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Purpose Air pollutant exposure constitutes a serious risk factor for the emergence or aggravation of (existing) pulmonary disease. The impact of pre-intensive care ambient air pollutant exposure on the duration of artificial ventilation was, however, not yet established. Methods The medical records of 2003 patients, admitted to the intensive care unit (ICU) of the Antwerp University Hospital (Flanders, Belgium), who were artificially ventilated on ICU admission or within 48 h after admission, for the duration of at least 48 h, were analyzed. For each patient's home address, daily air pollutant exposure [particulate matter with an aerodynamic diameter [less than or equal to] 2.5 [micro]m (PM.sub.2.5) and [less than or equal to] 10 [micro]m (PM.sub.10), nitrogen dioxide (NO.sub.2) and black carbon (BC)] up to 10 days prior to hospital admission was modeled using a high-resolution spatial-temporal model. The association between duration of artificial ventilation and air pollution exposure during the last 10 days before ICU admission was assessed using distributed lag models with a negative binomial regression fit. Results Controlling for pre-specified confounders, an IQR increment in BC (1.2 [micro]g/m.sup.3) up to 10 days before admission was associated with an estimated cumulative increase of 12.4% in ventilation duration (95% CI 4.7-20.7). Significant associations were also observed for PM.sub.2.5, PM.sub.10 and NO.sub.2, with cumulative estimates ranging from 7.8 to 8.0%. Conclusion Short-term ambient air pollution exposure prior to ICU admission represents an unrecognized environmental risk factor for the duration of artificial ventilation in the ICU., Author(s): Annick De Weerdt [sup.1] [sup.2], Bram G. Janssen [sup.3], Bianca Cox [sup.3], Esmée M. Bijnens [sup.3], Charlotte Vanpoucke [sup.4], Wouter Lefebvre [sup.5], Omar El Salawi [sup.2], Margot Jans [sup.2], [...]

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-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.Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Thyroid hormones are critical for fetal development and growth. Whether prenatal exposure to fine particle air pollution ([less than or equal to] 2.5 [micro]m; [PM.sub.2.5]) affects fetal thyroid function and what the impact is on birth weight in normal healthy pregnancies have not been studied yet. OBJECTIVES: We studied the impact of third-trimester [PM.sub.2.5] exposure on fetal and maternal thyroid hormones and their mediating role on birth weight. METHODS: We measured the levels of free thyroid hormones ([FT.sub.3], [FT.sub.4]) and thyroid-stimulating hormone (TSH) in cord blood (n = 499) and maternal blood (n = 431) collected after delivery from mother-child pairs enrolled between February 2010 and June 2014 in the ENVIROWAGE birth cohort with catchment area in the province of Limburg, Belgium. RESULTS: An interquartile range (IQR) increment (8.2 [micro]g/[m.sup.3]) in third-trimester [PM.sub.2.5] exposure was inversely associated with cord blood TSH levels (-11.6%; 95% CI: -21.8, -0.1) and the [FT.sub.4]/[FT.sub.3] ratio (-62.7%; 95% CI: -91.6, -33.8). A 10th-90th percentile decrease in cord blood [FT.sub.4] levels was associated with a 56 g decrease in mean birth weight (95% CI: -90, -23). Assuming causality, we estimated that cord blood [FT.sub.4] mediated 21% (-19 g; 95% CI: -37, -1) of the estimated effect of an IQR increment in third-trimester [PM.sub.2.5] exposure on birth weight. Thirdtrimester [PM.sub.2.5] exposure was inversely but not significantly associated with maternal blood [FT.sub.4] levels collected 1 day after delivery (-4.0%, 95% CI: -8.0, 0.2 for an IQR increment in third-trimester [PM.sub.2.5]). CONCLUSIONS: In our study population of normal healthy pregnancies, third-trimester exposure to [PM.sub.2.5] air pollution was associated with differences in fetal thyroid hormone levels that may contribute to reduced birth weight. Additional research is needed to confirm our findings in other populations and to evaluate potential consequences later in life., Introduction During prenatal life, thyroid hormones are critical for fetal growth and development, especially neurodevelopment (Burrow et al. 1994; Morreale de Escobar et al. 2004). Unbalanced thyroid function influences pregnancy [...]

BACKGROUND: As part of the lipidome, oxylipins are bioactive lipid compounds originating from oxidation of different fatty acids. Oxylipins could provide a new target in the developmental origins model or the ability of early life exposure to change biology. OBJECTIVES: We studied the association between in utero [PM.sub.2.5] (particulate matter with aerodynamic diameter < 2.5 [micro]m) exposure and oxylipin profiles in newborns. METHODS: Thirty-seven oxylipins reflecting the cyclooxygenase (COX), lipoxygenase (5-LOX and 12/15-LOX), and cytochrome P450 (CYP) pathways were assayed in 197 cord blood plasma samples from the ENVIROWAGE birth cohort. Principal component (PC) analysis and multiple regression models were used to estimate associations of in utero [PM.sub.2.5] exposure with oxylipin pathways and individual metabolites. RESULTS: A principal component representing the 5-LOX pathway (6 metabolites) was significantly positively associated with [PM.sub.2.5] exposure during the entire (multiple testing--adjusted q-value = 0.05) and second trimester of pregnancy (q = 0.05). A principal component representing the 12/15-LOX pathway (11 metabolites) was positively associated with [PM.sub.2.5] exposure during the second trimester of pregnancy (q = 0.05). [PM.sub.2.5] was not significantly associated with the COX pathway during any time period. There was a positive but nonsignificant association between second-trimester [PM.sub.2.5] and the CYP pathway (q = 0.16). CONCLUSION: In utero exposure to particulate matter, particularly during the second trimester, was associated with differences in the cord blood levels of metabolites derived from the lipoxygenase pathways. These differences may indicate an effect of air pollution during in utero life on the inflammatory state of the newborn at birth. Oxylipins may be important mediators between early life exposures and health outcomes later in life., Introduction Human exposure to particulate matter (PM) as a part of ambient air pollution has a substantial impact on human health outcomes such as cardiovascular morbidity and mortality and respiratory [...]

BACKGROUND: Particulate matter with a diameter [less than or equal to] 2.5 µm (PM2.5) affects human fetal development during pregnancy. Oxidative stress is a putative mechanism by which [PM.sub.2.5] may exert its effects. Leptin (LEP) is an energy-regulating hormone involved in fetal growth and development. OBJECTIVES: We investigated in placental tissue whether DNA methylation of the LEP promoter is associated with [PM.sub.2.5] and whether the oxidative/nitrosative stress biomarker 3-nitrotyrosine (3-NTp) is involved. Methods: LEP DNA methylation status of 361 placentas from the ENVIROAAGE birth cohort was assessed using bisulfite-PCR-pyrosequencing. Placental 3-NTp (n = 313) was determined with an ELISA assay. Daily [PM.sub.2.5] exposure levels were estimated for each mother's residence, accounting for residential mobility during pregnancy, using a spatiotemporal interpolation model. RESULTS: After adjustment for a priori chosen covariates, placental LEP methylation was 1.4% lower (95% CI: -2.7, -0.19%) in association with an interquartile range increment (7.5 µg/[m.sup.3]) in second-trimester [PM.sub.2.5] exposure and 0.43% lower (95% CI: -0.85, -0.02%) in association with a doubling of placental 3-NTp content. CONCLUSIONS: LEP methylation status in the placenta was negatively associated with [PM.sub.2.5] exposure during the second trimester, and with placental 3-NTp, a marker of oxidative/nitrosative stress. Additional research is needed to confirm our findings and to assess whether oxidative/ nitrosative stress might contribute to associations between [PM.sub.2.5] and placental epigenetic events. Potential consequences for health during the neonatal period and later in life warrant further exploration. http://dx.doi.org/ 10.1289/EHP38, Introduction The 'developmental origins of health and disease ' concept describes how the environment may affect intrauterine development and early childhood, and how it induces developmental changes bearing long-term consequences [...]

BACKGROUND: Telomere length and mitochondrial DNA (mtDNA) content are markers of aging and aging-related diseases. There is inconclusive evidence concerning the mechanistic effects of airborne particulate matter (PM) exposure on biomolecular markers of aging. OBJECTIVE: The present study examines the association between short- and long-term PM exposure with telomere length and mtDNA content in the elderly and investigates to what extent this association is mediated by expression of genes playing a role in the telomere-mitochondrial axis of aging. METHODS: Among 166 nonsmoking elderly participants, we used qPCR to measure telomere length and mtDNA content in leukocytes and RNA from whole blood to measure expression of SIRT1, TP53, PPARGC1A, PPARGC1B, NRF1, and NFE2L2. Associations between PM exposure and markers of aging were estimated using multivariable linear regression models adjusted for sex, age, BMI, socioeconomic status, statin use, past smoking status, white blood cell count, and percentage of neutrophils. Mediation analysis was performed to explore the role of age-related markers between the association of PM exposure and outcome. Annual [PM.sub2.5] exposure was calculated for each participant's home address using a high-resolution spatialtemporal interpolation model. RESULTS: Annual [PM.sub2.5] concentrations ranged from 15 to 23 µg/[m.sup.3]. A 5-µg/[m.sup.3] increment in annual [PM.sub2.5] concentration was associated with a relative decrease of 16.8% (95% CI: -26.0%, -7.4%, p = 0.0005) in telomere length and a relative decrease of 25.7% (95% CI: -35.2%, -16.2%, p < 0.0001) in mtDNA content. Assuming causality, results of the mediation analysis indicated that SIRT1 mediated 19.5% and 22.5% of the estimated effect of [PM.sub2.5] exposure on telomere length and mtDNA content, respectively. CONCLUSIONS: Our findings suggest that the estimated effects of [PM.sub2.5] exposure on the telomere-mitochondrial axis of aging may play an important role in chronic health effects of [PM.sub2.5]. http://dx.doi.org/10.1289/ehp.1509728, Introduction Telomeres are complexes of hexameric repeats at the distal end of chromosomes where they provide stability and protection to the coding DNA. Telomere length declines with each cell division [...]

BACKGROUND: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. OBJECTIVE: We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (N[O.sub.2]) exposure and birth weight. METHODS: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. RESULTS: Pooled estimates indicated that a 10-µg/[m.sup.3] increment in average N[O.sub.2] exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease (95% CI: -87, -9 g) in birth weight. However, the association with birth weight was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20 g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal N[O.sub.2] and birth weight was mediated by changes in placental mtDNA content. CONCLUSION: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight. http://dx.doi.org/10.1289/ehp.1408981, Introduction In recent years, traffic-related air pollution has been considered an important risk factor for adverse reproductive health effects. Prenatal exposure to nitrogen dioxide (N[O.sub.2]) has been associated with low [...]

BACKGROUND: Developmental processes in the placenta and the fetal brain are shaped by the same biological signals. Recent evidence suggests that adaptive responses of the placenta to the maternal environment may influence central nervous system development. OBJECTIVES: We studied the association between in utero exposure to fine particle air pollution with a diameter ≤ 2.5 µm ([PM.sub.2.5]) and placental expression of genes implicated in neural development. METHODS: Expression of 10 target genes in the brain-derived neurotrophic factor (BDNF) signaling pathway were quantified in placental tissue of 90 mother-infant pairs from the ENVIRONAGE birth cohort using quantitative real-time polymerase chain reaction. Trimester-specific [PM.sub.2.5] exposure levels were estimated for each mother's home address using a spatiotemporal model. Mixed-effects models were used to evaluate the association between the target genes and [PM.sub.2.5] exposure measured in different time windows of pregnancy. RESULTS: A 5-µg/[m.sup.3] increase in residential [PM.sub.2.5] exposure during the first trimester of pregnancy was associated with a 15.9% decrease [95% confidence interval (CI): -28.7, -3.2%, p = 0.015] in expression of placental BDNF at birth. The corresponding estimate for synapsin 1 (SYN1) was a 24.3% decrease (95% CI: -42.8, -5.8%,p = 0.011). CONCLUSIONS: Placental expression of BDNF and SYN1, two genes implicated in normal neurodevelopmental trajectories, decreased with increasing in utero exposure to [PM.sub.2.5]. Future studies are needed to confirm our findings and evaluate the potential relevance of associations between [PM.sub.2.5] and placental expression of BDNF and SYN1 on neurodevelopment. We provide the first molecular epidemiological evidence concerning associations between in utero fine particle air pollution exposure and the expression of genes that may influence neurodevelopmental processes., Introduction Ambient air pollution is a global public health threat (Nawrot et al. 2011). Recent evidence suggests that in utero exposure to particulate matter with a diameter ≤ 2.5 µm [...]

While previous studies have demonstrated that prenatal exposure to environmental stressors is associated with mitochondrial DNA (mtDNA) methylation, more recent investigations are questioning the accuracy of the methylation assessment and its biological relevance. In this study, we investigated placental mtDNA methylation while accounting for methodological issues such as nuclear contamination, bisulphite conversion, and PCR bias. From the ENVIRONAGE birth cohort, we selected three groups of participants (n = 20/group). One group with mothers who smoked during pregnancy (average 13.2 cig/day), one group with high air pollutant exposure (PM2.5: 16.0 ± 1.4 µg/m3, black carbon: 1.8 ± 0.3 µg/m3) and one control group (non-smokers, PM2.5: 10.6 ± 1.7 µg/m3, black carbon: 0.9 ± 0.1 µg/m3) with low air pollutant exposure. DNA methylation levels were quantified in two regions of the displacement loop control region (D-loop and LDLR2) by bisulphite pyrosequencing. Additionally, we measured DNA methylation on nuclear genes involved in mitochondrial maintenance (PINK1, DNA2, and POLG1) and assessed mtDNA content using qPCR. Absolute D-loop methylation levels were higher for mothers that smoked extensively (+0.36%, 95% CI: 0.06% to 0.66%), and for mothers that were highly exposed to air pollutants (+0.47%, 95% CI: 0.20% to 0.73%). The relevance of our findings is further supported, as D-loop methylation levels were correlated with placental mtDNA content (r = −0.40, p = 0.002) and associated with birth weight (−106.98 g, 95% CI: −209.60 g to −4.36 g for an IQR increase in D-loop methylation). Most notably, our data demonstrates relevant levels of mtDNA methylation in placenta tissue, with significant associations between prenatal exposure to environmental stressors and D-loop methylation. [ABSTRACT FROM AUTHOR]