Prenatal exposure to outdoor air pollution and miRNA expression in cord blood at birth: the NELA study

BACKGROUND AND AIM: Air pollution is a complex chemical mixture known as a risk factor for non-communicable diseases. Mechanisms underlying its adverse effects could involve changes in miRNA expression. We aimed to identify the effects of maternal exposure to air pollution during pregnancy on miRNAs expression in cord blood at birth; and to unravel windows of vulnerability across gestation. METHODS: Data came from 362 participants of the Nutrition in Early Life and Asthma (NELA) study, a prospective population-based birth cohort from Spain. RNA samples were isolated from umbilical vein cord blood samples at birth; miRNAs were hybridized and analyzed using SurePrint miRNA microarrays. Residential exposure to outdoor air pollution was estimated using dispersion/chemical transport modelling. Exposures showed high correlation coefficients, so a cluster analysis was performed to reduce dimensionality and avoid multi-collinearity. Associations between groups of exposure and miRNA expression were studied using multivariate linear regression models and over-representation analysis. Air pollutant mixture analyses were performed using the Bayesian Kernel machine regression model, to assess mixture effects and the relative contribution of each pollutant, and the Lagged kernel machine regression, to identify specific windows of vulnerability. RESULTS: Exposure to PM₁₀ and O₃ levels during the first and third trimesters of pregnancy showed changes in 32 miRNAs in cord blood, and two enriched pathways were found: Alzheimer’s disease and adherens junction. Mixture analysis estimated that maternal exposure to O₃ altered hsa-miR-30a-5p and hsa-miR-30c-5p expression, in the second and third trimester of pregnancy, respectively. CONCLUSIONS: Prenatal exposure to air pollution alters miRNA expression in the offspring at birth. Our results suggest that windows of vulnerability vary depending on the specific pollutant affecting distinct miRNA