Antibiotics during childhood and development of appendicitis—a nationwide cohort study
The Handling Editor for this article was Professor Jonathan Rhodes, and it was accepted for publication after full peer-review.
Funding information
This research was funded by the AP Moeller Foundation for the Advancement of Medical Science (17-L-0004), the Novo Nordisk Foundation (NNFOC0017740) and the Danish Council of Independent Research (F-12815-01-76). The funders had no role in the design and conduct of the study; management, analysis, and interpretation of the data; approval of the manuscript; and decision to submit the manuscript for publication. The content of this article is solely the responsibility of the authors.
Summary
Background
Appendicitis is a common disease with a lifespan risk of approximately 8%. The full range of specific causes for the disease remains elusive, but an aberrant microbiota have been identified as a potential risk factor.
Aim
To investigate if use of antibiotics in a paediatric population increases the risk of appendicitis in childhood and adolescence
Methods
We conducted a cohort study from 1 January 1995 to 31 December 2014. A total of 1 385 707 children (0-19 years of age) including 7 406 397 antibiotic prescriptions and 11 861 cases of appendicitis were included. Primary outcome was appendicitis requiring appendectomy according to previous use of antibiotics. Appendicitis and appendectomy were identified from nationwide hospital records, and exposure to antibiotics was identified from nationwide prescription register. Rate ratios (RRs) with 95% confidence intervals were estimated from Poisson and logistic regression models.
Results
Children who received at least one course of antibiotics were at increased risk of developing appendicitis compared to unexposed children (adjusted RR 1.72 [95% confidence interval 1.61-1.85]), mean age of developing appendicitis was 9.8 years (SD 4.1 years). The RR of appendicitis increased by 1.04 (1.04-1.04) per antibiotic course. A higher risk of appendicitis was observed in children exposed to antibiotics within the first 6 months of life (RR 1.46 [1.36-1.56]) and children exposed to broad-spectrum antibiotics (RR 1.33 [1.27-1.39]). After adjustment for number of antibiotic courses, the association between early age of antibiotic exposure and risk of appendicitis and the association between exposure to broad-spectrum antibiotics and the risk of appendicitis both disappeared.
Conclusion
Children who receive antibiotics are at increased and dose-dependent risk of appendicitis. The underlying mechanisms merit further investigation.
Open Research
DATA AVAILABILITY STATEMENT
The study is based on data from the Danish National Patient Register and the Danish Registry of Medicinal Product Statistics (https://sundhedsdatastyrelsen.dk). These registers are protected by the Danish Act on Processing of Personal Data and can be accessed through application to and approval from the Danish Data Protection Agency and the Danish Health Data Authority [https://sundhedsdatastyrelsen.dk/da/forskerservice/ansog-om-data] where the purpose and the feasibility of the intended analysis should be accounted for. Informed consent and assessment of the proposal in scientific ethical committees are not required for registry-based research in Denmark.
