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.

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Background: The notion of Crohn's disease (CD) as a chronic, progressive and disabling condition has led to the development of new indexes: the Lémann Index measuring cumulative bowel damage and the Inflammatory Bowel Disease (IBD) Disability Index, assessing functional disability.Aims: To measure the Lémann Index and the IBD Disability Index in a large prospective cohort of CD patients and to assess the correlation between these two indexes. Methods:We performed a prospective study in a tertiary referral centre including all consecutive CD outpatients. We assessed the Lémann Index and the IBD Disability Index questionnaire in all patients. Results:One hundred and thirty CD patients were consecutively included. The mean Lémann Index (±SD) was 11.9 ± 14.1 and ranged from 0 to 72.5 points. Factors associated with a high bowel damage score were: disease duration, anal location, previous intestinal resection, clinical and biological disease activity, exposure to immunosuppressants, and exposure to anti-TNF (P < 0.005). Among patients exposed to anti-TNF, the Lémann Index was lower in those who were exposed in the first 2 years of their disease (P = 0.015). The mean IBD Disability Index was 28.8 ± 6.3 and ranged from 0 to 71 points. The factors associated with high disability score were: female gender, anal location, extra digestive manifestations, clinical and biological disease activity and exposure to anti-TNF (P < 0.005). No correlation was observed between the Lémann Index and IBD Disability Index (P = 0.15). Conclusions:This is the first study to prospectively evaluate the Lémann Index and the IBD Disability Index in a large cohort of CD patients in a tertiary centre. Early introduction of anti-TNF treatment was associated with lower bowel damage scores, and no correlation was observed between the Lémann Index and the IBD Disability Index. Further dedicated prospective studies are necessary to confirm these results.