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Original Investigation |

Respiratory Infections in Early Life and the Development of Islet Autoimmunity in Children at Increased Type 1 Diabetes Risk:  Evidence From the BABYDIET Study

Andreas Beyerlein, PhD1; Fabienne Wehweck1; Anette-Gabriele Ziegler, MD1,2; Maren Pflueger, PhD1
[+] Author Affiliations
1Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes der Technischen Universität München, Munich, Germany
2Forschergruppe Diabetes e. V. am Helmholtz Zentrum München, Munich, Germany
JAMA Pediatr. 2013;167(9):800-807. doi:10.1001/jamapediatrics.2013.158.
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Published online

Importance  There is evidence for a role of infections within the pathogenesis of islet autoimmunity and type 1 diabetes mellitus (T1D), but previous studies did not allow assessment of potential critical time windows in this context.

Objective  To examine whether early, short-term, or cumulative exposures to episodes of infection and fever during the first 3 years of life were associated with the initiation of persistent islet autoimmunity in children at increased T1D risk.

Design  Prospective cohort study with daily infection records and regular assessment of islet autoimmunity.

Setting  Diabetes Research Institute, Munich, Germany.

Participants  A total of 148 children at high T1D risk with documentation of 1245 infectious events in 90 750 person-days during their first 3 years of life.

Main Outcomes and Measures  Hazard ratios (HRs) for seroconversion to persistent islet autoantibodies were assessed in Cox regression models with numbers of respiratory, gastrointestinal, and other infections, adjusting for sex, delivery mode, intervention group, season of birth, and antibiotic use.

Results  An increased HR of islet autoantibody seroconversion was associated with respiratory infections during the first 6 months of life (HR = 2.27; 95% CI, 1.32-3.91) and ages 6.0 to 11.9 months (HR = 1.32; 95% CI, 1.08-1.61). During the second year of life, no meaningful effects were detected for any infectious category. A higher number of respiratory infections in the 6 months prior to islet autoantibody seroconversion was also associated with an increased HR (HR = 1.42; 95% CI, 1.12-1.80).

Conclusions and Relevance  Respiratory infections in early childhood are a potential risk factor for the development of T1D.

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Figure 1.
Incidences of Infectious and Fever Events

Mean incidences of infectious and fever events per 100 documented days in the first 3 years of life in the BABYDIET data.

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Figure 2.
Rates of Islet Autoantibody Seroconversion

Rates of islet autoantibody seroconversion by total number of infectious events, including any infections (A) and respiratory infections (B), in the first year of life as recorded in the BABYDIET data.

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Figure 3.
Total Cumulative Numbers of Any Infections in Children With and Without Islet Autoantibody Seroconversion

A, Interquartile ranges of cumulative number of infections are depicted in 3-monthly intervals up to age 24 months. For each time point, subjects with prior seroconversion were excluded from the respective calculations. B, Cumulative numbers of infections at age 24 months are shown in detail.

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Figure 4.
Seventy-fifth Percentiles of Distributions of Total Cumulative Numbers of Infections

Seventy-fifth percentiles of the distributions of total cumulative numbers of respiratory, gastrointestinal, and other infections in children with and without islet autoantibody seroconversion in 3-monthly intervals up to age 24 months. For each time point, subjects with prior seroconversion were excluded from the respective calculations.

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