TY - JOUR
T1 - Early life exposures and the risk of inflammatory bowel disease
T2 - systematic review and meta-analyses
AU - Agrawal, Manasi
AU - Sabino, João
AU - Frias-Gomes, Catarina
AU - Hillenbrand, Christen M.
AU - Soudant, Celine
AU - Axelrad, Jordan E.
AU - Shah, Shailja C.
AU - Ribeiro-Mourão, Francisco
AU - Lambin, Thomas
AU - Peter, Inga
AU - Colombel, Jean Frederic
AU - Narula, Neeraj
AU - Torres, Joana
N1 - Funding Information:
MA receives research support from the Dickler Family Fund , New York Community Trust and the Leona M. and Harry B. Helmsley Charitable Trust for SECURE-IBD database; JS receives research support from Fonds Wetenschappelijk Onderzoek and the Helmsley Charitable Trust Fund ; CMH receives support from the Leona M. and Harry B. Helmsley Charitable Trust for the MELODY trial; JEA receives research support from the Crohn's and Colitis Foundation , the Judith & Stewart Colton Center for Autoimmunity , Lyanne and Michael Saperstein , and the NIH NIDDK Diseases K23DK124570 ; SCS has received the 2019 American Gastroenterological Association Research Scholar Award, and Veterans Affairs Career Development Award ICX002027A. TL receives grant support from Digest Science Foundation (Lille, France); IP receives support from the Leona M. and Harry B. Helmsley Charitable Trust for the MELODY trial; NN holds a McMaster University Department of Medicine Internal Career Award.
Funding Information:
The corresponding author confirms on behalf of all authors that there have been no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. JS reports personal fees from Takeda, Abbvie, and Janssen, and grants from Helmsley Charity Trust Fund and Fonds voor Wetenschappelijk Onderzoek – Vlaanderen, outside the submitted work. TL reports grants from DigestScience foundation and received travel accommodation from Adacyte Therapeutics. JFC reports grants and consultancy and lectures from Abbvie; consultancy and lectures from Ferring Pharmaceutical; consultancy from Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Enterome, Geneva, and Genentech; grants and consultancy from Janssen Pharmaceuticals; consultancy from Landos, LimmaTech Biologics AG, Ipsen, Imedex, Merck, Novartis, O Mass, Ostuka, and Pfizer; consultancy and lectures from Shire; grants, consultancy and lectures from Takeda; consultancy from Tigenix; and is a stock holder with Intestinal Biotech Development and Genfit, outside the submitted work. NN has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, and Ferring for advisory boards. JT has received research grants from Janssen and Abbvie, speaker fees from Janssen, and Advisory Board fees from Janssen, Pfizer, Arena Pharmaceuticals, Pfizer, Gilead and Galapagos. MA reports grants from Dickler Family Fund, New York Community Trust, grants from Leona M. and Harry B. Helmsley Charitable Trust for SECURE-IBD database, outside the submitted work. All other authors have nothing to disclose.
Publisher Copyright:
© 2021 The Authors
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - Early life
KW - Environmental exposure
KW - Epidemiology
KW - Inflammatory bowel disease
KW - Non-genetic
KW - Risk factors
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85106223976&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2021.100884
DO - 10.1016/j.eclinm.2021.100884
M3 - Article
C2 - 34308303
AN - SCOPUS:85106223976
SN - 2589-5370
VL - 36
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 100884
ER -
