Air quality and attributable mortality among city dwellers in Kampala, Uganda: results from 4 years of continuous PM2.5 concentration monitoring using BAM 1022 reference instrument.

BACKGROUND: Air pollution is a known risk factor for non-communicable diseases that causes substantial premature death globally. Rapid urban growth, burning of biomass and solid waste, unpaved sections of the road network, rising numbers of vehicles, some with highly polluting engines, contribute to the poor air quality in Kampala. OBJECTIVE: To provide evidence-based estimates of air pollution attributable mortality in Kampala city, with focus on ambient fine particulate matter (PM2.5). METHODS: We utilized a time series design and prospectively collected data on daily ambient PM2.5 concentration levels in micrograms per cubic meter (µg/m3) using a Beta Attenuation Monitor (BAM-1022) in Kampala city, Uganda. We combined the PM2.5 data with all-cause mortality data obtained from the Uganda Bureau of Statistics and the Ministry of Health in Kampala. We calculated attributable risk estimates for mortality using the WHO AirQ+ tools. RESULTS: Overall, the annual average concentration for PM2.5 for the period of 4 years, 2018-2021, was 39 µg/m3. There was seasonal variation, with the rainy season months (March-June and October-December) having lower values. PM2.5 concentrations tend to be highest in the morning (09.00 h) and in the evening (21.00 h.) likely due to increased vehicular emissions as well as the influence of weather patterns (atmospheric temperature, relative humidity and wind). Saturday has the most pollution (daily average over 4 years of 41.2 µg/m3). Regarding attributable risk, we found that of all the deaths in Kampala, 2777 (19.3%), 2136 (17.9%), 1281 (17.9%) and 1063 (19.8%) were attributable to long-term exposure to air pollution (i.e., exposure to PM2.5 concentrations above the WHO annual guideline of 5 µg/m3) from 2018 to 2021, respectively. For the 4 years and considering the WHO annual guideline as the reference, there were 7257 air pollution-related deaths in Kampala city. IMPACT: Our study is the first to estimate air pollution attributable deaths in Kampala city considering the target as the WHO annual guideline value for PM2.5 of 5 µg/m3. Our monitoring data show that fine particulate matter air pollution in Kampala is above the WHO Air Quality Guideline value, likely resulting in substantial adverse health effects and premature death. While further monitoring is necessary, there is a clear need for control measures to improve air quality in Kampala city.

Fine particulate matter air pollution and health implications for Nairobi, Kenya.

Background: Continuous ambient air quality monitoring in Kenya has been limited, resulting in a sparse data base on the health impacts of air pollution for the country. We have operated a centrally located monitor in Nairobi for measuring fine particulate matter (PM2.5), the pollutant that has demonstrated impact on health. Here, we describe the temporal levels and trends in PM2.5 data for Nairobi and evaluate associated health implications. Methods: We used a centrally located reference sensor, the beta attenuation monitor (BAM-1022), to measure hourly PM2.5 concentrations over a 3-year period (21 August 2019 to 20 August 2022). We used, at minimum, 75% of the daily hourly concentration to represent the 24-hour concentrations for a given calendar day. To estimate the deaths attributable to air pollution, we used the World Health Organization (WHO) AirQ+ tool with input as PM2.5 concentration data, local mortality statistics, and population sizes. Results: The daily (24-hour) mean (±SEM) PM2.5 concentration was 19. 2 ± 0.6 (µg/m3). Pollutant levels were lowest at 03:00 and, peaked at 20:00. Sundays had the lowest daily concentrations, which increased on Mondays and remained high through Saturdays. By season, the pollutant concentrations were lowest in April and highest in August. The mean annual concentration was 18.4 ± 7.1 (µg/m3), which was estimated to lead to between 400 and 1,400 premature deaths of the city's population in 2021 hence contributing 5%-8% of the 17,432 adult deaths excluding accidents when referenced to WHO recommended 2021 air quality guideline for annual thresholds of 5 µg/m3. Conclusion: Fine particulate matter air pollution in Nairobi showed daily, day-of-week, and seasonal fluctuations consistent with the anthropogenic source mix, particularly from motor vehicles. The long-term population exposure to PM2.5 was 3.7 times higher than the WHO annual guideline of 5 µg/m3 and estimated to lead to a substantial burden of attributable deaths. An updated regulation targeting measures to reduce vehicular emissions is recommended.

Identifying globally relevant learnings from Africa's challenges and solutions to climate change and air pollution-related health impacts: a data science scoping review protocol.

INTRODUCTION: Leveraging data science could significantly advance the understanding of the health impacts of climate change and air pollution to meet health systems' needs and improve public health in Africa. This scoping review will aim to identify and synthesise evidence on the use of data science as an intervention to address climate change and air pollution-related health challenges in Africa. METHODS AND ANALYSIS: The search strategy will be developed, and the search will be conducted in the Web of Science, Scopus, CAB Abstracts, MEDLINE and EMBASE electronic databases. We will also search the reference lists of eligible articles for additional records. We will screen titles, technical reports, abstracts and full texts and select studies reporting the use of data science in relation to the health effects and interventions associated with climate change and air pollution in Africa. ETHICS AND DISSEMINATION: There are no formal ethics requirements as we are not collecting primary data. Results, once published, will be disseminated via conferences and shared with policy-makers and public health, air pollution and climate change key stakeholders in Africa.

Physician Antipsychotic Overprescribing Letters and Cognitive, Behavioral, and Physical Health Outcomes Among People With Dementia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. Objective: To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients' health outcomes. Design, Setting, and Participants: This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. Interventions: PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. Main Outcomes and Measures: The primary outcome of this analysis was patients' total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Results: Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, -0.7 days; 95% CI, -1.3 to -0.1 days; P = .02) and community-dwelling patients (adjusted difference, -1.5 days; 95% CI, -1.8 to -1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, -0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, -0.2%; 95% CI -1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. Conclusions and Relevance: This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care. Trial Registration: ClinicalTrials.gov Identifier: NCT05172687.

Climate Change and Human Health in Africa in Relation to Opportunities to Strengthen Mitigating Potential and Adaptive Capacity: Strategies to Inform an African "Brains Trust".

Background: Africa faces diverse and complex population/human health challenges due to climate change. Understanding the health impacts of climate change in Africa in all its complexity is essential for implementing effective strategies and policies to mitigate risks and protect vulnerable populations. This study aimed to outline the major climate change-related health impacts in Africa in the context of economic resilience and to seek solutions and provide strategies to prevent or reduce adverse effects of climate change on human health and well-being in Africa. Methods: For this narrative review, a literature search was conducted in the Web of Science, Scopus, CAB Abstracts, MEDLINE and EMBASE electronic databases. We also searched the reference lists of retrieved articles for additional records as well as reports. We followed a conceptual framework to ensure all aspects of climate change and health impacts in Africa were identified. Results: The average temperatures in all six eco-regions of Africa have risen since the early twentieth century, and heat exposure, extreme events, and sea level rise are projected to disproportionately affect Africa, resulting in a larger burden of health impacts than other continents. Given that climate change already poses substantial challenges to African health and well-being, this will necessitate significant effort, financial investment, and dedication to climate change mitigation and adaptation. This review offers African leaders and decision-makers data-driven and action-oriented strategies that will ensure a more resilient healthcare system and safe, healthy populations-in ways that contribute to economic resiliency. Conclusions: The urgency of climate-health action integrated with sustainable development in Africa cannot be overstated, given the multiple economic gains from reducing current impacts and projected risks of climate change on the continent's population health and well-being. Climate action must be integrated into Africa's development plan to meet the Sustainable Development Goals, protect vulnerable populations from the detrimental effects of climate change, and promote economic development.

Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults.

RATIONALE: Electronic cigarette (e-cigarette) aerosol contains volatile aldehydes, including flavourings and oxidant metals with known pulmonary toxicity. OBJECTIVES: To evaluate the associations of e-cigarette use with symptoms of wheeze, bronchitic symptoms and shortness of breath (SOB) across 4 years of prospective data. METHODS: Participants completed questionnaires on respiratory symptoms and past 30-day e-cigarette, cigarette and cannabis use in 2014 (wave 1; N=2094; mean age 17.3 years, SD=0.6 years). Follow-up information was collected in 2015 (wave 2; n=1609), 2017 (wave 3; n=1502) and 2018 (wave 4; n=1637) using online surveys. Mixed-effects logistic regression models evaluated associations of e-cigarette use with respiratory symptoms. MEASUREMENTS AND MAIN RESULTS: Participants were mostly Hispanic white (51.8%) and evenly representative by sex (49.6% female; 50.4% male). Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of wheeze (OR 1.81; 95% CI 1.28, 2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58, 2.69) and SOB (OR 1.78; 95% CI 1.23, 2.57), adjusting for study wave, age, sex, race, lifetime asthma diagnosis and parental education. Effect estimates were attenuated (wheeze (OR 1.41; 95% CI 0.99, 2.01), bronchitic symptoms (OR 1.55; 95% CI 1.18, 2.05), SOB (OR 1.48; 95% CI 1.01, 2.18)), after adjusting additionally for current cigarette use, cannabis use and secondhand exposure to e-cigarettes/cigarettes/cannabis. CONCLUSIONS: E-cigarette use in young adults was associated with respiratory symptoms, independent of combustible cannabis and cigarette exposures.

Postprandial Metabolite Profiles and Risk of Prediabetes in Young People: A Longitudinal Multicohort Study.

OBJECTIVE: Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery and validation cohorts using logistic regression. RESULTS: Two metabolites (allylphenol sulfate and caprylic acid) were found to predict prediabetes beyond known risk factors, including sex, BMI, age, ethnicity, fasting/2-h glucose, total cholesterol, and triglycerides. In the discovery cohort, the area under the receiver operator characteristic curve (AUC) of the model with metabolites and known risk factors was 0.80 (95% CI 0.72-0.87), which was higher than the risk factor-only model (AUC 0.63 [0.53-0.73]; P = 0.001). When the predictive models developed in the discovery cohort were applied to the replication cohort, the model with metabolites and risk factors predicted prediabetes more accurately (AUC 0.70 [95% CI 40.55-0.86]) than the same model without metabolites (AUC 0.62 [0.46-0.79]). CONCLUSIONS: Metabolite profiles may help improve prediabetes prediction compared with traditional risk factors. Findings suggest that medium-chain fatty acids and phytochemicals are early indicators of prediabetes in high-risk youth.

Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study investigates if annual average PM2.5 and NO2 exposure at ages 9-10 years moderates age-related changes in internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at the baseline, 1-year follow-up, and 2-year follow-up visits, for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Against our hypothesis, there was no evidence that greater air pollution exposure was related to more behavioral problems with age over time.

Critical windows of greenness exposure during preconception and gestational periods in association with birthweight outcomes.

Few studies have examined the association between greenness exposure and birth outcomes. This study aims to identify critical exposure time windows during preconception and pregnancy for the association between greenness exposure and birth weight. A cohort of 13 890 pregnant women and newborns in Shanghai, China from 2016-2019 were included in the study. We assessed greenness exposure using Normalized Difference Vegetation Index (NDVI) during the preconception and gestational periods, and evaluated the association with term birthweight, birthweight z-score, small-for-gestational age, and large-for-gestational age using linear and logistic regressions adjusting for key maternal and newborn covariates. Ambient temperature, relative humidity, ambient levels of fine particles (PM2.5) and nitrogen dioxide (NO2) assessed during the same period were adjusted for as sensitivity analyses. Furthermore, we explored the potential different effects by urbanicity and park accessibility through stratified analysis. We found that higher greenness exposure at the second trimester of pregnancy and averaged exposure during the entire pregnancy were associated with higher birthweight and birthweight Z-score. Specifically, a 0.1 unit increase in second trimester averaged NDVI value was associated with an increase in birthweight of 10.2 g (95% CI: 1.8-18.5 g) and in birthweight Z-score of 0.024 (0.003-0.045). A 0.1 unit increase in an averaged NDVI during the entire pregnancy was associated with 10.1 g (95% CI: 1.0-19.2 g) increase in birthweight and 0.025 (0.001-0.048) increase in birthweight Z-score. Moreover, the associations were larger in effect size among urban residents than suburban residents and among residents without park accessibility within 500 m compared to those with park accessibility within 500 m. Our findings suggest that increased greenness exposure, particularly during the second trimester, may be beneficial to birth weight in a metropolitan area.

Identifying critical windows of air pollution exposure during preconception and gestational period on birthweight: a prospective cohort study.

BACKGROUND: Few studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods. METHODS: Leveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016-2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children's sex-specific associations were explored. RESULTS: After controlling for covariates, one standard deviation (SD) (11.5 µg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 - 26%) and 14% (95% CI: 1 - 29%) increase in SGA, respectively; and one SD (9.6 µg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 - 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22-32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found. CONCLUSION: Consistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

Prenatal ambient air pollution exposure and child weight trajectories from the 3rd trimester of pregnancy to 2 years of age: a cohort study.

BACKGROUND: Prenatal air pollution exposure may increase risk for childhood obesity. However, few studies have evaluated in utero growth measures and infant weight trajectories. This study will evaluate the associations of prenatal exposure to ambient air pollutants with weight trajectories from the 3rd trimester through age 2 years. METHODS: We studied 490 pregnant women who were recruited from the Maternal and Development Risks from Environmental and Social Stressors (MADRES) cohort, which comprises a low-income, primarily Hispanic population in Los Angeles, California. Nitrogen dioxide (NO2), particulate matter < 10 µm (PM10), particulate matter < 2.5 µm (PM2.5), and ozone (O3) concentrations during pregnancy were estimated from regulatory air monitoring stations. Fetal weight was estimated from maternal ultrasound records. Infant/child weight measurements were extracted from medical records or measured during follow-up visits. Piecewise spline models were used to assess the effect of air pollutants on weight, overall growth, and growth during each period. RESULTS: The mean (SD) prenatal exposure concentrations for NO2, PM2.5, PM10, and O3 were 16.4 (2.9) ppb, 12.0 (1.1) µg/m3, 28.5 (4.7) µg/m3, and 26.2 (2.9) ppb, respectively. Comparing an increase in prenatal average air pollutants from the 10th to the 90th percentile, the growth rate from the 3rd trimester to age 3 months was significantly increased (1.55% [95%CI 1.20%, 1.99%] for PM2.5 and 1.64% [95%CI 1.27%, 2.13%] for NO2), the growth rate from age 6 months to age 2 years was significantly decreased (0.90% [95%CI 0.82%, 1.00%] for NO2), and the attained weight at age 2 years was significantly lower (- 7.50% [95% CI - 13.57%, - 1.02%] for PM10 and - 7.00% [95% CI - 11.86%, - 1.88%] for NO2). CONCLUSIONS: Prenatal ambient air pollution was associated with variable changes in growth rate and attained weight from the 3rd trimester to age 2 years. These results suggest continued public health benefits of reducing ambient air pollution levels, particularly in marginalized populations.

Sex-specific effects in how childhood exposures to multiple ambient air pollutants affect white matter microstructure development across early adolescence.

Ambient air pollution is ubiquitous, yet questions remain as to how it might impact the developing brain. Large changes occur in the brain's white matter (WM) microstructure across adolescence, with noticeable differences in WM integrity in male and female youth. Here we report sex-stratified effects of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) on longitudinal patterns of WM microstructure from 9-13 years-old in 8,182 (49% female) participants using restriction spectrum imaging. After adjusting for key sociodemographic factors, multi-pollutant, sex-stratified models showed that one-year annual exposure to PM2.5 and NO2 was associated with higher, while O3 was associated with lower, intracellular diffusion at age 9. All three pollutants also affected trajectories of WM maturation from 9-13 years-old, with some sex-specific differences in the number and anatomical locations of tracts showing altered trajectories of intracellular diffusion. Concentrations were well-below current U.S. standards, suggesting exposure to these criteria pollutants during adolescence may have long-term consequences on brain development.

War and Health Care Services Utilization for Chronic Diseases in Rural and Semiurban Areas of Tigray, Ethiopia.

Importance: The war in Tigray, Ethiopia, has disrupted the health care system of the region. However, its association with health care services disruption for chronic diseases has not been well documented. Objective: To assess the association of the war with the utilization of health care services for patients with chronic diseases. Design, Setting, and Participants: Of 135 primary health care facilities, a registry-based cross-sectional study was conducted on 44 rural and semiurban facilities of Tigray. Data on health services utilization were extracted for patients with tuberculosis, HIV, diabetes, hypertension, and psychiatric disorders in the prewar period (September 1, to October 31, 2020) and during the first phase of the war period (November 4, 2020, to June 30, 2021). Main Outcomes and Measures: Records on the number of follow-up, laboratory tests, and patients undergoing treatment of the aforementioned chronic diseases were counted during the prewar and war periods. Results: Of 4645 records of patients with chronic diseases undergoing treatment during the prewar period, 998 records (21%) indicated having treatment during the war period. Compared with the prewar period, 59 of 180 individuals (33%; 95% CI, 26%-40%) had tuberculosis, 522 of 2211 (24%; 95% CI, 22%-26%) had HIV, 228 of 1195 (19%; 95% CI, 17%-21%) had hypertension, 123 of 632 (20%; 95% CI, 16%-22%) had psychiatric disorders, and 66 of 427 (15%; 95% CI, 12%-18%) had type 2 diabetes records, which revealed continued treatment during the war period. Of 174 records of patients with type 1 diabetes in the prewar period, at 2 to 3 months into the war, the numbers dropped to 10 with 94% decline compared with prewar observations. Conclusions and Relevance: This study found that the war in Tigray has resulted in critical health care service disruption and high loss to follow-up for patients with chronic disease, likely leading to increased morbidity and mortality. Local, national, and global policymakers must understand the extent and impact of the service disruption and urge their efforts toward restoration of those services.

War-related sexual and gender-based violence in Tigray, Northern Ethiopia: a community-based study.

INTRODUCTION: Sexual and gender-based violence (SGBV) during armed conflicts has serious ramifications with women and girls disproportionally affected. The impact of the conflict that erupted in November 2020 in Tigray on SGBV is not well documented. This study is aimed at assessing war-related SGBV in war-affected Tigray, Ethiopia. METHODS: A community-based survey was conducted in 52 (out of 84) districts of Tigray, excluding its western zone and some districts bordering Eritrea due to security reasons. Using a two-stage multistage cluster sampling technique, a total of 5171 women of reproductive age (15-49 years) were randomly selected and included in the study. Analysis used weighted descriptive statistics, regression modelling and tests of associations. RESULTS: Overall, 43.3% (2241/5171) of women experienced at least one type of gender-based violence. The incidents of sexual, physical and psychological violence, and rape among women of reproductive age were found to be 9.7% (500/5171), 28.6% (1480/5171), 40.4% (2090/5171) and 7.9% (411/5171), respectively. Of the sexual violence survivors, rape accounted for 82.2% (411/500) cases, of which 68.4% (247) reported being gang raped. Young women (aged 15-24 years) were the most affected by sexual violence, 29.2% (146/500). Commonly reported SGBV-related issues were physical trauma, 23.8% (533/2241), sexually transmitted infections, 16.5% (68/411), HIV infection, 2.7% (11/411), unwanted pregnancy, 9.5% (39/411) and depression 19.2% (431/2241). Most survivors (89.7%) did not receive any postviolence medical or psychological support. CONCLUSIONS: Systemic war-related SGBV was prevalent in Tigray, with gang-rape as the most common form of sexual violence. Immediate medical and psychological care, and long-term rehabilitation and community support for survivors are urgently needed and recommended.

Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence.

BACKGROUND: Air pollution is linked to neurodevelopmental delays, but its association with longitudinal changes in brain network development has yet to be investigated. We aimed to characterize the effect of PM2.5, O3, and NO2 exposure at ages 9-10 years on changes in functional connectivity (FC) over a 2-year follow-up period, with a focus on the salience (SN), frontoparietal (FPN), and default-mode (DMN) brain networks as well as the amygdala and hippocampus given their importance in emotional and cognitive functioning. METHODS: A sample of children (N = 9,497; with 1-2 scans each for a total of 13,824 scans; 45.6% with two brain scans) from the Adolescent Brain Cognitive Development (ABCD) Study® were included. Annual averages of pollutant concentrations were assigned to the child's primary residential address using an ensemble-based exposure modeling approach. Resting-state functional MRI was collected on 3T MRI scanners. First, developmental linear mixed-effect models were performed to characterize typical FC development within our sample. Next, single- and multi-pollutant linear mixed-effect models were constructed to examine the association between exposure and intra-network, inter-network, and subcortical-to-network FC change over time, adjusting for sex, race/ethnicity, income, parental education, handedness, scanner type, and motion. RESULTS: Developmental profiles of FC over the 2-year follow-up included intra-network integration within the DMN and FPN as well as inter-network integration between the SN-FPN; along with intra-network segregation in the SN as well as subcortical-to-network segregation more broadly. Higher PM2.5 exposure resulted in greater inter-network and subcortical-to-network FC over time. In contrast, higher O3 concentrations resulted in greater intra-network, but less subcortical-to-network FC over time. Lastly, higher NO2 exposure led to less inter-network and subcortical-to-network FC over the 2-year follow-up period. CONCLUSION: Taken together, PM2.5, O3, and NO2 exposure in childhood relate to distinct changes in patterns of network maturation over time. This is the first study to show outdoor ambient air pollution during childhood is linked to longitudinal changes in brain network connectivity development.

Air pollution and emotional behavior in adolescents across the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study examines how annual average PM2.5 and NO2 exposure at ages 9-10 years relates to internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at baseline and annually for two follow-up sessions for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Overall, the pollution effects moderated the main effects of age with higher levels of PM2.5 and NO2 leading to an even greater likelihood of having no behavioral problems (i.e., score of zero) with age over time, as well as fewer problems when problems are present as the child ages. Albeit this was on the order equal to or less than a 1-point change. Thus, one year of annual exposure at 9-10 years is linked with very small change in emotional behaviors in early adolescence, which may be of little clinical relevance.

Ambient fine particulate exposure and subcortical gray matter microarchitecture in 9- and 10-year-old children across the United States.

Neuroimaging studies showing the adverse effects of air pollution on neurodevelopment have largely focused on smaller samples from limited geographical locations and have implemented univariant approaches to assess exposure and brain macrostructure. Herein, we implement restriction spectrum imaging and a multivariate approach to examine how one year of annual exposure to daily fine particulate matter (PM2.5), daily nitrogen dioxide (NO2), and 8-h maximum ozone (O3) at ages 9-10 years relates to subcortical gray matter microarchitecture in a geographically diverse subsample of children from the Adolescent Brain Cognitive Development (ABCD) Study℠. Adjusting for confounders, we identified a latent variable representing 66% of the variance between one year of air pollution and subcortical gray matter microarchitecture. PM2.5 was related to greater isotropic intracellular diffusion in the thalamus, brainstem, and accumbens, which related to cognition and internalizing symptoms. These findings may be indicative of previously identified air pollution-related risk for neuroinflammation and early neurodegenerative pathologies.

Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study.

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardiometabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. OBJECTIVE: We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. METHODS: Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children's Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted Z-tests. RESULTS: In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (meta-analysis p=0.00002) and de novo fatty acid biosynthesis (p=0.03), among others. For example, when increasing all PFAS in the mixture from low (∼30th percentile) to high (∼70th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80). Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations. DISCUSSION: Exposure to PFAS is associated with alterations in amino acid metabolism and lipid metabolism in adolescents and young adults. https://doi.org/10.1289/EHP11372.

A systematic review of evidence for maternal preconception exposure to outdoor air pollution on Children's health.

The preconception period is a critical window for gametogenesis, therefore preconception exposure to air pollutants may have long-term effects on children. We systematically reviewed epidemiological evidence concerning the effects of preconception ambient air pollution exposure on children's health outcomes and identified research gaps for future investigations. We searched PubMed and Web of Science from journal inception up to October 2022 based on an established protocol (PROSPERO: CRD42022277608). We then identified 162 articles based on searching strategy, 22 of which met the inclusion criteria. Studies covered a wide range of health outcomes including birth defects, preterm birth, birthweight, respiratory outcomes, and developmental outcomes. Findings suggested that exposure to outdoor air pollutants during maternal preconception period were associated with various health outcomes, of which birth defects has the most consistent findings. A meta-analysis revealed that during 3-month preconception period, a 10 µg/m3 increase in PM10 and PM2.5 was associated with relative risk (RR) of birth defects of 1.06 (95% confidence interval (CI): 1.00, 1.02) and 1.14 (95% CI: 0.82, 1.59), respectively. Preterm birth, low birthweight, and autism have also been associated with maternal preconception exposure to PM2.5, PM10, O3 and SO2. However, the significance of associations and effect sizes varied substantially across studies, partly due to the heterogeneity in exposure and outcome assessments. Future studies should use more accurate exposure assessment methods to obtain individual-level exposures with high temporal resolution. This will allow the exploration of which specific time window (weeks or months) during the preconception period has the strongest effect. In future epidemiologic studies, integrating pathophysiologic biomarkers relevant to clinical outcomes may help improve the causal inference of associations between preconception exposure and health outcomes suggested by the current limited literature. Additionally, potential effects of paternal preconception exposure need to be studied.

Association Between Ambient Air Pollution and Birth Weight by Maternal Individual- and Neighborhood-Level Stressors.

Importance: Fetal growth is precisely programmed and could be interrupted by environmental exposures during specific times during pregnancy. Insights on potential sensitive windows of air pollution exposure in association with birth weight are needed. Objective: To examine the association of sensitive windows of ambient air pollution exposure with birth weight and heterogeneity by individual- and neighborhood-level stressors. Design, Setting, and Participants: Data on a cohort of low-income Hispanic women with singleton term pregnancy were collected from 2015 to 2021 in the ongoing Maternal and Developmental Risks from Environmental and Social Stressors cohort in Los Angeles, California. Exposures: Daily ambient particulate matter with aerodynamic diameter less than 10 µm (PM10) and aerodynamic diameter less than 2.5 µm (PM2.5), nitrogen dioxide (NO2), and 8-hour maximum ozone were assigned to residential locations. Weekly averages from 12 weeks before conception to 36 gestational weeks were calculated. Individual-level psychological stressor was measured by the Perceived Stress Scale. Neighborhood-level stressor was measured by the CalEnviroScreen 4.0. Main Outcomes and Measures: Sex-specific birth weight for gestational age z score (BWZ). The associations between air pollutant and BWZ were estimated using distributed lag models to identify sensitive windows of exposure, adjusting for maternal and meteorologic factors. We stratified the analyses by Perceived Stress Scale and CalEnviroScreen 4.0. We converted the effect size estimation in BWZ to grams to facilitate interpretation. Results: The study included 628 pregnant women (mean [SD] age, 22.18 [5.92] years) and their newborns (mean [SD] BWZ, -0.08 [1.03]). On average, an interquartile range (IQR) increase in PM2.5 exposure during 4 to 22 gestational weeks was associated with a -9.5 g (95% CI, -10.4 to -8.6 g) change in birth weight. In stratified models, PM2.5 from 4 to 24 gestational weeks was associated with a -34.0 g (95% CI, -35.7 to -32.4 g) change in birth weight and PM10 from 9 to 14 gestational weeks was associated with a -39.4 g (95% CI, -45.4 to -33.4) change in birth weight in the subgroup with high Perceived Stress Scale and high CalEnviroScreen 4.0 scores. In this same group, NO2 from 9 to 14 gestational weeks was associated with a -40.4 g (95% CI, -47.4 to -33.3 g) change in birth weight and, from 33 to 36 gestational weeks, a -117.6 g (95% CI, -125.3 to -83.7 g) change in birth weight. Generally, there were no significant preconception windows for any air pollutants or ozone exposure with birth weight. Conclusions and Relevance: In this cohort study, early pregnancy to midpregnancy exposures to PM2.5, PM10, and NO2 were associated with lower birth weight, particularly for mothers experiencing higher perceived stress and living in a neighborhood with a high level of stressors from environmental pollution.