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Objectives: To quantify the association of ambient air pollution (particulate matter, PM 2.5 ) exposure with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD)., Study Design: Single center, retrospective cohort study of preterm infants with BPD in Metropolitan Philadelphia. Multivariable logistic regression quantified associations of annual mean PM 2.5 exposure (per μg/m 3 ) at the census block group level with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge adjusting for age at neonatal intensive care unit (NICU) discharge, year, sex, race, insurance, BPD severity, and census tract deprivation. As a secondary analysis, we examined whether BPD severity modified the associations., Results: Of the 378 infants included in the analysis, 189 were non-Hispanic Black and 235 were publicly insured. Census block PM 2.5 level was not significantly associated with medically attended acute respiratory illnesses, ED visits, or hospital readmissions in the full study cohort. We observed significant effect modification by BPD grade; each 1 µg/m 3 higher annual PM 2.5 exposure was medically attended acute respiratory illness (adjusted odds ratio [aOR] 1.65, 95% CI: 1.06-2.63) among infants with Grade 1 BPD but not among infants with grade 3 BPD (aOR 0.83, 95% CI: 0.47-1.48) (interaction p = .024)., Conclusions: Cumulative PM 2.5 exposure in the year after NICU discharge was not significantly associated with medically attended acute respiratory illness among infants with BPD. However, infants with Grade 1 BPD had significantly higher odds with higher exposures. If replicated, these findings could inform anticipatory guidance for families of these infants to avoid outdoor activities during high pollution days after NICU discharge., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Introduction: Prenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America., Methods: We assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity., Results: In Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54)., Conclusions: Prenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Telomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM 2.5 ) and leukocyte telomere length (LTL) in children and explore sex differences., Methods: Analyses included 384 mother-child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM 2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4-6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM 2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification., Results: In trimester specific models, we found an association between 2nd trimester PM 2.5 and elongated LTL (β: 4.34, 95%CI [0.42, 8.42], per 5 μg/m 3 increase). There was suggestive effect modification by sex on average 2nd trimester PM 2.5 with stronger associations seen in females compared to males (β: 7.12, [95%CI: 0.98, 13.6] and β: 1.43 [95%CI: -3.46, 6.57]) per 5 μg/m 3 increase respectively., Conclusion: Second trimester PM 2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM 2.5 exposure may provide insights into telomere dynamics over early life., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2 nd and 3 rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2 nd trimester phthalates mixture and sex on FEV 1 and FVC z-scores. Higher 2 nd trimester phthalate concentrations were associated with higher FEV 1 (β = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (β = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV 1 , β = -0.017, 95 %CI: -0.066, 0.026; FVC, β = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

High ambient summertime temperatures are an increasing health concern with climate change. This is a particular concern for minoritized households in the United States, for which differential energy burden may compromise adaptive capacity to high temperatures. Our research question was: Do minoritized groups experience hotter summers than the area average, and do non-Hispanic white people experience cooler summers? Using a fine-scaled spatiotemporal air temperature model and U.S. census data, we examined local (within-county) differences in warm season cooling degree days (CDDs) by ethnoracial group as a proxy for local energy demand for space cooling across states of the northeast and mid-Atlantic U.S. in 2003-2019. Using state-specific regression models adjusted for year and county, we found that Black and Latino people consistently experienced more CDDs, non-Hispanic white people experienced fewer CDDs, and Asian populations showed mixed results. We also explored a concentration-based measure of residential segregation for each ethnoracial group as one possible pathway towards temperature disparities. We included the segregation measure as a smooth term in a regression model adjusted for county and year. The results were nonlinear, but higher concentrations of white people were associated with lower annual CDDs and higher concentrations of Latino people were associated with higher annual CDDs than the county average. Concentrations for Black and Asian people were nonmonotonic, sometimes with bowed associations. These findings suggest that present-day residential segregation, as modeled by spatially smoothed ethnoracial subgroup concentrations, may contribute to summertime air temperature disparities and influence adaptive capacity. We hope these findings can support place-based interventions, including targeting of energy insecurity relief programs.

Background and Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs., Methods: We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation., Results: In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05)., Conclusions: Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare., Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms., Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included., Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment., Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples., Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood., Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

Introduction: Neurotoxicity resulting from air pollution is of increasing concern. Considering exposure timing effects on neurodevelopmental impairments may be as important as the exposure dose. We used distributed lag regression to determine the sensitive windows of prenatal exposure to fine particulate matter (PM 2.5 ) on children's cognition in a birth cohort in Mexico., Methods: Analysis included 553 full-term (≥37 weeks gestation) children. Prenatal daily PM 2.5 exposure was estimated using a validated satellite-based spatiotemporal model. McCarthy Scales of Children's Abilities (MSCA) were used to assess children's cognitive function at 4-5 years old (lower scores indicate poorer performance). To identify susceptibility windows, we used Bayesian distributed lag interaction models to examine associations between prenatal PM 2.5 levels and MSCA. This allowed us to estimate vulnerable windows while testing for effect modification., Results: After adjusting for maternal age, socioeconomic status, child age, and sex, Bayesian distributed lag interaction models showed significant associations between increased PM 2.5 levels and decreased general cognitive index scores at 31-35 gestation weeks, decreased quantitative scale scores at 30-36 weeks, decreased motor scale scores at 30-36 weeks, and decreased verbal scale scores at 37-38 weeks. Estimated cumulative effects (CE) of PM 2.5 across pregnancy showed significant associations with general cognitive index ( C E ^ = -0.35, 95% confidence interval [CI] = -0.68, -0.01), quantitative scale ( C E ^ = -0.27, 95% CI = -0.74, -0.02), motor scale ( C E ^ = -0.25, 95% CI = -0.44, -0.05), and verbal scale ( C E ^ = -0.2, 95% CI = -0.43, -0.02). No significant sex interactions were observed., Conclusions: Prenatal exposure to PM 2.5 , particularly late pregnancy, was inversely associated with subscales of MSCA. Using data-driven methods to identify sensitive window may provide insight into the mechanisms of neurodevelopmental impairment due to pollution., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Extreme air pollution events and moderate exposure to fine particulate matter (PM2.5) are associated with increased cardiometabolic risk. The World Trade Center (WTC) Health Program general responder cohort includes responders to the WTC disaster. We investigated whether their exposure to this extreme air pollution event (2001) was associated with long-term metabolic outcomes, independently from the associations of intermediate-term PM2.5 exposure later in life (2004-2019). We included 22,447 cohort members with cholesterol (n = 96,155) and glucose (n = 81,599) laboratory results. Self-reported WTC exposure was derived from a questionnaire. PM2.5 exposure was derived from a satellite-based model. We observed an increase of 0.78 mg/dL (95% confidence interval (CI): 0.30, 1.26) in glucose and 0.67 mg/dL (95% CI: 1.00, 2.35) in cholesterol levels associated with an interquartile range increase in PM2.5 averaged 6 months before the study visit. Higher WTC-exposure categories were also associated with higher cholesterol (0.99 mg/dL, 95% CI: 0.30, 1.67, for intermediate exposure) and glucose (0.82 mg/dL, 95% CI: 0.22, 1.43, for high exposure) levels. Most associations were larger among people with diabetes. Extreme air pollution events and intermediate PM2.5 exposure have independent metabolic consequences. These exposures contributed to higher glucose and lipids levels among WTC responders, which may be translated into increased cardiovascular risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Satellite-based PM 2.5 predictions are being used to advance exposure science and air-pollution epidemiology in developed countries; including emerging evidence about the impacts of PM 2.5 on acute health outcomes beyond the cardiovascular and respiratory systems, and the potential modifying effects from individual-level factors in these associations. Research on these topics is lacking in low and middle income countries. We aimed to explore the association between short-term exposure to PM 2.5 with broad-category and cause-specific mortality outcomes in the Mexico City Metropolitan Area (MCMA), and potential effect modification by age, sex, and SES characteristics in such associations., Methods: We used a time-stratified case-crossover study design with 1,479,950 non-accidental deaths from the MCMA for the period of 2004-2019. Daily 1 × 1 km PM 2.5 (median = 23.4 μg/m 3 ; IQR = 13.6 μg/m 3 ) estimates from our satellite-based regional model were employed for exposure assessment at the sub-municipality level. Associations between PM 2.5 with broad-category (organ-system) and cause-specific mortality outcomes were estimated with distributed lag conditional logistic models. We also fit models stratifying by potential individual-level effect modifiers including; age, sex, and individual SES-related characteristics namely: education, health insurance coverage, and job categories. Odds ratios were converted into percent increase for ease of interpretation., Results: PM 2.5 exposure was associated with broad-category mortality outcomes, including all non-accidental, cardiovascular, cerebrovascular, respiratory, and digestive mortality. A 10-μg/m 3 PM 2.5 higher cumulative exposure over one week (lag 06 ) was associated with higher cause-specific mortality outcomes including hypertensive disease [2.28% (95%CI: 0.26%-4.33%)], acute ischemic heart disease [1.61% (95%CI: 0.59%-2.64%)], other forms of heart disease [2.39% (95%CI: -0.35%-5.20%)], hemorrhagic stroke [3.63% (95%CI: 0.79%-6.55%)], influenza and pneumonia [4.91% (95%CI: 2.84%-7.02%)], chronic respiratory disease [2.49% (95%CI: 0.71%-4.31%)], diseases of the liver [1.85% (95%CI: 0.31%-3.41%)], and renal failure [3.48% (95%CI: 0.79%-6.24%)]. No differences in effect size of associations were observed between age, sex and SES strata., Conclusions: Exposure to PM 2.5 was associated with non-accidental, broad-category and cause-specific mortality outcomes beyond the cardiovascular and respiratory systems, including specific death-causes from the digestive and genitourinary systems, with no indication of effect modification by individual-level characteristics., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Preterm birth (defined as birth <37 weeks of gestation) is a significant health concern globally, with lasting implications for individuals, families, and society. In the United States, high preterm birth rates among Black and low-income populations likely result from differences in environmental exposures. Structural racism and economic disadvantage have led to unequal distribution of polluting industrial sites and roadways across society as well as differential access to health-promoting resources which contribute to preterm birth risk. Once born, preterm infants remain at risk for numerous environmentally responsive adverse health outcomes that affect growth and development throughout childhood and adulthood. In this commentary, we describe associations of neighborhood environments with pregnancy and preterm infant health outcomes and propose strategies to address harmful exposures that affect families across the lifespan.

Objectives: To characterize associations of the CDC Social Vulnerability Index (SVI) with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD)., Study Design: Retrospective cohort of 378 preterm infants with BPD from a single center. Multivariable logistic regression quantified associations of SVI with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge. Mediation analysis quantified the extent to which differences in SVI may explain known Black-White disparities in medically attended acute respiratory illness., Results: SVI was associated with medically attended respiratory illness (per SVI standard deviation increment, aOR 1.44, 95% CI: 1.17-1.78). Adjustment for race and ethnicity attenuated the association (aOR 1.27, 95% CI: 0.97-1.64). SVI significantly mediated 31% of the Black-White disparity in ED visits (p = 0.04)., Conclusions: SVI was associated with, and may partially explain racial disparities in, medically attended acute respiratory illness among infants with BPD., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: Vaginal microbial communities can be dominated by anaerobic (community state type IV, CST IV) or Lactobacillus (other CSTs) species. CST IV is a risk factor for spontaneous preterm birth (sPTB) and is more common among Black than White populations. In the US, average air pollution exposures are higher among Black compared to White people and exert systemic health effects. We sought to (1) quantify associations of air pollution, specifically particulate matter <2.5 μm in diameter (PM 2.5 ), with CST IV and (2) explore the extent to which racial disparities in PM 2.5 exposure might explain racial differences in the prevalence of CST IV., Design: Methods: We performed a secondary analysis of 566 participants of the Motherhood & Microbiome study. PM 2.5 exposures were derived from a machine learning model integrating NASA satellite and EPA ground monitor data. Previously, cervicovaginal swabs from 15 to 20 weeks' gestation were analyzed using 16 S rRNA sequencing and hierarchical clustering assigned CSTs. Multivariable logistic regression models calculated adjusted odds ratios of CST IV (vs. other CSTs) per interquartile range (IQR) increment of PM 2.5 . Race-stratified and mediation analyses were performed., Results: Higher PM 2.5 exposure was associated with CST IV (aOR 1.39, 95% CI 1.02-1.91). Further adjustment for race/ethnicity attenuated the association (aOR 1.34, 95% CI: 0.97-1.83). Black participants (vs. White) had higher median PM 2.5 exposure (10.6 vs. 9.6 μg/m 3 , P < 0.001) and higher prevalence of CST IV (47% vs. 11%, P < 0.001). Mediation analysis revealed that higher PM 2.5 exposure may explain 3.9% (P = 0.038) and 3.3% (P = 0.15) of the Black-White disparity in CST IV in unadjusted and adjusted models, respectively., Conclusion: PM 2.5 was associated with CST IV, a risk factor for sPTB. Additionally, PM 2.5 exposure may partially explain racial differences in the prevalence of CST IV. Further research is warranted to discover how environmental exposures affect microbial composition and perpetuate racial health disparities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:MAE is a consultant with equity in Mirvie, South San Franscisco, CA. Mirvie did not fund this study nor did it play any role in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In recent years, there has been growing interest in developing air pollution prediction models to reduce exposure measurement error in epidemiologic studies. However, efforts for localized, fine-scale prediction models have been predominantly focused in the United States and Europe. Furthermore, the availability of new satellite instruments such as the TROPOsopheric Monitoring Instrument (TROPOMI) provides novel opportunities for modeling efforts. We estimated daily ground-level nitrogen dioxide (NO 2 ) concentrations in the Mexico City Metropolitan Area at 1-km 2 grids from 2005 to 2019 using a four-stage approach. In stage 1 (imputation stage), we imputed missing satellite NO 2 column measurements from the Ozone Monitoring Instrument (OMI) and TROPOMI using the random forest (RF) approach. In stage 2 (calibration stage), we calibrated the association of column NO 2 to ground-level NO 2 using ground monitors and meteorological features using RF and extreme gradient boosting (XGBoost) models. In stage 3 (prediction stage), we predicted the stage 2 model over each 1-km 2 grid in our study area, then ensembled the results using a generalized additive model (GAM). In stage 4 (residual stage), we used XGBoost to model the local component at the 200-m 2 scale. The cross-validated R 2 of the RF and XGBoost models in stage 2 were 0.75 and 0.86 respectively, and 0.87 for the ensembled GAM. Cross-validated rootmean-squared error (RMSE) of the GAM was 3.95 μg/m 3 . Using novel approaches and newly available remote sensing data, our multi-stage model presented high cross-validated fits and reconstructs fine-scale NO 2 estimates for further epidemiologic studies in Mexico City., Competing Interests: Competing Interests The author(s) declare that they have no competing interests. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Posttraumatic stress symptoms (PTSS) are common after acute coronary syndrome (ACS) and predict increased morbidity and mortality. Climate change contributes to worse mental and cardiovascular health outcomes, thus, PTSS represent a potential mechanism linking climate change to adverse cardiovascular outcomes. Because people living in areas with lower socioeconomic status (SES) experience greater climate vulnerability, have worse cardiovascular health, and may be more susceptible to PTSS, any effect of temperature on PTSS could be amplified in this population., Methods: Spatial regression models were estimated to test the association of temperature and temperature variability (within-day variability, directed change over time, and absolute change over time), census tract-level SES, and their interaction with PTSS 1 month post-hospital discharge in a longitudinal cohort study comprising 956 patients evaluated for ACS at an urban U.S. academic medical center between November 2013-May 2017. PTSS were self-reported in relation to the ACS event that brought the patient to the hospital. Census tract-level was computed as a composite score from the CDC Social Vulnerability Index, with higher values indicating lower SES., Results: No temperature or temperature variability metrics were associated with PTSS. Lower census tract-level SES was associated with greater PTSS at 1 month. There was a marginally significant interaction of SES with ACS status, such that we only observed evidence of an association among those with ACS., Conclusion: Temperature exposures were not associated with acute CVD-induced PTSS, which could be a result of a small sample size, mismatched timescale, or lack of a true effect. Conversely, lower census tract-level SES was associated with developing worse PTSS 1 month after evaluation for an ACS. This association appeared stronger in individuals with a true ACS. Early interventions to prevent PTSS could promote better mental and CVD outcomes in this at-risk population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cornelius, Casey, Just, Rowland and Edmondson.)

Objectives: Evidence from murine research supports that fine particulate matter (PM 2.5 ) may stimulate the hypothalamic-pituitary-adrenal axis, leading to elevated circulating glucocorticoid levels. Epidemiologic research examining parallel associations document similar associations. We examined these associations among a diverse sample of pregnant individuals exposed to lower levels of ambient PM 2.5 ., Materials and Methods: Participants included pregnant individuals enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pre-birth cohort. Daily residential PM 2.5 exposure was estimated using a satellite-based spatial-temporal hybrid model. Maternal 3rd trimester salivary cortisol levels were used to calculate several features of the diurnal cortisol rhythm. We used multivariable linear regression to examine PM 2.5 during the pre-conception period and during each trimester in relation to cortisol awakening rise (CAR), slope, and area under the curve relative to ground (AUC G )., Results and Discussion: The average PM 2.5 exposure level across pregnancy was 8.13 µg/m 3 . PM 2.5 in each exposure period was positively associated with AUC G , a measure of total cortisol output across the day. We also observed an inverse association between PM 2.5 in the 3rd trimester and diurnal slope, indicating a steeper decline in cortisol throughout the day with increasing exposure. We did not detect strong associations between PM 2.5 and slope for the other exposure periods or between PM 2.5 and CAR for any exposure period., Conclusions: In this sample, PM 2.5 exposure across the preconception and pregnancy periods was associated with increased cortisol output, even at levels below the U.S. National Ambient Air Quality Annual Standard for PM 2.5 of 12.0 µg/m 3 .

Data integration of epidemiologic studies across different geographic regions can provide enhanced exposure contrast and statistical power to examine adverse respiratory effects of early-life exposure to particulate matter <2.5 microns in diameter (PM 2.5 ). Methodological tools improve our ability to combine data while more fully accounting for study heterogeneity., Methods: Analyses included children enrolled in two longitudinal birth cohorts in Boston, Massachusetts, and Mexico City. Propensity score matching using the 1:3 nearest neighbor with caliper method was used. Residential PM 2.5 exposure was estimated from 2 months before birth to age 6 years using a validated satellite-based spatiotemporal model. Lung function was tested at ages 6-11 years and age, height, race, and sex adjusted z scores were estimated for FEV 1 , FVC, FEF 25-75% , and FEV 1 /FVC. Using distributed lag nonlinear models, we examined associations between monthly averaged PM 2.5 levels and lung function outcomes adjusted for covariates, in unmatched and matched pooled samples., Results: In the matched pooled sample, PM 2.5 exposure between postnatal months 35-44 and 35-52 was associated with lower FEV 1 and FVC z scores, respectively. A 5 µg/m 3 increase in PM 2.5 was associated with a reduction in FEV 1 z score of 0.13 (95% CI = -0.26, -0.01) and a reduction in FVC z score of 0.13 (95% CI = -0.25, -0.01). Additionally PM 2.5 during postnatal months 23-39 was associated with a reduction in FEF 25-75% z score of 0.31 (95% CI = -0.57, -0.05)., Conclusions: Methodological tools enhanced our ability to combine multisite data while accounting for study heterogeneity. Ambient PM 2.5 exposure in early childhood was associated with lung function reductions in middle childhood., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Emerging studies have investigated the adverse health effects of PM 2.5 using data from multiple cohorts, and results often are not generalizable across cohorts. We aimed to assess associations between prenatal PM 2.5 and childhood cognition in two U.S. cohorts while accounting for between-site heterogeneity., Methods: Analyses included 348 mother-child dyads enrolled in the dual site (New York City and Boston) PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort and in the First Thousand Days of Life (FTDL) study (Northern Virginia) participating in the Environmental influences on Child Health Outcomes (ECHO) national consortium. Residential prenatal PM 2.5 exposure was estimated using a validated satellite-based model and childhood cognition was measured using the NIH Toolbox Cognition Battery at three to eight years of age. We used a log-linear model applied to contingency tables formed by cross-classifying covariates by site to examine between-site heterogeneity using 3 rd trimester PM 2.5 exposure, age-corrected cognition scores, and covariates potentially causing heterogeneities. Multivariable linear regression models informed by the combinability analysis were used to estimate the coefficients and 95% confidence intervals (CIs) for the association between 3 rd trimester PM 2.5 exposure and age-corrected cognition scores (mean = 100, SD = 15)., Results: The log-linear model indicated that inter-study associations were similar between PRISM-NYC and FTDL, which were different from those in PRISM-Boston. Accordingly, we combined the data of PRISM-NYC and FTDL cohorts. We observed associations between 3 rd trimester PM 2.5 and cognition scores, findings were varying by site, childsex, and test. For example, a 1 μg/m 3 increase of 3 rd trimester PM 2.5 was associated with -4.35 (95% CI = -8.73, -0.25) mean early childhood cognition scores in females in PRISM-Boston. In the pooled NYC + FTDL site, the association between PM 2.5 and childhood cognition may be modified by maternal education and urbanicity., Conclusions: We found associations between prenatal PM 2.5 and impaired childhood cognition. Since multi-site analyses are increasingly conducted, our findings suggest the needed awareness of between-site heterogeneity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Greenspace may benefit sleep by enhancing physical activity, reducing stress or air pollution exposure. Studies on greenspace and children's sleep are limited, and most use satellite-derived measures that do not capture ground-level exposures that may be important for sleep. We examined associations of street view imagery (SVI)-based greenspace with sleep in Project Viva, a Massachusetts pre-birth cohort. We used deep learning algorithms to derive novel metrics of greenspace (e.g., %trees, %grass) from SVI within 250m of participant residential addresses during 2007-2010 (mid-childhood, mean age 7.9 years) and 2012-2016 (early adolescence, 13.2y) (N = 533). In early adolescence, participants completed >5 days of wrist actigraphy. Sleep duration, efficiency, and time awake after sleep onset (WASO) were derived from actigraph data. We used linear regression to examine cross-sectional and prospective associations of mid-childhood and early adolescence greenspace exposure with early adolescence sleep, adjusting for confounders. We compared associations with satellite-based greenspace (Normalized Difference Vegetation Index, NDVI). In unadjusted models, mid-childhood SVI-based total greenspace and %trees (per interquartile range) were associated with longer sleep duration at early adolescence (9.4 min/day; 95%CI:3.2,15.7; 8.1; 95%CI:1.7,14.6 respectively). However, in fully adjusted models, only the association between %grass at mid-childhood and WASO was observed (4.1; 95%CI:0.2,7.9). No associations were observed between greenspace and sleep efficiency, nor in cross-sectional early adolescence models. The association between greenspace and sleep differed by racial and socioeconomic subgroups. For example, among Black participants, higher NDVI was associated with better sleep, in neighborhoods with low socio-economic status (SES), higher %grass was associated with worse sleep, and in neighborhoods with high SES, higher total greenspace and %grass were associated with better sleep time. SVI metrics may have the potential to identify specific features of greenspace that affect sleep., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Machine-learning algorithms are becoming popular techniques to predict ambient air PM 2.5 concentrations at high spatial resolutions (1 × 1 km) using satellite-based aerosol optical depth (AOD). Most machine-learning models have aimed to predict 24 h-averaged PM 2.5 concentrations (mean PM 2.5 ) in high-income regions. Over Mexico, none have been developed to predict subdaily peak levels, such as the maximum daily 1-h concentration (max PM 2.5 )., Objective: Our goal was to develop a machine-learning model to predict mean PM 2.5 and max PM 2.5 concentrations in the Mexico City Metropolitan Area from 2004 through 2019., Methods: We present a new modeling approach based on extreme gradient boosting (XGBoost) and inverse-distance weighting that uses AOD, meteorology, and land-use variables. We also investigated applications of our mean PM 2.5 predictions that can aid local authorities in air-quality management and public-health surveillance, such as the co-occurrence of high PM 2.5 and heat, compliance with local air-quality standards, and the relationship of PM 2.5 exposure with social marginalization., Results: Our models for mean and max PM 2.5 exhibited good performance, with overall cross-validated mean absolute errors (MAE) of 3.68 and 9.20 μg/m 3 , respectively, compared to mean absolute deviations from the median (MAD) of 8.55 and 15.64 μg/m 3 . In 2010, everybody in the study region was exposed to unhealthy levels of PM 2.5 . Hotter days had greater PM 2.5 concentrations. Finally, we found similar exposure to PM 2.5 across levels of social marginalization., Significance: Machine learning algorithms can be used to predict highly spatiotemporally resolved PM 2.5 concentrations even in regions with sparse monitoring., Impact: Our PM 2.5 predictions can aid local authorities in air-quality management and public-health surveillance, and they can advance epidemiological research in Central Mexico with state-of-the-art exposure assessment methods., (© 2022. The Author(s).)

DNA methylation (DNAm) is vulnerable to dysregulation by environmental exposures during epigenetic reprogramming that occurs in embryogenesis. Sexual dimorphism in environmentally induced DNAm dysregulation has been identified and therefore it is important to understand sex-specific DNAm patterns. DNAm at several autosomal sites has been consistently associated with sex in cord blood and placental foetal tissues. However, there is limited research comparing sex-specific DNAm across tissues, particularly differentially methylated regions (DMRs). This study leverages DNAm data measured using the Illumina HumanMethylation450 BeadChip in cord blood (N = 179), placenta (N = 229), and umbilical artery samples (N = 229) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort to identify autosomal DMRs and differentially methylated positions (DMPs). A replication analyses was conducted in an independent cohort (GEO Accession GSE129841). We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs ( p Bonferroni < 0.05) in cord blood, placenta, and artery samples, respectively. Thirty-nine DMRs overlapped in all three tissues, overlapping with genes involved in spermatogenesis ( NKAPL, PIWIL2 and AURKC ) and X-inactivation ( LRIF1 ). In replication analysis, 85% of DMRs overlapped with those identified in PRISM. Overall, DMRs and DMPs had higher methylation levels among females in cord blood and artery samples, but higher methylation levels among males in placenta samples. Further research is necessary to understand biological mechanisms that contribute to differences in sex-specific DNAm signatures across tissues, as well as to determine if sexual dimorphism in the epigenome impacts response to environmental stressors.

Hormones play critical roles in facilitating pregnancy progression and the onset of parturition. Several classes of environmental contaminants, including fine particulate matter (PM 2.5 ) and ambient temperature, have been shown to alter hormone biosynthesis or activity. However, epidemiologic research has not considered PM 2.5 in relation to a broader range of steroid hormones, particularly in pregnant women. Using metabolomics data collected within 20-40 weeks of gestation in an ethnically diverse pregnancy cohort study, we identified 42 steroid hormones that we grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids) based on their biosynthesis type. We found that exposure to PM 2.5 during the pre-conception and early prenatal periods was associated with higher maternal androgen concentrations in late pregnancy. We also detected a positive association between early pregnancy PM 2.5 exposure and maternal pregnenolone levels and a marginal positive association between early pregnancy PM 2.5 exposure and progestin levels. When considering each hormone metabolite individually, we found positive associations between early pregnancy PM 2.5 exposure and five steroids, two of which survived multiple comparison testing: 11beta-hydroxyandrosterone glucuronide (a pregnenolone steroid) and adrosteroneglucuronide (a progestin steroid). None of the steroid classes were statistically significant associated with ambient temperature. In sex-stratified analyses, we did not detect any sex differences in our associations. This is the first study showing that exposure to fine particulate matter during the pre-conception and early prenatal periods can lead to altered steroid adaptation during the state of pregnancy, which has been shown to have potential consequences on maternal and child health., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Air pollution has been linked to obesity while higher ambient temperatures typically reduce metabolic demand in a compensatory manner. Both relationships may impact glucose metabolism, thus we examined the association between intermediate- and long-term exposure to fine particulate matter (PM 2.5 ) and ambient temperature and glycated hemoglobin(HbA1c), a longer-term marker of glucose control., Methods: We assessed 3-month, 6-month, and 12-month average air pollution and ambient temperature at 1-km 2 spatial resolution via satellite remote sensing models (2013-2019), and assessed HbA1c at four, six, and eight years postpartum in women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City. PM 2.5 and ambient temperature were matched to participants' addresses and confirmed by GPS tracker. Using linear mixed-effects models, we examined the association between 3-month, 6-month, and 12-month average PM 2.5 and ambient temperature with repeated log-transformed HbA1c values. All models included a random intercept for each woman and were adjusted for calendar year, season, and individual-level confounders (age, marital status, smoking, alcohol consumption level, and education level)., Results: We analyzed 1,265 HbA1c measurements of 484 women. Per 1 µg/m 3 increase in 3-month and 6-month PM 2.5 , HbA1c levels increased by 0.28% (95% confidence interval (95 %CI): 0.14, 0.42%) and 0.28% (95 %CI: 0.04, 0.52%) respectively. No association was seen for 12-month average PM 2.5 . Per 1 °C increase in ambient temperature, HbA1c levels decreased by 0.63% (95 %CI: -1.06, -0.21%) and 0.61% (95 %CI: -1.08, -0.13%), while the 12-month average again is not associated with HbA1c., Conclusions: Intermediate-term exposure to PM 2.5 and ambient temperature are associated with opposing changes in HbA1c levels, in this region of high PM 2.5 and moderate temperature fluctuation. These effects, measurable in mid-adult life, may portend future risk of type 2 diabetes and possible heart disease., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Phthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women., Objective: To determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery., Methods: We analyzed 15 urinary phthalate biomarker concentrations during the 2nd and 3rd trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2nd and 3rd trimesters), short-term weight (between 3rd trimester and 12 months post-delivery), and long-term weight (between 18 months and 6-7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers., Results: As a mixture, 2nd trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2nd and 3rd trimesters (interquartile range, IQR, difference: -0.07 standard deviations, SD; 95% credible interval, CrI: -0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2nd and 3rd trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6-7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP., Conclusions: Prenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: While evidence suggests that daily ambient temperature exposure influences stroke risk, little is known about the potential triggering role of ultra short-term temperature., Methods: We examined the association between hourly temperature and ischemic and hemorrhagic stroke, separately, and identified any relevant lags of exposure among adult New York State residents from 2000 to 2015. Cases were identified via ICD-9 codes from the New York Department of Health Statewide Planning and Reearch Cooperative System. We estimated ambient temperature up to 36 h prior to estimated stroke onset based on patient residential ZIP Code. We applied a time-stratified case-crossover study design; control periods were matched to case periods by year, month, day of week, and hour of day. Additionally, we assessed effect modification by leading stroke risk factors hypertension and atrial fibrillation., Results: We observed 578,181 ischemic and 164,755 hemorrhagic strokes. Among ischemic and hemorrhagic strokes respectively, the mean (standard deviation; SD) patient age was 71.8 (14.6) and 66.8 (17.4) years, with 55% and 49% female. Temperature ranged from -29.5 °C to 39.2 °C, with mean (SD) 10.9 °C (10.3 °C). We found linear relationships for both stroke types. Higher temperature was associated with ischemic stroke over the 7 h following exposure; a 10 °C increase over 7 h was associated with 5.1% (95% Confidence Interval [CI]: 3.8, 6.4%) increase in hourly stroke rate. In contrast, temperature was negatively associated with hemorrhagic stroke over 5 h, with a 5-h cumulative association of -6.2% (95% CI: 8.6, -3.7%). We observed suggestive evidence of a larger association with hemorrhagic stroke among patients with hypertension and a smaller association with ischemic stroke among those with atrial fibrillation., Conclusion: Hourly temperature was positively associated with ischemic stroke and negatively associated with hemorrhagic stroke. Our results suggest that ultra short-term weather influences stroke risk and hypertension may confer vulnerability., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Prenatal exposure to fine particulate matter with a diameter of ≤2.5 μm (PM 2.5 ) has been linked to adverse neurodevelopmental outcomes in later childhood, while research on early infant behavior remains sparse., Objectives: We examined associations between prenatal PM 2.5 exposure and infant negative affectivity, a stable temperamental trait associated with longer-term behavioral and mental health outcomes. We also examined sex-specific effects., Methods: Analyses included 559 mother-infant pairs enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort. Daily PM 2.5 exposure based on geocoded residential address during pregnancy was estimated using a satellite-based spatiotemporal model. Domains of negative affectivity (Sadness, Distress to Limitations, Fear, Falling Reactivity) were assessed using the Infant Behavior Questionnaire-Revised (IBQ-R) when infants were 6 months old. Subscale scores were calculated as the mean of item-specific responses; the global Negative Affectivity (NA) score was derived by averaging the mean of the four subscale scores. Bayesian distributed lag interaction models (BDLIMs) were used to identify sensitive windows for prenatal PM 2.5 exposure on global NA and its subscales, and to examine effect modification by sex., Results: Mothers were primarily racial/ethnic minorities (38% Black, 37% Hispanic), 40% had ≤12 years of education; most did not smoke during pregnancy (87%). In the overall sample, BDLIMs revealed that increased PM 2.5 at mid-pregnancy was associated with higher global NA, Sadness, and Fear scores, after adjusting for covariates (maternal age, education, race/ethnicity, sex). Among boys, increased PM 2.5 at early pregnancy was associated with decreased Fear scores, while exposure during late pregnancy was associated with increased Fear scores (cumulative effect estimate = 0.57, 95% CI: 0.03-1.41). Among girls, increased PM 2.5 during mid-pregnancy was associated with higher Fear scores (cumulative effect estimate = 0.82, 95% CI: 0.05-1.91)., Conclusions: Prenatal PM 2.5 exposure was associated with negative affectivity at age 6 months, and the sensitive windows may vary by subdomains and infant sex., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Lead is a ubiquitous pollutant with deleterious effects on human health and remains a major current public health concern in developing countries. This heavy metal may interfere with nucleic acids via oxidative stress or epigenetic changes that affect biological markers of aging, e.g., telomere length and DNA methylation (DNAm). Telomere shortening associates with biological age in newborns, and DNA methylation at specific CpG sites can be used to calculate "epigenetic clocks"., Objective: The aim of this study was to examine the associations of prenatal lead exposures with telomere length and DNA-methylation-based predictors of age in cord blood., Design: The study included 507 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a birth cohort in Mexico City. Maternal blood (second trimester, third trimester and at delivery) and bone lead levels (one month postpartum) were measured using inductively coupled plasma-mass spectrometry and X-ray fluorescence, respectively. Cord blood leukocyte telomere length was measured using quantitative PCR and apparent age by DNA methylation biomarkers, i.e., Horvath's DNA methylation age and the Knight's predictor of gestational age., Results: Average maternal age was 28.5 ± 5.5 years, and 51.5% reported low socioeconomic status. Children's mean telomere length was 1.2 ± 1.3 relative units, and mean DNA methylation ages using the Horvath's and Knight's clocks were -2.6 ± 0.1 years and 37.9 ± 1.4 weeks (mean ± SD), respectively. No significant associations were found between maternal blood and bone lead concentrations with telomere length and DNAm age in newborns., Conclusion: We found no associations of prenatal lead exposure with telomere length and DNA methylation age biomarkers., (Copyright © 2021. Published by Elsevier Inc.)

Air pollution exposure, especially particulate matter ≤2.5 μm in diameter (PM 2.5 ), is associated with poorer kidney function in adults and children. Perinatal exposure may occur during susceptible periods of nephron development. We used distributed lag nonlinear models (DLNMs) to examine time-varying associations between early life daily PM 2.5 exposure (periconceptional through age 8 years) and kidney parameters in preadolescent children aged 8-10 years. Participants included 427 mother-child dyads enrolled in the PROGRESS birth cohort study based in Mexico City. Daily PM 2.5 exposure was estimated at each participant's residence using a validated satellite-based spatio-temporal model. Kidney function parameters included estimated glomerular filtration rate (eGFR), serum cystatin C, and blood urea nitrogen (BUN). Models were adjusted for child's age, sex and body mass index (BMI) z-score, as well as maternal education, indoor smoking report and seasonality (prenatal models were additionally adjusted for average first year of life PM 2.5 exposure). We also tested for sex-specific effects. Average perinatal PM 2.5 was 22.7 μg/m 3 and ranged 16.4-29.3 μg/m 3 . Early pregnancy PM 2.5 exposures were associated with higher eGFR in preadolescence. Specifically, we found that PM 2.5 exposure between weeks 1-18 of gestation was associated with increased preadolescent eGFR, whereas exposure in the first 14 months of life after birth were associated with decreased eGFR. Specifically, a 5 μg/m 3 increase in PM 2.5 during the detected prenatal window was associated with a cumulative increase in eGFR of 4.44 mL/min/1.73 2 (95%CI: 1.37, 7.52), and during the postnatal window we report a cumulative eGFR decrease of -10.36 mL/min/1.73 2 (95%CI: -17.68, -3.04). We identified perinatal windows of susceptibility to PM 2.5 exposure with preadolescent kidney function parameters. Follow-up investigating PM 2.5 exposure with peripubertal kidney function trajectories and risk of kidney disease in adulthood will be critical., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: Adiposity trajectories reflect dynamic process of growth and may predict later life health better than individual measures. Prenatal phthalate exposures may program later childhood adiposity, but findings from studies examining these associations are conflicting. We investigated associations between phthalate biomarker concentrations during pregnancy with child adiposity trajectories., Methods: We followed 514 mother-child pairs from the Mexico City PROGRESS cohort from pregnancy through twelve years. We measured concentrations of nine phthalate biomarkers in 2nd and 3rd trimester maternal urine samples to create a pregnancy average using the geometric mean. We measured child BMI z-score, fat mass index (FMI), and waist-to-height ratio (WHtR) at three study visits between four and 12 years of age. We identified adiposity trajectories using multivariate latent class growth modeling, considering BMI z-score, FMI, and WHtR as joint indicators of latent adiposity. We estimated associations of phthalates biomarkers with class membership using multinomial logistic regression. We used quantile g-computation to estimate the potential effect of the total phthalate mixture and assessed effect modification by sex., Results: We identified three trajectories of child adiposity, a "low-stable", a "low-high", and a "high-high" group. A doubling of the sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHP), was associated with 1.53 (1.08, 2.19) greater odds of being in the "high-high" trajectory in comparison to the "low-stable" group, whereas a doubling in di-isononyl phthalate metabolites (ΣDiNP) was associated with 1.43 (1.02, 2.02) greater odds of being in the "low-high" trajectory and mono (carboxy-isononyl) phthalate (MCNP) was associated with 0.66 (0.45, 97) lower odds of being in the "low-high" trajectory. No sex-specific associations or mixture associations were observed., Conclusions: Prenatal concentrations of urinary DEHP metabolites, DiNP metabolites, and MCNP, a di-isodecyl phthalate metabolite, were associated with trajectories of child adiposity. The total phthalate mixture was not associated with early life child adiposity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Saliva is a widely used biological sample, especially in pediatric research, containing a heterogenous mixture of immune and epithelial cells. Associations of exposure or disease with saliva DNA methylation can be influenced by cell-type proportions. Here, we developed a saliva cell-type DNA methylation reference panel to estimate interindividual cell-type heterogeneity in whole saliva studies. Saliva was collected from 22 children (7-16 years) and sorted into immune and epithelial cells, using size exclusion filtration and magnetic bead sorting. DNA methylation was measured using the Illumina MethylationEPIC BeadChip. We assessed cell-type differences in DNA methylation profiles and tested for enriched biological pathways. Immune and epithelial cells differed at 181,577 (22.8%) DNA methylation sites (t-test p < 6.28 × 10 -8 ). Immune cell hypomethylated sites are mapped to genes enriched for immune pathways (p < 3.2 × 10 -5 ). Epithelial cell hypomethylated sites were enriched for cornification (p = 5.2 × 10 -4 ), a key process for hard palette formation. Saliva immune and epithelial cells have distinct DNA methylation profiles which can drive whole-saliva DNA methylation measures. A primary saliva DNA methylation reference panel, easily implemented with an R package, will allow estimates of cell proportions from whole saliva samples and improve epigenetic epidemiology studies by accounting for measurement heterogeneity by cell-type proportions.

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.

Background: Exposure to air pollution is the main risk factor for morbidity and mortality in the world. Exposure to particulate matter with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) is associated with cardiovascular and respiratory conditions, as well as with lung cancer, and there is evidence to suggest that it is also associated with type II diabetes (DM). The Mexico City Metropolitan Area (MCMA) is home to more than 20 million people, where PM 2.5 levels exceed national and international standards every day. Likewise, DM represents a growing public health problem with prevalence around 12%. In this study, the objective was to evaluate the association between exposure to PM 2.5 and DM in adults living in the MCMA., Methods: Data from the 2006 or 2012 National Health and Nutrition Surveys (ENSANUT) were used to identify subjects with DM and year of diagnosis. We estimated PM 2.5 exposure at a residence level, based on information from the air quality monitoring system (monitors), as well as satellite measurements (satellite). We analyzed the relationship through a cross-sectional approach and as a case - control study., Results: For every 10 μg/m 3 increase of PM 2.5 we found an OR = 3.09 (95% CI 1.17-8.15) in the 2012 sample. These results were not conclusive for the 2006 data or for the case - control approach., Conclusions: Our results add to the evidence linking PM 2.5 exposure to DM in Mexican adults. Studies in low- and middle-income countries, where PM 2.5 atmospheric concentrations exceed WHO standards, are required to strengthen the evidence., (© 2021. The Author(s).)

Introduction: Prenatal exposure to fine particulate matter air pollution (PM2.5) is an important, under-studied risk factor for neurodevelopmental dysfunction. We describe the relationships between prenatal PM2.5 exposure and vigilance and inhibitory control, executive functions related to multiple health outcomes in Mexico City children., Methods: We studied 320 children enrolled in Programming Research in Obesity, GRowth, Environment and Social Stressors, a longitudinal birth cohort study in Mexico City. We used a spatio-temporal model to estimate daily prenatal PM2.5 exposure at each participant's residential address. At age 9-10 years, children performed three Go/No-Go tasks, which measure vigilance and inhibitory control ability. We used Latent class analysis (LCA) to classify performance into subgroups that reflected neurocognitive performance and applied multivariate regression and distributed lag regression modeling (DLM) to test overall and time-dependent associations between prenatal PM2.5 exposure and Go/No-Go performance., Results: LCA detected two Go/No-Go phenotypes: high performers (Class 1) and low performers (Class 2). Predicting odds of Class 1 vs Class 2 membership based on prenatal PM2.5 exposure timing, logistic regression modeling showed that average prenatal PM2.5 exposure in the second and third trimesters correlated with increased odds of membership in low-performance Class 2 (OR = 1.59 (1.16, 2.17), p = 0.004). Additionally, DLM analysis identified a critical window consisting of gestational days 103-268 (second and third trimesters) in which prenatal PM2.5 exposure predicted poorer Go/No-Go performance., Discussion: Increased prenatal PM2.5 exposure predicted decreased vigilance and inhibitory control at age 9-10 years. These findings highlight the second and third trimesters of gestation as critical windows of PM2.5 exposure for the development of vigilance and inhibitory control in preadolescent children. Because childhood development of vigilance and inhibitory control informs behavior, academic performance, and self-regulation into adulthood, these results may help to describe the relationship of prenatal PM2.5 exposure to long-term health and psychosocial outcomes. The integrative methodology of this study also contributes to a shift towards more holistic analysis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Birthweight is a strong predictor of normal growth, healthy development, and survival. Several studies have found associations between temperature, fine particulate matter (PM 2.5 ), and birth weight. However, the relevant timing of exposures varies between studies and is yet unclear. Therefore, we assessed the difference in term birthweight (TBW) associated with weekly exposure to temperature and PM 2.5 throughout 37 weeks of gestation., Methods: We included all singleton live term births in Massachusetts, U.S between 2004 and 2015 (n = 712,438). Weekly PM 2.5 and temperature predictions were estimated on a 1 km grid from satellite-based models. We utilized a distributed lag nonlinear model (DLNM) to estimate the difference in TBW associated with weekly exposures from the last menstrual period to 37 weeks of gestation., Results: We found a nonlinear association with prenatal temperature exposure. Larger effects were observed in warmer temperatures, where higher temperatures were negatively associated with TBW. Temperature effects were larger in the first and final weeks of gestation. We observed a negative difference in TBW associated with PM 2.5 exposure. Overall, a 1 µg/m 3 increase in prenatal exposure was associated with 3.9 g lower TBW (95% CI -5.0 g; -2.9 g). PM 2.5 effects were larger in the final weeks of gestation., Conclusion: We found heat and PM 2.5 exposure to be related to lower TBW. Our findings suggest that women are more susceptible to both exposures towards the end of pregnancy. Susceptibility to heat was higher in the initial weeks of pregnancy as well. These critical windows of susceptibility can be communicated to pregnant women during routine prenatal visits to increase awareness and target interventions to reduce exposures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study., Aim: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems., Methods: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log 2 -transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex., Results: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (β = 0.57, 95% CI = 0.17, 1.13) and in girls (β = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (β = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (β = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21)., Discussion: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex., (Copyright © 2021 Elsevier Inc. All rights reserved.)