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Background: Nationwide evidence linking maternal ozone exposure with fetal growth restriction (FGR) was extensively scarce, especially in the Middle East with dry climate and distinct religious culture. Methods: We carried out a national retrospective birth cohort study using registry-based records from 749 hospitals across 31 provinces in Iran from 2013 to 2018. Monthly concentrations of maximum daily average 8-hour (MDA8) ozone at 0.125° × 0.125° resolution were extracted from well-validated spatiotemporal grid dataset. Linear and logistic regression models were employed to evaluate associations of maternal MDA8 ozone exposure with birthweight outcomes. Assuming causality, the comparative risk assessment framework was utilized to estimate the burden of low birthweight (LBW), small for gestational age (SGA), and birthweight loss per livebirth (BLL) attributable to ambient ozone pollution. Results: Of 4030383 livebirths included in the study, 264304 (6.6%) were LBW and 484405 (12.0%) were SGA. Each 10-ppb increase in MDA8 ozone exposure was associated with an odds ratio of 1.123 (95% confidence interval [CI]: 1.104 to 1.142) for LBW and 1.210 (95% CI: 1.197 to 1.223) for SGA, and a 30.5-g (95% CI: 29.0 to 32.0) reduction in birthweight. We observed approximately linear exposure-response relationships of maternal MDA8 ozone exposure with LBW (Pnonlinear= 0.786), SGA (Pnonlinear= 0.156), and birthweight reduction (Pnonlinear= 0.104). Under the premise of causal association, we estimated 6.6% (95% CI: 5.7 to 7.5) of LBW, 10.1% (95% CI: 9.6 to 10.6) of SGA, and 18.8 g (95% CI: 17.9 to 19.7) of BLL could be attributable to maternal ozone exposure in Iran. Considerably greater risk and burden of ozone-related FGR were observed among younger, less-educated, and rural-dwelling mothers. Conclusions: Our study provided compelling evidence that maternal ozone exposure was associated with heightened FGR risk and burden, particularly among socioeconomically disadvantaged mothers. These findings underscored the urgent need for government to incorporate socioeconomic factors into future ozone-related health policies, not only to mitigate pollution, but also minimize inequality.

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.

Abstract The nexus between prenatal greenspace exposure and low birth weight (LBW) remains largely unstudied in low- and middle-income countries (LMICs). We investigated a nationwide retrospective cohort of 4,021,741 live births (263,728 LBW births) across 31 provinces in Iran during 2013–2018. Greenness exposure during pregnancy was assessed using satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). We estimated greenness-LBW associations using multiple logistic models, and quantified avoidable LBW cases under scenarios of improved greenspace through counterfactual analyses. Association analyses provide consistent evidence for approximately L-shaped exposure-response functions, linking 7.0–11.5% declines in the odds of LBW to each 0.1-unit rise in NDVI/EVI with multiple buffers. Assuming causality, 3931–5099 LBW births can be avoided by achieving greenness targets of mean NDVI/EVI, amounting to 4.4–5.6% of total LBW births in 2015. Our findings suggest potential health benefits of improved greenspace in lowering LBW risk and burden in LMICs.

Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent. Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries. Methods: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 μm (PM10), PM ≤ 2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from 620 cities in 36 countries in the period 1995–2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants. Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75th to the 99th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM10 was equal to 10 or 90 μg/m3, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 μg/m3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 μg/m3 increment in PM10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1st and 99th city-specific percentiles, respectively. Corresponding mortality estimate for O3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM2.5 and NO2. Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.

Summary: Background: Identifying how greenspace impacts the temperature-mortality relationship in urban environments is crucial, especially given climate change and rapid urbanization. However, the effect modification of greenspace on heat-related mortality has been typically focused on a localized area or single country. This study examined the heat-mortality relationship among different greenspace levels in a global setting. Methods: We collected daily ambient temperature and mortality data for 452 locations in 24 countries and used Enhanced Vegetation Index (EVI) as the greenspace measurement. We used distributed lag non-linear model to estimate the heat-mortality relationship in each city and the estimates were pooled adjusting for city-specific average temperature, city-specific temperature range, city-specific population density, and gross domestic product (GDP). The effect modification of greenspace was evaluated by comparing the heat-related mortality risk for different greenspace groups (low, medium, and high), which were divided into terciles among 452 locations. Findings: Cities with high greenspace value had the lowest heat-mortality relative risk of 1·19 (95% CI: 1·13, 1·25), while the heat-related relative risk was 1·46 (95% CI: 1·31, 1·62) for cities with low greenspace when comparing the 99th temperature and the minimum mortality temperature. A 20% increase of greenspace is associated with a 9·02% (95% CI: 8·88, 9·16) decrease in the heat-related attributable fraction, and if this association is causal (which is not within the scope of this study to assess), such a reduction could save approximately 933 excess deaths per year in 24 countries. Interpretation: Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change. Funding: This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research Council-UK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), Academy of Finland (Grant ID: 310372), European Union's Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University's NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033 The funders had no role in the design, data collection, analysis, interpretation of results, manuscript writing, or decision to publication.

Summary: Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000–19. Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000–19. Temperature variability was calculated as the SD of the average of the same and previous days’ minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901–2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2–4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7–5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3–10·4), followed by Europe (4·4%, 2·2–5·6) and Africa (3·3, 1·9–4·6). Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. Funding: Australian Research Council, Australian National Health & Medical Research Council.