In utero particulate matter exposure in association with newborn mitochondrial ND4L10550A>G heteroplasmy and its role in overweight during early childhood

Abstract

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/m³ 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.

Keywords: Air pollution; Childhood overweight; DLMs; Mitochondria; SNP.