Journal Article

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

Smeets, Karen, Nawrot, Tim S., Sleurs, Hanne, Lefebvre, Wouter, Vanbrabant, Kenneth, Alfano, Rossella, Plusquin, Michelle, Dockx, Yinthe, Cosemans, Charlotte, Vanpoucke, Charlotte, Wang, Congrong, Martens, Dries S., Janssen, Bram G.

2022

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Age / Air pollution / Blood / Body mass index / Body weight / Carbon / Childhood / Childhood overweight / Children / Cord blood / Dehydrogenases / DLMs / Earth and Environmental Science / Energy metabolism / Environment / Environmental Health / Ethnicity / Exposure / Heteroplasmy / Intrauterine exposure / Metabolic disorders / Mitochondria / Mitochondrial DNA / Mothers / Mutation / Neonates / Nitrogen dioxide / Obesity / Occupational Medicine/Industrial Medicine / Organic chemicals / Overweight / Particulate matter / Pregnancy / Prenatal experience / Prenatal exposure / Public Health / Regression analysis / Regression models / SNP