早期接触农业、生物多样性和绿地与炎症性肠病风险之间的关系：一项基于人群的队列研究思维导图

Use “green space”OR“blue space” OR“biodiversity”OR “agriculture”OR“natural vegetation density index”OR“urban space”AND“inflammatory bowel disease”OR“Crohn’s disease”OR“ulcerative colitis” identify 296 studies.

report on the association between environmental exposures during the early life period and IBD risk

early life environmental exposures were associated with modulation of CD risk

conduct a nationwide cohort study contains all individuals born in Denmark from January 1,1995, to August 1, 2018. Their mothers were residents of Denmark during pregnancy.

exposures of interest: agricultural land use, biodiversity, green space, normalized difference vegetation index (NDVI), blue space and urban space

Measure exposure values at multiple time points, specifying the latest value measured before the start of the exposure window. During the exposure window, the updated measurements should be assigned a weighted average of the measurements before and after the update, and weighted based on the proportion of the exposure window before and after the update point.

Data source for land cover is the CORINE Land Cover Inventory， categorized as green space, urban space, agricultural land, or water bodies

The NDVI, an indicator of vegetation health and density. The index ranges from −1 to 1, with higher values indicating denser vegetation.

Biodiversity was defined by the bioscore, a measure of diversity of local flora and fauna.

Green space, urban space, and agriculture land use remained relatively stable over the study period. There were periodic variations in NDVI, due to lower rainfall and dry vegetation.

Use the cross-linked Danish National Patient Registry identified all study participants who were diagnosed with CD or UC based on a previously-used definition.

potential confounding variables：sex, maternal age at delivery, calendar year of birth, first-degree relative with IBD prior to the birth of the child, and two municipal-level indicators of socioeconomic status: The proportion of the population aged 25– who have only a basic level of education, and a socioeconomic index measuring relative municipal social spending needs.

Analyzed d the association between each exposure and the primary outcome IBD and secondary outcomes CD and UC using Cox proportional hazards regression analysis.

conducted sensitivity analyses to evaluate the robustness. Repeated main analyses to compare the highest decile of each exposure with the lowest quartile for outcomes IBD, CD, and UC.

The proportional hazards assumption was evaluated using Schoenfeld residuals and was found to hold.

The distribution of each exposure is demonstrated in Fig. 1A.

Correlation across all exposure variables is demonstrated in Fig. 1B.

Agriculture land use has a strong negative correlation with urban areas, while green space and biodiversity have a strong positive correlation.

The risk of IBD among individuals exposed to the third quartile of agriculture land use during early life, compared to the lowest quartile, was increased (aHR 1.13, 95% CI 1.01, 1.26).

The risk of IBD among those exposed to the third quartiles of biodiversity in early life, compared to the lowest quartile, was lower (aHR 0.90, 95% CI 0.81, 0.99).

With respect to environmental exposures green space, urban space, blue space, and NDVI, null associations were found across quartiles of each exposure and IBD risk.

The risk of CD among those exposed to the third quartile of biodiversity, compared to the lowest quartile, was lower (aHR 0.86, 95% CI 0.75, 0.98)

Data exposed to the highest quartile of green space, compared to the lowest quartile, was lower (aHR 0.87, 95% CI 0.78, 0.98).

No association between the highest quartile of green space and UC, or each of the remaining environmental exposures and UC

No association across quartiles of other environmental exposures and CD risk

protective effective of green space against IBD (0.84, 95% CI 0.75, 0.95) and CD （aHR 0.79, 95% CI 0.68, 0.92)

a protective effect of biodiversity against IBD (aHR 0.85, 95% CI 0.75, 0.97) and CD (aHR 0.80, 95% CI (0.66, 0.97)

A harmful effect of the highest decile of NDVI against CD （aHR 1.28, 95% 1.06, 1.55)

A detrimental effect of middle quartile agricultural space on CD (aHR 1.16, 95% CI 1.02, 1.32)

The use of a nationwide population-based cohort, prospectively collected unbiased exposure and covariate data, and long term follow up through linked registers.

The distribution of environmental exposures may not be representative of other populations.