatrics.2017.2905}},
  volume       = {{171}},
  year         = {{2017}},
}