Early life exposures and the risk of inflammatory bowel disease: Systematic review and meta-analyses

Manasi Agrawal, João Sabino, Catarina Frias-Gomes, Christen M. Hillenbrand, Celine Soudant, Jordan E. Axelrad, Shailja C. Shah, Francisco Ribeiro-Mourão, Thomas Lambin, Inga Peter, Jean Frederic Colombel, Neeraj Narula, Joana Torres

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Background: Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri‑, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. Methods: We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980. Findings: Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2–2.5) and tobacco smoke (OR 1.5; 95% CI 1.2–1.9), and early life otitis media (OR 2.1; 95% CI 1.2–3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous. Interpretation: Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies. Funding: This study did not receive any funding.

Original languageEnglish
Article number100884
StatePublished - Jun 2021


  • Crohn's disease
  • Early life
  • Environmental exposure
  • Epidemiology
  • Inflammatory bowel disease
  • Non-genetic
  • Risk factors
  • Ulcerative colitis


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