Cord blood DNA methylation as a potential mediator in the association between prenatal ambient air pollution and early infant allergic symptoms in a Shanghai birth cohort

Background

Prenatal exposure to ambient air pollution has been associated with early‐life allergic outcomes; however, underlying biological mechanisms remain incompletely understood.

Methods

A total of 101 mother‐infant pairs were ultimately included in this prospective birth cohort study. Maternal exposure to ambient air pollutants was assigned to geocoded residential addresses using spatiotemporal models. Allergic symptoms were defined as cumulative caregiver‐reported symptoms occurring from birth to 6 months and assessed at the 6‐month follow‐up. DNA methylation in naïve CD4 ⁺ T cells was analyzed in a subset of 30 cord blood samples using targeted bisulfite sequencing. Associations were evaluated using regression models, and statistical mediation analysis was performed under a counterfactual‐based approach.

Results

Higher first‐trimester exposure to PM ₁₀ (adjusted odds ratio [AOR], 2.27; 95% confidence interval [CI], 1.09–4.98) and NO ₂ (AOR, 2.11; 95% CI, 1.02–4.53) was associated with an increased likelihood of allergic symptoms within the first 6 months of life. In addition, third‐trimester exposure to PM _2.5 components, including sulfate (SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), and ammonium (NH ₄ ⁺ ), was positively associated with these outcomes. DNA methylation at a CpG site within the PRKACB promoter showed statistical evidence consistent with a potential mediating role in the association between third‐trimester sulfate exposure and allergic symptoms. Functional assays supported the regulatory relevance of this locus.

Conclusions

Prenatal ambient air pollution exposure was associated with early‐life allergic symptoms, and cord blood DNA methylation at the PRKACB locus may represent a potential molecular mechanism underlying these associations. These findings are exploratory and require confirmation in larger studies.

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