Associations of the first trimester exposure to PM2.5 components and offspring atopic dermatitis: Effect modification by systemic low-grade inflammation

Prenatal exposure to fine particulate matter (PM2.5) has been associated to childhood atopic dermatitis (AD), but the critical exposure window and the role of maternal inflammatory pathways remain unclear. We analyzed 4048 mother–child pairs from two prospective birth cohorts in Chongqing (PRHBIC & CSBC, 2014–2021). Trimester-specific mean exposure to PM2.5 components (BC, OM, SO42 −, NO3−, NH4+) were assigned to residential address. Systemic low-grade inflammation was quantified by trimester neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII). Physician-diagnosed AD up to age 3 was the outcome. We used generalized linear models, weighted quantile sum models (WQS), interaction analyses (additive & multiplicative) and mediation analyses. Of 4048 children, 1554 (38.3%) developed AD. Associations were strongest for first-trimester: SO4²⁻ showed the largest adjusted effect (OR per IQR = 1.187; 95% CI 1.080–1.304). WQS indicated a positive association for the PM2.5 component mixure (OR = 1.023; 95% CI: 1.009–1.039), with OM receiving the largest WQS weight among components. Maternal NLR and SII were positively associated with first-trimester PM2.5 components and partially mediated the pollutant–AD association. Additionally, SII demonstrated significant effect modification on the additive scale (RERI: 0.41–0.55; AP: 0.26–0.29). Early pregnancy represents a critical window for PM2.5-related offspring AD risk in our study. Reducing air pollution and modulating maternal inflammatory status during the first trimester may serve as dual strategies for AD prevention.