Search

Background: PAH exposure is associated with adverse health outcomes, but exposure sources in pregnancy are not well-understood., Objectives: We examined associations between urinary OH-PAHs during pregnancy and environmental tobacco smoke (ETS) and short-term ambient air pollution exposure. Participants included 1,603 pregnant non-smokers in three cohorts from 7 sites across the USA. We also examined associations with intake of foods typically high in PAHs in one cohort with dietary assessment data (n=801)., Methods: Urinary OH-PAHs were measured using LC-MS/MS; urinary cotinine was measured using SPE/UPLC-MS/MS. To accommodate different detection limits by cohort, ETS exposure was represented by modified cotinine quartiles; these combined concentrations below the highest detection limit in the first category (0-0.017 ng/mL), with the rest divided evenly into three categories (0.0171-0.2 ng/mL, 0.21-1.191 ng/mL, 1.192-1,465 ng/mL). Air pollution exposure was represented by quartiles of same-day ambient PM 2.5 in residential census tracts estimated from EPA's Downscaler Model. We fitted separate Tobit regression models for log-OH-PAH concentrations in association with cotinine or ambient PM 2.5 quartile adjusted for specific gravity, site, batch, household income, education, employment status, neighborhood deprivation index, season, and year. For the food model, PAH dietary intakes were estimated using food frequency questionnaire data and standard portion weights from a national database., Results: In adjusted models, the highest modified cotinine quartile vs. the lowest was associated with 48% (95% CI: 13%, 94%) higher urinary 1-hydroxynaphthalene, 36% (15%, 61%) higher 2-hydroxynaphthalene, 41% (23%, 63%) higher 3-hydroxyphenanthrene, and 70% (28%, 127%) higher 1-hydroxypyrene. Second and third quartile cotinine concentrations were associated with higher OH-PAHs, although not consistently. Same-day ambient PM 2.5 was not associated with any OH-PAH, nor was self-reported dietary intake., Conclusions: ETS is a major source of PAH exposure for pregnant people in the USA while ambient PM 2.5 and diet measured via usual intakes appear less influential. Our findings underscore the importance of policies/actions to reduce environmental tobacco smoke exposure among pregnant people., 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. Published by Elsevier Inc.)

Background: Evidence suggests that long-term exposure to air pollution may increase the risk of dementia and related cognitive outcomes. A major source of air pollution is automotive traffic, which is modifiable by technological and regulatory interventions., Objectives: We examined associations of four traffic-related air pollutants with rates of cognitive decline in a cohort of older adults., Methods: We analyzed data from the Chicago Health and Aging Project (CHAP), a longitudinal (1993-2012) community-based cohort study of older adults that included repeated assessments of participants' cognitive performance. Leveraging previously developed air pollution models, we predicted participant-level exposures to the tailpipe pollutants oxides of nitrogen ( NO X ) and nitrogen dioxide ( NO 2 ), plus the nontailpipe pollutants copper and zinc found in coarse particulate matter [PM with aerodynamic diameter 2.5 μ m to 10 μ m ( PM 2.5 - 10 , Cu ) and PM 2.5 - 10 , Zn , respectively], over the 3 y prior to each participant's baseline assessment. Using generalized estimating equations, we estimated covariate-adjusted associations of each pollutant with rates of cognitive decline. We probed the robustness of our results via several sensitivity analyses, including alterations to the length of the exposure assessment window and exploring the influence of pre- and post-baseline selection bias., Results: Using data from 6,061 participants, estimated associations of these pollutant exposures with cognitive decline were largely inconsistent with large adverse effects. For example, a standard deviation ( 5.8  ppb ) increment in NO X corresponded to a slightly slower rate of cognitive decline [e.g., mean difference in change in global score, 0.010 standard unit/5 y, 95% confidence interval (CI): -0 .016 , 0.036]. The results of most of our sensitivity analyses were in generally similar to those of our main analyses, but our prebaseline selection bias results suggest that our analytic results may have been influenced by differential survivorship into our study sample., Discussion: In this large prospective cohort study, we did not observe compelling evidence that long-term TRAP exposure is associated with cognitive decline. https://doi.org/10.1289/EHP14585.

Background: Ambient fine particulate matter (PM 2.5 ) exposure adversely impacts child airway health; however, research on prenatal PM 2.5 exposure, and child lung function is limited. We investigated these associations in the ECHO-PATHWAYS Consortium, focusing on the role of exposure timing during different phases of fetal lung development., Methods: We included 675 children in the CANDLE cohort born between 2007 and 2011 in Memphis, TN, USA. Prenatal exposure to ambient PM 2.5 was estimated using a spatiotemporal model based on maternal residential history and averaged over established prenatal periods of lung development. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were measured by spirometry at age 8-9 years. We used linear regression and Bayesian Distributed Lag Interaction Models (BDLIM) to estimate associations between exposure and lung function z-scores, adjusting for maternal/child characteristics, prenatal/postnatal tobacco exposure, and birth year/season, and evaluating effect modification by child sex and allergic sensitization., Results: The average ambient concentration of PM 2.5 during pregnancy was 11.1 µg/m 3 (standard deviation:1.0 µg/m 3 ). In the adjusted linear regression and BDLIM models, adverse, but not statistically significant, associations were observed between exposure during the pseudoglandular (5-16 weeks of gestation) and saccular (24-36 weeks) phases of lung development and FEV1 and FVC. The strongest association was between a 2 μg/m 3 higher concentration of PM 2.5 during the saccular phase and FEV1 z-score (-0.176, 95% Confidence Interval [CI]: -0.361, 0.010). The FEV1/FVC ratio was not associated with PM 2.5 in any exposure window. No effect modification by child sex or allergic sensitization was observed., Conclusions: We did not find strong evidence of associations between prenatal ambient PM 2.5 exposure and child lung function in a large, well-characterized study sample. However, there was a suggested adverse association between FEV1 and exposure during late pregnancy. The saccular phase of lung development might be an important window for exposure to PM 2.5 .

Introduction: Cervical cancer screening uptake among East African immigrants (EAI) in the US is low. Offering self-collected samples for human papillomavirus (HPV) testing increases screening coverage among underserved populations, but the potential impact on cervical cancer incidence and mortality is understudied., Methods: A Markov cohort state-transition model was used to predict the impact of primary HPV screening with self-sampling on cervical cancer incidence and mortality among EAI women in Washington state. The model estimated cervical cancer cases and deaths for a hypothetical cohort from ages 25-80 years under alternative screening, diagnostic colposcopy and treatment scenarios. Base case scenarios compared primary HPV testing by clinician-sampling exclusively (standard-of-care, SOC) with self-sampling exclusively, assuming higher screening coverage (70% vs. 63%) but lower colposcopy adherence with self-sampling (67% vs. 83%) with equal treatment coverage of 85%, based on Washington state patient data. Sensitivity analyses with varied coverages, and also the combinations of the two strategies were evaluated. The model was developed and fitted between 2022 and 2024 RESULTS: In the base case scenario, an exclusive self-sampling strategy results in 4% higher cervical cancer incidence and mortality compared to the SOC. Self-sampling results in lower cancer incidence and mortality if colposcopy adherence is raised to the level of the SOC and/or if coverage is increased beyond 90%. In scenarios combining clinician- with self-sampling, the benefits of reaching more women with self-sampling are attenuated if more than 34% of screening is done by self-sampling., Conclusions: Self-sampling has the potential to improve cervical cancer prevention for underserved populations. The impact of the strategy can be enhanced with stronger linkage to follow-up care., Competing Interests: Declaration of competing interest There is no conflict of interest, and all authors have read and approved this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Nationwide PM 2.5 exposure models typically rely on regulatory monitoring data as the only ground-level measurements. In this study, we develop a high-resolution spatiotemporal PM 2.5 model for the contiguous United States from 2000 to 2019 with dense monitoring data at both regulatory and residential sites. Specifically, we combine publicly-available data from 1843 regulatory monitors with our own set of multiple 2-week measurements at 939 residential locations. As we show, these additional data enhance the spatiotemporal prediction capabilities of the model. The model can handle varying data densities and regional variations; it predicts two-week average PM 2.5 concentrations at fine spatial scale for the contiguous United States. Cross-validation performance indicates a spatial R 2 of 0.93 and a root mean square error (RMSE) of 1.19 (μg/m 3 ), and a temporal R 2 of 0.85 and RMSE of 2.05 (μg/m 3 ). Regional spatial R 2 ranged from 0.80 (northwest) to 0.93 (northeast and central). Over time, the average PM 2.5 across the United Stats decreased from 7.6 μg/m 3 in 2000 to 4.7 μg/m 3 in 2019. Our model effectively captured local PM 2.5 gradients, highlighting its ability to address fine-scale variations related to local sources and roadways., 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 Ltd. All rights reserved.)

Background: Somali American individuals have lower cervical cancer screening rates than the U.S. general population. Offering HPV self-sampling in primary care clinics could increase screening rates in Somali American individuals by addressing screening barriers., Methods: The Isbaar Project is a Hybrid Type 2 effectiveness-implementation study of a patient-centered, culturally tailored HPV self-sampling intervention for Somali American individuals. Guided by the Consolidated Framework for Implementation Research and Social Cognitive Theory, we conducted focus groups with Somali American individuals, and interviews with clinicians and clinic staff to inform refinement and development of implementation strategies. HPV self-sampling was then implemented as a usual care screening option at 3 community-based primary care clinics in Minneapolis, Minnesota in February 2023. The primary objective is to assess the effect of implementing in-clinic HPV self-sampling on screening completion in Somali American individuals. The secondary objective is to assess the effect of implementing HPV self-sampling on screening completion in all patients. Using difference-in-difference methods, we will evaluate changes in screening rates one-year pre and post implementation and compare changes with control clinics followed over the same time period. Using RE-AIM, we will conduct a post-implementation mixed methods analysis of processes and strategies needed to successfully implement HPV self-sampling in primary care., Conclusions: The study was designed to evaluate a real-world in-clinic HPV self-sampling intervention for Somali American individuals, generating data on both effectiveness and implementation applicable to other community-based clinics in the U.S. The objective of this report is to describe the rationale and design of the study., 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 Inc. All rights reserved.)

Background: Exposure to ambient air pollution is associated with morbidity and mortality, making it an important public health concern. Emissions from motorized traffic are a common source of air pollution but evaluating the contribution of traffic-related air pollution (TRAP) emissions to health risks is challenging because it is difficult to disentangle the contribution of individual air pollution sources to exposure contrasts in an epidemiological study., Objective: This paper describes a new framework to identify whether air pollution differences reflect contrasts in TRAP exposures. Because no commonly measured pollutant is entirely specific to on-road motor vehicles, this exposure framework combined information on pollutants, spatial scale (i.e., geographic extent), and exposure assessment methods and their spatial scale to determine whether the estimated effect of air pollution in a given study was related to differences in TRAP., Methods: The exposure framework extended beyond the near-road environment to include differences in exposure to TRAP at neighborhood resolution ( ≤ 5 km) across urban, regional, and national scales. It also embedded a stricter set of criteria to identify studies that provided the strongest evidence that exposure contrasts were related to differences in traffic emissions., Results: Application of the framework to the transparent selection of epidemiological studies for a systematic review produced insights on assessing and improving comparability of TRAP exposure measures, particularly for indirect measures such as distances from roads. It also highlighted study design challenges related to the duration of measurements and the structure of epidemiological models., Impact Statement: This manuscript describes a new exposure framework to identify studies of traffic-related air pollution, a case study of its application in an HEI systematic review, and its implications for exposure science and air pollution epidemiology experts. It identifies challenges and provides recommendations for the field going forward. It is important to bring this information to the attention of researchers in air pollution exposure science and epidemiology because applying the broader lessons learned will improve the conduct and reporting of studies going forward., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Disability is a key marker of overall physical health in older adults and is often preceded by chronic disease. Although air pollution is a well recognised risk factor for multiple chronic diseases, its association with physical disability has not been well characterised. We investigated the associations of air pollutants with physical disability in a large cohort representative of older adults in the USA., Methods: We used biennial data on incident activities of daily living (ADL) disability collected from respondents of the Health and Retirement Survey between 2000 and 2016. As part of the Environmental Predictors of Cognitive Health and Aging study, we estimated 10-year average PM 2·5 , PM 10 - 2·5 , nitrogen dioxide (NO 2 ), and ozone (O 3 ) concentrations at participant residences before each survey using spatiotemporal prediction models. We used a time-varying, weighted Cox model to estimate hazard ratios (HRs) for incident physical disability per interquartile increase of air pollution with detailed adjustments for confounders., Findings: Among 15 411 respondents aged 65 years and older (mean age 70·2 [SD 6·5] years; 55% female, 45% male), 48% of respondents reported newly having ADL disability during a mean follow-up of 7·9 years (SD 4·7). In fully adjusted models, we found greater risks of ADL disability associated with higher concentrations of PM 2·5  (HR 1·03 per 3·7 μg/m³ [95% CI 0·99-1·08], p=0·16), PM 10 - 2·5 (1·05 per 4·9 μg/m³ [1·00-1·11], p=0·022), and NO 2 (1·03 per 7·5 ppb [0·99-1·08]. p=0·064), although not all these associations were statistically significant. In contrast, O 3 was associated with a lower risk of ADL disability (0·95 per 3·7 ppb [0·91-1·00], p=0·030). In a multi-pollutant model, associations were similar to the single-pollutant models for PM 10 - 2·5 (1·05 per 4·9 μg/m³ [1·00-1·11], p=0·041) and O 3 (0·94 per 3·7 ppb [0·88-1·01], p=0·083)., Interpretation: Our findings suggest that air pollution might be an underappreciated risk factor for physical disability in later life, although additional research is needed., Funding: National Institutes of Environmental Health Sciences and National Institute on Aging., Competing Interests: Declaration of interests JW, JF, RH, SDA, AS, and KML received a grant from the National Institute of Environmental Health Sciences (NIEHS) and the National Institute on Aging (NIA), which supported the present manuscript. JW and SDA received grants from the National Institute of Health (NIH) and the NIA for other research and consulting fees outside the submitted work. AS participates on the data monitoring committee of Achieving HIV viral suppression in refugee settlements in Uganda with Head StART, outside the submitted work. JF received grants from the NIH and consulting fees from Tufts University and the University of Texas Medical Branch, outside the submitted work. JF is an Associate Editor of the journal Discover Social Science and Health. KML receives grants and consulting fees on NIH-funded projects at Harvard University, the University of Pennsylvania, the University of Minnesota, the University of Colorado, Dartmouth University, and the University of Southern California, outside the submitted work. KML received payment for expert testimony for a legal case related to decisional capacity in a person with dementia, outside the submitted work. JDK received grants and contracts from the NIH and the US Environmental Protection Agency, outside the submitted work. SDA receives grants from the NIH–NIA and Centers for Disease Control and Prevention, and is the review committee member of Health Effects Institute, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Less than two-thirds of US adolescents are up-to-date with HPV vaccination. While mothers engaged in preventive care are more likely to seek preventive care for their children, current studies on associations between maternal cervical cancer screening (CCS) and adolescent HPV vaccination are needed. We assessed associations between maternal preventive service utilization and adolescent HPV vaccination using electronic health record data from a healthcare system in Washington State. We included adolescents (11-17 years) and their mothers with ≥ 1 primary care visit between 2018 and 2020. Outcomes were HPV vaccine initiation and completion. The primary exposure was maternal adherence to guideline-recommended CCS. Secondary exposures were maternal breast cancer screening adherence (for mothers ≥ 52 years) and ≥ 1 wellness visit ≤ 2 years. We used Generalized Estimating Equations to estimate prevalence ratios, and explore effect modification by adolescent sex, adolescent provider characteristics, and maternal language interpreter use. Of 4121 adolescents, 66% had a CCS-adherent mother, 82% initiated HPV vaccination, and 49% completed the series. CCS adherence was associated with higher initiation (adjusted prevalence ratio (APR):1.10, 95%CI:1.06-1.13) and completion (APR:1.16, 95%CI:1.08-1.23). Associations were stronger for male vs. female adolescents, adolescents who had a primary care provider in family practice vs. pediatrics, and adolescents who had the same primary care provider as their mother vs. not. Recent maternal wellness visit was also associated with higher initiation (APR:1.04, 95%CI:1.01-1.07) and completion (APR:1.12, 95%CI:1.05-1.20). Results suggest that delivering healthcare through a family-centered approach and engaging mothers in broad preventive care could increase adolescent HPV vaccination coverage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Evaluate the clinical utility of patient-collected dried blood spots (DBS) in measuring HIV-1 viral load (VL) for monitoring antiretroviral therapy (ART) compared to provider-collected DBS and blood plasma., Design: In a randomized trial of community-based delivery of ART in South Africa, we assessed performance of: (1) DBS specimens compared to plasma, and (2) participant-collected versus staff-collected DBS specimens, to measure HIV-1 VL., Methods: The bioMérieux NucliSENS EasyQ HIV-1 v2.0 assay was used for VL measurement. From October 2017 to November 2019, we collected 996 pairs of plasma/DBS specimens from 760 participants and 315 pairs of staff-/participant-collected DBS cards from 261 participants. We assessed DBS test sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using the WHO failure threshold of 1000 copies/mL. Log-transformed VL was compared using concordance correlation coefficients (CCC) and mean differences from linear mixed models., Results: In a population with 13% detectable VL, DBS VL compared with plasma VL had 91% (95% CI: 86-95) sensitivity, 99% (98-100) specificity, 94% (90-98) PPV, and 99% (98-99) NPV. We observed high agreement between staff-collected DBS VL and plasma VL (CCC: 0.94), and between participant-collected DBS VL and plasma VL (CCC: 0.92). Correlation between participant- and staff-collected DBS was very high (CCC: 0.97; mean difference for those with a detectable result: -0.10 log 10  copies/mL [-0.21-0.02])., Conclusions: VL results from participant-collected DBS are clinically comparable with those collected by clinical staff and using blood plasma. Self-collected DBS has potential for use for ART monitoring outside the clinic., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Missing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here, we present a multiple imputation method that accommodates high dimensional gene expression data by incorporating principal component analysis of the transcriptome into the multiple imputation prediction models to avoid bias. Simulation studies using three datasets show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias. This method is easily implemented via an R Bioconductor package, RNAseqCovarImpute that integrates with the limma-voom pipeline for differential expression analysis., (© 2024. The Author(s).)

Background: Reported associations between particulate matter with aerodynamic diameter ≤2.5 μm (PM 2.5 ) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity., Objectives: To assess agreement between PM 2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM 2.5 and cognitive or MRI outcomes., Methods: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM 2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM 2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM 2.5 exposure estimates with cognitive scores (n = 4678) and MRI outcomes (n = 1518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors., Results: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM 2.5 -cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors., Discussion: PM 2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Melinda Power reports financial support was provided by National Institutes of Health.Melinda Power reports a relationship with National Institutes of Health that includes: funding grants. Melinda Power reports a relationship with U.S. Department of Defense that includes: funding grants. Melinda Power reports a relationship with DC DEPARTMENT OF HEALTH that includes: funding grants. Melinda Power reports a relationship with Biogen that includes: consulting or advisory. Erin Bennett reports a relationship with Massachusetts General Hospital that includes: consulting or advisory. Eun Sug Park reports a relationship with National Institutes of Health that includes: funding grants. Jeff D. Yanosky reports a relationship with National Institutes of Health that includes: funding grants. Duanping Liao reports a relationship with National Institutes of Health that includes: funding grants. Joel D. Kaufman reports a relationship with National Institutes of Health that includes: funding grants. Joel D. Kaufman reports a relationship with U.S. Environmental Protection Agency that includes: funding grants. Lianne Sheppard reports a relationship with National Institutes of Health that includes: funding grants. Lianne Sheppard reports a relationship with Health Effects Institute that includes: funding grants. Adam Szpiro reports a relationship with National Institutes of Health that includes: funding grants. Adam Szpiro reports a relationship with Health Effects Institute that includes: funding grants. Adam Szpiro reports a relationship with Health Effects Institute that includes: consulting or advisory. Eric Whitsel reports a relationship with National Institutes of Health that includes: funding grants. Eric Whitsel reports a relationship with USFederal Aviation Administration that includes: funding grants.If there are other authors, they 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 Inc. All rights reserved.)

Background: Executive function, which develops rapidly in childhood, enables problem-solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited., Methods: We examined associations between early childhood air pollution exposure and school-aged executive function in 1235 children from three US pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5 µm in aerodynamic diameter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains, cognitive flexibility, working memory, and inhibitory control, using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution and child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity., Results: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO 2 exposure and working memory by neighborhood education opportunity were present ( Pinteraction = 0.05), with inverse associations more pronounced in the "high" and "very high" categories. Associations of interest did not differ by child sex or maternal education., Conclusion: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People living with HIV require reliable access to and adequate supply of antiretroviral therapy (ART) for viral suppression. The Deliver Health Study, a randomized trial conducted during the COVID-19 pandemic, found that home-delivered ART significantly increased viral suppression compared with clinic-based care. The effect of changing COVID-19 alert levels on self-reported ART use has not been quantified., Setting: KwaZulu-Natal, South Africa., Methods: Adults living with HIV were followed in the Deliver Health Study during October 2019-December 2020. We used difference-in-differences (DiD) to estimate the effect of changing COVID-19 alert levels during 3 distinct periods on self-reported missed ART doses (missed 0 vs. ≥1 doses in past week) for participants receiving home-delivered vs. clinic-based refills. We additionally estimated the effect of changing COVID-19 alert levels on late clinic ART refill visits (late vs. on-time). We used relative risk regression for both binary outcomes., Results: Of 155 participants, 46% were women and the median age was 36 years. The mean number of missed weekly doses was 0.11, 0, and 0.12 in the home-delivery group and 0.09, 0.08, and 0.18 in the clinic group during periods 1, 2, and 3, respectively. There were no differences in relative risk of self-reported daily ART use between refill groups when comparing across periods [DiDperiod 2 vs. 1 = 1.05; 95% confidence interval: 0.97, 1.13 and DiDperiod 3 vs. 2 = 0.99; 95% confidence interval (CI): 0.91, 1.08]. In the clinic group, the risk of late refill visits was significantly higher during COVID-19 restrictions (vs. before alert level 5 implementation) and even after the COVID-19 alert level was downgraded to level 1 (RRperiod 2 vs. 1 = 1.83, 95% CI: 1.34, 2.51 and RRperiod 3 vs. 2 = 1.71; 95% CI: 1.43, 2.04)., Conclusion: The COVID-19 pandemic did not differentially impact self-reported ART adherence by the method of ART refills, but the risk of late clinic refill visits was significantly higher during COVID-19 restrictions and sustained after restrictions were loosened., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium., Methods: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants)., Results: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51., Conclusion: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Masterson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited., Methods: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture., Results: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident., Conclusion: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases., Competing Interests: Declaration of competing interest All authors have confirmed that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: Cervical cancer screening (CCS) among East African immigrants (EAI) in the USA is under explored. This study aimed to investigate adherence to CCS and its correlates among EAI., Methods: We identified 1664 EAI women (25-65 years) with ≥ 1 primary care clinic visit(s) between 2017 and 2018, using University of Washington (UW) Medicine electronic health record data. CCS adherence was defined as Pap testing within 3 years or human papillomavirus/Pap co-testing within 5 years. We used Poisson regression with robust standard errors to cross-sectionally estimate associations with correlates of adherence. Twelve-month screening uptake was also evaluated among overdue women., Results: CCS adherence was 63%. Factors associated with higher adherence included older age (adjusted prevalence ratios [APRs]:1.47:95%CI:1.14-1.90, 1.38:95%CI:1.05-1.80, respectively, for ages 30-39 and 40-49 vs 25-29 years), longer duration of care at UW Medicine (APR:1.22:95%CI:1.03-1.45, comparing > 10 vs < 5 years), higher visit frequency (APR:1.23:95%CI:1.04-1.44, 1.46:95%CI:1.24-1.72, respectively, for 3-5 and ≥ 6 vs 1-2 visits), index visit in an obstetrics-gynecology clinic (APR:1.26:95%CI:1.03-1.55, vs family practice), having an assigned primary care provider (APR:1.35: 95%CI:1.02-1.79), breast cancer screening adherence (APR:1.66: 95%CI:1.27-2.17), and colorectal cancer screening adherence (APR:1.59:95%CI:1.24-2.03). Low BMI was associated with lower adherence (APR:0.50:95%CI:0.26-0.96, comparing < 18.5 kg/m 2 vs 18.5-24.9 kg/m 2 ). Among 608 (37%) overdue women, 9% were screened in the subsequent 12 months. Having commercial health insurance vs Medicare/Medicaid was associated with higher uptake (adjusted risk ratio:2.44:95%CI:1.15-5.18)., Conclusion: CCS adherence among EAI was lower than the national average of 80%. Interventions focused on increasing healthcare access/utilization or leveraging healthcare encounters to address barriers could increase CCS in EAIs., (© 2024. W. Montague Cobb-NMA Health Institute.)

Importance: Air pollution is a recognized risk factor associated with chronic diseases, including respiratory and cardiovascular conditions, which can lead to physical and cognitive impairments in later life. Although these losses of function, individually or in combination, reduce individuals' likelihood of living independently, little is known about the association of air pollution with this critical outcome., Objective: To investigate associations between air pollution and loss of independence in later life., Design, Setting, and Participants: This cohort study was conducted as part of the Environmental Predictors Of Cognitive Health and Aging study and used 1998 to 2016 data from the Health and Retirement Study. Participants included respondents from this nationally representative, population-based cohort who were older than 50 years and had not previously reported a loss of independence. Analyses were performed from August 31 to October 15, 2023., Exposures: Mean 10-year pollutant concentrations (particulate matter less than 2.5 μm in diameter [PM2.5] or ranging from 2.5 μm to 10 μm in diameter [PM10-2.5], nitrogen dioxide [NO2], and ozone [O3]) were estimated at respondent addresses using spatiotemporal models along with PM2.5 levels from 9 emission sources., Main Outcomes and Measures: Loss of independence was defined as newly receiving care for at least 1 activity of daily living or instrumental activity of daily living due to health and memory problems or moving to a nursing home. Associations were estimated with generalized estimating equation regression adjusting for potential confounders., Results: Among 25 314 respondents older than 50 years (mean [SD] baseline age, 61.1 [9.4] years; 11 208 male [44.3%]), 9985 individuals (39.4%) experienced lost independence during a mean (SD) follow-up of 10.2 (5.5) years. Higher exposure levels of mean concentration were associated with increased risks of lost independence for total PM2.5 levels (risk ratio [RR] per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.10), PM2.5 levels from road traffic (RR per 1-IQR of 10-year mean, 1.09; 95% CI, 1.03-1.16) and nonroad traffic (RR per 1-IQR of 10-year mean, 1.13; 95% CI, 1.03-1.24), and NO2 levels (RR per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.08). Compared with other sources, traffic-generated pollutants were most consistently and robustly associated with loss of independence; only road traffic-related PM2.5 levels remained associated with increased risk after adjustment for PM2.5 from other sources (RR per 1-IQR increase in 10-year mean concentration, 1.10; 95% CI, 1.00-1.21). Other pollutant-outcome associations were null, except for O3 levels, which were associated with lower risks of lost independence (RR per 1-IQR increase in 10-year mean concentration, 0.94; 95% CI, 0.92-0.97)., Conclusions and Relevance: This study found that long-term exposure to air pollution was associated with the need for help for lost independence in later life, with especially large and consistent increases in risk for pollution generated by traffic-related sources. These findings suggest that controlling air pollution could be associated with diversion or delay of the need for care and prolonged ability to live independently.

Accurately predicting ambient NO 2 concentrations has great public health importance, as traffic-related air pollution is of major concern in urban areas. In this study, we present a novel approach incorporating traffic contribution to NO 2 prediction in a fine-scale spatiotemporal model. We used nationally available traffic estimate dataset in a scalable dispersion model, Research LINE source dispersion model (RLINE). RLINE estimates then served as an additional input for a validated spatiotemporal pollution modeling approach. Our analysis uses measurement data collected by the Multi-Ethnic Study of Atherosclerosis and Air Pollution in the greater Los Angeles area between 2006 and 2009. We predicted road-type-specific annual average daily traffic (AADT) on road segments via national-level spatial regression models with nearest-neighbor Gaussian processes (spNNGP); the spNNGP models were trained based on over half a million point-level traffic volume measurements nationwide. AADT estimates on all highways were combined with meteorological data in RLINE models. We evaluated two strategies to integrate RLINE estimates into spatiotemporal NO 2 models: 1) incorporating RLINE estimates as a space-only covariate and, 2) as a spatiotemporal covariate. The results showed that integrating the RLINE estimates as a space-only covariate improved overall cross-validation R 2 from 0.83 to 0.84, and root mean squared error (RMSE) from 3.58 to 3.48 ppb. Incorporating the estimates as a spatiotemporal covariate resulted in similar model improvement. The improvement of our spatiotemporal model was more profound in roadside monitors alongside highways, with R 2 increasing from 0.56 to 0.66 and RMSE decreasing from 3.52 to 3.11 ppb. The observed improvement indicates that the RLINE estimates enhanced the model's predictive capabilities for roadside NO 2 concentration gradients even after considering a comprehensive list of geographic covariates including the distance to roads. Our proposed modeling framework can be generalized to improve high-resolution prediction of NO 2 exposure - especially near major roads in the U.S., 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.)

Placental corticotropin-releasing hormone (pCRH) is a neuroactive peptide produced in high concentrations in mid-late pregnancy, during key periods of fetal brain development. Some evidence suggests that higher pCRH exposure during gestation is associated with adverse neurodevelopment, particularly in female offspring. In 858 mother-child dyads from the sociodemographically diverse CANDLE cohort (Memphis, TN), we examined: (1) the slope of pCRH rise in mid-late pregnancy and (2) estimated pCRH at delivery as a measure of cumulative prenatal exposure. When children were 4 years-old, mothers reported on problem behaviors using the Child Behavior Checklist (CBCL) and cognitive performance was assessed by trained psychologists using the Stanford-Binet Intelligence Scales. We fitted linear regression models examining pCRH in relation to behavioral and cognitive performance measures, adjusting for covariates. Using interaction models, we evaluated whether associations differed by fetal sex, breastfeeding, and postnatal neighborhood opportunity. In the full cohort, log-transformed pCRH measures were not associated with outcomes; however, we observed sex differences in some models (interaction p-values≤0.01). In male offspring, an interquartile (IQR) increase in pCRH slope (but not estimated pCRH at delivery), was positively associated with raw Total (β=3.06, 95%CI: 0.40, 5.72), Internalizing (β=0.89, 95%CI: 0.03, 1.76), and Externalizing (β=1.25, 95%CI: 0.27, 2.22) Problem scores, whereas, in females, all associations were negative (Total Problems: β=-1.99, 95%CI: -3.89, -0.09; Internalizing: β=-0.82, 95%CI: -1.42, -0.23; Externalizing: β=-0.56, 95%CI: -1.34, 0.22). No associations with cognitive performance were observed nor did we observe moderation by breastfeeding or postnatal neighborhood opportunity. Our results provide further evidence that prenatal pCRH exposure may impact subsequent child behavior in sex-specific ways, however in contrast to prior studies suggesting adverse impacts in females, steeper mid-gestation pCRH rise was associated with more problem behaviors in males, but fewer in females., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We examined associations between prenatal fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) exposures and child respiratory outcomes through age 8-9 years in 1279 ECHO-PATHWAYS Consortium mother-child dyads. We averaged spatiotemporally modeled air pollutant exposures during four fetal lung development phases: pseudoglandular (5-16 weeks), canalicular (16-24 weeks), saccular (24-36 weeks), and alveolar (36+ weeks). We estimated adjusted relative risks (RR) for current asthma at age 8-9 and asthma with recent exacerbation or atopic disease, and odds ratios (OR) for wheezing trajectories using modified Poisson and multinomial logistic regression, respectively. Effect modification by child sex, maternal asthma, and prenatal environmental tobacco smoke was explored. Across all outcomes, 95% confidence intervals (CI) included the null for all estimates of associations between prenatal air pollution exposures and respiratory outcomes. Pseudoglandular PM 2.5 exposure modestly increased risk of current asthma (RR adj  = 1.15, 95% CI: 0.88-1.51); canalicular PM 2.5 exposure modestly increased risk of asthma with recent exacerbation (RR adj  = 1.26, 95% CI: 0.86-1.86) and persistent wheezing (OR adj  = 1.28, 95% CI: 0.86-1.89). Similar findings were observed for O 3 , but not NO 2 , and associations were strengthened among mothers without asthma. While not statistically distinguishable from the null, trends in effect estimates suggest some adverse associations of early pregnancy air pollution exposures with child respiratory conditions, warranting confirmation in larger samples., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Studies have linked prenatal maternal psychosocial stress to childhood wheeze/asthma but have rarely investigated factors that may mitigate risks., Objective: To investigate associations between prenatal stress and childhood wheeze/asthma, evaluating factors that may modify stress effects., Methods: Participants included 2056 mother-child dyads from Environmental influences on Child Health Outcomes (ECHO)-PATHWAYS, a consortium of 3 prospective pregnancy cohorts (the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study, The Infant Development and Environment Study, and a subset of the Global Alliance to Prevent Prematurity and Stillbirth study) from 6 cities. Maternal stressful life events experienced during pregnancy (PSLEs) were reported using the Pregnancy Risk Assessment Monitoring System Stressful Life Events questionnaire. Parents reported child wheeze/asthma outcomes at age 4 to 6 years using standardized questionnaires. We defined outcomes as ever asthma, current wheeze, current asthma, and strict asthma. We used modified Poisson regression with robust standard errors (SEs) to estimate risk ratios (RRs) and 95% CI per 1-unit increase in PSLE, adjusting for confounders. We evaluated effect modification by child sex, maternal history of asthma, maternal childhood traumatic life events, neighborhood-level resources, and breastfeeding., Results: Overall, we observed significantly elevated risk for current wheeze with increasing PSLE (RR, 1.09 [95% CI, 1.03-1.14]), but not for other outcomes. We observed significant effect modification by child sex for strict asthma (P interaction = .03), in which risks were elevated in boys (RR, 1.10 [95% CI, 1.02-1.19]) but not in girls. For all other outcomes, risks were significantly elevated in boys and not in girls, although there was no statistically significant evidence of effect modification. We observed no evidence of effect modification by other factors (P interactions > .05)., Conclusion: Risk of adverse childhood respiratory outcomes is higher with increasing maternal PSLEs, particularly in boys., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Statistical models of air pollution enable intra-urban characterization of pollutant concentrations, benefiting exposure assessment for environmental epidemiology. The new generation of low-cost sensors facilitate the deployment of dense monitoring networks and can potentially be used to improve intra-urban models of air pollution., Objective: Develop and evaluate a spatiotemporal model for nitrogen dioxide (NO 2 ) in the Puget Sound region of WA, USA for the Adult Changes in Thought Air Pollution (ACT-AP) study and assess the contribution of low-cost sensor data to the model's performance through cross-validation., Methods: We developed a spatiotemporal NO 2 model for the study region incorporating data from 11 agency locations, 364 supplementary monitoring locations, and 117 low-cost sensor (LCS) locations for the 1996-2020 time period. Model features included long-term time trends and dimension-reduced land use regression. We evaluated the contribution of LCS network data by comparing models fit with and without sensor data using cross-validated (CV) summary performance statistics., Results: The best performing model had one time trend and geographic covariates summarized into three partial least squares components. The model, fit with LCS data, performed as well as other recent studies (agency cross-validation: CV- root mean square error (RMSE) = 2.5 ppb NO 2 ; CV- coefficient of determination ( R 2 ) = 0.85). Predictions of NO 2 concentrations developed with LCS were higher at residential locations compared to a model without LCS, especially in recent years. While LCS did not provide a strong performance gain at agency sites (CV-RMSE = 2.8 ppb NO 2 ; CV- R 2  = 0.82 without LCS), at residential locations, the improvement was substantial, with RMSE = 3.8 ppb NO 2 and R 2  = 0.08 (without LCS), compared to CV-RMSE = 2.8 ppb NO 2 and CV- R 2  = 0.51 (with LCS)., Impact: We developed a spatiotemporal model for nitrogen dioxide (NO 2 ) pollution in Washington's Puget Sound region for epidemiologic exposure assessment for the Adult Changes in Thought Air Pollution study. We examined the impact of including low-cost sensor data in the NO 2 model and found the additional spatial information the sensors provided predicted NO 2 concentrations that were higher than without low-cost sensors, particularly in recent years. We did not observe a clear, substantial improvement in cross-validation performance over a similar model fit without low-cost sensor data; however, the prediction improvement with low-cost sensors at residential locations was substantial. The performance gains from low-cost sensors may have been attenuated due to spatial information provided by other supplementary monitoring data., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Inequities in urban greenspace have been identified, though patterns by race and socioeconomic status vary across US settings. We estimated the magnitude of the relationship between a broad mixture of neighborhood-level factors and residential greenspace using weighted quantile sum (WQS) regression, and compared predictive models of greenspace using only neighborhood-level, only individual-level, or multi-level predictors. Greenspace measures included the Normalized Difference Vegetation Index (NDVI), tree canopy, and proximity of the nearest park, for residential locations in Shelby County, Tennessee of children in the CANDLE cohort. Neighborhood measures include socioeconomic and education resources, as well as racial composition and racial residential segregation. In this sample of 1012 mother-child dyads, neighborhood factors were associated with higher NDVI and tree canopy (0.021 unit higher NDVI [95% CI: 0.014, 0.028] per quintile increase in WQS index); homeownership rate, proximity of and enrollment at early childhood education centers, and racial composition, were highly weighted in the WQS index. In models constrained in the opposite direction (0.028 unit lower NDVI [95% CI: - 0.036, - 0.020]), high school graduation rate and teacher experience were highly weighted. In prediction models, adding individual-level predictors to the suite of neighborhood characteristics did not meaningfully improve prediction accuracy for greenspace measures. Our findings highlight disparities in greenspace for families by neighborhood socioeconomic and early education factors, and by race, suggesting several neighborhood indicators for consideration both as potential confounders in studies of greenspace and pediatric health as well as in the development of policies and programs to improve equity in greenspace access., (© 2024. The Author(s).)

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013-2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM 2.5 , NO 2 , and O 3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM 2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 μg/m 3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO 2 and O 3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM 2.5 , NO 2 , and O 3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM 2.5 with SAB incidence in Canada., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lauren A. Wise and Elizabeth E. Hatch reports financial support was provided by National Institute of Environmental Health Sciences. Lauren A. Wise reports a relationship with AbbVie Inc that includes: consulting or advisory. Dr. Lauren Wise serves as a consultant for AbbVie, Inc. and the Gates Foundation. She also receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility apps). All of these relationships are for work unrelated to this manuscript. The remaining authors report no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aim: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium., Methods: We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8-9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression., Results: The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant., Conclusions: In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8-9 years, though some adverse associations were observed among girls., (© 2024. The Author(s).)

Importance: Students who ride older school buses are often exposed to high levels of exhaust during their commutes, which may adversely affect health and school attendance. As a result, the US Environmental Protection Agency (EPA) has awarded millions of dollars to school districts to replace older, highly polluting school buses with newer, cleaner buses., Objective: To leverage the EPA's randomized allocation of funding under the 2012-2016 School Bus Rebate Programs to estimate the association between replacing old, highly polluting buses and changes in district-average standardized test scores., Design, Setting, and Participants: This study examined changes in reading and language arts (RLA) and math test scores among US school district applicants to the EPA's 2012-2016 national School Bus Rebate Programs 1 year before and after each lottery by selection status. Data analysis was conducted from January 15 to July 30, 2023., Exposure: Selection to receive EPA funding to replace older school buses with newer, cleaner alternatives., Main Outcomes and Measures: School district changes in RLA and math test scores among students in grades 3 through 8 before and after the EPA funding lotteries by selection status were measured using an intention-to-treat approach., Results: This study included 1941 school district applicants to the 2012-2106 EPA School Bus Rebate Programs. These districts had a mean (SD) of 14.6 (33.7) schools per district, 8755 (23 776) students per district, and 41.3% (20.2%) of students with free lunch eligibility. Among the applicants, 209 districts (11%) were selected for the clean bus funding. District-average student test scores did not improve among selected districts overall. In secondary analyses, however, districts replacing the oldest, highest polluting buses (ie, pre-1990) experienced significantly greater improvements in district-average test scores in the year after the lottery for RLA and math (SD improvement in test scores, 0.062 [95% CI, 0.050-0.074] and 0.025 [95% CI, 0.011-0.039], respectively) compared with districts without replacements., Conclusions and Relevance: In this study, the EPA funding was not associated with student test scores overall, but in secondary analyses, the replacement of the oldest school buses was associated with improved educational performance. These findings support prioritizing clean bus replacement of the oldest buses as an actionable way for improving students' educational performance.

A multimorbidity-focused approach may reflect common etiologic mechanisms and lead to better targeting of etiologic agents for broadly impactful public health interventions. Our aim was to identify clusters of chronic obesity-related, neurodevelopmental, and respiratory outcomes in children, and to examine associations between cluster membership and widely prevalent chemical exposures to demonstrate our epidemiologic approach. Early to middle childhood outcome data collected 2011-2022 for 1092 children were harmonized across the ECHO-PATHWAYS consortium of 3 prospective pregnancy cohorts in six U.S. cities. 15 outcomes included age 4-9 BMI, cognitive and behavioral assessment scores, speech problems, and learning disabilities, asthma, wheeze, and rhinitis. To form generalizable clusters across study sites, we performed k-means clustering on scaled residuals of each variable regressed on study site. Outcomes and demographic variables were summarized between resulting clusters. Logistic weighted quantile sum regressions with permutation test p-values associated odds of cluster membership with a mixture of 15 prenatal urinary phthalate metabolites in full-sample and sex-stratified models. Three clusters emerged, including a healthier Cluster 1 (n = 734) with low morbidity across outcomes; Cluster 2 (n = 192) with low IQ and higher levels of all outcomes, especially 0.4-1.8-standard deviation higher mean neurobehavioral outcomes; and Cluster 3 (n = 179) with the highest asthma (92 %), wheeze (53 %), and rhinitis (57 %) frequencies. We observed a significant positive, male-specific stratified association (odds ratio = 1.6; p = 0.01) between a phthalate mixture with high weights for MEP and MHPP and odds of membership in Cluster 3 versus Cluster 1. These results identified subpopulations of children with co-occurring elevated levels of BMI, neurodevelopmental, and respiratory outcomes that may reflect shared etiologic pathways. The observed association between phthalates and respiratory outcome cluster membership could inform policy efforts towards children with respiratory disease. Similar cluster-based epidemiology may identify environmental factors that impact multi-outcome prevalence and efficiently direct public policy efforts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by National Institutes of Health. Drew B. Day & Emily S. Barrett reports financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Determining the most feasible and cost-effective approaches to improving PM 2.5 exposure assessment with low-cost monitors (LCMs) can considerably enhance the quality of its epidemiological inferences. We investigated features of fixed-site LCM designs that most impact PM 2.5 exposure estimates to be used in long-term epidemiological inference for the Adult Changes in Thought Air Pollution (ACT-AP) study. We used ACT-AP collected and calibrated LCM PM 2.5 measurements at the two-week level from April 2017 to September 2020 (N of monitors [measurements] = 82 [502]). We also acquired reference-grade PM 2.5 measurements from January 2010 to September 2020 (N = 78 [6186]). We used a spatiotemporal modeling approach to predict PM 2.5 exposures with either all LCM measurements or varying subsets with reduced temporal or spatial coverage. We evaluated the models based on a combination of cross-validation and external validation at locations of LCMs included in the models (N = 82), and also based on an independent external validation with a set of LCMs not used for the modeling (N = 30). We found that the model's performance declined substantially when LCM measurements were entirely excluded (spatiotemporal validation R 2 [RMSE] = 0.69 [1.2 μg/m 3 ]) compared to the model with all LCM measurements (0.84 [0.9 μg/m 3 ]). Temporally, using the farthest apart measurements (i.e., the first and last) from each LCM resulted in the closest model's performance (0.79 [1.0 μg/m 3 ]) to the model with all LCM data. The models with only the first or last measurement had decreased performance (0.77 [1.1 μg/m 3 ]). Spatially, the model's performance decreased linearly to 0.74 (1.1 μg/m 3 ) when only 10% of LCMs were included. Our analysis also showed that LCMs located in densely populated, road-proximate areas improved the model more than those placed in moderately populated, road-distant areas., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4-6 years., Methods: Children's internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures-residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity-averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms., Results: Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant., Conclusions: Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health., (© 2024. The Author(s).)

Background: In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter ( PM 10 - 2.5 , particulate matter with aerodynamic diameter ≤ 10 μ m  and > 2.5 μ m ). Toxicological research suggests that these pathways might be important processes by which PM 10 - 2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM 10 - 2.5 monitoring network., Objectives: We used new spatiotemporal exposure models to examine associations of both 1-y and 1-month average PM 10 - 2.5 concentrations with markers of inflammation and coagulation., Methods: We leveraged data from 7,071 Multi-Ethnic Study of Atherosclerosis and ancillary study participants 45-84 y of age who had repeated plasma measures of inflammatory and coagulation biomarkers. We estimated PM 10 - 2.5 at participant addresses 1 y and 1 month before each of up to four exams (2000-2012) using spatiotemporal models that incorporated satellite, regulatory monitoring, and local geographic data and accounted for spatial correlation. We used random effects models to estimate associations with interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and D-dimer, controlling for potential confounders., Results: Increases in PM 10 - 2.5 were not associated with greater levels of inflammation or coagulation. A 10 - μ g / m 3 increase in annual average PM 10 - 2.5 was associated with a 2.5% decrease in CRP [95% confidence interval (CI): - 5.5 , 0.6]. We saw no association between annual average PM 10 - 2.5 and the other markers (IL-6: - 0.7 % , 95% CI: - 2.6 , 1.2; fibrinogen: - 0.3 % , 95% CI: - 0.9 , 0.3; D-dimer: - 0.2 % , 95% CI: - 2.6 , 2.4). Associations consistently showed that a 1 0 - μ g / m 3 increase in 1-month average PM 10 - 2.5 was associated with reduced inflammation and coagulation, though none were distinguishable from no association (IL-6: - 1.2 % , 95% CI: - 3.0   , 0.5; CRP: - 2.5 % , 95% CI: - 5.3 , 0.4; fibrinogen: - 0.4 % , 95% CI: - 1.0 , 0.1; D-dimer: - 2.0 % , 95% CI: - 4.3 , 0.3)., Discussion: We found no evidence that PM 10 - 2.5 is associated with higher inflammation or coagulation levels. More research is needed to determine whether the inflammation and coagulation pathways are as important in explaining observed PM 10 - 2.5 health impacts in humans as they have been shown to be in toxicology studies or whether PM 10 - 2.5 might impact human health through alternative biological mechanisms. https://doi.org/10.1289/EHP12972.

Introduction: Significant progress has been made in the HIV response in South Africa; however, gaps remain in ensuring engagement in care to support life-long medication adherence and viral suppression. The National Department of Health (NDoH) has introduced community-based and clinic-based HIV differentiated service delivery (DSD) models to tackle suboptimal adherence and retention in care. Nevertheless, differentiated care models require adaptation to better serve clients who struggle with adherence. There is limited research on the acceptability of fee for home delivery of ART in resource-constrained settings. The current study investigates the acceptability of fee for home delivery of ART among people living with HIV in South Africa., Methods: Two mixed-gender focus group discussions (FGDs) took place between June and November 2019, consisting of 10 participants in each group. A purposive sampling strategy was employed to identify and select 10 people living with HIV who were ART-eligible but not in care, and 10 people living with HIV who were currently taking ART and in care. Participants were grouped according to their treatment status. A coding framework, informed by a priori categories and derived from topics in the interview guide, was developed and utilized to facilitate analysis., Results: Participants expressed enthusiasm for having ART home-delivered, as it would save the time spent waiting in long queues at the clinic. However, some participants raised concerns about potential payment difficulties due to high unemployment rates in the community. Some participants believed this would be acceptable, as patients already incur costs for travel and food when visiting the clinic. Participants in both FGDs expressed strong concerns about home delivery of their ART based on fear of accidental disclosure, especially for those who have not disclosed to their immediate families and partners., Conclusion: Our study suggests that charging a fee for home delivery is an acceptable and innovative approach to supporting PLHIV in maintaining adherence to their medication and remaining in care., (© 2024. The Author(s).)

Background: Ozone (O 3 ) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O 3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups., Methods: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O 3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV 1 ) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O 3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization., Results: In our sample (n = 648), O 3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O 3 exposure were observed with either FEV 1 (β = 0.12, 95% CI: -0.04, 0.29) or FVC (β = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O 3 ., Conclusions: In this sample with low O 3 concentrations, we did not observe adverse associations between O 3 exposures averaged from birth to age 8 and lung function in middle childhood., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Human papillomavirus (HPV) self-collect shows promise to increase cervical cancer screening rates in underscreened populations, such as Somali patients, but little is known about how to integrate such an approach in primary care. In this study, primary care providers and staff who provide primary care services to Somali women were asked for their views on integrating HPV self-collect into routine care to address cervical cancer screening disparities. Thirty primary care providers and staff participated in semi-structured interviews exploring their views on HPV self-collect and their anticipated needs or barriers to implementing this approach into the clinic generally and with specific patient populations, such as Somali women. A thematic analysis using the constructivist version of grounded theory was undertaken. Providers and staff anticipate positive patient reaction to the option of HPV self-collect, and were interested in using this approach both for Somali patients and for all patients in general. HPV self-collect was viewed as straightforward to integrate into existing clinic workflows. Providers largely lacked awareness of the evidence supporting primary HPV testing and HPV self-collect specifically, sharing concerns about effectiveness of self-collect and the lack of a physical exam. Providers felt clinic-wide staff education and patient education, along with strategies to address disparities, such as cultural and linguistic tailoring would be needed for successful implementation. Integrating HPV self-collect as an option in the cervical cancer screening process in a primary care clinical encounter offers considerable opportunity to address health disparities and may benefit all patients., Competing 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., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear., Objectives: Our objective is to compare particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses., Methods: We assigned annual PM 2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women's Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM 2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region., Results: With a few exceptions, relative agreement of approach-specific PM 2.5 exposure estimates was high for PM 2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM 2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM 2.5 . There was no evidence of large differences in health effects associations with PM 2.5 among estimation approaches in analyses adjusted for climate region., Conclusions: Different estimation approaches produced similar spatial patterns of PM 2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM 2.5 -health effects associations were similar among estimation approaches. PM 2.5 estimates and PM 2.5 -health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM 2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest. https://doi.org/10.1289/EHP12995.

Background: While epidemiologic evidence links higher levels of exposure to fine particulate matter (PM 2.5 ) to decreased cognitive function, fewer studies have investigated links with traffic-related air pollution (TRAP), and none have examined ultrafine particles (UFP, ≤100 nm) and late-life dementia incidence., Objective: To evaluate associations between TRAP exposures (UFP, black carbon [BC], and nitrogen dioxide [NO 2 ]) and late-life dementia incidence., Methods: We ascertained dementia incidence in the Seattle-based Adult Changes in Thought (ACT) prospective cohort study (beginning in 1994) and assessed ten-year average TRAP exposures for each participant based on prediction models derived from an extensive mobile monitoring campaign. We applied Cox proportional hazards models to investigate TRAP exposure and dementia incidence using age as the time axis and further adjusting for sex, self-reported race, calendar year, education, socioeconomic status, PM 2.5 , and APOE genotype. We ran sensitivity analyses where we did not adjust for PM 2.5 and other sensitivity and secondary analyses where we adjusted for multiple pollutants, applied alternative exposure models (including total and size-specific UFP), modified the adjustment covariates, used calendar year as the time axis, assessed different exposure periods, dementia subtypes, and others., Results: We identified 1,041 incident all-cause dementia cases in 4,283 participants over 37,102 person-years of follow-up. We did not find evidence of a greater hazard of late-life dementia incidence with elevated levels of long-term TRAP exposures. The estimated hazard ratio of all-cause dementia was 0.98 (95 % CI: 0.92-1.05) for every 2000 pt/cm 3 increment in UFP, 0.95 (0.89-1.01) for every 100 ng/m 3 increment in BC, and 0.96 (0.91-1.02) for every 2 ppb increment in NO 2 . These findings were consistent across sensitivity and secondary analyses., Discussion: We did not find evidence of a greater hazard of late-life dementia risk with elevated long-term TRAP exposures in this population-based prospective cohort study., 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. Published by Elsevier Ltd.)

Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4-6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother-child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ambient air pollution, including traffic-related air pollution (TRAP), increases cardiovascular disease risk, possibly through vascular alterations. Limited information exists about in-vehicle TRAP exposure and vascular changes., Objective: To determine via particle filtration the effect of on-roadway TRAP exposure on blood pressure and retinal vasculature., Design: Randomized crossover trial. (ClinicalTrials.gov: NCT05454930)., Setting: In-vehicle scripted commutes driven through traffic in Seattle, Washington, during 2014 to 2016., Participants: Normotensive persons aged 22 to 45 years ( n = 16)., Intervention: On 2 days, on-road air was entrained into the vehicle. On another day, the vehicle was equipped with high-efficiency particulate air (HEPA) filtration. Participants were blinded to the exposure and were randomly assigned to the sequence., Measurements: Fourteen 3-minute periods of blood pressure were recorded before, during, and up to 24 hours after a drive. Image-based central retinal arteriolar equivalents (CRAEs) were measured before and after. Brachial artery diameter and gene expression were also measured and will be reported separately., Results: Mean age was 29.7 years, predrive systolic blood pressure was 122.7 mm Hg, predrive diastolic blood pressure was 70.8 mm Hg, and drive duration was 122.3 minutes (IQR, 4 minutes). Filtration reduced particle count by 86%. Among persons with complete data ( n = 13), at 1 hour, mean diastolic blood pressure, adjusted for predrive levels, order, and carryover, was 4.7 mm Hg higher (95% CI, 0.9 to 8.4 mm Hg) for unfiltered drives compared with filtered drives, and mean adjusted systolic blood pressure was 4.5 mm Hg higher (CI, -1.2 to 10.2 mm Hg). At 24 hours, adjusted mean diastolic blood pressure (unfiltered) was 3.8 mm Hg higher (CI, 0.02 to 7.5 mm Hg) and adjusted mean systolic blood pressure was 1.1 mm Hg higher (CI, -4.6 to 6.8 mm Hg). Adjusted mean CRAE (unfiltered) was 2.7 μm wider (CI, -1.5 to 6.8 μm)., Limitations: Imprecise estimates due to small sample size; seasonal imbalance by exposure order., Conclusion: Filtration of TRAP may mitigate its adverse effects on blood pressure rapidly and at 24 hours. Validation is required in larger samples and different settings., Primary Funding Source: U.S. Environmental Protection Agency and National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1309.

Background: There is a long tradition in environmental health of using frameworks for evidence synthesis, such as those of the U.S. Environmental Protection Agency for its Integrated Science Assessments and the International Agency for Research on Cancer Monographs. The framework, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), was developed for evidence synthesis in clinical medicine. The U.S. Office of Health Assessment and Translation (OHAT) elaborated an approach for evidence synthesis in environmental health building on GRADE., Methods: We applied a modified OHAT approach and a broader "narrative" assessment to assess the level of confidence in a large systematic review on traffic-related air pollution and health outcomes., Discussion: We discuss several challenges with the OHAT approach and its implementation and suggest improvements for synthesizing evidence from observational studies in environmental health. We consider the determination of confidence using a formal rating scheme of up- and downgrading of certain factors, the treatment of every factor as equally important, and the lower initial confidence rating of observational studies to be fundamental issues in the OHAT approach. We argue that some observational studies can offer high-confidence evidence in environmental health. We note that heterogeneity in magnitude of effect estimates should generally not weaken the confidence in the evidence, and consistency of associations across study designs, populations, and exposure assessment methods may strengthen confidence in the evidence. We mention that publication bias should be explored beyond statistical methods and is likely limited when large and collaborative studies comprise most of the evidence and when accrued over several decades. We propose to identify possible key biases, their most likely direction, and their potential impacts on the results. We think that the OHAT approach and other GRADE-type frameworks require substantial modification to align better with features of environmental health questions and the studies that address them. We emphasize that a broader, "narrative" evidence assessment based on the systematic review may complement a formal GRADE-type evaluation. https://doi.org/10.1289/EHP11532.

Background: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. However, the level of evidence is limited and specific pollutants driving the association are inconsistent across studies., Methods: We used data from a web-based preconception cohort study of pregnancy planners enrolled during 2013-2019 (Pregnancy Study Online; PRESTO). Eligible participants self-identified as female, were aged 21-45 years, resided in the United States (U.S.) or Canada, and were trying to conceive without fertility treatments. Participants completed a baseline questionnaire and bi-monthly follow-up questionnaires until conception or 12 months. We analyzed data from 8,747 participants (U.S.: 7,304; Canada: 1,443) who had been trying to conceive for < 12 cycles at enrollment. We estimated residential ambient concentrations of particulate matter < 2.5 µm (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) using validated spatiotemporal models specific to each country. We fit country-specific proportional probabilities regression models to estimate the association between annual average, menstrual cycle-specific, and preconception average pollutant concentrations with fecundability, the per-cycle probability of conception. We calculated fecundability ratios (FRs) and 95% confidence intervals (CIs) and adjusted for individual- and neighborhood-level confounders., Results: In the U.S., the FRs for a 5-µg/m 3 increase in annual average, cycle-specific, and preconception average PM 2.5 concentrations were 0.94 (95% CI: 0.83, 1.08), 1.00 (95% CI: 0.93, 1.07), and 1.00 (95% CI: 0.93, 1.09), respectively. In Canada, the corresponding FRs were 0.92 (95% CI: 0.74, 1.16), 0.97 (95% CI: 0.87, 1.09), and 0.94 (95% CI: 0.80, 1.09), respectively. Likewise, NO 2 and O 3 concentrations were not strongly associated with fecundability in either country., Conclusions: Neither annual average, menstrual cycle-specific, nor preconception average exposure to ambient PM 2.5 , NO 2 , and O 3 were appreciably associated with reduced fecundability in this cohort of pregnancy planners., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lauren A. Wise and Elizabeth E. Hatch reports financial support was provided by National Institutes of Health. Lauren A. Wise reports a relationship with AbbVie Inc that includes: consulting or advisory. Dr. Lauren Wise serves as a consultant for AbbVie, Inc. and the Gates Foundation, She also receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility apps). All of these relationships are for work unrelated to this manuscript.]., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related somatic mutation associated with incident hematologic cancer. Environmental stressors which, like air pollution, generate oxidative stress at the cellular level, may induce somatic mutations and some mutations may provide a selection advantage for persistence and expansion of specific clones., Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) N = 4,379 and the Women's Health Initiative (WHI) N = 7,701 to estimate cross-sectional associations between annual average air pollution concentrations at participant address the year before blood draw using validated spatiotemporal models. We used covariate-adjusted logistic regression to estimate risk of CHIP per interquartile range increases in particulate matter (PM2.5; 4 μg/m3) and nitrogen dioxide (NO2; 10 ppb) as ORs (95% confidence intervals)., Results: Prevalence of CHIP at blood draw (variant allele fraction > 2%) was 4.4% and 8.7% in MESA and WHI, respectively. The most common CHIP driver mutation was in DNMT3A. Neither pollutant was associated with CHIP: ORMESA PM2.5 = 1.00 (0.68-1.45), ORMESA NO2 = 1.05 (0.69-1.61), ORWHI PM2.5 = 0.97 (0.86-1.09), ORWHI NO2 = 0.98 (0.88-1.10); or with DNMT3A-driven CHIP., Conclusions: We did not find evidence that air pollution contributes to CHIP prevalence in two large observational cohorts., Impact: This is the first study to estimate associations between air pollution and CHIP., (©2023 American Association for Cancer Research.)

Importance: Emerging evidence indicates that exposure to fine particulate matter (PM2.5) air pollution may increase dementia risk in older adults. Although this evidence suggests opportunities for intervention, little is known about the relative importance of PM2.5 from different emission sources., Objective: To examine associations of long-term exposure of total and source-specific PM2.5 with incident dementia in older adults., Design, Setting, and Participants: The Environmental Predictors of Cognitive Health and Aging study used biennial survey data from January 1, 1998, to December 31, 2016, for participants in the Health and Retirement Study, which is a nationally representative, population-based cohort study in the US. The present cohort study included all participants older than 50 years who were without dementia at baseline and had available exposure, outcome, and demographic data between 1998 and 2016 (N = 27 857). Analyses were performed from January 31 to May 1, 2022., Exposures: The 10-year mean total PM2.5 and PM2.5 from 9 emission sources at participant residences for each month during follow-up using spatiotemporal and chemical transport models., Main Outcomes and Measures: The main outcome was incident dementia as classified by a validated algorithm incorporating respondent-based cognitive testing and proxy respondent reports. Adjusted hazard ratios (HRs) were estimated for incident dementia per IQR of residential PM2.5 concentrations using time-varying, weighted Cox proportional hazards regression models with adjustment for the individual- and area-level risk factors., Results: Among 27 857 participants (mean [SD] age, 61 [10] years; 15 747 [56.5%] female), 4105 (15%) developed dementia during a mean (SD) follow-up of 10.2 [5.6] years. Higher concentrations of total PM2.5 were associated with greater rates of incident dementia (HR, 1.08 per IQR; 95% CI, 1.01-1.17). In single pollutant models, PM2.5 from all sources, except dust, were associated with increased rates of dementia, with the strongest associations for agriculture, traffic, coal combustion, and wildfires. After control for PM2.5 from all other sources and copollutants, only PM2.5 from agriculture (HR, 1.13; 95% CI, 1.01-1.27) and wildfires (HR, 1.05; 95% CI, 1.02-1.08) were robustly associated with greater rates of dementia., Conclusion and Relevance: In this cohort study, higher residential PM2.5 levels, especially from agriculture and wildfires, were associated with higher rates of incident dementia, providing further evidence supporting PM2.5 reduction as a population-based approach to promote healthy cognitive aging. These findings also indicate that intervening on key emission sources might have value, although more research is needed to confirm these findings.

Background: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer's disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants., Methods: We used a chemical transport model with data fusion to estimate ambient concentrations of PM 2.5 and its components, NO 2 , NO x , O 3 (24-hour and 8-hour), CO, and airborne trace metals. We linked concentrations to geocoded participant addresses and calculated 10-year mean exposures (2002 to 2011). Brain amyloid deposition was measured using florbetapir amyloid positron emission tomography (PET) scans in 346 participants without dementia in 2012-2014, and we defined amyloid positivity as a global cortical standardized uptake value ratio ≥ the sample median of 1.2. We used logistic regression models to quantify the association between amyloid positivity and each air pollutant, adjusting for putative confounders. In sensitivity analyses, we considered whether use of alternate air pollution estimation approaches impacted findings for PM 2.5 , NO 2 , NO x , and 24-hour O 3 ., Results: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We did not find evidence of associations between long-term exposure to any pollutant and brain amyloid positivity in adjusted models. Findings were materially unchanged in sensitivity analyses using alternate air pollution estimation approaches for PM 2.5 , NO 2 , NO x , and 24-hour O 3 ., Conclusions: Air pollution may impact cognition and dementia independent of amyloid accumulation, though whether air pollution influences AD pathogenesis later in the disease course or at higher exposure levels deserves further consideration., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Fine particulate matter air pollution (PM2.5) has been consistently associated with cardiovascular disease, which, in turn, is associated with an increased risk of dementia. As such, vascular dysfunction might be a mechanism by which PM2.5 mediates dementia risk, yet few prior epidemiological studies have examined this potential mechanism., Objective: To investigate whether hypertension and stroke serve as mediators and modifiers of the association of PM2.5 with incident dementia., Design, Setting, and Participants: As part of the Environmental Predictors of Cognitive Health and Aging (EPOCH) Project, this cohort study used biennial survey data collected between 1998 and 2016 from respondents of the Health and Retirement Study (HRS), a nationally representative, population-based, cohort in the US. Eligible participants were those over 50 years of age who were free of dementia at baseline and had complete exposure, mediator, outcome, and demographic data from the HRS. Data analysis was conducted from August to November 2022., Exposures: Exposure to PM2.5, calculated for the 10 years preceding each person's baseline examination according to residential histories and spatiotemporal models., Main Outcomes and Measures: Incident dementia was identified using a validated algorithm based on cognitive testing and informant reports. The 4-way decomposition causal mediation analysis method was used to quantify the degree to which hypertension and stroke mediated or modified the association of PM2.5 with incident dementia after adjustment for individual-level and area-level covariates., Results: Among 27 857 participants (mean [SD] age at baseline, 61 [10] years; 15 747 female participants [56.5%]; 19 249 non-Hispanic White participants [69.1%]), 4105 (14.7%) developed dementia during the follow-up period (mean [SD], 10.2 [5.6] years). Among participants with dementia, 2204 (53.7%) had a history of hypertension at baseline and 386 (9.4%) received a diagnosis of hypertension during the follow up. A total of 378 participants (9.2%) had a history of stroke at baseline and 673 (16.4%) developed stroke over the follow-up period. The IQR of baseline PM2.5 concentrations was 10.9 to 14.9 μg/m3. In fully adjusted models, higher levels of PM2.5 (per IQR) were not associated with increased risk of incident dementia (HR, 1.04; 95% CI, 0.98 to 1.11). Although there were positive associations of prevalent stroke (HR, 1.67; 95% CI, 1.48 to 1.88) and hypertension (HR, 1.15; 95% CI, 1.08 to 1.23) with incident dementia compared with those free of stroke and hypertension during follow-up, there was no statistically significant association of PM2.5 with stroke (odds ratio per IQR increment in PM2.5, 1.08; 95%CI, 0.91 to 1.29) and no evidence of an association of PM2.5 with hypertension (odds ratio per IQR increment in PM2.5, 0.99; 95%CI, 0.92 to 1.07). Concordantly, there was no evidence that hypertension or stroke acted as mediators or modifiers of the association of PM2.5 with incident dementia. Although the nonmediated interaction between PM2.5 and hypertension accounted for 39.2% of the total excess association (95% CI, -138.5% to 216.9%), the findings were not statistically significant., Conclusions and Relevance: These findings suggest that although hypertension may enhance the susceptibility of individuals to air pollution, hypertension and stroke do not significantly mediate or modify the association of PM2.5 with dementia, indicating the need to investigate other pathways and potential mediators of risk.

Background: Epidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure., Objective: We investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study., Methods: We included mother-child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4-6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ., Results: In the combined sample, PAH metabolites were not associated with IQ after full adjustment, nor did we observe associations with PAH mixtures. Tests of effect modification were null except for the association between 2-hydroxynaphthalene and IQ, which was negative in males (β males  = -0.67 [95%CI:-1.47,0.13]) and positive in females (β females  = 0.31 [95%CI:-0.52,1.13])(p interaction  = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (β = -1.28 [95%CI:-2.53,-0.03]) and in early pregnancy (β = -1.14 [95%CI:-2.00,-0.28])., Significance: In this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year., Methods: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models., Results: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma., Conclusion: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Traffic-related air pollution (TRAP), a common exposure, potentially impacts pregnancy through altered placental function. We investigated associations between prenatal TRAP exposure and placental gene expression., Methods: Whole transcriptome sequencing was performed on placental samples from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle and Yakima, WA) (n = 205), cohorts of the ECHO-PATHWAYS Consortium. Residential NO 2 exposures were computed via spatiotemporal models for full-pregnancy, each trimester, and the first/last months of pregnancy. Individual cohort-specific, covariate-adjusted linear models were fit for 10,855 genes and respective exposures (NO 2 or roadway proximity [≤150 m]). Infant-sex/exposure interactions on placental gene expression were tested with interaction terms in separate models. Significance was based on false discovery rate (FDR<0.10)., Results: In GAPPS, final-month NO 2 exposure was positively associated with MAP1LC3C expression (FDR p-value = 0.094). Infant-sex interacted with second-trimester NO 2 on STRIP2 expression (FDR interaction p-value = 0.011, inverse and positive associations among male and female infants, respectively) and roadway proximity on CEBPA expression (FDR interaction p-value = 0.045, inverse among females). In CANDLE, infant-sex interacted with first-trimester and full-pregnancy NO 2 on RASSF7 expression (FDR interaction p-values = 0.067 and 0.013, respectively, positive among male infants and inverse among female infants)., Discussion: Overall, pregnancy NO 2 exposure and placental gene expression associations were primarily null, with exception of final month NO 2 exposure and placental MAP1LC3C association. We found several interactions of infant sex and TRAP exposures on placental expression of STRIP2, CEBPA, and RASSF7. These highlighted genes suggest influence of TRAP on placental cell proliferation, autophagy, and growth, though additional replication and functional studies are required for validation., Competing Interests: Declaration of competing interest All authors have read and approved the submission of the manuscript. The Institutional Review Boards of all participating institutions approved study protocols. Neither the authors nor the institutions with which they are affiliated have any direct or indirect financial interest in the subject matter of our research. All authors report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)