Associations of the first trimester exposure to PM_2.5 components and offspring atopic dermatitis: Effect modification...

Prenatal exposure to fine particulate matter (PM_2.5) 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 PM_2.5 components (BC, OM, SO₄^2 -, 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 PM_2.5 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 PM_2.5 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 PM_2.5-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.