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. 2021 May 15:36:100884.
doi: 10.1016/j.eclinm.2021.100884. eCollection 2021 Jun.

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

Manasi Agrawal  1 , João Sabino  2 , Catarina Frias-Gomes  3 , Christen M Hillenbrand  4 , Celine Soudant  5   6 , Jordan E Axelrad  7 , Shailja C Shah  8   9 , Francisco Ribeiro-Mourão  10   11   12 , Thomas Lambin  13 , Inga Peter  4 , Jean-Frederic Colombel  1 , Neeraj Narula  14 , Joana Torres  1   3   15
Affiliations

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

Manasi Agrawal et al. EClinicalMedicine. .

Abstract

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.

Keywords: Crohn's disease; Early life; Environmental exposure; Epidemiology; Inflammatory bowel disease; Non-genetic; Risk factors; Ulcerative colitis.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
PRISMA 2009 Flow Diagram for selection of studies in the meta-analyses and systematic review.
Fig. 2
Fig. 2
Forest plots of the association between maternal smoking during pregnancy and subsequent diagnosis of (A) IBD, (B) CD or (C) UC in the offspring. Abbreviations: IBD – inflammatory bowel disease; CD – Crohn's disease; UC – Ulcerative colitis.
Fig. 3
Fig. 3
Forest plots of the association between (A) prenatal exposure to antibiotics and (B) exposure to antibiotics during infancy and subsequent diagnosis of IBD. Abbreviation: IBD – inflammatory bowel disease.
Fig. 4
Fig. 4
Forest plot of the association between otitis media between 0 and 5 years of age and subsequent diagnosis of IBD (A) and CD (B) Abbreviation: IBD - inflammatory bowel disease; CD – Crohn's disease.
Fig. 5
Fig. 5
Summary of prenatal and postnatal exposures that may modulate IBD risk. Abbreviation: IBD – inflammatory bowel disease.
See this image and copyright information in PMC

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