Environmental Health Perspectives

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.

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.

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.

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.

Abstract This protocol is reported in accordance with the SPIRIT 2025 guidelines for clinical trial protocols. Introduction: Young 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 randomized studies evaluating their effectiveness in reducing young children's sick-related absences in early care and education (ECE) classrooms. Methods and Analysis: The OK-AIR study is a longitudinal, cluster-randomized 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 randomized 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 m (PM1), [&le;]2.5 m (PM2.5), [&le;]4 m (PM4), and [&le;]10 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 children's 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 children's 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 Dissemination: This 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. ISRCTN Trial Registration: ISRCTN78764448 Disclaimer: The 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 Study: {middle dot} Real-world longitudinal cluster RCT: The study uses a rigorous longitudinal cluster-randomized 2x2 factorial design in real-world ECE settings. {middle dot} Combined interventions: Interventions target both air filtration and disinfection, allowing for combined and comparative evaluation. {middle dot} Objective air quality monitoring: Continuous monitoring of IAQ metrics provides objective and reliable data on environmental change. {middle dot} Environmental pathogen surveillance: qPCR on surface swabs yields an objective biological outcome to triangulate with IAQ and absences. {middle dot} Comprehensive 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 children's longer-term health data available through Health Insurance Portability and Accountability Act (HIPAA) authorization. {middle dot} Clustered/temporal complexity: Seasonal design accounts for variation over time but may introduce complexity in modeling temporal effects. {middle dot} Practical Implications: Study findings will have practical implications for Head Start and other ECE programs striving to maximize child attendance with cost effective strategies. Keywords: Early childhood; Head Start; indoor air quality (IAQ); air purifiers; filtration; ultraviolet germicidal irradiation; cluster randomized trial; absenteeism; environmental pathogens; DECA; cost-benefit analysis

The co-occurrence of per- and polyfluoroalkyl substances (PFAS) and volatile organic compounds (VOCs) in industrial environments poses complex toxicological risks that standard additive models fail to capture. This study elucidates a novel "metabolic blockade" mechanism wherein PFAS competitively inhibits the renal excretion of VOC metabolites, thereby amplifying neurotoxic burdens. Utilizing a Double Machine Learning (DML) framework on data from National Health and Nutrition Examination Survey (2005-2020), we analyzed a final intersectional cohort of 1,975 participants. We identified a robust inhibition of VOC metabolite clearance by serum PFAS. Specifically, PFNA significantly suppressed the excretion of the benzene metabolite URXPMA (Causal {beta}TMLE = -0.219, p < 0.001), with efficacy dependent on perfluorinated chain length. Molecular docking simulations revealed the biophysical basis of this antagonism: long-chain PFNA exhibited superior binding affinity to the Organic Anion Transporter 1 (OAT1) ({Delta}G = -6.333 kcal/mol) compared to native VOC metabolites ({Delta}G = -4.957 kcal/mol), confirming high-affinity competitive inhibition at the renal interface. In a neurocognitive sub-cohort (N = 1,200), this interference translated into functional synergism; high-PFNA exposure magnified VOC-associated cognitive impairment by 1.5-fold and significantly exacerbated the negative association between VOC burden and processing speed ({beta}int = -0.263, p = 0.004). These findings define PFAS as a "metabolic amplifier" of co-contaminant toxicity, necessitating a paradigm shift toward mixture-based hazardous material regulations that account for transporter-level interactions.

AbstractO_ST_ABSImportanceC_ST_ABSGeneral responders of the World Trade Center (WTC) Health Program (WTCHP), who were uniquely exposed to chemical toxicants and extreme psychological stress during the 2001 terrorist attack, now experience a wide range of unusually prevalent health outcomes for a mid-aged population, including frailty, Post Traumatic Stress Disorder (PTSD), and depression. ObjectiveWe investigated whether these outcomes are associated with urban environmental exposures experienced in the two decades post 9/11. DesignProspective cohort study. SettingWTCHP general responders cohort. ParticipantsWe included 18,861 WTCHP general responders between the years 2003 to 2023 who took part in rescue, recovery, and clean-up tasks following the 9/11/2001 attack on the WTC. ExposuresWe evaluated the distinct and combined associations with annual fine particulate matter (PM2.5), temperature, and Green View Index (GVI) and assessed interactions with WTC-exposures. OutcomesWe assessed frailty using a validated index developed specifically for the WTCHP. We determined PTSD and depression status based on repeated test scores from validated tools administered during the monitoring visits. ResultsWe included 18,861 responders, 81.89% were males, and the mean age at entry was 47. Interquartile range increases in PM2.5 and temperature were significantly associated with increased frailty, PTSD, and depression scores, while greenness (GVI) was protective. A decile increase in the overall exposure mixture was associated with a 0.50% (95% confidence interval 0.08; 0.94) increase in frailty and a 0.10 unit (0.02; 0.18) increase in PTSD scores, primarily driven by temperature. Importantly, the exposure-mixture was associated with an increased risk of reaching a clinical threshold for PTSD (odds ratio: 1.013[1.001,1.024]). Finally, the associations between the exposure-mixture and mental health were significantly amplified among responders with high WTC-exposures, though no such modification was observed for frailty. Conclusion and relevanceExposures to heat and PM2.5 were associated with increased frailty, PTSD, and depression, while greenness exposure was protective. Responders who experienced more intense WTC exposures were more vulnerable to later-life environmental exposure-mixture effects on mental health. These findings may help explain the elevated burden of these conditions among WTCHP responders and suggest avenues for public health interventions including education on risk mitigation strategies.

Indigenous, mountain communities residing upstream of Bhumibol Dam, Thailand, rely on vulnerable natural water sources for their water supply, yet remain unaware of the associated health risks. This study assessed the water quality, usage patterns and contamination pathways across six villages upstream of Bhumibol Dam to shed light on the obstacles to sustainable water security . Samples from 38 water sources of drinking and/or non-drinking water, soil, and the edible parts of crops were subjected to analyses of physical, chemical (NO3-N, pH), and qualitative pesticide-related variables, alongside a 6-month assessment of a community water filter system. Principal component analysis identified a "at-risk group" of preferred drinking water sources all exhibiting high NO3-N, highly alkaline pH, and substantial pesticide contamination, which was found to likely be caused by agricultural run-off. This was reinforced by the detection of pesticide residues in all soil samples and, critically, in the below-ground edible parts of crops (taro, lemongrass, arrowroot), confirming dietary exposure in the local communities. Further compounding the risks posed by the unsafe water supply, the community water filter was found to be ineffective throughout the 6-month analysis with there being no significant difference in water quality between before and after filtration. The residents paradoxical preference for high-risk, still water (from sand-filtered puddles) for drinking, rather than water from flowing sources, which they used only for cooking and cleaning. These findings reveal a severe, compounded public health threat of chronic exposure to minerals linked to urolithiasis and agrochemicals, highlighting the urgent need for quantitative risk assessment and the implementation of resilient, decentralized water treatment solutions in these mountain communities.

We utilized traditional aerosol sampling to collect PM1 samples, and further apply redundancy analysis (RDA) to investigate the association of environmental factors (including PM1 chemical composition, oxidative potential, meteorological factors and gaseous pollutants) and airborne bacterial community. Our findings revealed that Bacteroidota positively correlated with Sn and Mn, Firmicutes with local primary pollutants, and Proteobacteria with transportation-related pollutants. Variance partitioning analysis (VPA) showed that PM1 chemical composition, meteorological factors and gaseous pollutants collectively explained up to 43.7% of community variance, and synergistic effects may exist among the three factors. In contrast, oxidative potential had minimal influence. Additionally, to investigate airborne viral presence, we employed a novel bioaerosol sampler targeting SARS-CoV-2 in hospital and campus settings. Viral loads were highest in negative pressure isolation rooms, followed by general hospital and campus areas. Also, the detection rates follow the same pattern, which is 87.5%, 58.3%, and 25.0%, respectively. Notably, detection rates near isolation wards increased during patient admissions, implying possible biocontamination despite containment measures. Peak human traffic flow emerged as a significant factor influencing viral detection. These results highlight how environmental factors shaping airborne microbial communities.

BackgroundAir pollution is a potentially modifiable risk factor for dementia with a population attributable risk fraction of 3%. Little is known about the causal mechanisms behind the association, so we aimed to investigate this. MethodsData from the UK Biobank were used to investigate the association between six measures of air pollution (NO2, NOx, PM2{middle dot}5-10, PM2{middle dot}5, PM2{middle dot}5 absorbance and PM10) and dementia incidence. Indirect pathways through four mediators (cardiovascular conditions, mental health treatment, insufficient exercise and social isolation) were explored. Logistic regression was used to model the associations between air pollution, mediators and dementia. Casual mediation analysis implemented using the g-formula was used to investigate the joint indirect effect through the mediators. FindingsExposure to the highest quintile of PM2{middle dot}5 (Rte:1{middle dot}14, 95% CI:1{middle dot}06-1{middle dot}23), NOx (Rte:1{middle dot}11, 95% CI:1{middle dot}03-1{middle dot}20) or NO2 (Rte:1{middle dot}08, 95% CI:0{middle dot}99-1{middle dot}16), compared to the lowest quintile, was associated with higher dementia risk. Most of the observed association resulted from the direct effect of air pollution, consisting of pathways not captured through considered mediators. Amongst those in the highest PM2{middle dot}5 quintile, jointly intervening on the four mediators would result in a 1% reduction in risk of dementia (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}01-1{middle dot}02). The randomised pure natural indirect effect was similar for NO2 (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}00-1{middle dot}01) and NOx (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}01-1{middle dot}02). InterpretationMost of the association between dementia and PM2{middle dot}5, NO2 and NOx occurs through the direct effect of air pollution, or other unmeasured mediators, and not pathways through these four mediators. FundingMedical Research Council (Grant MR/W006774/1).

IntroductionWhile longitudinal studies aid in understanding and preventing long-latency disorders like dementia, evidence for cadmiums role in these conditions is still limited. We evaluated associations between cadmium exposure and incident Alzheimers disease (AD) and all-cause dementia in US adults. MethodsNational Health and Nutrition Examination Survey (NHANES) III (1988-1994) and continuous NHANES (1999-2016) data were linked with Medicare claims to identify incident AD and dementia cases through 2018. Urinary and/or blood cadmium were measured during NHANES. We used covariate-adjusted, survey-weighted Cox proportional hazard models to evaluate the associations between cadmium exposure biomarkers and AD/dementia over follow-up. ResultsIn NHANES III (N=6,122), baseline age was 53.9{+/-}0.5 years and urinary cadmium was 0.8{+/-}0.02 ug/L. Over a follow-up of 20.4{+/-}0.3 years, 743 AD and 1,508 all-cause dementia cases occurred. Urinary cadmium was not associated with AD (HR: 1.01, 95% CI: 0.9-1.0) nor all-cause dementia incidence (HR: 1.02, 95% CI: 0.96-1.08). In continuous NHANES (urinary cadmium N=2,833; blood cadmium N=8,038), baseline age was 64.1{+/-}0.2 years, urinary cadmium was 0.5{+/-}0.03 ug/L, and blood cadmium was 0.6{+/-}0.01 ug/L. Over 9.5{+/-}0.1 years, 587 AD and 1,260 all-cause dementia cases occurred. Urinary and blood cadmium showed no associations with AD (HR [95% CI]: 1.09 [0.9, 1.4]; 1.06 [0.9, 1.2]) nor all-cause dementia (HR [95% CI]: 1.07 [0.9, 1.3]; 1.06 [0.95, 1.2]). ConclusionNo association between cadmium exposure and dementia incidence was observed. Our null findings should be interpreted while considering potential methodological issues and verified by subsequent studies.

Hospital-acquired infections are a known and growing problem worldwide. Far-UVC is a novel disinfection method that inactivates bacteria with limited penetration into human skin or eyes. A clustered, unmatched, randomized control trial (RCT) will be implemented in two Bolivian hospitals. The intervention arm will receive functioning Far-UVC lamps, whereas the control arm will receive identical lamps that do not emit UV light (shams). Based on baseline data, 40 lamp fixtures will be installed above hospital sinks, 10 per arm per hospital. Environmental samples (air and surface swabs) will be collected and analyzed via culture and sequencing. Simultaneously, air chemical monitoring data will be collected.

BackgroundLung cancer compensation systems for occupational exposure to asbestos commonly apply Helsinki criteria, which assume 4% excess lung cancer risk per fibre-year of asbestos exposure. The Probability of Causation (PoC) is [&ge;]50% at 25 fibre-years (risk doubling threshold). Large case-control studies have suggested steeper exposure-response relations at lower exposures. We aimed to estimate PoC of asbestos-related lung cancer to evaluate exposure thresholds for compensation of lung cancer cases occupationally exposed to asbestos. MethodsRelative risk of asbestos-related lung cancer was estimated using two approaches: O_LIA meta-regression of 22 occupational studies forming the core evidence on cumulative asbestos exposure and lung cancer since the 1980s (130,341 participants). C_LIO_LIA meta-analysis of the recently conducted SYNERGY pooled case-control study (14 studies, 37,866 participants), adjusted for age, sex, smoking, and study. C_LI The likelihood that lung cancer was caused by asbestos was estimated as the PoC with 95% prediction intervals (95%PI). ResultsOccupational cohort studies produced a shallow exposure-response relation with substantial heterogeneity (I{superscript 2} = 92.7%). SYNERGY showed a steeper relation with 6.8% (95%PI: 0%-17.7%) lung cancer risk increase per fibre-year and lower heterogeneity (I{superscript 2} = 63.4%). PoC [&ge;]50% occurred at 62.93 (point estimate) and 18.2 fibre-years (upper 95%PI) for occupational asbestos studies, compared to 10.5 and 4.3, respectively, in SYNERGY. ConclusionsThe SYNERGY pooled case-control study provided exposure-response estimates that are more representative of current exposure to lower mixed asbestos fibres in the Netherlands, supporting lower exposure thresholds than the existing Helsinki criteria when estimating PoC in compensation contexts.

BackgroundWhile coal mine fire smoke has been linked to short-term increases in cardiovascular events, there is little evidence on long-term risks. We investigated longer-term risk of major adverse cardiovascular events (MACE) following the 2014 Hazelwood coal mine fire in regional Victoria, Australia. MethodsIn this cohort study, combined administrative data on ambulance attendances, emergency department presentations, hospital admissions, and mortality from March 2014 to June 2022, with survey data from 2016/17. Time-location diaries for the mine-fire period were combined with modelled fire-related particulate matter [&le;]2.5{micro}m in diameter (PM2.5) to estimate individual exposures. We analysed the association between PM2.5 exposure and time to MACE using a recurrent event survival analysis, adjusting for key confounders. Outcomes were examined over 8 years of follow-up and stratified by time. ResultsN = 2,725 cohort members agreed to linking their survey responses to administrative data. There was no detectable effect of fire-related PM2.5 exposure on overall risk of MACE during 8-year follow-up. However, there was weak evidence suggesting increase in MACE risk in the first 3 years post-fire, with hazard ratios ranging from 1.05-1.18 per 10{micro}g/m3 of daily average PM2.5 exposure. Nearly all analyses of cardiovascular death detected an increased risk across the entire follow-up period, with hazard ratios ranging from 1.19-1.25 per 10{micro}g/m3. ConclusionsWe found smoke exposure predicted an increase in cardiovascular health service use in the three years after the mine fire. There was additional evidence that the mine fire increased risk of cardiovascular death over the entire 8-year follow-up. This suggests that cardiovascular screening should be a routine component of planning recovery after landscape fires.

Acute heat exposure, which is increasing with climate change, likely increases preterm birth risk. However, few studies consider susceptible exposure windows for extreme heat events, particularly among historically unexposed populations. The 2021 Pacific Northwest Heat Dome produced the highest temperatures ever recorded in usually temperate Oregon and Washington State, offering an ideal study setting. We used 2016-2022 vital statistics records to estimate the gestation month-specific impact of the Heat Dome on preterm birth. Using an interrupted time series design with a synthetic control, we compared the observed odds of preterm birth in the exposed (in utero November 2020-July 2021) Oregon and Washington conception cohorts to counterfactual odds had the Heat Dome not happened. Analysis included 716,096 exposed births across 67 monthly conception cohorts. We identified increased odds of preterm birth in cohorts exposed during months 2-3 (11% increase, 95% CI: [1%, 22%]) and 6-7 (14% increase, 95% CI: [5%, 24%]) of pregnancy. These findings partially agree with literature reporting elevated preterm birth risk after heat exposure in all trimesters. As extreme heat events are now expected once to twice per decade rather than once every thousand years, they pose risks to perinatal health.

BackgroundGiardia is the most common enteric parasite among children in low-resource settings, causing diarrhoea and leading to prolonged infection or asymptomatic carriage. We assessed whether the effect of water, sanitation and handwashing (WSH) interventions on Giardia infection among rural Bangladeshi children varies with seasonal conditions. MethodsWe conducted a secondary analysis of the WASH Benefits Bangladesh cluster-randomized trial, with 450 clusters assigned to four arms in a 2x2 factorial design (WSH: WSH, WSH+Nutrition; no WSH: Control, Nutrition). Giardia infection was measured by multiplex real-time PCR in stool samples after two years of intervention. Effects were estimated by marginal treatment and assessed for heterogeneity by season when Giardia was measured. We also assessed heterogeneity by cumulative exposure to dry and monsoon seasons from birth to measurement age to estimate the exposure history of Giardia. ResultsGiardia prevalence, measured among 2773 children (median age: 30 months, range: 22-38 months), was higher in the dry seasons (32%) than in the monsoon (21%). The effect of WSH was consistent on the relative (20% reduction) and absolute scales, with slightly greater absolute reduction during the dry season (dry: -6.1%, -10.1% to -2.1%). With increasing dry-season exposure, the period of highest risk, prevalence remained consistently lower in the WSH group, with the largest differences between study groups among children with more than 17 months of dry-season exposure by age over two years. ConclusionWe demonstrate how WSH provides resilience to seasonal variation in infection risk and mitigates climate-driven, seasonally varying Giardia transmission. Key MessagesO_LIWhat your research question was We investigated whether the effect of water, sanitation and handwashing (WSH) interventions on Giardia infection among rural Bangladeshi children varies with seasonal conditions. C_LIO_LIWhat you found We found that Giardia risk varied seasonally, with improved WSH providing consistent relative and absolute reductions -- slightly greater on the absolute scale during the dry season -- and larger reductions among children with greater cumulative exposure to dry months, reflecting higher baseline risk and demonstrating how WSH enhances resilience to seasonally varying infection risk. C_LIO_LIWhy it is important Since the dry and monsoon seasonal cycle is extreme in Bangladesh, this study demonstrates how WSH can mitigate seasonally varying Giardia infection risk. C_LI

BackgroundSmoking is a major preventable risk factor for all-cause mortality and disability worldwide. It leads to age-related diseases, but the effects and reversibility of smoking behaviors on different epigenetic clocks are not fully explored. ObjectiveTo characterize the association of epigenetic age acceleration in whole blood with active and secondhand smoking (SHS), smoking intensity, and time since cessation among U.S. adults. MethodsThis is a cross-sectional study in adults from the NHANES 1999-2002 survey cycles, a population-based survey representative of the U.S. adult civilian non-institutionalized population. We analyzed 2,320 adults aged [&ge;]50 years, including non-Hispanic White, non-Hispanic Black, Mexican American, and other populations. Those without available self-reported smoking status data were excluded. Smoking exposure was analyzed in terms of self-reported smoking status (current, former, never), intensity (packs in the last month), years since smoking cessation, and SHS (serum cotinine levels: 0.05-10 ng/ml). Epigenetic age was estimated using 12 DNA methylation age biomarkers. Survey-weighted linear models were used to estimate the association of smoking exposure with epigenetic age acceleration while adjusting for confounders and multiple comparisons. ResultsWe analyzed 1,043 never, 903 former, and 374 current smokers (mean age: 65.1{+/-}9.3 years, female: 49.1%). GrimAge2 was 9.1 years (95% CI: 8.0, 10.2) and 2.8 years (95% CI: 2.3, 3.3) higher in current and former smokers, respectively, than in never smokers. Smokers showed an increased pace of aging, with current smokers aging 0.15 (95% CI: 0.13, 0.17) and former smokers 0.04 (95% CI: 0.03, 0.05) additional years per chronological year, and shorter methylation-predicted telomere length (current: -132{+/-}19 bp; former: -30{+/-}15 bp). Each cigarette pack smoked in the past month was associated with increases of 0.1 years in GrimAge2 and PhenoAge, and 0.01 aged months/year in aging pace. Among former smokers, each year since smoking cessation was associated with a deceleration of -0.14 (GrimAge2) and -0.06 (PhenoAge) years, and -0.03 aged months/year in aging pace. Cotinine analyses supported dose-dependent associations of epigenetic aging with smoking and suggested a 0.8-year increase in GrimAge2 with SHS exposure. ConclusionsSmoking was associated in a dose-dependent manner with accelerated epigenetic aging in former and current smokers. However, epigenetic age acceleration declines with time since smoking cessation among former smokers.

BackgroundDengue outbreaks have become a severe threat to Bangladesh as the infections and mortality numbers are skyrocketing in recent years. Favorable environmental and anthropogenic conditions have established the capital of Bangladesh, Dhaka city as the epicenter of dengue outbreak. Studies have showed that climate change induced extreme weather events are exacerbating Aedes mosquito breeding and dengue virus transmission conditions. Methodology/Principal FindingsIn this study, short-term (0-6 weeks) associations of maximum temperature and heatwave days on dengue cases in Dhaka city were examined through Distributed Lag Non-linear Model (DLNM) methodology for weekly measurement of 2016-2024, taking into account relative humidity, cumulative rainfall, seasonality and hospital closure effect. Two separate negative binomial models were constructed. The maximum temperature model rendered an overall inverted U-shaped association, where the maximum temperature range of 31.5-33.2{degrees}C showed a sustained elevated dengue risk, with highest risk estimate at 33.2{degrees}C [relative risk (RR): 1.186, 95% CI: 1.002, 1.403]. Whereas, results of weekly heatwave days showed an overall protective effect (RR<1) for dengue cases. The lowest risk of infection was found at 3 heatwave days per week, with RR 0.275 (95% CI: 0.178, 0.423). Multiple sensitivity analyses were conducted for both models to evaluate their robustness. Lastly, the optimized models were analyzed under three distinct sub-periods, to capture the association of exposure variables with predominant circulating serotypes. Conclusions/SignificanceThe findings of the study aim to support public health policymakers and healthcare authorities in designing and implementing effective vector control interventions under emerging climatic emergencies. Author SummaryDengue disease is one of the most buringing issue in Bangladesh in recent years. This vector-borne disease is inherently influenced by climatic variables, i.e., temperature, rainfall, humidity, etc. Moreover, these relations are complex and non-linearly associated. Due to shift in climatic conditions, the occurance of extreme weather events are becoming frequent, with increased magnitude and longer duration. In this study, the nonlinear and delayed association of dengue infections due to the exposure of extreme temperature events were assessed in climate-change vulnerable Dhaka city. To do this, a statistical method was used, called distributed lag nonlinear methodology (DLNM). The results showed that dengue infections had an inverted U-shaped (parabolic) relationship with maximum temperature, while compared to mean maximum temperature, and a suppressive association with heatwaves relative to days without heatwaves. The findings aim to work as an early warning system, and support to policymakes and healthcare authorities to tackle the dengue surge in the changing climate.

IntroductionThe coverage of access to basic drinking water and sanitation facilities in India was estimated to be 93% and 60%, respectively, in 2017. The monitoring of the burden of diarrhoeal illnesses, especially in children, remains important to assess the impact of the expansion of water and sanitation (WaSH) in the Indian setting. This study aimed to estimate the burden of diarrhoea in an established longitudinal pediatric cohort in an urban settlement of Vellore in South India. MethodsThe Surveillance for Enteric Fever in India (SEFI) cohort established in an urban settlement of Vellore, south India, enrolled 6760 children aged between 6 months and 15 years. The cohort was followed up for typhoid and paratyphoid fever between 2017 and 2019. Field research assistants contacted caregivers of these children weekly to elicit any diarrhoeal illness in the child in the preceding week. As a part of SEFI environmental surveillance, drinking water samples from the study households were tested for coliforms. Sociodemographic characteristics, including source of drinking water, sanitation and hygiene practices, were collected. Incidence of diarrhoea was estimated and expressed as the number of diarrhoeal episodes over child-years of observation (CYO). Poisson regression analysis was performed to identify predictors of diarrhoeal episodes. ResultsThe estimated incidence of diarrhoea in the 6501 children followed up between November 1, 2017, and October 31, 2019, was 31.1 episodes per 100 CYO, with children in the age group of 6 months and <5 years having a higher incidence of diarrhoea than those aged between 5 and 15 years (58.6 versus 22 episodes per 100 CYO). Of the 6467 children with information on WaSH available, 5812 (89.9%) used the public distribution system for drinking water. Of the 1804 drinking water samples tested, 1346 (74.6%) had coliform counts >10,000/100 mL. Only about one-third of the cohort (n=2293, 35.5%) lived in households with access to improved sanitation. Multivariable analysis showed that children aged <2 years, residing in crowded settlements, using the public distribution system for drinking water and from households with poor hygiene practices related to excreta disposal of under-five children had a higher risk for diarrhoea. ConclusionApproximately 8 in 10 children in urban Vellore lack access to safely managed drinking water, and thereby, are at a high risk for diarrheal illnesses, especially in the under-5 children. With rapidly expanding urbanisation in the Indian setting, it is pertinent that emphasis be laid on robust planning and provision of safely managed water and sanitation.

BackgroundPreeclampsia is a leading cause of maternal morbidity and mortality in sub-Saharan Africa (SSA). Lead exposure remains widespread across the region, yet its contribution to preeclampsia risk has not been quantified at the population level. The World Health Organization (WHO, 2025) estimated that in 2023, there were approximately 182,000 maternal deaths in SSA (70 % of global deaths), and that approximately 16% of these deaths were due to hypertensive disorders of pregnancy (HDP) (Say et al, 2014). This implies that there were approximately 29,000 HDP-related maternal deaths annually in the SSA (with pre-eclampsia/eclampsia constituting a substantial fraction). MethodsWe synthesized maternal blood lead level (BLL) data from pregnancy biomonitoring studies conducted in SSA and supplemented these with soil-derived exposure scenarios representing severely contaminated settings. Using published meta-analytic evidence indicating a 1.6% increase in the odds of preeclampsia per 1 {micro}g/dL increase in maternal BLL (Poropat et al., 2018), we modelled relative odds and predicted absolute preeclampsia risk under a range of plausible baseline prevalence assumptions. Sensitivity analyses examined uncertainty related to exposure extrapolation and baseline preeclampsia prevalence, and population attributable fractions were estimated across baseline scenarios. ResultsBiomonitoring-derived maternal BLLs were associated with modest but consistent increases in predicted pre-eclampsia risk across baseline scenarios. Soil-derived exposure scenarios representing severe environmental contamination yielded sharply increasing predicted risks under uncapped extrapolation. Sensitivity analyses demonstrated that relative exposure-response gradients were robust to modelling assumptions, while absolute risk and attributable burden estimates varied with baseline prevalence. Central tendency maternal blood lead levels reported in sub-Saharan Africa are several-fold higher than those observed in contemporary biomonitoring programs in Europe, North America, East Asia, and Latin America. ConclusionMaternal lead exposure may contribute meaningfully to pre-eclampsia risk in sub-Saharan Africa, with modest effects at commonly observed exposure levels and potentially substantial effects in severely contaminated settings. These findings support the inclusion of environmental lead exposure prevention within broader maternal health strategies.