Association of Prenatal Ambient Air Pollution Exposure With Placental Mitochondrial DNA Copy Number, Telomere Length and Preeclampsia.

Background: Studies have shown that ambient air pollution is linked to preeclampsia (PE), possibly via generation of oxidative stress in the placenta. Telomere length and mitochondrial DNA copy number (mtDNAcn) are sensitive to oxidative stress damage. Objective: To study the association between prenatal exposure to ambient nitrogen oxides (NOx, a marker for traffic-related air pollution), and PE, as well as potential mediation effects by placental telomere length and mtDNAcn. Methods: This is a cross-sectional study of 42 preeclamptic and 95 arbitrarily selected normotensive pregnant women with gestational ambient NOx exposure assessment in southern Scania, Sweden. Hourly concentrations of NOx were estimated at the residential addresses by a Gaussian-plume dispersion model with 100 × 100 m spatial resolutions and aggregated into trimester-specific mean concentrations. Placental relative mtDNAcn and telomere length were measured using qPCR. Linear and logistic regression models were used to investigate associations, adjusted for perinatal and seasonal characteristics. Results: Exposure was categorized into low and high exposures by median cut-offs during first [11.9 µg/m3; interquartile range (IQR) 7.9, 17.9], second (11.6 µg/m3; IQR: 7.1, 21.1), third trimesters (11.9 µg/m3; IQR: 7.7, 19.5) and entire pregnancy (12.0 µg/m3; IQR: 7.6, 20.1). Increased risk of PE was found for high prenatal NOx exposure during the first trimester (OR 4.0; 95% CI: 1.4, 11.1; p = 0.008), and entire pregnancy (OR 3.7; 95% CI: 1.3, 10.4; p = 0.012). High exposed group during the first trimester had lower placental relative mtDNAcn compared with low exposed group (-0.20; 95% CI: -0.36, -0.04; p = 0.01). Changes in relative mtDNAcn did not mediate the association between prenatal NOx exposure and PE. No statistically significant association was found between placental relative telomere length, prenatal NOx exposure and PE. Conclusion: In this region with relatively low levels of air pollution, ambient NOx exposure during the first trimester was associated with reduced placental relative mtDNAcn and an increased risk of PE. However, we did not find any evidence that mtDNAcn or TL mediated the association between air pollution and PE. Future research should further investigate the role of mtDNAcn for pregnancy complications in relation to exposure to ambient air pollution during pregnancy.

Early Pregnancy Exposure to Ambient Air Pollution among Late-Onset Preeclamptic Cases Is Associated with Placental DNA Hypomethylation of Specific Genes and Slower Placental Maturation.

Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants' residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.

Maternal Exposure to Ambient Air Pollution and Risk of Preeclampsia: A Population-Based Cohort Study in Scania, Sweden.

The aim of this study was to investigate the risk of developing preeclampsia (PE) associated with gestational exposure to ambient air pollutants in southern Sweden, a low-exposure area. We used a cohort of 43,688 singleton pregnancies and monthly mean exposure levels of black carbon (BC), local and total particulate matter (PM2.5 and PM10), and NOX at the maternal residential address estimated by Gaussian dispersion modeling from 2000 to 2009. Analyses were conducted using binary logistic regression. A subtype analysis for small-for-gestational age (SGA) was performed. All analyses were adjusted for obstetrical risk factors and socioeconomic predictors. There were 1286 (2.9%) PE cases in the analysis. An adjusted odds ratio (AOR) of 1.35 with a 95% confidence interval (CI) of 1.11-1.63 was found when comparing the lowest quartile of BC exposure to the highest quartile in the third trimester The AOR for PE associated with each 5 µg/m3 increase in locally emitted PM2.5 was 2.74 (95% CI: 1.68, 4.47) in the entire pregnancy. Similar patterns were observed for each 5 µg/m3 increment in locally emitted PM10. In pregnancies complicated by PE with SGA, the corresponding AOR for linear increases in BC was 3.48 (95% CI: 1.67, 7.27). In this low-level setting, maternal exposure to ambient air pollution during gestation was associated with the risk of developing PE. The associations seemed more pronounced in pregnancies with SGA complications, a finding that should be investigated further.