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Original Article
Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study
  1. Anne K Örtqvist1,
  2. Cecilia Lundholm1,
  3. Jonas Halfvarson2,
  4. Jonas F Ludvigsson1,3,
  5. Catarina Almqvist1,4
  1. 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  3. 3Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
  4. 4Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Professor Catarina Almqvist, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE 171 77, Sweden; Catarina.Almqvist{at}ki.se

Abstract

Objective Earlier studies on antibiotics exposure and development of IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) may have been biased by familial factors and gastroenteritis. We aimed to estimate the association between antibiotics during pregnancy or infantile age and very early onset (VEO) IBD.

Design In this cohort study of 827 239 children born in Sweden between 2006 and 2013, we examined the link between exposure to systemic antibiotics and VEO-IBD (diagnosis <6 years of age), using Cox proportional hazard regression models. Information on antibiotics and IBD was retrieved from the nationwide population-based Swedish Prescribed Drug Register and the National Patient Register. We specifically examined potential confounding from parental IBD and gastroenteritis.

Results Children exposed to antibiotics during pregnancy were at increased risk of IBD compared with general population controls (adjusted HR (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to 6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72 (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children with gastroenteritis 12 months prior to the first IBD diagnosis retained similar aHR for antibiotics during pregnancy and CD, while the association no longer remained significant for IBD.

Conclusion We found that exposure to antibiotics during pregnancy, but not in infantile age, is associated with an increased risk of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in pregnancy may be due to changes in the microbiota.

  • antibiotics
  • epidemiology
  • crohn’s colitis
  • inflammatory bowel disease
  • ulcerative colitis

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Footnotes

  • Contributors The study was initiated by JFL and CA, and designed by AKÖ, CL, JFL and CA. AKÖ and CL performed the statistical analysis and wrote the initial draft together with JFL, JH and CA. All authors contributed with invaluable support for data analyses, interpretation of findings and critical revision of the article. CA obtained the financial support. All authors had full access to data, reviewed and approved the final version of the article submitted for publication. AKÖ, CL, JFL, JH and CA are the guarantors for the study and accept full responsibility for the work, had access to the data and controlled the decision to publish.

  • Funding Financial support was provided from the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) framework grant no. 340-2013-5867, grants provided by the Stockholm County Council (ALF projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association’s Research Foundation.

  • Disclaimer All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf.

  • Competing interests None declared.

  • Ethics approval The Regional Ethical Review Board in Stockholm, Sweden.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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