Background: Celiac disease(CeD) is a lifelong T-cell mediated disorder. Although 30-40% of general population carries the HLA-DQ2/DQ8 susceptibility haplotypes, only a small proportion develop CeD, suggesting environmental factors contribute to disease pathogenesis. Prospective birth cohorts show that many genetically at-risk children develop CeD within the first five years of life. Early life residential greenspace exposure has been associated with improved immune regulation and a decreased risk of inflammatory bowel disease, possibly mediated by alterations in the gut microbiome.
Objective: To determine whether residential greenspace exposure during early childhood is associated with risk of pediatric CeD. We hypothesize that greater early-life greenspace exposure is associated with a lower risk of CeD.
Methods: We analyzed data from 274(27 cases; 247 controls) US children enrolled in the Celiac Disease Genomic, Environmental, Microbiome and Metabolomic(CDGEMM) study, a prospective cohort of children at increased risk for CeD due to a first-degree family member with CeD. Residential greenspace exposure was estimated using normalized difference vegetation index(NDVI), derived from Landsat satellite imagery at 270m and 1,230m residential buffers from 2013–2021. Mean cumulative NDVI was calculated through ages one, three, and five years. Associations between NDVI and CeD seroconversion were evaluated using Cox proportional hazards and mixed-effects Cox regression models adjusted for birth delivery mode and early antibiotic exposure
Results: No statistically significant associations were observed between residential greenspace exposure and risk of CeD seroconversion across any buffer distance, time window, or model. For the 1,230m buffer, unadjusted hazard ratios ranged from 2.05(95% CI: 0.08–51.03, p=0.66) for the first three years to 2.84(95% CI: 0.14–59.44, p=0.50) through age 1 year.
Conclusion: In this US cohort of children at increased genetic risk for CeD, early-life residential greenspace exposure was not associated with CeD seroconversion. Further studies in larger, more diverse populations are warranted.