Background
Specific pollutants and environmental exposures are implicated in modulating inflammatory bowel disease (IBD) risk. Crohn’s disease (CD) clustering has been reported in agricultural areas. However, the role of environmental exposures, particularly in early life, towards IBD risk, has not been systematically evaluated.

Methods
We conducted a nationwide population-based cohort study during the study period extending from January 1, 1995, to September 1, 2020, using cross-linked Danish registers, maps, and inventories to ascertain the impact of agricultural land use, biodiversity, green space, urban space, blue space, and natural vegetation density index during pregnancy and the first two years of life on IBD, CD, and ulcerative colitis (UC) risk, using adjusted Cox proportional hazards regression analyses. We adjusted for the following covariates: sex, maternal age at delivery, calendar year of birth, municipal-level socioeconomic status, and first-degree relative with IBD.

Results
Of 1,438,487 individuals included in the study who were followed from age 2 years until a median (IQR) age of 14 (8-20) years, 3,768 individuals were diagnosed with IBD. Exposure to the highest and third quartiles of agriculture land use during early life, relative to the lowest quartile, were associated with increased IBD risk (aHR 1.16, 95% CI 1.02, 1.31 and 1.19, 95% CI 1.07, 1.32, respectively). Conversely, exposure to the highest and third quartiles of biodiversity in early life, compared to the lowest quartile, were associated with a lower IBD risk (aHR 0.90, 95% CI 0.82, 1.00 and 0.90, 95% CI 0.82, 0.99, respectively). These associations were driven by differences in CD risk (Figure), but there was no association with UC risk. Other environmental exposures were not associated with IBD risk.

Conclusion
In a nationwide cohort with long-term follow up data, early life exposure to agriculture land use was associated with an increase in CD risk, while higher biodiversity was protective.

Anne Vinkel Hansen

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