Background: Early life exposures impact immune system development and therefore the risk of immunemediated 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 1.2À2.5) and tobacco smoke (OR 1.5; 95% CI 1.2À1.9), and early life otitis media (OR 2.1; 95% CI 1.2À3.6) 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.

ESD in Europe seems to be performed at a few centers, with most endoscopists performing a low number of procedures, achieving a high rate of efficacy and a moderate rate of major complications. However, as a potential selection bias may have occurred, multicenter registries should be conducted to help address the problem of dissemination of this technique.

Introduction A family history of IBD is the strongest risk factor for disease. However, some first-degree relatives (FDRs) will develop disease, while others will not. Methods Using the nationwide Danish National Patient Register, we examined risk factors in families with ≥2 affected FDRs. First, we compared exposures between siblings with and without IBD within the same family (within family analysis). Second, we compared exposures between individuals with and without IBD across all families (across family analysis). Exposures included sex, birth order, mode of delivery, antibiotics, personal and family history of immune-mediated diseases, gastrointestinal infections, and surgical history preceding diagnosis. Uni- and multivariable conditional logistic regression analyses were conducted. Results In the “within family analysis”, 1669 families were included (1,732 cases, 2,447 controls). Female sex (adjusted odds ratio (aOR): 1.40, 95% CI 1.23, 1.59), history of ankylosing spondylitis (aOR: 2.88, 95% CI 1.05, 7.91) and exposure to antibiotics (aOR: 1.28, 95% CI 1.02, 1.61), increased the risk for IBD. In the “across family analysis”, 1,254 cases and 37,584 controls were included, confirming association with prior ankylosing spondylitis (aOR: 3.92, 95% CI 1.38, 11.12), and exposure to antibiotics (aOR: 1.29, 95% CI 1.04, 1.60). Having ≥2 relatives (aOR: 6.26, 95% CI 1.34, 29.29) or a sibling with IBD (aOR: 1.36, 95% CI 1.18, 1.57), increased the risk of IBD. Appendectomy reduced the risk of UC (aOR: 0.32, 95% CI 0.14, 0.72). Conclusion In families with IBD, we identified risk factors for the unaffected FDR to develop disease. These findings provide an opportunity for counselling IBD relatives.