AbstractBackgroundMitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>Gheteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5exposure is associated with cord blood MT-ND4L10550A>Gheteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>Gheteroplasmy in overweight during early childhood is investigated.MethodsThis study included 386 mother-newborn pairs. Outdoor PM2.5concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>Gheteroplasmy was determined using Droplet Digital PCR. Associations were explored using logistic regression models and distributed lag linear models. Mediation analysis was performed to quantify the effects of prenatal PM2.5exposure on childhood overweight mediated by cord blood MT-ND4L10550A>Gheteroplasmy.ResultsPrenatal PM2.5exposure was positively associated with childhood overweight during the whole pregnancy (OR = 2.33; 95% CI: 1.20 to 4.51;p = 0.01), which was mainly driven by the second trimester. In addition, prenatal PM2.5exposure was associated with cord blood MT-ND4L10550A>Gheteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m3increment in PM2.5was linked with cord blood MT-ND4L10550A>Gheteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>Gheteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50;p = 0.02). The effect of prenatal PM2.5exposure on childhood overweight was mainly direct (total effect OR = 1.18; 95% CI: 0.99 to 1.36; natural direct effect OR = 1.20; 95% CI: 1.01 to 1.36)) and was not mediated by cord blood MT-ND4L10550A>Gheteroplasmy.ConclusionsCord blood MT-ND4L10550A>Gheteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>Gheteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>Gheteroplasmy in the association between PM2.5exposure and childhood overweight.