In utero particulate matter exposure in association with newborn mitochondrial ND4L(10550A>G) heteroplasmy and its role in overweight during early childhood

BACKGROUND: Mitochondria 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-ND4L(10550A>G) heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM(2.5) exposure is associated with cord blood MT-ND4L(10550A>G) heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L(10550A>G) heteroplasmy in overweight during early childhood is investigated. METHODS: This study included 386 mother-newborn pairs. Outdoor PM(2.5) concentrations were determined at the maternal residential address. Cord blood MT-ND4L(10550A>G) heteroplasmy 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 PM(2.5) exposure on childhood overweight mediated by cord blood MT-ND4L(10550A>G) heteroplasmy. RESULTS: Prenatal PM(2.5) exposure 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 PM(2.5) exposure was associated with cord blood MT-ND4L(10550A>G) heteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m(3) increment in PM(2.5) was linked with cord blood MT-ND4L(10550A>G) heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L(10550A>G) heteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50; p = 0.02). The effect of prenatal PM(2.5) exposure 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-ND4L(10550A>G) heteroplasmy. CONCLUSIONS: Cord blood MT-ND4L(10550A>G) heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM(2.5) during the first trimester of pregnancy was associated with cord blood MT-ND4L(10550A>G) heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L(10550A>G) heteroplasmy in the association between PM(2.5) exposure and childhood overweight. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12940-022-00899-z.