Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.

INTRODUCTION: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. METHOD: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. RESULTS: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. CONCLUSION: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.

Role of social determinants of health in differential respiratory exposure and health outcomes among children.

BACKGROUND: Attributes defining the Social Determinants of Health (SDoH) are associated with disproportionate exposures to environmental hazards and differential health outcomes among communities. The dynamics between SDoH, disproportionate environmental exposures, and differential health outcomes are often specific to micro-geographic areas. METHODS: This study focused on children less than 20 years of age who lived in Douglas County, Nebraska, during 2016-2019. To assess the role of SDoH in differential exposures, we evaluated the association between SDoH metrics and criteria pollutant concentrations and the association between SDoH and pediatric asthma exacerbations to quantify the role of SDoH in differential pediatric asthma outcomes. The Bayesian Poisson regression model with spatial random effects was used to evaluate associations. RESULTS: We identified significant positive associations between the annual mean concentration of criteria pollutants (carbon monoxide, particulate matter2.5, nitrogen dioxide, sulfur dioxide) with race (Non-Hispanic Black and Hispanic/Latino), financial stability, and literacy. Additionally, there were significant positive associations between higher rates of pediatric asthma emergency department visits and neighborhoods with more Non-Hispanic Black children, children without health insurance coverage, and households without access to a vehicle. CONCLUSIONS: Non-Hispanic Black and Hispanic/Latino children living in Douglas County, NE experience disproportionately higher exposure to criteria pollutant concentrations. Additionally, higher rates of asthma exacerbations among Non-Hispanic Black children could be due to reduced access to respiratory care that is potentially the result of financial instability and vehicle access. These results could inform city planners and health care providers to mitigate respiratory risks among these higher at-risk populations.

Projections of Extreme Temperature-Related Deaths in the US.

Importance: Extreme heat in the US is increasing due to climate change, while extreme cold is projected to decline. Understanding how extreme temperature along with demographic changes will affect population health is important for devising policies to mitigate the health outcome of climate change. Objective: To assess the burden of extreme temperature-related deaths in the contiguous US currently (2008-2019) and estimate the burden in the mid-21st century (2036-2065). Design, Setting, and Participants: This cross-sectional study used historical (1979-2000) daily mean temperatures to calculate monthly extreme heat (>97.5th percentile value) and extreme cold days (<2.5th percentile value) for all contiguous US counties for 2008 to 2019 (current period). Temperature projections from 20 climate models and county population projections were used to estimate extreme temperature-related deaths for 2036 to 2065 (mid-21st century period). Data were analyzed from November 2023 to July 2024. Exposure: Current monthly frequency of extreme heat days and projected mid-21st century frequency using 2 greenhouse gas emissions scenarios: Shared Socioeconomic Pathway (SSP)2-4.5, representing socioeconomic development with a lower emissions increase, and SSP5-8.5, representing higher emissions increase. Main Outcomes and Measures: Mean annual estimated number of extreme temperature-related excess deaths. Poisson regression model with county, month, and year fixed effects was used to estimate the association between extreme temperature and monthly all-cause mortality for older adults (aged ≥65 years) and younger adults (aged 18-64 years). Results: Across the contiguous US, extreme temperature days were associated with 8248.6 (95% CI, 4242.6-12 254.6) deaths annually in the current period and with 19 348.7 (95% CI, 11 388.7-27 308.6) projected deaths in the SSP2-4.5 scenario and 26 574.0 (95% CI, 15 408.0-37 740.1) in the SSP5-8.5 scenario. The mortality data included 30 924 133 decedents, of whom 15 573 699 were males (50.4%), with 6.3% of Hispanic ethnicity, 11.5% of non-Hispanic Black race, and 79.3% of non-Hispanic White race. Non-Hispanic Black adults (278.2%; 95% CI, 158.9%-397.5%) and Hispanic adults (537.5%; 95% CI, 261.6%-813.4%) were projected to have greater increases in extreme temperature-related deaths from the current period to the mid-21st century period compared with non-Hispanic White adults (70.8%; 95% CI, -5.8% to 147.3%). Conclusions and Relevance: This cross-sectional study found that extreme temperature-related deaths in the contiguous US were projected to increase substantially by mid-21st century, with certain populations, such as non-Hispanic Black and Hispanic adults, projected to disproportionately experience this increase. The results point to the need to mitigate the adverse outcome of extreme temperatures for population health.

Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells.

Background: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations. Method: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways. Results: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta. Conclusion: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta. Supplementary Information: The online version contains supplementary material available at 10.1186/s43682-024-00027-7.

Evaluating Changes in Health Risk from Drought over the Contiguous United States.

The outcomes of drought can be difficult to assess due to the complexity of its effects. While most risk assessments of drought are developed for agriculture or water resources, the associations with human health are not well studied due to unclear and complex pathways. This study is the first to assess potential changes in health risk from droughts during the last decade in the contiguous United States. To assess the risk, we spatially superimposed vulnerability variables associated with drought on historical drought exposure over the last decade. Different variations in Local Moran's I statistics were used to assess the spatial distribution of health vulnerability, risk of drought, and changes in the two five-year study periods (2010-2014 and 2015-2019). Our results show large clusters of the western United States had a significant increase in risk during the latter part of the study period due to increases in vulnerability and hazard. In addition, southern areas of the United States were consistently above the national average in drought risk. Since our vulnerability variables include agriculture, drinking water, and sociodemographic indicators, the results of this study can help various experts interested in drought preparedness efforts associated with human health.

Factors Associated with Musculoskeletal Discomfort in Farmers and Ranchers in the U.S. Central States.

Agricultural work involves ergonomic and psychosocial strain, which contribute to musculoskeletal conditions. The aim of this study was to assess if specific ergonomic, psychosocial, and preventive factors are linked to musculoskeletal pain or discomfort symptoms (MSS) in farmers and ranchers. We analyzed data from the Central States Center for Agricultural Safety and Health survey that was conducted in 2018 in a seven-state region of the central United States. MSS were assessed with questions from the Standardized Nordic Questionnaire. The survey included questions on demographic, ergonomic, psychosocial and preventive factors. Farm production variables were added from the Farm Market iD database. We analyzed the data using Generalized Estimating Equations. The overall prevalence of MSS for all body sites combined was 59% among 4,354 farmers and ranchers who responded (19% response rate). After controlling for age, sex, and operator status, three factors (high stress level, sleep deprivation, and exhaustion/fatigue) showed the strongest associations with MSS in any body site, with adjusted odds ratios (OR) ranging from 4.8 to 5.6. Forceful exertions, repetitive tasks, awkward postures, frequent manual labor, and vibration were also significantly associated with MSS, with adjusted ORs ranging from 1.8 to 3.3. Recommended preventive techniques were not protective for MSS. New effective strategies are needed to reduce the high burden of musculoskeletal outcomes among farmers and agricultural workers.

Prevalence and Risk Factors for Pulmonary Conditions among Farmers and Ranchers in the Central United States.

This study was conducted to evaluate the prevalence and risk factors for work-related respiratory conditions (asthma, farmer's lung, sinusitis, rhinitis, and environmental allergies, diagnosed by a physician) among farm and ranch operators in the central US. A survey was conducted by the Central States Center for Agricultural Safety and Health (CS-CASH) in 2018, focusing on work-related injuries, illnesses, exposures, and preventive measures in a seven-state region (Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, and South Dakota). Farms and ranches (n = 16,818) with an email address and annual sales exceeding $5,000 were randomly selected for the survey. Agricultural production and weather data were merged with survey responses. The relationship between exposures and respiratory conditions was analyzed using generalized estimating equations. We received responses from 3,268 agricultural operations (19% response rate) containing information on 4,064 individual operators. The life-time prevalence of (any) respiratory conditions among farm/ranch operators was 18%. Risk factors for respiratory conditions included exposures to grain/hay/feed dust (OR 2.41), animal confinement dust (OR 1.57), field/road dust (OR 2.11), manure/silage gasses (OR 1.66), anhydrous ammonia (OR 1.51), fuels/solvents/paints (OR 1.92), older age group >70 vs. <43 (OR 1.40), female gender (OR 1.82), and being primary vs. third operator (OR 1.61). Farmers and ranchers have a high prevalence of respiratory conditions associated with dust and gas exposures at work. More effective protective measures are needed using the hierarchy of controls, including improved use of respiratory protection.

Evaluating the Sensitivity of Heat Wave Definitions among North Carolina Physiographic Regions.

Exposure to extreme heat is a known risk factor that is associated with increased heat-related illness (HRI) outcomes. The relevance of heat wave definitions (HWDs) could change across health conditions and geographies due to the heterogenous climate profile. This study compared the sensitivity of 28 HWDs associated with HRI emergency department visits over five summer seasons (2011−2016), stratified by two physiographic regions (Coastal and Piedmont) in North Carolina. The HRI rate ratios associated with heat waves were estimated using the generalized linear regression framework assuming a negative binomial distribution. We compared the Akaike Information Criterion (AIC) values across the HWDs to identify an optimal HWD. In the Coastal region, HWDs based on daily maximum temperature with a threshold > 90th percentile for two or more consecutive days had the optimal model fit. In the Piedmont region, HWD based on the daily minimum temperature with a threshold value > 90th percentile for two or more consecutive days was optimal. The HWDs with optimal model performance included in this study captured moderate and frequent heat episodes compared to the National Weather Service (NWS) heat products. This study compared the HRI morbidity risk associated with epidemiologic-based HWDs and with NWS heat products. Our findings could be used for public health education and suggest recalibrating NWS heat products.

Joint association between ambient air pollutant mixture and pediatric asthma exacerbations.

Exposure to air pollutants is known to exacerbate asthma, with prior studies focused on associations between single pollutant exposure and asthma exacerbations. As air pollutants often exist as a complex mixture, there is a gap in understanding the association between complex air pollutant mixtures and asthma exacerbations. We evaluated the association between the air pollutant mixture (52 pollutants) and pediatric asthma exacerbations. Method: This study focused on children (age ≤ 19 years) who lived in Douglas County, Nebraska, during 2016-2019. A seasonal-scale joint association between the outdoor air pollutant mixture adjusting for potential confounders (temperature, precipitation, wind speed, and wind direction) in relation to pediatric asthma exacerbation-related emergency department (ED) visits was evaluated using the generalized weighted quantile sum (qWQS) regression with repeated holdout validation. Results: We observed associations between air pollutant mixture and pediatric asthma exacerbations during spring (lagged by 5 days), summer (lag 0-5 days), and fall (lag 1-3 days) seasons. The estimate of the joint outdoor air pollutant mixture effect was higher during the summer season (adjusted-ßWQS = 1.11, 95% confidence interval [CI]: 0.66, 1.55), followed by spring (adjusted-ßWQS = 0.40, 95% CI: 0.16, 0.62) and fall (adjusted-ßWQS = 0.20, 95% CI: 0.06, 0.33) seasons. Among the air pollutants, PM2.5, pollen, and mold contributed higher weight to the air pollutant mixture. Conclusion: There were associations between outdoor air pollutant mixture and pediatric asthma exacerbations during the spring, summer, and fall seasons. Among the 52 outdoor air pollutant metrics investigated, PM2.5, pollen (sycamore, grass, cedar), and mold (Helminthosporium, Peronospora, and Erysiphe) contributed the highest weight to the air pollutant mixture.

Geospatial Distribution of Age-Adjusted Incidence of the Three Major Types of Pediatric Cancers and Waterborne Agrichemicals in Nebraska.

This study was conducted to examine, at the county level, the relationship between pediatric cancer incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in groundwater. The age-adjusted brain and other CNS cancer incidence was higher than the national average in 63% of the Nebraska counties. After controlling for the counties socio-economic status and nitrate concentrations in groundwater, counties with groundwater atrazine concentrations above 0.0002 µg/L had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with groundwater atrazine concentrations in the reference group (0.0000-0.0002 µg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR = 8.39; 95% CI: 8.24-8.54), leukemia (IRR = 7.35; 95% CI: 7.22-7.48), and lymphoma (IRR = 5.59; CI: 5.48-5.69) after adjusting for atrazine groundwater concentration and the county socio-economic status. While these findings do not indicate a causal relationship, because other contaminants or cancer risk factors have not been accounted for, they suggest that atrazine and nitrate may pose a risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma.

Estimating the Burden of Heat-Related Illness Morbidity Attributable to Anthropogenic Climate Change in North Carolina.

Climate change is known to increase the frequency and intensity of hot days (daily maximum temperature ≥30°C), both globally and locally. Exposure to extreme heat is associated with numerous adverse human health outcomes. This study estimated the burden of heat-related illness (HRI) attributable to anthropogenic climate change in North Carolina physiographic divisions (Coastal and Piedmont) during the summer months from 2011 to 2016. Additionally, assuming intermediate and high greenhouse gas emission scenarios, future HRI morbidity burden attributable to climate change was estimated. The association between daily maximum temperature and the rate of HRI was evaluated using the Generalized Additive Model. The rate of HRI assuming natural simulations (i.e., absence of greenhouse gas emissions) and future greenhouse gas emission scenarios were predicted to estimate the HRI attributable to climate change. Over 4 years (2011, 2012, 2014, and 2015), we observed a significant decrease in the rate of HRI assuming natural simulations compared to the observed. About 3 out of 20 HRI visits are attributable to anthropogenic climate change in Coastal (13.40% [IQR: -34.90,95.52]) and Piedmont (16.39% [IQR: -35.18,148.26]) regions. During the future periods, the median rate of HRI was significantly higher (78.65%: Coastal and 65.85%: Piedmont), assuming a higher emission scenario than the intermediate emission scenario. We observed significant associations between anthropogenic climate change and adverse human health outcomes. Our findings indicate the need for evidence-based public health interventions to protect human health from climate-related exposures, like extreme heat, while minimizing greenhouse gas emissions.