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BACKGROUND: Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media complex (IM-GSM), is a novel subclinical atherosclerosis marker with lower values indicating greater lipid deposition. Our longitudinal study investigated IM-GSM from childhood to adulthood and its associated risk factors. METHODS AND RESULTS: A total of 240 participants from the Southern California CHS (Children's Health Study) underwent carotid artery ultrasounds in 2008 (mean age±SD): (11.2±0.6 years), and again around 2022 (24.2±1.6 years) to assess IM-GSM, carotid artery intima-media thickness, and carotid artery distensibility. Questionnaires and anthropometric and blood pressure measurements were completed by participants at both times. Mean and SD of IM-GSM were 108.2±24.6 in childhood and 75.6±15.8 in adulthood. Each 1-year increase in age was associated with -2.52 change in IM-GSM (95% CI, -2.76 to -2.27). Childhood and adulthood IM-GSMs were highly correlated (ß=0.13 [95% CI, 0.05-0.22]). In childhood, Hispanic ethnicity, lower parental education levels and prenatal father smoking were significantly associated with lower IM-GSM. In adulthood, higher systolic blood pressure, carotid artery intima-media thickness, hypertension, and lower distensibility were significantly associated with lower IM-GSM. Weight status exhibited a consistent association with both childhood and adulthood IM-GSM. During the transition from childhood to adulthood, individuals who shifted from normal weight to overweight/obese or normal blood pressure to hypertension or experienced an increase in carotid artery intima-media thickness displayed lower levels of IM-GSM in adulthood. CONCLUSIONS: IM-GSM decreases with age. Maintaining healthy weight and blood pressure levels in children could potentially aid in preventing subclinical atherosclerosis.
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Arterias Carótidas , Enfermedades de las Arterias Carótidas , Grosor Intima-Media Carotídeo , Humanos , Femenino , Masculino , Niño , Estudios Longitudinales , Adulto Joven , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/fisiopatología , Factores de Riesgo , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/fisiopatología , Adolescente , California/epidemiología , Factores de Edad , Presión Sanguínea/fisiología , Adulto , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Precision Health aims to revolutionize disease prevention by leveraging information across multiple omic datasets (multi-omics). However, existing methods generally do not consider personalized environmental risk factors (e.g., environmental pollutants). OBJECTIVE: To develop and apply a precision health framework which combines multiomic integration (including early, intermediate, and late integration, representing sequential stages at which omics layers are combined for modeling) with mediation approaches (including high-dimensional mediation to identify biomarkers, mediation with latent factors to identify pathways, and integrated/quasi-mediation to identify high-risk subpopulations) to identify novel biomarkers of prenatal mercury induced metabolic dysfunction-associated fatty liver disease (MAFLD), elucidate molecular pathways linking prenatal mercury with MAFLD in children, and identify high-risk children based on integrated exposure and multiomics data. METHODS: This prospective cohort study used data from 420 mother-child pairs from the Human Early Life Exposome (HELIX) project. Mercury concentrations were determined in maternal or cord blood from pregnancy. Cytokeratin 18 (CK-18; a MAFLD biomarker) and five omics layers (DNA Methylation, gene transcription, microRNA, proteins, and metabolites) were measured in blood in childhood (age 6-10 years). RESULTS: Each standard deviation increase in prenatal mercury was associated with a 0.11 [95% confidence interval: 0.02-0.21] standard deviation increase in CK-18. High dimensional mediation analysis identified 10 biomarkers linking prenatal mercury and CK-18, including six CpG sites and four transcripts. Mediation with latent factors identified molecular pathways linking mercury and MAFLD, including altered cytokine signaling and hepatic stellate cell activation. Integrated/quasi-mediation identified high risk subgroups of children based on unique combinations of exposure levels, omics profiles (driven by epigenetic markers), and MAFLD. CONCLUSIONS: Prenatal mercury exposure is associated with elevated liver enzymes in childhood, likely through alterations in DNA methylation and gene expression. Our analytic framework can be applied across many different fields and serve as a resource to help guide future precision health investigations.
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BACKGROUND: Depression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy. METHODS: This study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR). RESULTS: Participants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP. CONCLUSIONS: Our findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression.
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Telomere length is associated with chronic diseases and in younger populations, may represent a biomarker of disease susceptibility. As growing evidence suggests that environmental factors, including metals, may impact telomere length, we investigated the association between 17 metals measured in toenail samples and leukocyte relative telomere length (RTL), among 472 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. In single exposure linear regression models, a doubling of arsenic (As) and mercury (Hg) (µg/g) were associated with a -0.21 (95%CI: -0.032, -0.010; p=0.0005) and -0.017 (95%CI: -0.029, -0.004; p=0.006) difference in RTL, respectively. In Bayesian Kernel Machine Regression (BKMR) mixture models, the overall metal mixture was inversely associated with RTL (P-for-trend <0.001). Negative associations with RTL were observed with both log2-As and log2-Hg, while an inverted U-shaped association was observed for log2-zinc (Zn) with RTL. We found little evidence of interaction among metals. Sex-stratification identified stronger associations of the overall mixture and log2-As with RTL among females, compared to males. Our study suggests that As and Hg may independently influence RTL in mid-childhood. Further studies are needed to investigate potential long-term impacts of metal-associated telomere shortening in childhood on health outcomes in adult life.
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BACKGROUND: This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults. METHODS AND RESULTS: This cross-sectional study included 240 young adults (age 24.2±1.6 years) who underwent a carotid ultrasound between 2018 and 2022. LE8 score was calculated from 4 health factors (body mass index, non-high-density lipoprotein cholesterol, fasting glucose, and blood pressure), and 4 health behaviors (dietary intake, physical activity, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better health and better adherence to American Heart Association guidelines. Carotid artery outcomes included carotid artery intima-media thickness, arterial stiffness (eg, distensibility), and echogenicity determined by grayscale median of the intima media complex. Results of linear regression analyses, adjusting for age, sex, ethnicity, and parents' highest degree, indicated that a 1-SD increase in LE8 score was associated with 12.14 µm lower carotid artery intima-media thickness (95% CI, -20.93 to 3.35), 1.17 (10-6×m2/N) greater distensibility (95% CI, 0.09-2.24), suggesting less arterial stiffness, and 2.66 µm greater grayscale median of the intima media complex (95% CI, 0.58-4.75), suggesting less lipid deposition. Analyses using LS7 score demonstrated comparable findings. Health factor metrics demonstrated stronger association with carotid artery outcomes, as compared with behavior metrics. CONCLUSIONS: Greater adherence to the American Heart Association's cardiovascular health guidelines is associated with lower risk for subclinical atherosclerosis in young adults. LE8 and LS7 demonstrated comparable associations with carotid artery outcomes.
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American Heart Association , Grosor Intima-Media Carotídeo , Humanos , Masculino , Femenino , Estudios Transversales , Adulto Joven , Estados Unidos/epidemiología , Adulto , Rigidez Vascular/fisiología , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades Asintomáticas , Conductas Relacionadas con la Salud , Aterosclerosis/epidemiología , Aterosclerosis/diagnóstico , Medición de Riesgo , Factores de Riesgo , Estado de Salud , Arterias Carótidas/diagnóstico por imagenRESUMEN
RATIONALE: Few studies have examined the effects of long-term childhood air pollution exposure on adult respiratory health, including whether childhood respiratory effects underlie this relation. OBJECTIVES: To evaluate associations between childhood air pollution exposure and self-reported adult bronchitic symptoms, while considering child respiratory health, in the Southern California Children's Health Study. METHODS: Nitrogen dioxide (NO2), ozone, particulate matter<2.5µm (PM2.5) and <10µm (PM10) exposures assessed using inverse-distance-squared spatial interpolation based on childhood (birth-17 years) residential histories. Bronchitic symptoms (bronchitis, cough, or phlegm in last 12 months) were ascertained via questionnaire in adulthood. Associations between mean air pollution exposure across childhood and self-reported adult bronchitic symptoms were estimated using logistic regression. We further adjusted for childhood bronchitic symptoms and asthma to understand whether associations operated beyond childhood respiratory health impacts. Effect modification was assessed for family history of asthma, childhood asthma, and adult allergies. MEASUREMENTS AND MAIN RESULTS: 1308 participants were included (mostly non-Hispanic White [56%] or Hispanic [32%]). At adult assessment (age mean=32.0 years, standard deviation [SD]=4.7) 25% reported bronchitic symptoms. Adult bronchitic symptoms were associated with NO2 and PM10 childhood exposures. Odds ratios per SD increase: 1.69 (95%CI:1.14,2.49) for NO2 (SD=11.1ppb); 1.51 (95%CI:1.00,2.27) for PM10 (SD=14.2µg/m3). Adjusting for childhood bronchitic symptoms or asthma produced similar results. NO2 and PM10 associations were modified by childhood asthma, with larger associations among asthmatics. CONCLUSION: Childhood NO2 and PM10 exposures were associated with adult bronchitic symptoms. Associations were not explained by childhood respiratory health impacts; however, participants with childhood asthma had stronger associations.
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Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.
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Fluoruros , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Preescolar , Fluoruros/orina , Fluoruros/efectos adversos , Estudios Prospectivos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Masculino , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Desarrollo Infantil/efectos de los fármacos , Conducta Infantil/efectos de los fármacos , Tercer Trimestre del Embarazo/orina , Los Angeles/epidemiologíaRESUMEN
BACKGROUND: Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. OBJECTIVE: To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. METHODS: This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. RESULTS: BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. IMPACT STATEMENT: Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.
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Exposición a Riesgos Ambientales , Metales , Humanos , Grecia/epidemiología , Femenino , Preescolar , Masculino , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Metales/sangre , Estudios de Cohortes , Selenio/sangre , Lípidos/sangre , Teorema de Bayes , Contaminación por Humo de Tabaco/efectos adversos , Contaminantes Ambientales/sangre , Mercurio/sangre , LDL-Colesterol/sangre , Cobalto/sangre , Manganeso/sangre , Molibdeno/sangre , Cadmio/sangre , Metales Pesados/sangre , Triglicéridos/sangre , Plomo/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiologíaRESUMEN
BACKGROUND: Ambient air pollution has been linked to postpartum depression. However, few studies have investigated the effects of traffic-related NOx on postpartum depression and whether any pregnancy-related factors might increase susceptibility. OBJECTIVES: To evaluate the association between traffic-related NOx and postpartum depressive and anxiety symptoms, and effect modification by pregnancy-related hypertension. METHODS: This study included 453 predominantly low-income Hispanic/Latina women in the MADRES cohort. Daily traffic-related NOx concentrations by road class were estimated using the California LINE-source dispersion model (CALINE4) at participants' residential locations and averaged across pregnancy. Postpartum depressive and anxiety symptoms were evaluated by a validated questionnaire (Postpartum Distress Measure, PDM) at 1, 3, 6 and 12 months postpartum. Multivariate linear regressions were performed to estimate the associations at each timepoint. Interaction terms were added to the linear models to assess effect modification by hypertensive disorders of pregnancy (HDPs). Repeated measurement analyses were conducted by using mixed effect models. RESULTS: We found prenatal traffic-related NOx was associated with increased PDM scores. Specifically, mothers exposed to an IQR (0.22 ppb) increase in NOx from major roads had 3.78% (95% CI: 0.53-7.14%) and 5.27% (95% CI: 0.33-10.45%) significantly higher 3-month and 12-month PDM scores, respectively. Similarly, in repeated measurement analyses, higher NOx from major roads was associated with 3.06% (95% CI: 0.43-5.76%) significantly higher PDM scores across the first year postpartum. Effect modification by HDPs was observed: higher freeway/highway and total NOx among mothers with HDPs were associated with significantly higher PDM scores at 12 months postpartum compared to those without HDPs. IMPACT: This study shows that prenatal traffic-related air pollution was associated with postpartum depressive and anxiety symptoms. The study also found novel evidence of greater susceptibility among women with HDPs, which advances the understanding of the relationships between air pollution, maternal cardiometabolic health during pregnancy and postpartum mental health. Our study has potential implications for clinical intervention to mitigate the effects of traffic-related pollution on postpartum mental health disorders. The findings can also offer valuable insights into urban planning strategies concerning the implementation of emission control measures and the creation of green spaces.
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Past studies support the hypothesis that the prenatal period influences childhood growth. However, few studies explore the joint effects of exposures that occur simultaneously during pregnancy. To explore the feasibility of using mixtures methods with neighborhood-level environmental exposures, we assessed the effects of multiple prenatal exposures on body mass index (BMI) from birth to age 24 months. We used data from two cohorts: Healthy Start (n = 977) and Maternal and Developmental Risks from Environmental and Social Stressors (MADRES; n = 303). BMI was measured at delivery and 6, 12, and 24 months and standardized as z-scores. We included variables for air pollutants, built and natural environments, food access, and neighborhood socioeconomic status (SES). We used two complementary statistical approaches: single-exposure linear regression and quantile-based g-computation. Models were fit separately for each cohort and time point and were adjusted for relevant covariates. Single-exposure models identified negative associations between NO2 and distance to parks and positive associations between low neighborhood SES and BMI z-scores for Healthy Start participants; for MADRES participants, we observed negative associations between O3 and distance to parks and BMI z-scores. G-computations models produced comparable results for each cohort: higher exposures were generally associated with lower BMI, although results were not significant. Results from the g-computation models, which do not require a priori knowledge of the direction of associations, indicated that the direction of associations between mixture components and BMI varied by cohort and time point. Our study highlights challenges in assessing mixtures effects at the neighborhood level and in harmonizing exposure data across cohorts. For example, geospatial data of neighborhood-level exposures may not fully capture the qualities that might influence health behavior. Studies aiming to harmonize geospatial data from different geographical regions should consider contextual factors when operationalizing exposure variables.
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Índice de Masa Corporal , Exposición a Riesgos Ambientales , Humanos , Femenino , Lactante , Embarazo , Masculino , Estudios de Cohortes , Recién Nacido , Preescolar , Características de la Residencia , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Factores Socioeconómicos , Salud Infantil , Contaminantes Atmosféricos/análisisRESUMEN
Environmental toxicants and pollutants are causes of adverse health consequences, including well-established associations between environmental exposures and cardiovascular diseases. Environmental degradation is widely prevalent and has a long latency period between exposure and health outcome, potentially placing a large number of individuals at risk of these health consequences. Emerging evidence suggests that environmental exposures in early life may be key risk factors for cardiovascular conditions across the life span. Children are a particularly sensitive population for the detrimental effects of environmental toxicants and pollutants given the long-term cumulative effects of early-life exposures on health outcomes, including congenital heart disease, acquired cardiac diseases, and accumulation of cardiovascular disease risk factors. This scientific statement highlights representative examples for each of these cardiovascular disease subtypes and their determinants, focusing specifically on the associations between climate change and congenital heart disease, airborne particulate matter and Kawasaki disease, blood lead levels and blood pressure, and endocrine-disrupting chemicals with cardiometabolic risk factors. Because children are particularly dependent on their caregivers to address their health concerns, this scientific statement highlights the need for clinicians, research scientists, and policymakers to focus more on the linkages of environmental exposures with cardiovascular conditions in children and adolescents.
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American Heart Association , Enfermedades Cardiovasculares , Exposición a Riesgos Ambientales , Humanos , Exposición a Riesgos Ambientales/efectos adversos , Estados Unidos/epidemiología , Niño , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/epidemiología , Cardiología/normas , Factores de Riesgo , Adolescente , Contaminantes Ambientales/efectos adversosRESUMEN
BACKGROUND: Prenatal air pollution exposure has been associated with individual inflammatory, cardiovascular, and metabolic biomarkers in mothers and neonates. However, studies of air pollution and a comprehensive panel of biomarkers across maternal and cord blood samples remain limited. Few studies used data-driven methods to identify biomarker groupings that converge biomarkers from multiple biological pathways. This study aims to investigate the impacts of prenatal air pollution on groups of biomarkers in maternal and cord blood samples. METHODS: In the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort, 87 biomarkers were quantified from 45 trimester 1 maternal blood and 55 cord blood samples. Pregnancy and trimester 1-averaged concentrations of particulate matter ≤2.5 µm and ≤10 µm in diameter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated, using inverse distance squared weighted spatial interpolation from regulatory air monitoring stations. Traffic-related NOx was assessed using California Line Source Dispersion Model: freeway/highway roads, non-freeway major roads, non-freeway minor roads, and their sum as total NOx. Elastic Net (EN) regression within the rexposome R package was used to group biomarkers and assess their associations with air pollution. RESULTS: In maternal samples, trimester 1-averaged PM10 was associated with elevated inflammation biomarkers and lowered cardiovascular biomarkers. NO2 exhibited positive associations with cardiovascular and inflammation markers. O3 was inversely associated with inflammation, metabolic, and cardiovascular biomarkers. In cord blood, pregnancy-averaged PM2.5 was associated with higher cardiovascular biomarkers and lower metabolic biomarkers. PM10 was associated with lower inflammation and higher cardiovascular biomarkers. Total and major road NOx was associated with lower cardiovascular biomarkers. CONCLUSION: Prenatal air pollution exposure was associated with changes in biomarkers related to inflammation, cardiovascular, metabolic, cancer, and neurological function in both mothers and neonates. This study shed light on mechanisms by which air pollution can influence biological function during pregnancy.
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Contaminantes Atmosféricos , Contaminación del Aire , Biomarcadores , Sangre Fetal , Exposición Materna , Material Particulado , Humanos , Femenino , Biomarcadores/sangre , Embarazo , Recién Nacido , Exposición Materna/efectos adversos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Adulto , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Sangre Fetal/química , Material Particulado/análisis , Inflamación/inducido químicamente , Inflamación/sangre , Adulto Joven , Ozono/análisis , Ozono/efectos adversos , Dióxido de Nitrógeno/análisis , California/epidemiologíaRESUMEN
BACKGROUND: Air pollution has been associated with gestational hypertension (GH) and preeclampsia, but susceptible windows of exposure and potential vulnerability by comorbidities, such as prenatal depression, remain unclear. METHODS: We ascertained GH and preeclampsia cases in a prospective pregnancy cohort in Los Angeles, CA. Daily levels of ambient particulate matters (with a diameter of ≤10 µm [PM10] or ≤2.5 µm [PM2.5]), nitrogen dioxide, and ozone were averaged for each week from 12 weeks preconception to 20 gestational weeks. We used distributed lag models to identify susceptible exposure windows, adjusting for potential confounders. Analyses were additionally stratified by probable prenatal depression to explore population vulnerability. RESULTS: Among 619 participants, 60 developed preeclampsia and 42 developed GH. We identified a susceptible window for exposure to PM2.5 from 1 week preconception to 11 weeks postconception: higher exposure (5 µg/m3) within this window was associated with an average of 8% (95% CI, 1%-15%) higher risk of GH. Among participants with probable prenatal depression (n=179; 32%), overlapping sensitive windows were observed for all pollutants from 8 weeks before to 10 weeks postconception with increased risk of GH (PM2.5, 16% [95% CI, 3%-31%]; PM10, 39% [95% CI, 13%-72%]; nitrogen dioxide, 65% [95% CI, 17%-134%]; and ozone, 45% [95% CI, 9%-93%]), while the associations were close to null among those without prenatal depression. Air pollutants were not associated with preeclampsia in any analyses. CONCLUSIONS: We identified periconception through early pregnancy as a susceptible window of air pollution exposure with an increased risk of GH. Prenatal depression increases vulnerability to air pollution exposure and GH.
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Contaminación del Aire , Hipertensión Inducida en el Embarazo , Material Particulado , Humanos , Embarazo , Femenino , Contaminación del Aire/efectos adversos , Adulto , Hipertensión Inducida en el Embarazo/epidemiología , Estudios Prospectivos , Material Particulado/efectos adversos , Los Angeles/epidemiología , Depresión/epidemiología , Preeclampsia/epidemiología , Ozono/efectos adversos , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Factores de Riesgo , Dióxido de Nitrógeno/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: The Children's Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study is a prospective cohort study of environmental influences on respiratory health in a rural, southeastern region of California (CA), which aims to longitudinally examine the contribution of a drying saline lake to adverse health impacts in children. OBJECTIVES: This cohort was established through a community-academic partnership with the goal of assessing the health effects of childhood exposures to wind-blown particulate matter (PM) and inform public health action. We hypothesize that local PM sources are related to poorer children's respiratory health. POPULATION: Elementary school children in Imperial Valley, CA. DESIGN: Prospective cohort study. METHODS: Between 2017 and 2019, we collected baseline information on 731 children, then follow-up assessments yearly or twice-yearly since 2019. Data have been collected on children's respiratory health, demographics, household characteristics, physical activity and lifestyle, via questionnaires completed by parents or primary caregivers. In-person measurements, conducted since 2019, repeatedly assessed lung function, height, weight and blood pressure. Exposure to air pollutants has been assessed by multiple methods and individually assigned to participants using residential and school addresses. Health data will be linked to ambient and local sources of PM, during and preceding the study period to understand how spatiotemporal trends in these environmental exposures may relate to respiratory health. PRELIMINARY RESULTS: Analyses of respiratory symptoms indicate a high prevalence of allergies, bronchitic symptoms and wheezing. Asthma diagnosis was reported in 24% of children at enrolment, which exceeds both CA state and US national prevalence estimates for children. CONCLUSIONS: The Children's AIRE cohort, while focused on the health impacts of the drying Salton Sea and air quality in Imperial Valley, is poised to elucidate the growing threat of drying saline lakes and wind-blown dust sources to respiratory health worldwide, as sources of wind-blown dust emerge in our changing climate.
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Exposición a Riesgos Ambientales , Enfermedades Respiratorias , Humanos , Niño , Femenino , Masculino , Exposición a Riesgos Ambientales/efectos adversos , California/epidemiología , Estudios Prospectivos , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/etiología , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Salud Infantil , Contaminación del Aire/efectos adversos , Población Rural/estadística & datos numéricosRESUMEN
In this study, the effect of cumulative ACEs experienced on human maternal DNA methylation (DNAm) was estimated while accounting for interaction with domains of ACEs in prenatal peripheral blood mononuclear cell samples from the Maternal and Developmental Risks from Environmental Stressors (MADRES) pregnancy cohort. The intergenerational transmission of ACE-associated DNAm was also explored used paired maternal (N = 120) and neonatal cord blood (N = 69) samples. Replication in buccal samples was explored in the Children's Health Study (CHS) among adult parental (N = 31) and pediatric (N = 114) samples. We used a four-level categorical indicator variable for ACEs exposure: none (0 ACEs), low (1-3 ACEs), moderate (4-6 ACEs), and high (>6 ACEs). Effects of ACEs on maternal DNAm (N = 240) were estimated using linear models. To evaluate evidence for intergenerational transmission, mediation analysis (N = 60 mother-child pairs) was used. Analysis of maternal samples displayed some shared but mostly distinct effects of ACEs on DNAm across low, moderate, and high ACEs categories. CLCN7 and PTPRN2 was associated with maternal DNAm in the low ACE group and this association replicated in the CHS. CLCN7 was also nominally significant in the gene expression correlation analysis among maternal profiles (N = 35), along with 11 other genes. ACE-associated methylation was observed in maternal and neonatal profiles in the COMT promoter region, with some evidence of mediation by maternal COMT methylation. Specific genomic loci exhibited mutually exclusive maternal ACE effects on DNAm in either maternal or neonatal population. There is some evidence for an intergenerational effect of ACEs, supported by shared DNAm signatures in the COMT gene across maternal-neonatal paired samples.
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Experiencias Adversas de la Infancia , Femenino , Adulto , Recién Nacido , Embarazo , Humanos , Niño , Metilación de ADN , Mucosa Bucal , Leucocitos Mononucleares , Madres , Padres , Canales de CloruroRESUMEN
BACKGROUND: Diet during pregnancy may be a potential intervention for preventing hypertensive disorders of pregnancy that disproportionally burdens Hispanic/Latina women. METHODS AND RESULTS: The MADRES (Maternal And Developmental Risks from Environmental and Social stressors) study (n=451) is a prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles, California, who completed up to 2 staff-administered 24-hour dietary recalls in the third trimester of pregnancy. Hypertensive disorders of pregnancy were abstracted from medical records and based on a physician's diagnosis or systolic or diastolic blood pressure (≥140 or ≥90 mm Hg, respectively) at ≥2 consecutive prenatal visits. Using multivariable logistic regression, we evaluated associations of 2 previously derived dietary patterns in this population (solid fats, refined grains, and cheese and vegetables, oils, and fruit) and the Healthy Eating Index 2015 with (1) gestational hypertension, (2) preeclampsia, and (3) any hypertensive disorder of pregnancy (either gestational hypertension or preeclampsia). In separate models, we additionally tested interactions with prepregnancy body mass index. Comparing highest-to-lowest quartiles, the solid fats, refined grains, and cheese dietary pattern was associated with an increased odds of any hypertensive disorder of pregnancy (odds ratio [OR], 3.99 [95% CI, 1.44-11.0]; Ptrend=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25-13.5]; Ptrend=0.036), whereas the vegetables, oils, and fruit pattern was associated with reduced odds of preeclampsia (OR, 0.32 [95% CI, 0.10-0.99]; Ptrend=0.041). Among the overweight prepregnancy body mass index category, inverse associations of vegetables, oils, and fruit and Healthy Eating Index 2015 with preeclampsia were more pronounced (both Pinteractions=0.017). Healthy Eating Index 2015 findings were generally nonsignificant. CONCLUSIONS: While the solid fats, refined grains, and cheese diet was strongly associated with preeclampsia during pregnancy, findings suggest the vegetables, oils, and fruit diet may be more relevant than Healthy Eating Index 2015 for preventing preeclampsia among low-income Hispanic/Latina women.
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Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Preeclampsia/epidemiología , Preeclampsia/prevención & control , Factores de Riesgo , Estudios Prospectivos , Patrones Dietéticos , Verduras , Hispánicos o Latinos , AceitesRESUMEN
BACKGROUND: We investigated how childhood-to-adulthood perceived stress patterns predict adult cardiometabolic risk. METHODS AND RESULTS: This study included 276 participants from the Southern California Children's Health Study (2003-2014), and a follow-up assessment (2018-2021). Perceived stress (Perceived Stress Scale) was initially reported by participants' parents for themselves during early childhood (mean age, 6.3 years), and later self-reported during adolescence (13.3 years) and young adulthood (23.6 years). Participants were grouped into 4 stress patterns: consistently high, decreasing, increasing, and consistently low. Cardiometabolic risk was assessed in young adulthood by carotid artery intima-media thickness, systolic and diastolic blood pressure, obesity, percent body fat, android/gynoid ratio, and glycated hemoglobin. A cardiometabolic risk score was generated by summing the clinically abnormal markers. Multivariable linear and logistic regression models were used to (1) examine the associations between Perceived Stress Scale at 3 time points and adult cardiometabolic risk, and (2) assess the impact of stress pattern on adult cardiometabolic risk. Findings suggested that in adulthood, higher Perceived Stress Scale score was associated with increased overall cardiometabolic risk (ß=0.12 [95% CI, 0.01-0.22]), carotid artery intima-media thickness (ß=0.01 [95% CI, 0.0003-0.02]), systolic blood pressure (ß=1.27 [95% CI, 0.09-2.45]), and diastolic blood pressure (ß=0.94 [95% CI, 0.13-1.75]). Individuals with a consistently high adolescence-to-adulthood stress pattern had greater overall cardiometabolic risk (ß=0.31 [95% CI, 0.02-0.60]), android/gynoid ratio (ß=0.07 [95% CI, 0.02-0.13]), percent body fat (ß=2.59 [95% CI, 0.01-5.17]), and greater odds of obesity (odds ratio, 5.57 [95% CI, 1.62-19.10]) in adulthood, compared with those with a consistently low Perceived Stress Scale score. CONCLUSIONS: Consistently high perceived stress from adolescence to adulthood may contribute to greater cardiometabolic risk in young adulthood.
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Enfermedades Cardiovasculares , Grosor Intima-Media Carotídeo , Pruebas Psicológicas , Autoinforme , Adulto , Niño , Adolescente , Humanos , Preescolar , Adulto Joven , Estudios Prospectivos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Obesidad , Estrés Psicológico/epidemiología , Índice de Masa CorporalRESUMEN
We examined the associations between social support and postpartum mental health in 137 U.S. and foreign-born Latinas in the MADRES pregnancy cohort. We also examined whether language, years in the U.S., and country of birth moderates these relationships. Participants were administered PROMIS support measures 1 month postpartum; the Perceived Stress and Postpartum Distress Measure 3, 6, and 12 months postpartum; and the CESD scale 12 months postpartum. Perceived stress was lower at 6 months postpartum for women reporting higher emotional (p = 0.01), informational (p = 0.03), and instrumental support (p < 0.001); and lower at 12 months postpartum for women reporting higher emotional support (p = 0.01). Distress at 6 months was lower in women reporting higher emotional support (p = 0.03). Interactions suggest that associations were stronger for mothers that speak Spanish, spent fewer years in the U.S., and were born in Central America.
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Depresión Posparto , Salud Mental , Embarazo , Femenino , Humanos , Aculturación , Periodo Posparto , Madres/psicología , Hispánicos o Latinos/psicología , Apoyo SocialRESUMEN
Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (ORfine = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (pinteraction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (pinteraction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males ORgross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males ORfine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.
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Retardadores de Llama , Efectos Tardíos de la Exposición Prenatal , Masculino , Niño , Lactante , Embarazo , Humanos , Femenino , Ésteres/orina , Organofosfatos/metabolismo , Fosfatos , Retardadores de Llama/metabolismoRESUMEN
In-utero exposure to fine particulate matter (PM2.5) and specific sources and components of PM2.5 have been linked with lower birthweight. However, previous results have been mixed, likely due to heterogeneity in sources impacting PM2.5 and due to measurement error from using ambient data. Therefore, we investigated the effect of PM2.5 sources and their high-loading components on birthweight using data from 198 women in the 3rd trimester from the MADRES cohort 48-h personal PM2.5 exposure monitoring sub-study. The mass contributions of six major sources of personal PM2.5 exposure were estimated for 198 pregnant women in the 3rd trimester using the EPA Positive Matrix Factorization v5.0 model, along with their 17 high-loading chemical components using optical carbon and X-ray fluorescence approaches. Single- and multi-pollutant linear regressions evaluated the association between personal PM2.5 sources/components and birthweight, adjusting for gestational age, maternal age, race, infant sex, parity, diabetes status, temperature, maternal education, and smoking history. Participants were predominately Hispanic (81%), with a mean (SD) gestational age of 39.1 (1.5) weeks and age of 28.2 (6.0) years. Mean birthweight was 3295.8 g (484.1) and mean PM2.5 exposure was 21.3 (14.4) µg/m3. A 1 SD increase in the mass contribution of the fresh sea salt source was associated with a 99.2 g decrease in birthweight (95% CI - 197.7, - 0.6), and aged sea salt was associated with a 70.1 g decrease in birthweight (95% CI - 141.7, 1.4). Magnesium, sodium, and chlorine were associated with lower birthweight, which remained after adjusting for PM2.5 mass. This study found evidence that major sources of personal PM2.5 including fresh and aged sea salt were negatively associated with birthweight, with the strongest effect on birthweight from Na and Mg. The effect of crustal and fuel oil sources differed by infant sex with negative associations seen in boys compared to positive associations in girls.