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. 2014 Nov 28:349:g6979.
doi: 10.1136/bmj.g6979.

Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis

Anne K Örtqvist  1 , Cecilia Lundholm  2 , Helle Kieler  3 , Jonas F Ludvigsson  4 , Tove Fall  5 , Weimin Ye  2 , Catarina Almqvist  6
Affiliations

Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis

Anne K Örtqvist et al. BMJ. .

Erratum in

  • BMJ. 2014;349:g7395

Abstract

Objective: To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors.

Design: Nationwide prospective population based cohort study, including sibling control design.

Setting: Swedish population identified from national demographic and health registers.

Participants: 493,785 children born 2006-10; 180,894 of these were eligible for sibling analyses.

Main outcome measure: Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma.

Results: Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55).

Conclusions: Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. and declare that HK has received institutional fees from RTI Health Solutions, Abbott, Abbvie, Astellas, Astra-Zeneca, Bayer, Janssen, Biotech, Janssen-Cilag, Lundbeck, MSD, Schering-Plough, and Pfizer for performing post-approval safety studies and comparative effectiveness studies outside the submitted work.

Figures

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Fig 1 Final study populations for cohort and sibling control analyses. *Estimated first start of pregnancy 1 July 2005; first child born on 8 January 2006. †93% of families had two children; 7% of families had three to five children; 12 364 were twins and 267 were triplets. Registers at National Board of Health and Welfare: MBR=Medical Birth Register; SPDR=Swedish Prescribed Drug Register; NPR=National Patient Register. Registers at Statistics Sweden: TPR=Total Population Register; LISA=Longitudinal integration database for health insurance and labour market studies; MGR=Multi-Generation Register
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Fig 2 Adjusted hazard ratio and 95% confidence interval for asthma in relation to time (in years) since first exposure to various antibiotics in childhood. Hazard ratio adjusted for attained age, sex, birth weight, gestational age, mode of delivery, respiratory diagnoses as newborn, maternal age at delivery, parity, family situation, mother’s country of birth, and parental education. UTI=urinary tract infection
See this image and copyright information in PMC

References

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