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1.
Transl Psychiatry ; 10(1): 398, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184255

RESUMO

Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10-7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10-7. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.

2.
Environ Int ; 146: 106248, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212358

RESUMO

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.

3.
Environ Sci Technol ; 54(22): 14502-14513, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33124810

RESUMO

Mechanisms underlying adverse birth and later in life health effects from exposure to air pollution during the prenatal period have not been not fully elucidated, especially in the context of mixtures. We assessed the effects of prenatal exposure to mixtures of air pollutants of particulate matter (PM), PM2.5, PM10, nitrogen oxides, NO2, NOx, ultrafine particles (UFP), and oxidative potential (OP) of PM2.5 on infant birthweight in four European birth cohorts and the mechanistic underpinnings through cross-omics of metabolites and inflammatory proteins. The association between mixtures of air pollutants and birthweight z-scores (standardized for gestational age) was assessed for three different mixture models, using Bayesian machine kernel regression (BKMR). We determined the direct effect for PM2.5, PM10, NO2, and mediation by cross-omic signatures (identified using sparse partial least-squares regression) using causal mediation BKMR models. There was a negative association with birthweight z-scores and exposure to mixtures of air pollutants, where up to -0.21 or approximately a 96 g decrease in birthweight, comparing the 75th percentile to the median level of exposure to the air pollutant mixture could occur. Shifts in birthweight z-scores from prenatal exposure to PM2.5, PM10, and NO2 were mediated by molecular mechanisms, represented by cross-omics scores. Interleukin-17 and epidermal growth factor were identified as important inflammatory responses underlyingair pollution-associated shifts in birthweight. Our results signify that by identifying mechanisms through which mixtures of air pollutants operate, the causality of air pollution-associated shifts in birthweight is better supported, substantiating the need for reducing exposure in vulnerable populations.

4.
Environ Int ; 146: 106174, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33099063

RESUMO

BACKGROUND: The urban environment is characterised by many exposures that may influence hypertension development from early life onwards, but there is no systematic evaluation of their impact on child blood pressure (BP). METHODS: Systolic and diastolic blood pressure were measured in 4,279 children aged 4-5 years from a multi-centre European cohort (France, Greece, Spain, and UK). Urban environment exposures were estimated during pregnancy and childhood, including air pollution, built environment, natural spaces, traffic, noise, meteorology, and socioeconomic deprivation index. Single- and multiple-exposure linear regression models and a cluster analysis were carried out. RESULTS: In multiple exposure models, higher child BP, in particular diastolic BP, was observed in association with higher exposure to air pollution, noise and ambient temperature during pregnancy, and with higher exposure to air pollution and higher building density during childhood (e.g., mean change [95% confidence interval] for an interquartile range increase in prenatal NO2 = 0.7 mmHg[0.3;1.2]). Lower BP was observed in association with higher temperature and better street connectivity during childhood (e.g., temperature = -1.1[-1.6;-0.6]). Some of these associations were not robust in the sensitivity analyses. Mother-child pairs were grouped into six urban environment exposure clusters. Compared to the cluster representing the least harmful urban environment, the two clusters representing the most harmful environment (high in air pollution, traffic, noise, and low in green space) were both associated with higher diastolic BP (1.3[0.1;2.6] and 1.5[0.5;2.5]). CONCLUSION: This first large systematic study suggests that living in a harmful urban environment may impact BP regulation in children. These findings reinforce the importance of designing cities that promote healthy environments to reduce long-term risk of hypertension and other cardiovascular diseases.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33105572

RESUMO

Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children's ADHD-like symptoms at ages 4-5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, ß = -0.19 (-0.32, -0.07), for boys. Comparing ferritin level by tertiles, significant differences were observed between the first tertile ([1.98, 20.92]) and the second ([20.92, 38.79]) and third tertiles ([38.79, 216.5]) (mg/L).The number of symptoms was lower for those in the third tertile, ß = -0.3 (-0.55, -0.5), and for those in the second one, ß = -0.37 (-0.6, -0.14). The model stratification by sex also showed this inverse association for boys only, ß = -0.21 (-0.34, -0.08). No associations were found between ferritin level and hyperactivity or total ADHD symptoms. High ferritin levels during pregnancy show a protective association with child inattentive-type ADHD symptoms.

6.
Psychol Med ; : 1-9, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924895

RESUMO

BACKGROUND: Attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are child-onset neurodevelopmental disorders frequently accompanied by cognitive difficulties. In the current study, we aim to examine the genetic overlap between ADHD and ASD and cognitive measures of working memory (WM) and attention performance among schoolchildren using a polygenic risk approach. METHODS: A total of 1667 children from a population-based cohort aged 7-11 years with data available on genetics and cognition were included in the analyses. Polygenic risk scores (PRS) were calculated for ADHD and ASD using results from the largest GWAS to date (N = 55 374 and N = 46 351, respectively). The cognitive outcomes included verbal and numerical WM and the standard error of hit reaction time (HRTSE) as a measure of attention performance. These outcomes were repeatedly assessed over 1-year period using computerized version of the Attention Network Test and n-back task. Associations were estimated using linear mixed-effects models. RESULTS: Higher polygenic risk for ADHD was associated with lower WM performance at baseline time but not over time. These findings remained significant after adjusting by multiple testing and excluding individuals with an ADHD diagnosis but were limited to boys. PRS for ASD was only nominally associated with an increased improvement on verbal WM over time, although this association did not survive multiple testing correction. No associations were observed for HRTSE. CONCLUSIONS: Common genetic variants related to ADHD may contribute to worse WM performance among schoolchildren from the general population but not to the subsequent cognitive-developmental trajectory assessed over 1-year period.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32950652

RESUMO

OBJECTIVE: The commonly observed Subclinical Obsessive-Compulsive (OC) symptoms in healthy children may predispose to Obsessive-Compulsive Disorder (OCD). Therefore, investigating the underlying neurobiology may be relevant to identify alterations in specific brain circuits potentially accounting for clinical heterogeneity in OCD without the confounding effects of clinical samples. Herein, we analyzed the brain correlates of different OC symptoms in a large group of healthy children using functional connectivity measures. METHOD: We evaluated 227 healthy children (52% girls, mean age±SD=9.71±0.86 years, range 8-12.1). Participants underwent clinical assessment with the Obsessive-Compulsive Inventory-Child Version and a resting-state functional magnetic resonance imaging examination. Total and symptom-specific severity were correlated with voxel-wise global functional connectivity degree values. Significant clusters were then used as seeds of interest in seed-to-voxel analyses. Modulating effects of age and sex were also assessed. RESULTS: Global functional connectivity of the left ventral putamen and medial-dorsal thalamus correlated negatively with total OC severity. Seed-to-voxel analyses revealed specific negative correlations from these clusters with limbic, sensorimotor and insular regions in association with obsessing, ordering and doubt-checking symptoms, respectively. Hoarding symptoms were associated with negative correlations between the left medial-dorsal thalamus and a widespread pattern of regions, being such associations modulated by sex and age. CONCLUSION: Our findings concur with prevailing neurobiological models of OCD on the importance of cortico-striato-thalamo-cortical (CSTC) dysfunction to account for symptom severity. Notably, we showed that changes in CSTC connectivity are present at subclinical stages, which may result in an increased vulnerability for OCD. Moreover, we mapped different symptom dimensions onto specific CSTC circuit attributes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32764493

RESUMO

BACKGROUND: We aimed to assess how lifestyle factors such as diet, sleep, screen viewing, and physical activity, individually, as well as in a combined score, were associated with neuropsychological development in pre-school age children. METHODS: We conducted a cross-sectional study in 1650 children of 4 years of age, from the Environment and Childhood Project (INMA) population-based birth cohorts in four regions of Spain. Children were classified per a childhood healthy lifestyle score (CHLS) with a range of 0 to 4 that included eating in concordance with the Mediterranean diet (1 point); reaching recommended sleep time (1 point); watching a maximum recommended screen time (1 point); and being physically active (1 point). The McCarthy Scales of Children's Abilities (MSCA) were used to test neuropsychological development. Multi-adjusted linear regression models were created to assess the association with the lifestyle factors individually and as a combined score. RESULTS: CHLS was not associated with MSCA general cognitive score (1-point increment = -0.5, 95% CI: -1.2, 0.2). Analyzed by separate lifestyle factors, physical activity had a significant negative association with MSCA score and less TV/screen time had a negative association with MSCA score. CONCLUSION: In this cross-sectional study, a combined score of lifestyle factors is not related to neuropsychological development at pre-school age.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32764502

RESUMO

Exposure to greenspace has been related to improved mental health, but the available evidence is limited and findings are heterogeneous across different areas. We aimed to evaluate the associations between residential exposure to greenspace and specific psychopathological and psychosomatic symptoms related to mental health among mothers from a Spanish birth cohort. Our study was based on data from 1171 women participating in two follow-ups of a population-based cohort in Valencia, Sabadell, and Gipuzkoa (2004-2012). For each participant, residential surrounding greenspace was estimated as the average of the satellite-based Normalized Difference Vegetation Index (NDVI) across different buffers around the residential address at the time of delivery and at the 4-year follow-up. The Symptom Checklist 90 Revised (SCL-90-R) was applied to characterize mental health at the 4-year follow-up. We developed mixed-effects logistic regression models controlled for relevant covariates to evaluate the associations. Higher residential surrounding greenspace was associated with a lower risk of somatization and anxiety symptoms. For General Severity Index (GSI), obsessive-compulsive, interpersonal sensitivity, depression, hostility, phobic anxiety, paranoid ideation, and psychoticism symptoms, we generally observed protective associations, but none attained statistical significance. Findings from this study suggested a potential positive impactof greenspace on mental health.

11.
Environ Pollut ; 266(Pt 1): 115228, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32763773

RESUMO

Exposure to greenspace has been associated with a wide range of health benefits; however, the available evidence on the association of this exposure with telomere length (TL), an early marker of ageing, is still scarce. We investigated the association of greenspace exposure with TL in a sample of 200 preschool children (aged 5-7 years) residing in Sabzevar, Iran (2017). We comprehensively characterized different aspects of greenspace exposure encompassing residential, kindergarten, and total (including both residential and kindergarten) surrounding greenspace (using satellite-derived Normalized Difference Vegetation Index), residential and kindergarten distance to green spaces, time spent in private gardens and public green spaces, and the number of plant pots at home. Relative leukocyte TL (LTL) in blood samples of the study participants was measured using quantitative polymerase chain reaction (qPCR). We applied mixed effects linear regression models with kindergarten and qPCR plate as random effects, to estimate the association of indicators of greenspace exposure (one at a time) with LTL, controlled for relevant covariates. We observed an inverse association between distance from home and kindergarten to green spaces larger than 5000 m2 and LTL. Moreover, higher total surrounding greenspace at 300m and 500m buffers and higher surrounding greenspace at 300m buffer around kindergarten and home were associated with longer LTL. Furthermore, longer time spent (h/week) in the public green spaces was associated with longer LTL. Our findings for residential and kindergarten distance to any green space (regardless of the size), residential surrounding greenspace at 100m and 500m buffers, kindergarten surrounding greenspace at 100m buffer, time spent in private gardens (h/week) and the number of plant pots at home were not conclusive. Our findings were generally suggestive for a positive association between greenspace exposure and LTL in preschool children. More studies are needed to confirm these findings in other settings with different climates and populations.


Assuntos
Meio Ambiente , Telômero , Envelhecimento , Criança , Pré-Escolar , Humanos , Irã (Geográfico) , Leucócitos
12.
Eur Respir J ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855223

RESUMO

Previous studies have related early postnatal growth with later lung function but their interpretation is limited by the methods used to assess child's growth. We aimed to assess the association of early childhood growth, measured by body mass index (BMI) trajectories up to 4 years, with lung function at 7 years.We included 1257 children from the Spanish Infancia y Medio Ambiente population-based birth cohort. Early childhood growth was classified in five categories based on BMI trajectories up to 4 years previously identified using latent class growth analysis. These trajectories differed in birth size ("lower", "average", "higher") and in BMI gain velocity ("slower", "accelerated"). We related these trajectories with lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow at 25-75% (FEF25-75)) at 7 years, using multivariable mixed regression.Compared to children with average birth size and slower BMI gain (reference), children with higher birth size and accelerated BMI gain had higher percent predicted FVC (3.3% [95% CI: 1.0; 5.6]) and lower percent predicted FEV1/FVC (-1.5% [-2.9; -0.1]) at 7 years. Similar associations were observed for children with lower birth size and accelerated BMI gain. Children with lower birth size and slower BMI gain had lower percent predicted FVC at 7 years. No association was found for FEF25-75Independently of birth size, children with accelerated BMI gain in early childhood had higher lung function at 7 years but showed airflow limitation. Children with lower birth size and slower BMI gain in early childhood had lower lung function at 7 years.

13.
Eur J Epidemiol ; 35(7): 709-724, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32705500

RESUMO

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.


Assuntos
Exposição Ambiental , Doenças não Transmissíveis , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Saúde Ambiental , União Europeia , Feminino , Humanos , Lactente , Masculino , Pais , Gravidez , Fatores de Risco , Fatores Socioeconômicos
14.
Environ Health Perspect ; 128(6): 67009, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32579081

RESUMO

BACKGROUND: Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. OBJECTIVES: Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. METHODS: The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. RESULTS: The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. DISCUSSION: This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975.

15.
Metabolism ; 110: 154292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32553738

RESUMO

BACKGROUND: Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. METHODS: To investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts (n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations. RESULTS: This dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n = 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns. CONCLUSIONS: Our data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight.


Assuntos
Peso ao Nascer , Colesterol/metabolismo , Sangue Fetal/química , Quimiocina CCL22/metabolismo , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Masculino , Metaboloma , Metilação
16.
Environ Health Perspect ; 128(6): 67014, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32589457

RESUMO

BACKGROUND: Arterial stiffness, and its progression with age, is an important indicator of cardiovascular aging. Greenspace exposure may protect against arterial stiffness by promoting physical activity, fostering social cohesion, and reducing stress and exposure to air pollution and noise. OBJECTIVES: The aim of this study was to investigate the association of long-term exposure to outdoor greenspace with arterial stiffness and its progression over time. METHODS: This prospective cohort study was based on 4,349 participants (55-83 years of age) of the Whitehall II Study, United Kingdom. Arterial stiffness was assessed in two medical examinations (2007-2009 and 2012-2013) by measuring the carotid-femoral pulse wave velocity (cf-PWV). Residential surrounding greenspace was characterized using satellite-based indices of greenspace including normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), and vegetation continuous fields (VCF) across buffers of 500 and 1,000m surrounding the participants' residential locations at each follow-up. The association between the greenspace indicators and baseline cf-PWV and 4-year progression of cf-PWV was assessed using linear mixed-effects models with the participant as a random effect, controlling for demographic, lifestyle, and (individual and area) socioeconomic factors. RESULTS: No statistically significant associations were observed between residential surrounding greenspace and baseline or 4-y progression of cf-PWV; interquartile range (IQR) increases in NDVI, EVI, and VCF in the 500-m buffer were associated with -0.04m/s [95% confidence interval (CI): -0.12, 0.04], -0.03m/s (95% CI: -0.10, 0.05), and -0.02m/s (95% CI: -0.08, 0.04) in baseline cf-PWV and 0.06m/s (95% CI: -0.02, 0.14), 0.05m/s (95% CI: -0.03, 0.14), and 0.00m/s (95% CI: -0.09, 0.09) in 4-y progression in cf-PWV, respectively. The associations were similar when using 1,000-m buffers. CONCLUSIONS: We did not observe any consistent association between residential surrounding greenspace and arterial stiffness. https://doi.org/10.1289/EHP6159.

17.
Environ Int ; 139: 105734, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32361533

RESUMO

OBJECTIVE: Air pollution is a leading preventable risk factor for cardiovascular diseases. Previous studies mostly relied on concentrations at residence, which might not represent personal exposure. Personal air pollution exposure has a greater variability compared with levels of ambient air pollution, facilitating evaluation of exposure-response functions and vascular pathophysiology. We aimed to evaluate the association between predicted annual personal exposure to PM2.5 and black carbon (BC) and three vascular damage markers in peri-urban South India. METHODS: We analyzed the third wave of the APCAPS cohort (2010-2012), which recruited participants from 28 villages. We used predicted personal exposure to PM2.5 and BC derived from 610 participant-days of 24 h average gravimetric PM2.5 and BC measurements and predictors related to usual time-activity. Outcomes included carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx). We fit linear mixed models, adjusting for potential confounders and accounting for the clustered data structure. We evaluated nonlinear associations using generalized additive mixed models. RESULTS: Of the 3017 participants (mean age 38 years), 1453 (48%) were women. The average PM2.5 exposure was 51 µg/m3 (range 13-85) for men, and 61 µg/m3 (range 40-120) for women, while the average BC was 4 µg/m3 (range 3-7) for men and 8 µg/m3 (range 3-22) for women. A 10 µg/m3 increase of PM2.5 was positively associated with CIMT (0.026 mm, 95% CI 0.014, 0.037), cf-PWV (0.069 m/s, 95% CI 0.008, 0.131) and AIx (0.8%, 95% CI 0.3, 1.3) among men. The exposure-response function for PM2.5 and AIx among men showed non-linearity, particularly within the exposure range dominated by tobacco smoking and occupational exposures. Both PM2.5 and BC were positively associated with AIx among women (0.6%, 95% CI 0.2, 1.0, per 10 µg/m3 PM2.5; 0.5%, 95% CI 0.1, 0.8, per 2 µg/m3 BC). CONCLUSIONS: Personal exposure to particulate matter was associated with vascular damage in a peri-urban population in South India. Personal exposure to particulate matter appears to have gender-specific effects on the type of vascular damage, potentially reflecting differences in sources of personal exposure by gender.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Espessura Intima-Media Carotídea , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Índia , Masculino , Material Particulado/análise , Análise de Onda de Pulso
18.
Artigo em Inglês | MEDLINE | ID: mdl-32456201

RESUMO

Airborne particulate matter with an aerodynamic diameter smaller than 2.5 µg, PM2.5 was regularly sampled in classrooms (indoor) and playgrounds (outdoor) of primary schools from Barcelona. Three of these schools were located downtown and three in the periphery, representing areas with high and low traffic intensities. These aerosols were analyzed for organic molecular tracers and polycyclic aromatic hydrocarbons (PAHs) to identify the main sources of these airborne particles and evaluate the air quality in the urban location of the schools. Traffic emissions were the main contributors of PAHs to the atmospheres in all schools, with higher average concentrations in those located downtown (1800-2700 pg/m3) than in the periphery (760-1000 pg/m3). The similarity of the indoor and outdoor concentrations of the PAH is consistent with a transfer of outdoor traffic emissions to the indoor classrooms. This observation was supported by the hopane and elemental carbon concentrations in PM2.5, markers of motorized vehicles, that were correlated with PAHs. The concentrations of food-related markers, such as glucoses, sucrose, malic, azelaic and fatty acids, were correlated and were higher in the indoor atmospheres. These compounds were also correlated with plastic additives, such as phthalic acid and diisobutyl, dibutyl and dicyclohexyl phthalates. Clothing constituents, e.g., adipic acid, and fragrances, galaxolide and methyl dihydrojasmonate were also correlated with these indoor air compounds. All these organic tracers were correlated with the organic carbon of PM2.5, which was present in higher concentrations in the indoor than in the outdoor atmospheres.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Hidrocarbonetos Policíclicos Aromáticos , Instituições Acadêmicas , Aerossóis , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Espanha , Emissões de Veículos/análise
19.
Clin Epigenetics ; 12(1): 60, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32354366

RESUMO

BACKGROUND: Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. RESULTS: Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in cord blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. CONCLUSIONS: Maternal CRP levels measured during each trimester were not associated with cord blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in cord blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00467363, Registered April 30, 2007, http://www.clinicaltrials.gov/ct2/show/NCT00467363.

20.
Lancet Diabetes Endocrinol ; 8(6): 501-510, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32445737

RESUMO

BACKGROUND: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight. METHODS: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496. FINDINGS: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT4]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (pinteraction=0·10). Each 1 SD increase in FT4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second. INTERPRETATION: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy. FUNDING: Netherlands Organization for Scientific Research (grant 401.16.020).


Assuntos
Peso ao Nascer/fisiologia , Hipotireoidismo/fisiopatologia , Complicações na Gravidez/fisiopatologia , Glândula Tireoide/fisiologia , Glândula Tireoide/fisiopatologia , Feminino , Idade Gestacional , Humanos , Hipotireoidismo/complicações , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Gravidez , Testes de Função Tireóidea/tendências
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