Association between the external urban exposome and systemic inflammation in pregnant women

Systemic inflammation during pregnancy is associated with adverse health outcomes for both mother and child. C-reactive protein (CRP) is a widely used biomarker of inflammation, and its levels may be influenced by environmental factors. This study examined the association between 26 components of the external urban exposome-including air pollutants, land use, and access to green and blue spaces-and CRP concentrations in 1547 pregnant women from the INMA birth cohort in Spain (Gipuzkoa, Sabadell, and Valencia). Environmental exposures during the first trimester were assessed using GIS-based indicators and land-use regression models, and were grouped into low, moderate, and high exposome clusters using hierarchical clustering on principal components. Associations between exposome clusters and CRP were evaluated using multivariable linear regression models and meta-analyses, adjusting for maternal and lifestyle covariates. No significant associations were found between exposome clusters and CRP levels. However, specific air pollutants-fine particulate matter (PM₂.₅: 1.08% increase per unit; 95% CI: 1.02-1.15) and nitrogen oxides (NO_x: 1.03%; 95% CI: 1.00-1.06)-were positively associated with CRP. No associations were observed for green space indicators or other built environment variables. CRP concentrations also varied by region, with the highest levels observed in Valencia (3.2 ± 4.6 mg/dL). These findings suggest that while overall urban exposome profiles may not predict systemic inflammation, individual air pollutants such as PM₂.₅ and NO_x are key contributors. Targeting these exposures in maternal health strategies may help mitigate inflammation-related risks during pregnancy, supporting the need for more detailed and component-specific exposome assessments.