Use of antibiotics in early life and development of diseases in childhood: nationwide registry study.

Objective: To investigate the association between the use of antibiotics in early life and the development of immune mediated diseases in children and adolescents. Design: Nationwide registry study. Setting: National Danish registries: Danish Civil Registration System identified children born in Denmark; information on the use of antibiotics from the Danish National Prescription Registry; disease outcomes from the Danish National Prescription Registry and the Danish National Patient Registry; and relevant covariates from the Danish Medical Birth Register and the Employment Classification Module. Study period from 1 January 1998 to 31 December 2016. Participants: Of 648 507 children born in Denmark in 1998-2006, 518 483 resided in Denmark during their first year of life, had no disease outcomes before the age of one year, and formed the final study population. The sibling population was 272 753 (126 632 sibships). Main outcome measures: Risk of developing immune mediated diseases (asthma, allergy, eczema, coeliac disease, juvenile arthritis, and type 1 diabetes) and overweight in the total population and in a sibling matched cohort (to mitigate the influence of familial factors and unmeasured confounding), by survival analysis with Cox regression. Results: Children were followed up for a mean of 13.2 years (standard deviation 3.12). Among the total study population, 40.3% (n=209 013) of children were prescribed systemic antibiotics before the age of one year. Use of antibiotics was associated with an increased risk of several immune mediated diseases (adjusted hazard ratios 1.20-1.53). A dose-response relation was found. When analysing sibling pairs, only asthma and eczema outcomes (adjusted hazard ratios 1.07-1.35) were associated with the use of antibiotics. No specific trends about the timing of use or type of antibiotic were found. Conclusions: In this study, use of antibiotics in early life was linked with immune mediated diseases in childhood and adolescence, but familial and unmeasured factors within the family might provide partial explanations. The study emphasises the need to better understand the interactions between antibiotics, familial susceptibility, and immune mediated pathogenesis to identify potential preventive strategies.