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-ND4L10550A>G heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5 exposure is associated with cord blood MT-ND4L10550A>G heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>G heteroplasmy in overweight during early childhood is investigated. This study included 386 mother-newborn pairs. Outdoor PM2.5 concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>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 PM2.5 exposure on childhood overweight mediated by cord blood MT-ND4L10550A>G heteroplasmy. Prenatal PM2.5 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 PM2.5 exposure was associated with cord blood MT-ND4L10550A>G heteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m3 increment in PM2.5 was linked with cord blood MT-ND4L10550A>G heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>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 PM2.5 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-ND4L10550A>G heteroplasmy. Cord blood MT-ND4L10550A>G heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5 during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>G heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>G heteroplasmy in the association between PM2.5 exposure and childhood overweight.

中文翻译：

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与新生儿线粒体 ND4L10550A>G 异质性相关的子宫内颗粒物暴露及其在儿童早期超重中的作用

线粒体在能量代谢中起重要作用，易受环境污染。产前空气污染暴露与儿童肥胖有关。胎盘 mtDNA 突变与产前颗粒物暴露相关，MT-ND4L10550A>G 异质性与成人 BMI 相关。因此，我们假设子宫内 PM2.5 暴露与脐带血 MT-ND4L10550A>G 异质性和早期生命生长有关。此外，研究了脐带血 MT-ND4L10550A>G 异质性在儿童早期超重中的作用。这项研究包括 386 对母婴。室外 PM2.5 浓度在产妇居住地址测定。脐带血 MT-ND4L10550A>G 异质性使用液滴数字 PCR 测定。使用逻辑回归模型和分布式滞后线性模型探索关联。进行中介分析以量化产前 PM2.5 暴露对脐带血 MT-ND4L10550A>G 异质性介导的儿童超重的影响。产前 PM2.5 暴露与整个孕期儿童超重呈正相关（OR = 2.33；95% CI：1.20 至 4.51；p = 0.01），这主要受孕中期驱动。此外，产前 PM2.5 暴露与妊娠第 9-13 周的脐带血 MT-ND4L10550A>G 异质性有关。在第 10 周观察到最大影响，其中 PM2.5 增加 5 µg/m3 与脐带血有关血液 MT-ND4L10550A>G 异质性（OR = 0.93；95% CI：0.87 至 0.99）。脐带血 MT-ND4L10550A>G 异质性也与儿童超重有关（OR = 3.04；95% CI：1.15 至 7.50；p = 0.02)。产前 PM2.5 暴露对儿童超重的影响主要是直接的（总效应 OR = 1.18；95% CI：0.99 至 1.36；自然直接效应 OR = 1.20；95% CI：1.01 至 1.36））并且不受以下因素介导脐带血 MT-ND4L10550A>G 异质性。脐带血 MT-ND4L10550A>G 异质性与儿童超重有关。此外，妊娠前三个月子宫内暴露于 PM2.5 与新生儿脐带血 MT-ND4L10550A>G 异质性有关。我们的分析未揭示脐带血 MT-ND4L10550A>G 异质性在 PM2.5 暴露与儿童超重之间的关联中的任何中介作用。自然直接效应 OR = 1.20；95% CI：1.01 至 1.36))，并且不受脐带血 MT-ND4L10550A>G 异质性介导。脐带血 MT-ND4L10550A>G 异质性与儿童超重有关。此外，妊娠前三个月子宫内暴露于 PM2.5 与新生儿脐带血 MT-ND4L10550A>G 异质性有关。我们的分析未揭示脐带血 MT-ND4L10550A>G 异质性在 PM2.5 暴露与儿童超重之间的关联中的任何中介作用。自然直接效应 OR = 1.20；95% CI：1.01 至 1.36))，并且不受脐带血 MT-ND4L10550A>G 异质性介导。脐带血 MT-ND4L10550A>G 异质性与儿童超重有关。此外，妊娠前三个月子宫内暴露于 PM2.5 与新生儿脐带血 MT-ND4L10550A>G 异质性有关。我们的分析未揭示脐带血 MT-ND4L10550A>G 异质性在 PM2.5 暴露与儿童超重之间的关联中的任何中介作用。