Abstract
Rationale Early-life antibiotic use has been associated with the development of atopic diseases, but the aetiology remains unclear. To elucidate the aetiology, we used a discordant twin design to control for genetic and environmental confounding.
Methods We conducted a retrospective cohort study in twins aged 3–10 years from the Netherlands Twin Register (NTR, n=35 365) and a replication study in twins aged 9 years from the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7916). Antibiotic use was recorded at age 0–2 years. Doctor-diagnosed asthma and eczema were reported by parents when children were aged 3–12 years in both cohorts. Individuals were included in unmatched analyses and in co-twin control analyses with disease discordant twin pairs.
Results Early-life antibiotic use was associated with increased risk of asthma (NTR OR 1.34, 95% CI 1.28–1.41; CATSS OR 1.45, 95% CI 1.34–1.56) and eczema (NTR OR 1.08, 95% CI 1.03–1.13; CATSS OR 1.07, 95% CI 1.01–1.14) in unmatched analyses. Co-twin analyses in monozygotic and dizygotic twin pairs showed similar results for asthma (NTR OR 1.54, 95% CI 1.20–1.98; CATSS OR 2.00, 95% CI 1.28–3.13), but opposing results for eczema in the NTR (OR 0.99, 95% CI 0.80–1.25) and the CATSS (OR 1.67, 95% CI 1.12–2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS OR 1.45, 95% CI 1.34–1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS OR 1.02, 95% CI 0.88–1.17).
Conclusion Children exposed to early-life antibiotic use, particularly prescribed for respiratory infections, may be at higher risk of asthma. This risk can still be observed when correcting for genetic and environmental factors. Our results could not elucidate whether the relationship between early-life antibiotic use and eczema is confounded by familial and genetic factors.
Abstract
Large twin studies show that antibiotics in early life are associated with risk of asthma, regardless of familial environment and genetics, and possibly due to early infections. Risks and benefits of antibiotics use in infants should be considered. http://bit.ly/372Qu5A
Footnotes
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: E.M.A. Slob has nothing to disclose.
Conflict of interest: B.K. Brew has nothing to disclose.
Conflict of interest: S.J.H. Vijverberg has nothing to disclose.
Conflict of interest: C.J.A.R. Kats has nothing to disclose.
Conflict of interest: C. Longo has nothing to disclose.
Conflict of interest: M.W. Pijnenburg has nothing to disclose.
Conflict of interest: T.C.E.M. van Beijsterveldt has nothing to disclose.
Conflict of interest: C.V. Dolan has nothing to disclose.
Conflict of interest: M. Bartels has nothing to disclose.
Conflict of interest: P. Magnusson has nothing to disclose.
Conflict of interest: P. Lichtenstein has nothing to disclose.
Conflict of interest: T. Gong has nothing to disclose.
Conflict of interest: G.H. Koppelman reports grants from Lung Foundation of the Netherlands, Teva, Ubbo Emmius Foundation, Tetri Foundation, GSK and Vertex, outside the submitted work; and has participated in a global advisory board on paediatric asthma for GSK.
Conflict of interest: C. Almqvist has nothing to disclose.
Conflict of interest: D.I. Boomsma has nothing to disclose.
Conflict of interest: A.H. Maitland-van der Zee reports grants and personal fees for advisory board work from GSK and Boehringer Ingelheim, personal fees for advisory board work from AstraZeneca, grants from Chiesi, outside the submitted work.
Support statement: E.M.A. Slob was supported by the Dutch Lung Foundation, Amsterdam Public Health, AMC Young Talent Fund and Jo Kolk Studiefonds. The Netherlands Twin Registry gratefully acknowledges NWO-Groot (grant 480-15-001/674: Netherlands Twin Registry Repository) and the Royal Netherlands Academy of Science Professor Award (PAH/6635) to D.I. Boomsma. Financial support for the Childhood and Adolescent Twin Study in Sweden was provided from the Swedish Research Council (framework grant 340-2013-5867), grants from the Stockholm County Council (ALF-projects) and the Swedish Heart–Lung Foundation. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council (grant 2017-00641). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received October 14, 2019.
- Accepted January 30, 2020.
- Copyright ©ERS 2020
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