Environmental Health Perspectives

BackgroundEnvironment-wide association studies (ExWAS) offer a systematic approach to identifying chemical biomarker-health outcome associations, yet few have applied rigorous multi-stage validation. MethodsWe screened 92 chemical biomarkers against 48 health outcomes in NHANES 2017-2018 (2,796 tests across four screening rounds; not all chemicals were crossed with all outcomes). Associations passing an initial FDR screen were subjected to cross-cycle validation in NHANES 2015-2016--the primary inferential safeguard given the adaptive screening design--followed by dose-response analysis and multiple sensitivity specifications. Survey-weighted regression models adjusted for age, sex, race/ethnicity, poverty-income ratio, BMI, and smoking. ResultsOf 26 associations passing FDR correction, 21 were testable in cross-cycle validation; of these, 15 (71%) replicated with concordant direction and p < 0.05 in a temporally independent NHANES 2015-2016 sample. Of these 15, 14 remained robust after analyte-specific sensitivity checks; urinary creatinine adjustment identified one association (iodine-BMI) as a dilution artifact. Two novel findings emerged: dimethylarsonic acid with uric acid ({beta} = 0.20 mg/dL per log-unit DMA, 95% CI: 0.15-0.26) and urinary perchlorate with BUN ({beta} = 1.21 mg/dL per log-unit perchlorate, 95% CI: 0.97-1.45); a third high-novelty association (methylmercury-waist circumference) is likely explained by fish consumption patterns. ConclusionsMulti-stage ExWAS with cross-cycle validation identified 14 robust chemical-health associations. Two novel findings--DMA-uric acid and perchlorate-BUN--survived all sensitivity checks and warrant prospective investigation.

Traffic-related air pollution (TRAP) poses significant health risks particularly for children, with adverse effects that may impact health in later life. Low emission zones are a public health policy designed to reduce TRAP in urban areas. The CHILL (Childrens Health in London and Luton) Study will evaluate the impact of Londons Ultra Low Emission Zone (ULEZ) on childrens health, using a prospective two-arm parallel longitudinal cohort design. CHILL will examine associations between air pollution metrics and lung function growth, plus secondary outcomes. Here we describe the characteristics of the CHILL cohort at baseline, prior to the introduction of the ULEZ. We recruited 3414 children aged 6-9 years attending 84 schools (London - intervention site: 1664 children, 44 schools; Luton - comparator site: 1750 children, 40 schools). Baseline health assessments were conducted in 2018-2019 (before the introduction of the ULEZ in London). 97.0% of recruited children were assessed (London 96.5%, Luton 97.4%), with the primary outcome measure of post-bronchodilator forced expiratory volume in one second being successfully measured in 76.7% (London 76.9%, Luton 76.5%). 92.1% returned a completed parental questionnaire (London 89.3%, Luton 94.7%), including data for analysis of the secondary outcomes. Demographic characteristics and outcomes were similar across the two sites. We established well-matched cohorts of school children, in our intervention (London) and comparator (Luton) sites. Data on primary and secondary outcomes have been successfully collected, which, combined with detailed air quality metrics, provides a robust platform for evaluating the impact of Londons ULEZ on childrens health and development. ClinicalTrials.gov NCT04695093 (05/01/2021)

Environmental exposures to toxic chemicals can profoundly alter the transcriptome and epigenome in both humans and animals, contributing to disease development across the lifespan. To elucidate how early-life exposure to toxicants exerts such persistent effects, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 2,564 epigenomes and 1,043 transcriptomes from longitudinal studies in mice. All data are publicly available through the TaRGET II data portal and the WashU Epigenome Browser. This resource from target (liver, brain, lung, heart) and surrogate (blood) tissues at weaning (3 weeks) and two adult time-points (5 and 10 months) characterized the molecular response to arsenic (As), lead (Pb), bisphenol-A (BPA), di-2-ethylhexyl phthalate(DEHP), tributyltin (TBT), tetrachlorodibenzo-p-dioxin (TCDD), and particulate matter with a diameter of <2.5m (PM2.5). The findings revealed persistent, toxicant-specific, sex-dependent epigenomic and transcriptomic perturbations, resulting in disrupted expression of 14,908 genes, altered chromatin accessibility at 87,409 regulatory elements, DNA methylation changes at 113,186 genomic regions, and chromatin state switching of histone modifications. The resulting high-resolution map of how environmental exposures reprogram the epigenome and transcriptome is broadly accessible via ToxiTaRGET database, offering unparalleled opportunities for the scientific community to investigate the molecular underpinnings of environmental toxicant exposures and their contributions to disease pathogenesis.

Small particulate matter air pollution (PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC) among non-smoking individuals. Inhaled PM2.5 recruits pro-inflammatory macrophages to the air-lung interface, which promotes malignant lung epithelial cell growth and progression to overt cancer. We sought to determine whether clonal hematopoiesis of indeterminate potential (CHIP), a common age-related condition characterized by hyperinflammatory macrophages, exacerbates PM2.5-associated NSCLC in non-smokers using genetic, environmental, and phenotypic data from 413,901 individuals in the UK Biobank. Among non-smokers, PM2.5 is not associated with NSCLC and not associated with prevalence of CHIP, but CHIP is associated with a doubling of NSCLC risk (hazard ratio (HR) 2.01, 95% confidence interval (CI): 1.34-3.00). Moreover, CHIP-associated NSCLC risk is exacerbated in the setting of above-median PM2.5 levels (HR 2.70, 95% CI: 1.60-4.55). PM2.5 x CHIP is also associated with significantly greater markers of systemic inflammation (CRP, IL-6, and IL-1{beta}) than expected. Altogether, these results suggest CHIP and PM2.5 form a novel gene x environment interaction promoting NSCLC tumorigenesis in non-smokers.

BackgroundMaternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications. ObjectiveWe examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2-ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver. MethodsFemale mice were exposed to human relevant doses of either Pb (32ppm) via drinking water or DEHP (5 mg/kg-day) via chow for two weeks prior to mating through offspring weaning. Whole genome bisulfite sequencing (WGBS) was utilized to examine DNAm changes in offspring cortex, blood, and liver at 5 months of age. Metilene and methylSig were used to identify differentially methylated regions (DMRs). Annotatr and Chipenrich were used for genomic annotations and geneset enrichment tests of DMRs, respectively. ResultsThe cortex contained the majority of DMRs associated with Pb (69%) and DEHP (58%) exposure. The cortex also contained the greatest degree of overlap in DMR signatures between sexes (n = 17 and 14 DMRs with Pb and DEHP exposure, respectively) and exposure types (n = 79 and 47 DMRs in males and females, respectively). In all tissues, detected DMRs were preferentially found at genomic regions associated with gene expression regulation (e.g., CpG islands and shores, 5 UTRs, promoters, and exons). An analysis of GO terms associated with DMR-containing genes identified imprinted genes to be impacted by both Pb and DEHP exposure. Of these, Gnas and Grb10 contained DMRs across tissues, sexes, and exposures. DMRs were enriched in the imprinting control regions (ICRs) of Gnas and Grb10, with 15 and 17 ICR-located DMRs across cortex, blood, and liver in each gene, respectively. The ICRs were also the location of DMRs replicated across target and surrogate tissues, suggesting epigenetic changes these regions may be potentially viable biomarkers. ConclusionsWe observed Pb- and DEHP-specific DNAm changes in cortex, blood, and liver, and the greatest degree of overlap in DMR signatures was seen between exposures followed by sex and tissue type. DNAm at imprinted control regions was altered by both Pb and DEHP, highlighting the susceptibility of genomic imprinting to these exposures during the perinatal window of development.

BackgroundCurrent evidence on prenatal exposure to heat stress and childhood neurodevelopment is sparse. Cerebral palsy (CP) is the most common neuromotor disorder in childhood and there are growing concerns that environmental factors may play an etiological role. Our aim was to investigate whether prenatal exposure to high ambient temperature was associated with CP risk in the offspring. MethodsWe conducted a nested case-control study in California that included all CP cases identified from a statewide service system on developmental disabilities and randomly selected 20% of all live births without CP as controls during 2005-2015. Gestational weekly average temperatures were calculated from high resolution (1 km) daily mean temperature data based on maternal residential address. Extreme heat was defined as weekly averages above the 90th percentile of the local temperature distribution. We implemented a distributed lag model within a logistic regression framework to estimate the associations between ambient temperatures increase, extreme heat and CP risk, across gestational week 0 to 31 covering early- and mid-pregnancy, and in the final seven weeks preceding birth capturing the late pregnancy. We also examined possible heterogeneity across maternal socio-demographic characteristics. Finally, we performed a sibling analysis to consider the influence of uncontrolled confounding. FindingsThe study population included 5,938 CP cases and 1,092,313 controls. There was an associated 2% increased odds of CP (95% credible interval: 1% to 5%) per 5 {degrees}C increase in ambient temperature in gestational week 0 to 3, and higher odds of 1.03 to 1.05 for extreme heat. A similar susceptible window in early pregnancy was observed in sibling analysis. We also observed a tendency of more pronounced associations for neighborhoods with higher social vulnerability and a cumulative association with higher temperature in the final seven weeks preceding births. InterpretationEarly-pregnancy exposure to high ambient temperatures were associated with increased risk of childhood CP. While the estimated magnitude was small, our findings suggest that CP risk should be monitored in the population within the context of climate change. FundingYale Planetary Solutions, National Institutes of Environmental Health Sciences

Elevated manganese (Mn) exposure is associated with attentional deficits in children, and is an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn exposure causes lasting attention and sensorimotor deficits in a rat model of early childhood Mn exposure, and that these deficits are associated with a hypofunctioning catecholaminergic system in the prefrontal cortex (PFC), though the mechanistic basis for these deficits is not well understood. To address this, male Long-Evans rats were exposed orally to Mn (50 mg/kg/d) over PND 1-21 and attentional function was assessed in adulthood using the 5-Choice Serial Reaction Time Task. Targeted catecholaminergic system and epigenetic gene expression, followed by unbiased differential DNA methylation and gene regulation expression transcriptomics in the PFC, were performed in young adult littermates. Results show that developmental Mn exposure causes lasting focused attention deficits that are associated with reduced gene expression of tyrosine hydroxylase, dopamine transporter, and DNA methyltransferase 3a. Further, developmental Mn exposure causes broader lasting methylation and gene expression dysregulation associated with epigenetic regulation, inflammation, cell development, and hypofunctioning catecholaminergic neuronal systems. Pathway enrichment analyses uncovered mTOR and Wnt signaling pathway genes as significant transcriptomic regulators of the Mn altered transcriptome, and Western blot of total, C1 and C2 phospho-mTOR confirmed mTOR pathway dysregulation. Our findings deepen our understanding of the mechanistic basis of how developmental Mn exposure leads to lasting catecholaminergic dysfunction and attention deficits, which may aid future therapeutic interventions of environmental exposure associated disorders. Significance StatementAttention deficit hyperactivity disorder (ADHD) is associated with environmental risk factors, including exposure to neurotoxic agents. Here we used a rodent model of developmental manganese (Mn) exposure producing lasting attention deficits to show broad epigenetic and gene expression changes in the prefrontal cortex, and to identify disrupted mTOR and Wnt signaling pathways as a novel mechanism for how developmental Mn exposure may induce lasting attention and catecholaminergic system impairments. Importantly, our findings establish early development as a critical period of susceptibility to lasting deficits in attentional function caused by elevated environmental toxicant exposure. Given that environmental health threats disproportionately impact communities of color and low socioeconomic status, our findings can aid future studies to assess therapeutic interventions for vulnerable populations.

Despite the substantial evidence on the health effects of short-term exposure to ambient fine particles (PM2.5), including increasing studies focusing on those from wildland fire smoke, the impacts of long-term wildland fire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildland fire smoke PM2.5 and non-accidental mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous U.S., 2007-2020. Controlling for non-smoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a non-linear association between 12-month moving average concentration of smoke PM2.5 and monthly non-accidental mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 g/m3, non-accidental mortality increased by 0.16-0.63 and 2.11 deaths per 100,000 people per month when the 12-month moving average of PM2.5 concentration was of 0.1-5 and 5+ g/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality were all found to be associated with long-term wildland fire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 11,415 non-accidental deaths/year (95% CI: 6,754, 16,075) in the contiguous U.S. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 above. Positive interaction effects with extreme heat (monthly number of days with daily mean air temperature higher than the countys 90th percentile warm season air temperature) were also observed. Our study identified the detrimental effects of long-term exposure to wildland fire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communications that span the health risks of both short- and long-term exposure. Significance StatementThe area burned by wildland fire has greatly increased in the U.S. in recent decades. Short-term exposure to smoke pollutants emitted by wildland fires, particularly PM2.5, is associated with numerous adverse health effects. However, the impacts of long-term exposure to wildland fire smoke PM2.5 on health and specifically mortality remain unclear. Utilizing wildland fire smoke PM2.5 and mortality data in the contiguous U.S. during 2007-2020, we found positive associations between long-term smoke PM2.5 exposure and increased non-accidental, cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality rates. Each year, in addition to the well-recognized mortality burden from non-smoke PM2.5, smoke PM2.5 contributed to an estimated over 10 thousand non-accidental deaths in the U.S. This study demonstrates the detrimental effects of wildland fire smoke PM2.5 on a wide range of health outcomes, and calls for more effective public health actions and communications that span the health risks of both short- and long-term exposure.

Infertility affects 10-15% of couples worldwide and is increasingly attributed to environmental exposures, particularly endocrine-disrupting chemicals (EDCs) such as phthalates. While gestational exposures are well studied, little is known about how preconception exposures influence fertility and offspring health. Phthalate exposure altered estrous cyclicity, with dams spending more time in proestrus and less in metestrus but did not significantly impact implantation or litter size. At E14.5, exposed fetuses exhibited increased bodyweights, accompanied by an expansion of the placental junctional zone in males. Altered bodyweight persisted into adulthood, however adulthood offspring displayed a reduction in bodyweight. RNA-sequencing revealed widespread transcriptional reprogramming in female placentas (518 DEGs) affecting immune regulation, steroid metabolism, and extracellular matrix remodeling, while male placentas exhibited only 9 DEGs but showed structural alterations. In offspring livers, transcriptomic shifts were sex-specific: females displayed downregulation of metabolic and immune genes (e.g., Cyp7a1, Mthfr, H2-DMB1), while males showed upregulation of immune and signaling genes (e.g., Elf4, Adm2, Ly6a). Collectively, these findings demonstrate that preconception phthalate exposure induces subtle but biologically meaningful maternal endocrine disruption, alters placental structure and function, and reprograms offspring growth and liver transcriptomes in a sex-specific manner. This work identifies the preconception window as a critical period of vulnerability for EDC impacts on reproductive success and intergenerational health.

BackgroundAs the coronavirus pandemic rages on, 692,000 (August 7, 2020) human lives and counting have been lost worldwide to COVID-19. Understanding the relationship between short- and long-term exposure to air pollution and adverse COVID-19 health outcomes is crucial for developing solutions to this global crisis. ObjectivesTo conduct a scoping review of epidemiologic research on the link between short- and long-term exposure to air pollution and COVID-19 health outcomes. MethodWe searched PubMed, Web of Science, Embase, Cochrane, MedRxiv, and BioRxiv for preliminary epidemiological studies of the association between air pollution and COVID-19 health outcomes. 28 papers were finally selected after applying our inclusion/exclusion criteria; we categorized these studies as long-term studies, short-term time-series studies, or short-term cross-sectional studies. One study included both short-term time-series and a cross-sectional study design. Results27 studies of the 28 reported evidence of statistically significant positive associations between air pollutant exposure and adverse COVID-19 health outcomes; 11 of 12 long-term studies and all 16 short-term studies reported statistically significant positive associations. The 28 identified studies included various confounders, spatial and temporal resolutions of pollution concentrations, and COVID-19 health outcomes. DiscussionWe discuss methodological challenges and highlight additional research areas based on our findings. Challenges include data quality issues, ecological study design limitations, improved adjustment for confounders, exposure errors related to spatial resolution, geographic variability in testing, mitigation measures and pandemic stage, clustering of health outcomes, and a lack of publicly available data and code.

BackgroundThe rapid evolution and diversity of sensor technologies, coupled with inconsistencies in how sensor metadata is reported across formats and sources, present significant challenges for generating exposomes and exposure health research. ObjectiveDespite the development of standardized metadata schemas, the process of extracting sensor metadata from unstructured sources remains largely manual and unscalable. To address this bottleneck, we developed and evaluated a large language model (LLM)-based pipeline for automating sensor metadata extraction and harmonization from exposure health literature publicly available. MethodsUsing GPT-4 in a zero-shot setting, we constructed a pipeline that parses full-text PDFs to extract metadata and harmonizes output into structured formats. Results: Our automated pipeline achieved substantial efficiency gains in completing extractions much faster than manual review and demonstrated strong performance with average accuracy and precision of 94.74%, recall of 100%, and F1-score of 97.28%. ConclusionsThis study demonstrates the feasibility and scalability of leveraging LLMs to automate sensor metadata extraction for exposure health, reducing manual burden while enhancing metadata completeness and consistency. Our findings support the integration of LLM-driven pipelines into exposure health informatics platforms.

BackgroundEvidence suggests maternal exposure to ambient air pollution increases the risk of stillbirth, but few studies conducted in the United States have evaluated temporally varying exposures or susceptibility across gestational windows. Moreover, the generalizability of existing findings is often limited by restricted geographic coverage or reliance on selected study populations. MethodsUsing Georgia vital records from 2005 to 2014, we conducted a matched case-control study including 8,384 stillbirths and 33,459 live birth controls matched on maternal county of residence and conception month. We used stratified Cox proportional hazards models with time-varying covariates to estimate hazard ratios (HRs) for ten air pollutants across five exposure windows (first month, weekly, and first, second, and third trimester). Our primary analysis included all stillbirths combined, with subgroup analyses separating second and third trimester losses. ResultsStillbirths had a median gestational age of 27 weeks (IQR: 6.67) compared with 38 weeks for live births (IQR: 2.13). Particulate matter showed strong associations in the second trimester exposure window for all stillbirths (PM10: HR = 1.07; 95% CI: 1.04, 1.11; PM2.5: HR = 1.05; 95% CI: 1.01, 1.09). This pattern was consistent for NO2 and NH4, which also exhibited positive associations across early and entire pregnancy exposure windows (first month, first trimester, weekly), with the strongest associations for the second trimester exposures. Associations were larger for second trimester stillbirths, whereas estimates for third trimester stillbirths were largely null or negative. ConclusionsIn this population-based study in Georgia, time-varying ambient air pollution exposures during pregnancy were associated with increased risk of stillbirth, particularly for second trimester exposures and for stillbirths occurring earlier in pregnancy. These findings highlight the importance of considering gestational timing when evaluating environmental risk factors for stillbirth. What this study addsThis study is the first to evaluate maternal ambient air pollution exposure and stillbirth using time-varying exposures on vital records in the state of Georgia. By examining ten air pollutants across multiple gestational windows and subset analyses by timing of stillbirth, we identified second trimester susceptibility to NO2, PM10, PM2.5, and NH4. These findings highlight periods of vulnerability to ambient air pollution during pregnancy.

This protocol is reported in accordance with the SPIRIT 2025 guidelines for clinical trial protocols. IntroductionYoung children, from birth to age 5 y are particularly vulnerable to indoor air pollutants and respiratory pathogens. Portable air purifiers (or filtration) and upper-room ultraviolet germicidal irradiation (UVGI) are two widely used interventions with the potential to improve indoor air quality (IAQ) and reduce sick-related absences. However, a review of the literature revealed no real-world randomised studies evaluating their effectiveness in reducing young childrens sick-related absences in early care and education (ECE) classrooms. Methods and AnalysisThe OK-AIR study is a longitudinal, cluster-randomised 2x2 factorial trial conducted in Head Start centers using two implementation cohorts: Cohort 1 (five Head Start centers and 20 classrooms from 2023 to 2024) and Cohort 2 (11 centers and 59 classrooms from 2025 to 2026), with expanded inclusion of rural areas. Cohort 1 enrolled 204 children, 48 teachers and 5 site directors, and Cohort 2 enrolled 462 children, 97 teachers and 11 site directors. Within each center, four classrooms are randomised to: (1) control; (2) portable filtration; (3) upper-room ultraviolet germicidal irradiation (UVGI); or (4) both interventions. Cohort 2 was initially planned as a second factorial trial but was amended to a purifier-only design due to funding changes; details are provided in the protocol amendments section. We collect continuous IAQ data, including particulate matter (PM) with aerodynamic diameters [&le;]1 {micro}m (PM1), [&le;]2.5 {micro}m (PM2.5), [&le;]4 {micro}m (PM4), and [&le;]10 {micro}m (PM10); total volatile organic compounds (TVOCs) index; nitrogen oxides (NOx) index; carbon monoxide (CO), noise; temperature; and relative humidity, alongside daily child absences. Seasonal environmental surface swabs (dining tables and toilet flooring) are tested by Reverse-Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR) for Influenza A/B, Respiratory Syncytial Virus (RSV), Human Parainfluenza Virus Type 3 (HPIV3), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and Norovirus. IAQ monitoring is structured across Winter, Spring, Summer, and Fall, including designated baseline/off-period weeks to characterize temporal and seasonal variability in environmental measures across classrooms and centers. Multi-informant surveys (Director, Teacher, Parent) capture contextual factors, and childrens social-emotional development is assessed using teacher ratings on the Devereux Early Childhood Assessment (DECA). The primary outcome is the sick-related absence rate, analyzed as cumulative absences over the attendance year while accounting for clustering by school and classroom using generalized mixed-effects models. Secondary outcomes include childrens social-emotional ratings, IAQ metrics and pathogen detection rates; analyses of IAQ incorporate time/seasonal structure, and season-stratified absenteeism analyses will be treated as secondary/exploratory refinements. An economic evaluation will estimate incremental intervention costs and cost-effectiveness/cost-benefit (such as cost per sick-related absence day averted). Ethics and DisseminationThis study was approved by the Institutional Review Board (IRB) at the University of Oklahoma. Findings will be shared through peer-reviewed publications; presentations at local, state, and national conferences; research briefs developed for lay and policy audiences; and community briefings prioritizing the participating early childhood programs and communities. DisclaimerThe views expressed are those of the authors and do not reflect the official views of the Uniformed Services University or the United States Department of War. Strengths and Limitations of This StudyO_LIReal-world longitudinal cluster RCT: The study uses a rigorous longitudinal cluster-randomised 2x2 factorial design in real-world ECE settings. C_LIO_LICombined interventions: Interventions target both air filtration and disinfection, allowing for combined and comparative evaluation. C_LIO_LIObjective air-quality monitoring: Continuous monitoring of IAQ metrics provides objective and reliable data on environmental change. C_LIO_LIEnvironmental pathogen surveillance: qPCR on surface swabs yields an objective biological outcome to triangulate with IAQ and absences. C_LIO_LIComprehensive context and child measures: Multi-method and multi-reporter data collection includes Head Start attendance records, continuous air monitoring, pathogen detection, contextual surveys completed by center directors, teachers, and parents, and standardized social-emotional assessments (DECA) completed by classroom teachers. Head Start program records providing childrens longer-term health data available through Health Insurance Portability and Accountability Act (HIPAA) authorization. C_LIO_LIClustered/temporal complexity: Seasonal design accounts for variation over time but may introduce complexity in modeling temporal effects. C_LIO_LIPractical Implications: Study findings will have practical implications for Head Start and other ECE programs striving to maximize child attendance with cost effective strategies. C_LI

BackgroundEnvironmental health services in healthcare facilities --including water, sanitation, hygiene, waste management, cleaning, and infection control--prevent disease and strengthen healthcare delivery. Yet environmental health service provision is inadequate in many low- and middle-income countries (LMICs). Despite the importance of monitoring and improving services, no comprehensive evidence map exists to describe global knowledge and gaps for action and improvement. The study objectives were to comprehensively catalog published literature on environmental health services in healthcare facilities in LMICs by service domain, study type, and relevance to policy and practice. MethodsWe conducted a systematic literature search in 2023 and performed an update in 2025. Through a title/abstract screening and tagging process, we developed a literature inventory that categorized studies by topic, design, and relevance to policy and practice objectives. ResultsThe literature inventory included 4,381 studies. Fifty-eight percent of the studies were baseline assessments of environmental health services, 36% involved formative research (e.g., qualitative methods), and 13% evaluated interventions or implementation strategies. Most studies (62%) examined hygiene at points of care, while 9% examined water and 6% sanitation. Twenty-seven percent of studies examined services in the context of the COVID-19 pandemic. ConclusionsThere is little evidence for effective interventions and implementation strategies to improve and sustain environmental health services, especially for water and sanitation services. Formative research on under-studied services can help policymakers and practitioners identify areas to prioritize investment and programming. Findings can inform the development of research agendas and practical guidelines for improving access to safe healthcare environments.

BackgroundOutdoor workers are particularly vulnerable to the adverse impacts of heat, but many studies focus on heat exposure in residential settings only. This leads to a limited understanding of the full mortality burden due to occupational heat exposures. Here, we aimed to improve estimates of the total, short-term mortality burden attributable to outdoor occupational heat exposure in the United States (US). MethodsWe developed a panel data set for 3,108 US counties during 2010-2019 by linking all-cause mortality among the working age population, derived from CDC WONDER, with the prevalence of workers exposed to outdoor occupational heat, which integrates data on wet bulb globe temperature, workplace activities, and employment counts. We developed a quasi-Poisson regression model adjusted for ambient temperature, total precipitation, and county and state-year fixed effects to estimate short-term excess deaths attributable to outdoor occupational heat exposure. FindingsNationwide, approximately 3.8% (95% CI: 2.5-5.8%) of all workers were annually exposed to dangerous wet-bulb globe temperatures. This outdoor occupational heat exposure resulted in approximately 9,800 (3,100-17,000) annual excess deaths in the working age population. An estimated 62% of excess deaths occurred in the most socially vulnerable counties despite accounting for 25% of workers. InterpretationThe mortality burden of occupational heat exposure is likely far larger than 39 officially reported annual deaths that the Bureau of Labor Statistics reports for this time period. The workplace should be an explicit focus of heat policies, advocacy, and adaptation measures. FundingUS Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health.

Millions of outdoor workers cannot avoid wildfire smoke, likely leading to inequalities in exposure and health risk. We characterized work-related exposure to wildfire PM2.5 for 3,108 contiguous US counties during 2006-2019. Despite experiencing less ambient exposure to wildfire PM2.5, counties with higher portions of non-Hispanic Black and Hispanic Americans experienced higher work-related exposure. We also find suggestive evidence that the effect of ambient smoke fine particulate matter (PM2.5) concentrations on all-cause mortality may differ by workplace exposure. These findings suggest that workplace exposures should be considered in wildfire smoke adaptation measures.

BackgroundWaste incineration in Baltimore, USA, involves two major facilities: a municipal solid waste incinerator (WIN Waste) and the nations largest medical waste incinerator (Curtis Bay Medical Waste Incinerator). Both operate in socio-economically disadvantaged communities, raising concerns about cumulative environmental exposures and health disparities from hazardous air pollutants. MethodsWe estimated health impacts from available criteria incinerator emissions data (PM, NOx, SO2, CO). We used AERMOD to model ground-level pollutant concentrations, linked these to U.S. Census tracts, and monetized health damages using established relative risk and cost of illness data. Health disparities were evaluated by modeling incinerator-attributable mortality against the Social Vulnerability Index (SVI). FindingsIn 2024, the WIN Waste incinerator caused an estimated $53.8 million in health damages in Maryland and Washington DC. On average, the Curtis Bay Medical Waste Incinerator releases black smoke emissions for 52.5 minutes/day, a regulatory violation. The facility causes $36.9 million/year in health damages and is permitted to burn enough waste to cause up to $107.1 million/year; enforcing pollution controls at this site could prevent $13.8 million in annual harm in Baltimore. Combined, the two incinerators cause $97.0 million in damages annually. All-cause mortality from incinerator pollution was more common in communities with higher socioeconomic vulnerability. InterpretationDespite being required to install new pollution control equipment following community and regulatory pressure, the WIN Waste incinerator still causes significant health damages to Maryland and Washington DC. Meanwhile, repeated black smoke emissions from the Curtis Bay incinerator indicate that ongoing, uncontrolled pollution is also a major threat to public health in the region. Health damages from these incinerators disproportionately affect communities least able to bear the economic burden. Our conservative estimates highlight the need for urgent policy reforms, including stricter emissions monitoring, phasing out non-essential incineration, and ongoing cumulative impact assessments. FundingKJT and SD were funded by the University of Maryland Baltimore Provosts Climate Health & Resilience internship program. KJT was supported by a Point Foundation Internship & Professional Development Award and the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. BS, MAA, and CDH were supported by the National Institute of Environmental Health Sciences (NIEHS) P30 Center for Community Health: Addressing Regional Maryland Environmental Determinants of Disease (CHARMED) [grant no. P30ES032756]. BS, MAA, and CDH were supported by the Johns Hopkins Community Science and Innovation for Environmental Justice (CSI EJ) Initiative. CDH was supported by the National Institute for Occupational Safety and Health (NIOSH) Education and Research Center [grant no. T42OH0008428]. GS and CS are affiliated with the Curtis Bay Community Association and South Baltimore Community Land Trust. The authors have no other conflicts of interest to report.

We report small-sample evidence from a randomized experiment among a set of urban Ecuadorian households who owned both electric induction and gas stoves. We randomly assigned households to cook only with one stove during a prescribed two-day monitoring period, and then cook only with the other stove in a subsequent two-day period. The order of stove use was randomized, and air pollution was measured during each period. We found that mean 48-hour personal NO2 exposure was 9.9 ppb higher (95% CI, 4.5-15.3) -- a 50% increase over the 48-hour induction mean -- when households were randomized to gas as compared to induction. Mean kitchen area NO2 concentrations were 1 ppb higher (95% CI, 0.4-2.1) (a 6% increase) and mean personal PM2.5 exposure was 11 gm-3 higher (95% CI, -0.1-22.8) (a 44% increase) during study periods when randomized to gas. We use time-resolved cooking and pollution data to illustrate that these differences are driven by LPG cooking, which was associated with a 5.0 ppb increase in 5-minute average NO2 kitchen area concentrations (95% CI, 3.4-6.7) and a 20.8 gm-3 increase in 5-minute average personal PM2.5 exposure (95% CI 8.9-32.6). In contrast, cooking with induction was not associated with changes to short-term NO2 kitchen area concentrations, though it was associated with short-term increased personal PM2.5 exposure (10.8, 95% CI, 5.7-15.9).

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the contextual and spatial risk factors for PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified contextual and spatial risk factors from nearly 200 environmental characteristics for 23 PASC symptoms and conditions of eight organ systems. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each contextual and spatial factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) contextual and spatial characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), criteria air pollutants (e.g., sulfur dioxide), particulate matter (PM2.5) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, respiratory, blood, circulatory, endocrine, and other organ systems. Specific contextual and spatial risk factors for each PASC condition and symptom were different across New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular contextual and spatial characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.

PFAS are ubiquitous endocrine-disrupting pollutants that cross the placenta and impact offspring health, but the extent and timing of their transfer to both placental and fetal compartments remain poorly understood. We aimed to characterize the relationship between trimester-specific maternal serum levels of prenatal PFAS and paired placental and cord levels at term. Data came from Glowing, a prospective birth cohort (n=151). Seventeen PFAS were measured in maternal serum, cord serum, and pulverized flash-frozen villous placenta with liquid chromatography-tandem mass spectrometry. Mixed effects models tested transplacental transfer efficiency (TTE) over pregnancy. Regularization models, stochastic intervention, and quantile g-computation models tested the association between maternal and placental or cord PFAS levels. TTE increased linearly across trimesters for all PFAS (p<0.001). Quartile increases in maternal PFAS were strongly associated with placental levels (0.018-0.24 ng/g, p<0.001). Stochastic intervention identified T1 PFNA and PFDA; T2 PFOS, PFOA, PFHxS, and PFNA; and T3 PFHxS as robust predictors (p<0.001) of placental levels, consistent with quantile-based contributions. Quartile increases in maternal and placental PFAS concentrations were associated with cord levels (0.08 ng/g-0.55 ng/g, p<0.001). Stochastic intervention identified T1 PFOS and PFHxS; T2 PFOS and PFNA; T3 PFOA; and placental PFOA as important predictors (p<0.05) of cord levels, consistent with quantile-based contributions. Early-to-mid gestation, especially 2nd trimester PFAS measures, were the strongest sentinels of placental and cord serum levels, apart from PFOA which was best reflected by 3rd trimester or placental levels. Placental PFOS and PFOA strongly influenced cord levels. Our findings underscore the heterogeneity in PFAS transfer or metabolism across pregnancy and the placenta.