Rainfall events and daily mortality across 645 global locations: two stage time series analysis.

OBJECTIVE: To examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality. DESIGN: Two stage time series analysis. SETTING: 645 locations across 34 countries or regions. POPULATION: Daily mortality data, comprising a total of 109 954 744 all cause, 31 164 161 cardiovascular, and 11 817 278 respiratory deaths from 1980 to 2020. MAIN OUTCOME MEASURE: Association between daily mortality and rainfall events with return periods (the expected average time between occurrences of an extreme event of a certain magnitude) of one year, two years, and five years, with a 14 day lag period. A continuous relative intensity index was used to generate intensity-response curves to estimate mortality risks at a global scale. RESULTS: During the study period, a total of 50 913 rainfall events with a one year return period, 8362 events with a two year return period, and 3301 events with a five year return period were identified. A day of extreme rainfall with a five year return period was significantly associated with increased daily all cause, cardiovascular, and respiratory mortality, with cumulative relative risks across 0-14 lag days of 1.08 (95% confidence interval 1.05 to 1.11), 1.05 (1.02 to 1.08), and 1.29 (1.19 to 1.39), respectively. Rainfall events with a two year return period were associated with respiratory mortality only, whereas no significant associations were found for events with a one year return period. Non-linear analysis revealed protective effects (relative risk <1) with moderate-heavy rainfall events, shifting to adverse effects (relative risk >1) with extreme intensities. Additionally, mortality risks from extreme rainfall events appeared to be modified by climate type, baseline variability in rainfall, and vegetation coverage, whereas the moderating effects of population density and income level were not significant. Locations with lower variability of baseline rainfall or scarce vegetation coverage showed higher risks. CONCLUSION: Daily rainfall intensity is associated with varying health effects, with extreme events linked to an increasing relative risk for all cause, cardiovascular, and respiratory mortality. The observed associations varied with local climate and urban infrastructure.

Association of holidays and the day of the week with suicide risk: multicounty, two stage, time series study.

OBJECTIVES: To assess the short term temporal variations in suicide risk related to the day of the week and national holidays in multiple countries. DESIGN: Multicountry, two stage, time series design. SETTING: Data from 740 locations in 26 countries and territories, with overlapping periods between 1971 and 2019, collected from the Multi-city Multi-country Collaborative Research Network database. PARTICIPANTS: All suicides were registered in these locations during the study period (overall 1 701 286 cases). MAIN OUTCOME MEASURES: Daily suicide mortality. RESULTS: Mondays had peak suicide risk during weekdays (Monday-Friday) across all countries, with relative risks (reference: Wednesday) ranging from 1.02 (95% confidence interval (CI) 0.95 to 1.10) in Costa Rica to 1.17 (1.09 to 1.25) in Chile. Suicide risks were lowest on Saturdays or Sundays in many countries in North America, Asia, and Europe. However, the risk increased during weekends in South and Central American countries, Finland, and South Africa. Additionally, evidence suggested strong increases in suicide risk on New Year's day in most countries with relative risks ranging from 0.93 (95% CI 0.75 to 1.14) in Japan to 1.93 (1.31 to 2.85) in Chile, whereas the evidence on Christmas day was weak. Suicide risk was associated with a weak decrease on other national holidays, except for Central and South American countries, where the risk generally increased one or two days after these holidays. CONCLUSIONS: Suicide risk was highest on Mondays and increased on New Year's day in most countries. However, the risk of suicide on weekends and Christmas varied by country and territory. The results of this study can help to better understand the short term variations in suicide risks and define suicide prevention action plans and awareness campaigns.

Mortality burden and economic loss attributable to cold and heat in Central and South America.

Background: We quantify the mortality burden and economic loss attributable to nonoptimal temperatures for cold and heat in the Central and South American countries in the Multi-City Multi-Country (MCC) Collaborative Research Network. Methods: We collected data for 66 locations from 13 countries in Central and South America to estimate location-specific temperature-mortality associations using time-series regression with distributed lag nonlinear models. We calculated the attributable deaths for cold and heat as the 2.5th and 97.5th temperature percentiles, above and below the minimum mortality temperature, and used the value of a life year to estimate the economic loss of delayed deaths. Results: The mortality impact of cold varied widely by country, from 9.64% in Uruguay to 0.22% in Costa Rica. The heat-attributable fraction for mortality ranged from 1.41% in Paraguay to 0.01% in Ecuador. Locations in arid and temperate climatic zones showed higher cold-related mortality (5.10% and 5.29%, respectively) than those in tropical climates (1.71%). Arid and temperate climatic zones saw lower heat-attributable fractions (0.69% and 0.58%) than arid climatic zones (0.92%). Exposure to cold led to an annual economic loss of $0.6 million in Costa Rica to $472.2 million in Argentina. In comparison, heat resulted in economic losses of $0.05 million in Ecuador to $90.6 million in Brazil. Conclusion: Most of the mortality burden for Central and South American countries is caused by cold compared to heat, generating annual economic losses of $2.1 billion and $290.7 million, respectively. Public health policies and adaptation measures in the region should account for the health effects associated with nonoptimal temperatures.

Temperature-mortality associations by age and cause: a multi-country multi-city study.

Background: Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries. Methods: We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults. Results: We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages. Conclusions: There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults.

Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

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.

Nitrogen dioxide exposure, attentional function, and working memory in children from 4 to 8 years: Periods of susceptibility from pregnancy to childhood.

BACKGROUND: Air pollution exposure during pregnancy and childhood has been linked to executive function impairment in children, however, very few studies have assessed these two exposure periods jointly to identify susceptible periods of exposure. We sought to identify potential periods of susceptibility of nitrogen dioxide (NO2) exposure from conception to childhood on attentional function and working memory in school-aged children. METHODS: Within the Spanish INMA Project, we estimated residential daily NO2 exposures during pregnancy and up to 6 years of childhood using land use regression models (n = 1,703). We assessed attentional function at 4-6 years and 6-8 years, using the Conners Kiddie Continuous Performance Test and the Attention Network Test, respectively, and working memory at 6-8 years, using the N-back task. We used distributed lag non-linear models to assess the periods of susceptibility of each outcome, adjusting for potential confounders and correcting for multiple testing. We also stratified all models by sex. RESULTS: Higher exposure to NO2 between 1.3 and 1.6 years of age was associated with higher hit reaction time standard error (HRT-SE) (0.14 ms (95 % CI 0.05; 0.22) per 10 µg/m3 increase in NO2) and between 1.5 and 2.2 years of age with more omission errors (1.02 (95 % CI 1.01; 1.03) of the attentional function test at 4-6 years. Higher exposure to NO2 between 0.3 and 2.2 years was associated with higher HRT-SE (10.61 ms (95 % CI 3.46; 17.75) at 6-8 years only in boys. We found no associations between exposure to NO2 and working memory at 6-8 years. CONCLUSION: Our findings suggest that NO2 exposure during the first two years of life is associated with poorer attentional function in children from 4 to 8 years of age, especially in boys. These findings highlight the importance of exploring long-term effects of traffic-related air pollution exposure in older age groups.

Ambient air temperature exposure and foetal size and growth in three European birth cohorts.

INTRODUCTION: Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. METHODS: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers' residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). RESULTS: Weekly temperatures ranged from -5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1-28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: -1.6 SDS [95 %CI -2.0; -0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1-7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: -0.1 cm/week [-0.2; -0.04]), with a susceptibility period from weeks 4-12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. CONCLUSIONS: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.

Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.

OBJECTIVE: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort. METHODS: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories. RESULTS: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth. CONCLUSION: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

Seasonality of mortality under climate change: a multicountry projection study.

BACKGROUND: Climate change can directly impact temperature-related excess deaths and might subsequently change the seasonal variation in mortality. In this study, we aimed to provide a systematic and comprehensive assessment of potential future changes in the seasonal variation, or seasonality, of mortality across different climate zones. METHODS: In this modelling study, we collected daily time series of mean temperature and mortality (all causes or non-external causes only) via the Multi-Country Multi-City Collaborative (MCC) Research Network. These data were collected during overlapping periods, spanning from Jan 1, 1969 to Dec 31, 2020. We projected daily mortality from Jan 1, 2000 to Dec 31, 2099, under four climate change scenarios corresponding to increasing emissions (Shared Socioeconomic Pathways [SSP] scenarios SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). We compared the seasonality in projected mortality between decades by its shape, timings (the day-of-year) of minimum (trough) and maximum (peak) mortality, and sizes (peak-to-trough ratio and attributable fraction). Attributable fraction was used to measure the burden of seasonality of mortality. The results were summarised by climate zones. FINDINGS: The MCC dataset included 126 809 537 deaths from 707 locations within 43 countries or areas. After excluding the only two polar locations (both high-altitude locations in Peru) from climatic zone assessments, we analysed 126 766 164 deaths in 705 locations aggregated in four climate zones (tropical, arid, temperate, and continental). From the 2000s to the 2090s, our projections showed an increase in mortality during the warm seasons and a decrease in mortality during the cold seasons, albeit with mortality remaining high during the cold seasons, under all four SSP scenarios in the arid, temperate, and continental zones. The magnitude of this changing pattern was more pronounced under the high-emission scenarios (SSP3-7.0 and SSP5-8.5), substantially altering the shape of seasonality of mortality and, under the highest emission scenario (SSP5-8.5), shifting the mortality peak from cold seasons to warm seasons in arid, temperate, and continental zones, and increasing the size of seasonality in all zones except the arid zone by the end of the century. In the 2090s compared with the 2000s, the change in peak-to-trough ratio (relative scale) ranged from 0·96 to 1·11, and the change in attributable fraction ranged from 0·002% to 0·06% under the SSP5-8.5 (highest emission) scenario. INTERPRETATION: A warming climate can substantially change the seasonality of mortality in the future. Our projections suggest that health-care systems should consider preparing for a potentially increased demand during warm seasons and sustained high demand during cold seasons, particularly in regions characterised by arid, temperate, and continental climates. FUNDING: The Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency, provided by the Ministry of the Environment of Japan.

Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement.

Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

Relation of prenatal and postnatal PM2.5 exposure with cognitive and motor function among preschool-aged children.

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM2.5 on each MSCA outcome. Effect estimates were calculated per 5 µg/m3 increase in PM2.5 and aggregated across adjacent statistically significant lags using cumulative ß (ßcum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM2.5 with fetal growth and child sex. We did not observe associations of PM2.5 exposure with lower GCI scores. We found a period of susceptibility to PM2.5 on fine motor scores in gestational weeks 1-9 (ßcum = -2.55, 95%CrI = -3.53,-1.56) and on gross motor scores in weeks 7-17 (ßcum = -2.27,95%CrI = -3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (ßcum = -0.17, 95%CrI = -0.26,-0.09). In the postnatal period (from age 0.5-1.2 years), we observed a window of susceptibility to PM2.5 on lower perceptual-performance (ß = -2.42, 95%CrI = -3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM2.5 for children's perceptual-performance.

Susceptible windows of prenatal and postnatal fine particulate matter exposures and attention-deficit hyperactivity disorder symptoms in early childhood.

Few prior studies have explored windows of susceptibility to fine particulate matter (PM2.5) in both the prenatal and postnatal periods and children's attention-deficit/hyperactivity disorder (ADHD) symptoms. We analyzed data from 1416 mother-child pairs from the Spanish INMA (INfancia y Medio Ambiente) Study (2003-2008). Around 5 years of age, teachers reported the number of ADHD symptoms (i.e., inattention, hyperactivity/impulsivity) using the ADHD Diagnostic and Statistical Manual of Mental Disorders. Around 7 years of age, parents completed the Conners' Parent Rating Scales, from which we evaluated the ADHD index, cognitive problems/inattention, hyperactivity, and oppositional subscales, reported as age- and sex-standardized T-scores. Daily residential PM2.5 exposures were estimated using a two-stage random forest model with temporal back-extrapolation and averaged over 1-week periods in the prenatal period and 4-week periods in the postnatal period. We applied distributed lag non-linear models within the Bayesian hierarchical model framework to identify susceptible windows of prenatal or postnatal exposure to PM2.5 (per 5-µg/m3) for ADHD symptoms. Models were adjusted for relevant covariates, and cumulative effects were reported by aggregating risk ratios (RRcum) or effect estimates (ßcum) across adjacent susceptible windows. A similar susceptible period of exposure to PM2.5 (1.2-2.9 and 0.9-2.7 years of age, respectively) was identified for hyperactivity/impulsivity symptoms assessed ~5 years (RRcum = 2.72, 95% credible interval [CrI] = 1.98, 3.74) and increased hyperactivity subscale ~7 years (ßcum = 3.70, 95% CrI = 2.36, 5.03). We observed a susceptibility period to PM2.5 on risk of hyperactivity/impulsivity symptoms ~5 years in gestational weeks 16-22 (RRcum = 1.36, 95% CrI = 1.22, 1.52). No associations between PM2.5 exposure and other ADHD symptoms were observed. We report consistent evidence of toddlerhood as a susceptible window of PM2.5 exposure for hyperactivity in young children. Although mid-pregnancy was identified as a susceptible period of exposure on hyperactivity symptoms in preschool-aged children, this association was not observed at the time children were school-aged.

Joint effect of heat and air pollution on mortality in 620 cities of 36 countries.

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.

Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis.

OBJECTIVE: To investigate potential interactive effects of fine particulate matter (PM2.5) and ozone (O3) on daily mortality at global level. DESIGN: Two stage time series analysis. SETTING: 372 cities across 19 countries and regions. POPULATION: Daily counts of deaths from all causes, cardiovascular disease, and respiratory disease. MAIN OUTCOME MEASURE: Daily mortality data during 1994-2020. Stratified analyses by co-pollutant exposures and synergy index (>1 denotes the combined effect of pollutants is greater than individual effects) were applied to explore the interaction between PM2.5 and O3 in association with mortality. RESULTS: During the study period across the 372 cities, 19.3 million deaths were attributable to all causes, 5.3 million to cardiovascular disease, and 1.9 million to respiratory disease. The risk of total mortality for a 10 µg/m3 increment in PM2.5 (lag 0-1 days) ranged from 0.47% (95% confidence interval 0.26% to 0.67%) to 1.25% (1.02% to 1.48%) from the lowest to highest fourths of O3 concentration; and for a 10 µg/m3 increase in O3 ranged from 0.04% (-0.09% to 0.16%) to 0.29% (0.18% to 0.39%) from the lowest to highest fourths of PM2.5 concentration, with significant differences between strata (P for interaction <0.001). A significant synergistic interaction was also identified between PM2.5 and O3 for total mortality, with a synergy index of 1.93 (95% confidence interval 1.47 to 3.34). Subgroup analyses showed that interactions between PM2.5 and O3 on all three mortality endpoints were more prominent in high latitude regions and during cold seasons. CONCLUSION: The findings of this study suggest a synergistic effect of PM2.5 and O3 on total, cardiovascular, and respiratory mortality, indicating the benefit of coordinated control strategies for both pollutants.

Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study.

BACKGROUND: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. METHODS: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5°â€ˆ× 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. FINDINGS: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. INTERPRETATION: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate. FUNDING: Australian Research Council and Australian National Health and Medical Research Council.

Prenatal Vitamin D Levels Influence Growth and Body Composition until 11 Years in Boys.

BACKGROUND: Gestational vitamin D levels may influence offspring growth and modulate adipogenesis. Findings from prospective studies are inconsistent, and few have evaluated the persistence of these associations into late childhood. OBJECTIVE: To examine the association between prenatal vitamin D levels and growth and adiposity in late childhood. METHODS: We included 2027 mother-child pairs from the INMA birth cohort. 25-hydroxyvitamin D3 (vitamin D3) levels were measured in serum at 13 weeks of pregnancy. Sex- and age-specific body mass index z-scores were calculated at 7 and 11 years, overweight was defined as z-score ≥ 85th percentile, and body fat mass was measured at 11 years. Z-score body mass index (zBMI) trajectories from birth to 11 years were identified using latent class growth analysis. RESULTS: The prevalence of vitamin D3 deficiency (<20 ng/mL) was 17.5%, and around 40% of the children had overweight at both ages. Associations between vitamin D levels and outcomes differed by sex. In boys, maternal vitamin D3 deficient status was associated with higher zBMI, higher fat mass percentage, higher odds of being overweight, and with an increased risk of belonging to lower birth size followed by accelerated BMI gain trajectory. In girls no associations were observed. CONCLUSION: Our results support a sex-specific programming effect of early pregnancy vitamin D3 levels on offspring body composition into late childhood observed in boys.

Correction: Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

Heat-related cardiorespiratory mortality: Effect modification by air pollution across 482 cities from 24 countries.

BACKGROUND: Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. OBJECTIVES: We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries. METHODS: Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model. RESULTS: Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6-7.7), 11.3% (95%CI 11.2-11.3), and 14.3% (95% CI 14.1-14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5-1.6), 5.1 (95%CI 5.1-5.2), and 8.7 (95%CI 8.7-8.8) at low, medium, and high levels of O3, respectively. DISCUSSION: We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development.