000308 - The Role of Cord Blood DNA Methylation in Mediating the Effect of Prenatal Air Pollution Exposure on the Development of Allergic Diseases in Offspring

While prenatal air pollution is a known risk factor for children’s atopic diseases, evidence regarding its impact on allergic symptoms within the first six months of life is scarce. The underlying epigenetic mechanisms are also poorly understood. We aimed to investigate the association between prenatal air pollution exposure and allergic symptoms in early infancy, and to evaluate the potential mediating role of cord blood DNA methylation.

In this prospective cohort study, we enrolled 101 mother–infant pairs in Shanghai between 2022 and 2023. Prenatal air pollution exposures were estimated for each trimester based on maternal residential addresses. Infant allergic symptoms were ascertained at 6 months of age. Targeted bisulfite sequencing was performed to analyze DNA methylation of candidate genes (MAP3K5 and PRKACB) in naïve CD4+ T cells from a subset of 30 cord blood samples. Linear and logistic regression models, along with causal mediation analysis, were used to evaluate the associations.

Increased first-trimester exposure to particulate matter with an aerodynamic diameter ≤10 μm (PM₁₀) (adjusted odds ratio [AOR] = 2.27, 95% confidence interval [CI]: 1.09–4.98) and nitrogen dioxide (NO₂) (AOR = 2.11, 95% CI: 1.02–4.53) was associated with a higher risk of infant allergic symptoms. Furthermore, causal mediation analysis revealed that DNA methylation at a specific locus within the PRKACB gene significantly mediated the association between third-trimester exposure to fine particulate matter (PM₂.₅), particularly its sulfate (SO₄²⁻) component, and the development of allergic symptoms at 6 months of age.

Prenatal air pollution exposure may contribute to allergic symptoms in early infancy through epigenetic mechanisms. Specifically, cord blood DNA methylation at a locus within the PRKACB gene may serve as a potential mediator in this pathway, providing new insights into the molecular mechanisms underlying early-life allergic diseases.