Background: Epidemiologic studies have reported associations between fine particles (aerodynamic diameter ≤ 2.5 µm; PM₂.₅) and mortality. However, concerns have been raised regarding the sensitivity ...of the results to model specifications, lower exposures, and averaging time. Objective: We addressed these issues using 11 additional years of follow-up of the Harvard Six Cities study, incorporating recent lower exposures. Methods: We replicated the previously applied Cox regression, and examined different time lags, the shape of the concentration—response relationship using penalized splines, and changes in the slope of the relation over time. We then conducted Poisson survival analysis with time-varying effects for smoking, sex, and education. Results: Since 2001, average PM₂.₅ levels, for all six cities, were < 18 µg/m³. Each increase in PM₂.₅ (10 µg/m³) was associated with an adjusted increased risk of all-cause mortality (PM₂.₅ average on previous year) of 14% 95% confidence interval (CI): 7, 22, and with 26% (95% CI: 14, 40) and 37% (95% CI: 7, 75) increases in cardiovascular and lung-cancer mortality (PM₂.₅ average of three previous years), respectively. The concentration-response relationship was linear down to PM₂.₅ concentrations of 8 µg/m³. Mortality rate ratios for PM₂.₅ fluctuated over time, but without clear trends despite a substantial drop in the sulfate fraction. Poisson models produced similar results. Conclusions: These results suggest that further public policy efforts that reduce fine particulate matter air pollution are likely to have continuing public health benefits.
A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent.
We aimed to quantify the ...association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association.
Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM(10) and PM(2.5) (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates.
In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05 and PM(2.5) (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM(10) exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (-8.9 g; 95% CI: -13.2, -4.6 g). Meta-regressions revealed that centers with higher median PM(2.5) levels and PM(2.5):PM(10) ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations.
Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.
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•We estimated 13 urban exposures and cognitive and motor function in 5403 children.•Connectivity and land use diversity are negatively associated with verbal abilities.•PM2.5 mediate ...the positive association of greenness and verbal abilities.•PM2.5 is negatively associated with fine motor function.
The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children.
We used data from 5403 mother–child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-exposure models using the Deletion-Substitution-Addition algorithm.
Higher greenness exposure within 300 m during pregnancy was associated with higher verbal abilities (1.5 points (95% confidence interval 0.4, 2.7) per 0.20 unit increase in greenness). Higher connectivity density within 100 m and land use diversity during pregnancy were related to lower verbal abilities. Childhood exposure to PM2.5 mediated 74% of the association between greenness during childhood and verbal abilities. Higher exposure to PM2.5 during pregnancy was related to lower fine motor function (-1.2 points (-2.1, -0.4) per 3.2 μg/m3 increase in PM2.5). No associations were found with non-verbal abilities and gross motor function.
This study suggests that built environment, greenness, and air pollution may impact child cognitive and motor function at five years old. This study adds evidence that well-designed urban planning may benefit children’s cognitive and motor development.
The identification of expression quantitative trait methylation (eQTMs), defined as associations between DNA methylation levels and gene expression, might help the biological interpretation of ...epigenome-wide association studies (EWAS). We aimed to identify autosomal cis eQTMs in children's blood, using data from 832 children of the Human Early Life Exposome (HELIX) project.
Blood DNA methylation and gene expression were measured with the Illumina 450K and the Affymetrix HTA v2 arrays, respectively. The relationship between methylation levels and expression of nearby genes (1 Mb window centered at the transcription start site, TSS) was assessed by fitting 13.6 M linear regressions adjusting for sex, age, cohort, and blood cell composition.
We identified 39,749 blood autosomal cis eQTMs, representing 21,966 unique CpGs (eCpGs, 5.7% of total CpGs) and 8,886 unique transcript clusters (eGenes, 15.3% of total transcript clusters, equivalent to genes). In 87.9% of these cis eQTMs, the eCpG was located at <250 kb from eGene's TSS; and 58.8% of all eQTMs showed an inverse relationship between the methylation and expression levels. Only around half of the autosomal cis-eQTMs eGenes could be captured through annotation of the eCpG to the closest gene. eCpGs had less measurement error and were enriched for active blood regulatory regions and for CpGs reported to be associated with environmental exposures or phenotypic traits. In 40.4% of the eQTMs, the CpG and the eGene were both associated with at least one genetic variant. The overlap of autosomal cis eQTMs in children's blood with those described in adults was small (13.8%), and age-shared cis eQTMs tended to be proximal to the TSS and enriched for genetic variants.
This catalogue of autosomal cis eQTMs in children's blood can help the biological interpretation of EWAS findings and is publicly available at https://helixomics.isglobal.org/ and at Dryad (doi:10.5061/dryad.fxpnvx0t0).
The study has received funding from the European Community's Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 (HELIX project); the H2020-EU.3.1.2. - Preventing Disease Programme under grant agreement no 874583 (ATHLETE project); from the European Union's Horizon 2020 research and innovation programme under grant agreement no 733206 (LIFECYCLE project), and from the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL and Instituto de Salud Carlos III) under the grant agreement no AC18/00006 (NutriPROGRAM project). The genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and co-funded by European Union (ERDF, "A way to make Europe") and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; "Rhea Plus": Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15). We acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. MV-U and CR-A were supported by a FI fellowship from the Catalan Government (FI-DGR 2015 and #016FI_B 00272). MC received funding from Instituto Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128).
Few studies have been performed on air pollution effects on lung function in the elderly, a vulnerable population with low reserve capacity, and even fewer have looked at changes in the rate of lung ...function decline.
We evaluated the effect of long-term exposure to black carbon on levels and rates of decline in lung function in the elderly.
FVC and FEV1 were measured one to six times during the period 1995-2011 in 858 men participating in the Normative Aging Study. Exposure to black carbon, a tracer of traffic emissions, was estimated by a spatiotemporal land use regression model. We investigated the effects of moving averages of black carbon of 1-5 years before the lung function measurement using linear mixed models.
A 0.5 μg/m(3) increase in long-term exposure to black carbon was associated with an additional rate of decline in FVC and FEV1 of between 0.5% and 0.9% per year, respectively, depending on the averaging time. In addition, black carbon exposure before the baseline visit was associated with lower levels of both FVC and FEV1, with effect estimates increasing up to 6-7% with a 5-year average exposure.
Our results support adverse effects of long-term exposure to traffic particles on lung function level and rate of decline in the elderly and suggest that functionally significant differences in health and risk of disability occur below the annual Environmental Protection Agency National Air Quality Standards.
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•Early life is an important window of susceptibility to environmental exposures.•Environmental exposures can influence on biological aging.•Biological aging can be evaluated using ...epigenetic clocks.•Pregnancy and childhood exposure to tobacco smoke might accelerate epigenetic aging.•Childhood exposure to indoor PMabs is related to accelerated epigenetic aging.
The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath’s Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips. We performed an exposure-wide association study between prenatal and childhood exposome and age acceleration. Maternal tobacco smoking during pregnancy was nominally associated with increased age acceleration. For childhood exposures, indoor particulate matter absorbance (PMabs) and parental smoking were nominally associated with an increase in age acceleration. Exposure to the organic pesticide dimethyl dithiophosphate and the persistent pollutant polychlorinated biphenyl-138 (inversely associated with child body mass index) were protective for age acceleration. None of the associations remained significant after multiple-testing correction. Pregnancy and childhood exposure to tobacco smoke and childhood exposure to indoor PMabs may accelerate epigenetic aging from an early age.
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Exposure to phthalates during pregnancy may alter DNA methylation in the placenta, a crucial organ for the growth and development of the fetus.
We studied associations between urinary ...concentrations of phthalate biomarkers during pregnancy and placental DNA methylation.
We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22 and 29 gestational weeks in 202 pregnant women. We analyzed DNA methylation levels in placental tissue (fetal side) collected at delivery. We first investigated changes in global DNA methylation of repetitive elements Alu and LINE-1. We then performed an adjusted epigenome-wide association study using IlluminaHM450 BeadChips and identified differentially methylated regions (DMRs) associated with phthalate exposure.
Monobenzyl phthalate concentration was inversely associated with placental methylation of Alu repeats. Moreover, all phthalate biomarkers except for monocarboxy-iso-octyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were associated with at least one DMR. All but three DMRs showed increased DNA methylation with increased phthalate exposure. The largest identified DMR (22 CpGs) was positively associated with monocarboxy-iso-nonyl phthalate and encompassed heat shock proteins (HSPA1A, HSPA1L). The remaining DMRs encompassed transcription factors and nucleotide exchange factors, among other genes.
This is the first description of genome-wide modifications of placental DNA methylation in association with pregnancy exposure to phthalates. Our results suggest epigenetic mechanisms by which exposure to these compounds could affect fetal development. Of interest, four identified DMRs had been previously associated with maternal smoking, which may suggest particular sensitivity of these genomic regions to the effect of environmental contaminants.
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•Weather during critical windows in pregnancy may lead to lower term birthweight.•These critical windows appear to differ between male and female infants.•Temperature variability, not ...just mean temperature, may impact term birthweight.•Even apart from temperature, mean humidity may affect term birthweight.
Heat stress during pregnancy may limit fetal growth, with ramifications throughout the life course. However, critical exposure windows are unknown, and effects of meteorological variability have not been investigated.
We aimed to identify sensitive windows for the associations of mean and variability of temperature and humidity with term birthweight.
We analyzed data from two French mother–child cohorts, EDEN and PELAGIE (n = 4771), recruited in 2002–2006. Temperature exposure was assessed using a satellite-based model with daily 1-km2 resolution, and relative humidity exposure data were obtained from Météo France monitors. Distributed lag models were constructed using weekly means and standard deviation (SD, to quantify variability) from the first 37 gestational weeks. Analyses were then stratified by sex. Results for each exposure were adjusted for the other exposures, gestational age at birth, season and year of conception, cohort and recruitment center, and individual confounders.
There was no evidence of association between term birthweight and mean temperature. We identified a critical window in weeks 6–20 for temperature variability (cumulative change in term birthweight of −54.2 g 95% CI: −102, −6 for a 1 °C increase in SD of temperature for each week in that window). Upon stratification by sex of the infant, the relationship remained for boys (weeks 1–21, cumulative change: −125 g 95% CI: −228, −21). For mean humidity, there was a critical window in weeks 26–37, with a cumulative change of −28 g (95% CI: −49, −7) associated with a 5% increase in humidity for each week. The critical window was longer and had a stronger association in boys (weeks 29–37; −37 g, 95% CI: −63, −11) than girls (week 14; −1.8 g, 95% CI: −3.6, −0.1).
Weekly temperature variability and mean humidity during critical exposure windows were associated with decreased term birthweight, especially in boys.
Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a ...meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.
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