Early-life exposure to antibiotics and subsequent development of atopic dermatitis

ABSTRACT

Background

Antibiotic exposure may be associated with atopic dermatitis (AD). We assessed the risk of developing AD among children early exposed to antibiotics.

Research design and methods

From the Italian Pedianet database, children aged 0-14 years between 2004-2017 were enrolled from birth up to at least one year. Cox proportional-hazards models were fitted to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CI) for the association between antibiotic exposure during the first year of life with incident AD. Exposure was also considered as a time-varying variable. 

Results

73,816 children were included in the final cohort, of which 34,202 had at least one antibiotic prescription. Incident AD was present in 8% of unexposed and exposed children. Early antibiotic exposure was not associated with any excess risk of AD compared to unexposed children (HR: 1.02, 95% CI: 0.97-1.07), and no dose-response effect was observed. In the time-varying analysis, antibiotic exposure was significantly associated with AD onset (1.12, 1.07-1.17). However, when taking into account the time-lag between exposure and outcome, risks progressively decreased, suggesting possible protopathic bias.

Conclusion

These results are not suggestive of any significant association between exposure to antibiotics and subsequent AD onset and support the possible presence of protopathic bias.

KEYWORDS:

• Dermatitis
• atopic dermatitis
• antibiotic exposure
• early exposure
• birth cohort

Acknowledgments

The authors thank all the family paediatricians collaborating in Pedianet.

Author contributions

Conceptualization: A Cantarutti, CB Amidei and C Canova; methodology: A Cantarutti and C Canova; validation: A Cantarutti, CB Amidei and C Canova; formal analysis: AS Bonaugurio; writing—original draft preparation: A Cantarutti, CB Amidei, P Rescigno and C Canova; supervision: A Cantarutti, CB Amidei, P Rescigno and C Canova. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The data used in this study cannot be made available in the manuscript, the supplemental files or in a public repository due to Italian data protection laws. The anonymized datasets generated during and/or analyzed during the current study can be provided on reasonable request, from the corresponding author, after written approval by the Internal Scientific Committee ([email protected]; https://www.pedianet.it/en/contacts).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethics approval

This is an observational, retrospective, non-interventional study. According to a by-law on the classification and implementation of observational drug-related research, as issued by the Italian National Drug Agency (an entity belonging to the Italian Ministry of Health), the present study does not require approval by an Ethics Committee in Italy (Italian Drug Agency note of 3 August 2007). This study followed the principles of the Declaration of Helsinki and compliant with the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance Guide on Methodological Standards in Pharmacoepidemiology.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This paper was not funded.