TY - JOUR T1 - Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02021-2019 SP - 1902021 AU - Slob, Elise M.A. AU - Brew, Bronwyn K. AU - Vijverberg, Susanne J.H. AU - Kats, Chantal J.A.R. AU - Longo, Cristina AU - Pijnenburg, Mariëlle W. AU - van Beijsterveldt, Toos C.E.M. AU - Dolan, Conor V. AU - Bartels, Meike AU - Magnusson, Patrick AU - Lichtenstein, Paul AU - Gong, Tong AU - Koppelman, Gerard H. AU - Almqvist, Catarina AU - Boomsma, Dorret I. AU - Maitland-van der Zee, Anke H. Y1 - 2020/01/01 UR - //www.qdcxjkg.com/content/early/2020/02/06/13993003.02021-2019.abstract N2 - Rationale Early-life antibiotic use has been associated with development of atopic diseases, but the aetiology remains unclear. To elucidate aetiology, we used a discordant twin design to control for genetic and environmental confounding.Methods We conducted a retrospective cohort study in twins (3–10 years) from the Netherlands Twin Register (NTR, n=34 352) and a replication study at age 9 in the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7906). Antibiotic use was recorded at 0–2 years. Doctor diagnosed asthma and eczema were reported by parents when children were 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 1.45 95%CI 1.34–1.56) and eczema (NTR OR 1.08 95%CI 1.03–1.13; CATSS 1.07 95%CI 1.01–1.14) in unmatched analyses. Co-twin analyses in mono- and dizygotic twin pairs showed similar results for asthma (NTR 1.54 95%CI 1.20–1.98 and CATSS 2.00 95%CI 1.28–3.13), but opposing results for eczema in NTR (0.99 95%CI 0.80–1.25) and CATSS (1.67 95%CI 1.12–2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS 1.45 95%CI 1.34–1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Drs. Slob has nothing to disclose.Conflict of interest: Dr. Brew has nothing to disclose.Conflict of interest: Dr. Vijverberg has nothing to disclose.Conflict of interest: Dr. Kats has nothing to disclose.Conflict of interest: Dr. Longo has nothing to disclose.Conflict of interest: Dr. Pijnenburg has nothing to disclose.Conflict of interest: Dr. van Beijsterveldt has nothing to disclose.Conflict of interest: Prof. dr. Dolan has nothing to disclose.Conflict of interest: Prof. dr. Bartels has nothing to disclose.Conflict of interest: Prof. dr. Magnusson has nothing to disclose.Conflict of interest: Prof. dr. Lichtenstein has nothing to disclose.Conflict of interest: Dr. Gong has nothing to disclose.Conflict of interest: Dr. koppelman reports grants from Lung Foundation of the Netherlands, TEVA the Netherlands, UBBO EMMIUS Foundation, TETRI Foundation, GSK, and VERTEX, outside the submitted work; and GHK partipated in a global advisory board on pediatric asthma for GSK.Conflict of interest: Prof. dr. Almqvist has nothing to disclose.Conflict of interest: Prof. Dr. Boomsma has nothing to disclose.Conflict of interest: Dr. Maitland-van der Zee reports grants and personal fees from GSK, grants and personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, grants from Chiesi, outside the submitted work. ER -