In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates

Mitochondria are sensitive to oxidative stress, which can be caused by traffic-related air pollution. Placental mitochondrial DNA (mtDNA) mutations have been previously linked with air pollution. However, the relationship between prenatal air pollution and cord-blood mtDNA mutations has been poorly understood. Therefore, we hypothesized that prenatal particulate matter (PM_2.5) and NO₂ exposures are associated with cord-blood mtDNA heteroplasmy. As part of the ENVIRONAGE cohort, 200 mother–newborn pairs were recruited. Cord-blood mitochondrial single-nucleotide polymorphisms were identified by whole mitochondrial genome sequencing, and heteroplasmy levels were evaluated based on the variant allele frequency (VAF). Outdoor PM_2.5 and NO₂ concentrations were determined by a high-resolution spatial–temporal interpolation method based on the maternal residential address. Distributed lag linear models were used to determine sensitive time windows for the association between NO₂ exposure and cord-blood mtDNA heteroplasmy. A 5 μg/m³ increment in NO₂ was linked with MT-D-Loop_16311T>C heteroplasmy from gestational weeks 17–25. MT-CYTB_14766C>T was negatively associated with NO₂ exposure in mid pregnancy, from weeks 14–17, and positively associated in late pregnancy, from weeks 31–36. No significant associations were observed with prenatal PM_2.5 exposure. This is the first study to show that prenatal NO₂ exposure is associated with cord-blood mitochondrial mutations and suggests two critical windows of exposure in mid-to-late pregnancy.