Early-Life Exposure to Antibiotics and Risk for Crohn's Disease: A Nationwide Danish Birth Cohort Study

Inflamm Bowel Dis. 2021 May 14;izab085. doi: 10.1093/ibd/izab085. Online ahead of print.

Anders Mark-Christensen 1 2, Aksel Lange 1, Rune Erichsen 1, Trine Frøslev 1, Buket Öztürk Esen 1, Henrik Toft Sørensen 1, Michael D Kappelman 3


Author information

  • 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
  • 2Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
  • 3Department of Pediatrics, Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.


Background: Early-life antibiotic use can alter the intestinal flora and modify the risk of developing Crohn disease (CD), but rigorous epidemiological evidence is limited, with inconsistent results.

Methods: We identified all children born in Denmark from 1995 to 2009 and followed them from birth until death, emigration, a diagnosis of CD, or January 1, 2013. Using Cox regression, we assessed the association between antibiotic exposure in the first year of life and subsequent risk for CD, adjusting for sex, degree of urbanization, birth order, birth year, route of delivery, gestational age, smoking during pregnancy, intake of nonsteroidal anti-inflammatory drugs in the first year of life, and family history of CD.

Results: During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children. Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4; 95% confidence interval [CI], 1.1-1.8), with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1; 95% CI, 2.0-8.5). A family history of CD did not modify these risk associations. The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16‰ (95% CI, 0.11‰-0.22‰) compared to 0.11‰ (95% CI, 0.08‰-0.15‰) for children unexposed to antibiotics in their first year of life.

Conclusions: Antibiotic use in the first year of life is associated with a modestly increased risk for CD, although the absolute risk is very low.

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