Prenatal fine particulate matter exposure associated with placental small extracellular vesicle derived microRNA and child neurodevelopmental delays

Prenatal fine particulate matter (PM2.5) exposure has been linked to adverse neurodevelopment. However, epidemiological evidence remains inconclusive and little information about the effects of various PM2.5 components on child neurodevelopment is currently known. The underlying mechanism was also not elucidated. The study aimed to evaluate the effects of PM2.5 and components exposure on child neurodevelopmental delays and the role of placental small extracellular vesicles (sEVs)-derived miRNAs in the associations.We included 267 mother-child pairs in this analysis. Prenatal PM2.5 and components (i.e. elements, water-soluble ions, and PAHs) exposure during three trimesters were monitored through personal PM2.5 sampling. Child neurodevelopment at 2, 6, and 12 months old were evaluated by Ages and Stages Questionnaire (ASQ). We isolated sEVs from placental tissue to analyze the change of sEVs-derived miRNAs in response to PM2.5. Associations between the PM2.5-associated miRNAs and child neurodevelopment were evaluated using multivariate linear regression models.The PM2.5 exposure levels in the three trimesters range from 2.51 to 185.21 μg/m3. Prenatal PM2.5 and the components of Pb, Al, V and Ti exposure in the second and third trimester were related to decreased ASQ scores communication, problem-solving and personal-social domains in children aged 2 or 6 months. RNA sequencing identified fifteen differentially expressed miRNAs. The miR-101-3p and miR-520d-5p were negatively associated with PM2.5 and Pb component. miR-320a-3p expression was positively associated with PM2.5 and V component. Meanwhile, the miR-320a-3p was associated with decreased ASQ scores, as reflected by ASQ-T (β: -2.154, 95 % CI: -4.313, -0.516) and problem-solving domain (β: -0.605, 95 % CI: -1.111, -0.099) in children aged 6 months.Prenatal exposure to PM2.5 and its Pb, Al, V & Ti component were associated with infant neurodevelopmental delays. The placenta sEVs derived miRNAs, especially miR-320a-3p, might contribute to an increased risk of neurodevelopmental delays.