Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study

Elise M A Slob; Bronwyn K Brew; Susanne J H Vijverberg; Chantal J A R Kats; Cristina Longo; Mariëlle W Pijnenburg; Toos C E M van Beijsterveldt; Conor V Dolan; Meike Bartels; Patrick Magnusson; Paul Lichtenstein; Tong Gong; Gerard H Koppelman; Catarina Almqvist; Dorret I Boomsma; Anke H Maitland-van der Zee

doi:10.1183/13993003.02021-2019

Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study

Elise M A Slob, Bronwyn K Brew, Susanne J H Vijverberg, Chantal J A R Kats, Cristina Longo, Mariëlle W Pijnenburg, Toos C E M van Beijsterveldt, Conor V Dolan, Meike Bartels, Patrick Magnusson, Paul Lichtenstein, Tong Gong, Gerard H Koppelman, Catarina Almqvist, Dorret I Boomsma, Anke H Maitland-van der Zee

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Abstract

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.

Original language	English
Article number	1902021
Pages (from-to)	1-11
Number of pages	11
Journal	European Respiratory Journal
Volume	55
Issue number	4
Early online date	5 Mar 2020
DOIs	https://doi.org/10.1183/13993003.02021-2019
Publication status	Published - Apr 2020

Bibliographical note

Funding

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. 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.

Funders	Funder number
ALF-projects
Amsterdam Public Health
Jo Kolk Studiefonds
NWO-Groot	480-15-001/674
Royal Netherlands Academy of Science	PAH/6635
Stichting Jo Kolk Studiefonds
Hjärt-Lungfonden
Karolinska Institutet	2017-00641
Stockholms Läns Landsting
Vetenskapsrådet	340-2013-5867
Lung Foundation Netherlands

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1183/13993003.02021-2019

Earlylife antibiotic use and risk of asthma and eczema_results of a discordant twin studyFinal published version, 421 KBLicence: Article 25fa Dutch Copyright Act

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Slob, E. M. A., Brew, B. K., Vijverberg, S. J. H., Kats, C. J. A. R., Longo, C., Pijnenburg, M. W., van Beijsterveldt, T. C. E. M., Dolan, C. V., Bartels, M., Magnusson, P., Lichtenstein, P., Gong, T., Koppelman, G. H., Almqvist, C., Boomsma, D. I., & Maitland-van der Zee, A. H. (2020). Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study. European Respiratory Journal, 55(4), 1-11. Article 1902021. https://doi.org/10.1183/13993003.02021-2019

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abstract = "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.",

author = "Slob, {Elise M A} and Brew, {Bronwyn K} and Vijverberg, {Susanne J H} and Kats, {Chantal J A R} and Cristina Longo and Pijnenburg, {Mari{\"e}lle W} and {van Beijsterveldt}, {Toos C E M} and Dolan, {Conor V} and Meike Bartels and Patrick Magnusson and Paul Lichtenstein and Tong Gong and Koppelman, {Gerard H} and Catarina Almqvist and Boomsma, {Dorret I} and {Maitland-van der Zee}, {Anke H}",

note = "Copyright {\textcopyright}ERS 2020.",

year = "2020",

month = apr,

doi = "10.1183/13993003.02021-2019",

language = "English",

volume = "55",

pages = "1--11",

journal = "European Respiratory Journal",

issn = "0903-1936",

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Slob, EMA, Brew, BK, Vijverberg, SJH, Kats, CJAR, Longo, C, Pijnenburg, MW, van Beijsterveldt, TCEM, Dolan, CV , Bartels, M, Magnusson, P, Lichtenstein, P, Gong, T, Koppelman, GH, Almqvist, C, Boomsma, DI & Maitland-van der Zee, AH 2020, 'Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study', European Respiratory Journal, vol. 55, no. 4, 1902021, pp. 1-11. https://doi.org/10.1183/13993003.02021-2019

TY - JOUR

T1 - Early-life antibiotic use and risk of asthma and eczema

T2 - results of a discordant twin study

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

PY - 2020/4

Y1 - 2020/4

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.

AB - 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.

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U2 - 10.1183/13993003.02021-2019

DO - 10.1183/13993003.02021-2019

M3 - Article

C2 - 32139457

SN - 0903-1936

VL - 55

SP - 1

EP - 11

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 4

M1 - 1902021

ER -

Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study

Abstract

Bibliographical note

Funding

Cohort Studies

UN SDGs

Access to Document

Persistent URL (handle)

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