Health Impacts of Long-Term NO2 Exposure and Inequalities among the Chinese Population from 2013 to 2020.

Nitrogen dioxide (NO2) is associated with mortality and many other adverse health outcomes. In 2021, the World Health Organization established a new NO2 air quality guideline (AQG) (annual average <10 µg/m3). However, the burden of diseases attributable to long-term NO2 exposure above the AQG is unknown in China. Nitrogen oxide is a major air pollutant in populous cities, which are disproportionately impacted by NO2; this represents a form of environmental inequality. We conducted a nationwide risk assessment of premature deaths attributable to long-term NO2 exposure from 2013 to 2020 based on the exposure-response relationship, high-resolution annual NO2 concentrations, and gridded population data (considering sex, age, and residence [urban vs rural]). We calculated health metrics including attributable deaths, years of life lost (YLL), and loss of life expectancy (LLE). Inequality in the distribution of attributable deaths and YLLs was evaluated by the Lorenz curve and Gini index. According to the health impact assessments, in 2013, long-term NO2 exposure contributed to 315,847 (95% confidence interval [CI]: 306,709-319,269) premature deaths, 7.90 (7.68-7.99) million YLLs, and an LLE of 0.51 (0.50-0.52) years. The high-risk subgroup (top 20%) accounted for 85.7% of all NO2-related deaths and 85.2% of YLLs, resulting in Gini index values of 0.81 and 0.67, respectively. From 2013 to 2020, the estimated health impact from NO2 exposure was significantly reduced, but inequality displayed a slightly increasing trend. Our study revealed a considerable burden of NO2-related deaths in China, which were disproportionally frequent in a small high-risk subgroup. Future clean air initiatives should focus not only on reducing the average level of NO2 exposure but also minimizing inequality.

The association of birthweight with fine particle exposure is modifiable by source sector: Findings from a cross-sectional study of 17 low- and middle-income countries.

BACKGROUND: Low birthweight attributable to fine particulate matter (PM2.5) exposure is a global issue affecting infant health, especially in low- and middle-income countries (LMICs). However, large-population studies of multiple LMICs are lacking, and little is known about whether the source of PM2.5 is a determinant of the toxic effect on birthweight. OBJECTIVE: We examined the effect on birthweight of long-term exposure to PM2.5 from different sources in LMICs. METHODS: The birthweights of 53,449 infants born between September 16, 2017 and September 15, 2018 in 17 LMICs were collected from demographic and health surveys. Long-term exposure to PM2.5 in 2017 produced by 20 different sources was estimated by combining chemical transport model simulations with satellite-based concentrations of total mass. Generalized linear regression models were used to investigate the associations between birthweight and each source-specific PM2.5 exposure. A multiple-pollutant model with a ridge penalty on the coefficients of all 20-source-specific components was employed to develop a joint exposure-response function (JERF) of the PM2.5 mixtures. The estimated JERF was then used to quantify the global burden of birthweight reduction attributable to PM2.5 mixtures and to PM2.5 from specific sources. RESULTS: The fully adjusted single-pollutant model indicated that exposure to a 10 µg/m3 increase in total PM2.5 was significantly associated with a -6.6 g (95% CI -11.0 to -2.3) reduction in birthweight. In single- and multiple-pollutant models, significant birthweight changes were associated with exposure to PM2.5 produced by international shipping (SHP), solvents (SLV), agricultural waste burning (GFEDagburn), road transportation (ROAD), waste handling and disposal (WST), and windblown dust (WDUST). Based on the global average exposure to PM2.5 mixtures, the JERF showed that the overall change in birthweight could mostly be attributed to PM2.5 produced by ROAD (-37.7 g [95% CI -49.2 to -24.4] for a global average exposure of 2.2 µg/m3), followed by WST (-27.5 g [95% CI -42.6 to -10.7] for a 1.6-µg/m3 exposure), WDUST (-19.5 g [95% CI -26.7 to -12.6] for a 8.6-µg/m3 exposure), and SHP (-19.0 g [95% CI -32.3 to -5.7] for a 0.2-µg/m3 exposure), which, with the exception of WDUST, are anthropogenic sources. The changes in birthweight varied geographically and were co-determined by the concentration as well as the source profile of the PM2.5 mixture. CONCLUSION: PM2.5 exposure is associated with a reduction in birthweight, but our study shows that the magnitude of the association differs depending on the PM2.5 source. A source-targeted emission-control strategy that considers local features is therefore critical to maximize the health benefits of air quality improvement, especially with respect to promoting maternal and child health.

Gestational exposure to landscape fire increases under-5 child death via reducing birthweight: A risk assessment based on mediation analysis in low- and middle-income countries.

BACKGROUND: Exposure to landscape fire smoke (LFS) is linked to child mortality and birthweight. It is unknown whether gestational exposure to LFS affects child survival rate. We aimed to link under-five death (U5D) to gestational LFS exposure by performing a causal mediation analysis based on birthweight. METHOD: We conducted a sibling-matched case-control study of children under 5 years of age who were affiliated with the same mothers from Demographic and Health Surveys in 54 low- and middle-income countries, during the period from 2000 to 2014. LFS exposure was quantified as the surface concentration of fine particulate matter (PM2.5) attributable to landscape fires, estimated using a global atmospheric model. Three pairwise associations between fire-sourced PM2.5, birthweight, and U5D were assessed using fixed-effects regressions. We used a bootstrap-based mediation test of regression coefficients to examine whether the LFS-birthweight-U5D pathway was statistically significant. We also conducted three pairwise exposure-response functions using nonlinear models and used them to estimate the pathway-specific disease burden from 2000 to 2014. RESULTS: After adjustments for multiple confounders, each 1-µg/m3 increase in gestational exposure to fire-sourced PM2.5 was associated with a reduction of 2.179 (95% confidence interval [CI]: -3.777, -0.580) g in birthweight. Each 1-g birthweight reduction was associated with a 0.072% (95% CI: 0.065%, 0.078%) increase in U5D. Furthermore, each increase in exposure to fire-sourced PM2.5 was associated with a 2.853% (95% CI: 0.835%, 4.911%) increase in U5D; 7.294% (95% CI: 0.710%, 24.254%) of the linkage was explained by LFS-attributable birthweight reduction. Based on the estimated exposure-response functions, from 2000 to 2014, global exposure to fire-sourced PM2.5 contributed a mean birthweight reduction of 10.30 (95% CI: 2.93, 19.47) g, contributing to 60,350 (18,111, 106,619) premature U5Ds annually. CONCLUSION: In low- and middle-income countries, gestational exposure to LFS can increase mortality during infancy; appropriate interventions are needed to promote health in childhood.

Greenspace exposure and poststroke disability: A nationwide longitudinal study.

INTRODUCTION: Exposure to greenspace has been reported to reduce stroke mortality, but there is a lack of evidence regarding poststroke disability. This study aimed to investigate the association between long-term greenspace exposure and the risk of poststroke disability. METHODS: Based on the China National Stroke Screening Survey from 2013 to 2019, a total of 65,892 visits from 28,085 stroke survivors with ≥ 2 visits were included in this longitudinal study. Long-term greenspace exposure was assessed by a 3-year average of the Normalized Difference Vegetation Index (NDVI) and the proportion of green land cover according to participants' residential communities. Poststroke functional status was assessed with the modified Ranking Score (mRS) at each visit; a cutoff score > 2 indicated disability. Fixed effects regressions were used to examine the association of greenspace exposure with continuous mRS scores or binary indicators for disability. RESULTS: The annual mean NDVI value was 0.369 (standard deviation = 0.120) for all visits among stroke survivors. With full adjustments, each 0.05 increase in NDVI was associated with a 0.056-unit (95 % confidence interval (CI): 0.034, 0.079) decrease in the mRS score and a 46.6 % (95 % CI: 10.0 %, 68.3 %) lower risk of poststroke disability. An L-shaped curve was observed for the nonlinear associations between NDVI and mRS score or disability. Additionally, each 1 % increase in grasslands, savannas, forest, and croplands was associated with 0.008- (95 % CI: 0.002, 0.014), 0.003- (95 % CI: 0.001, 0.005), 0.001- (95 % CI: -0.015, 0.018), and 0.002-unit (95 % CI: -0.003, 0.007) decreases in the mRS score, respectively. CONCLUSIONS: Increasing greenspace was inversely associated with mRS score. Greenspace planning can be a potential intervention to prevent poststroke disability.

Association of maternal exposure to ambient particulate pollution with incident spontaneous pregnancy loss.

BACKGROUND: Maternal exposure to ambient fine particulate matter (PM2.5) is a potential risk factor for pregnancy loss, but the extant findings are inconsistent. One reason for the inconsistency is the difficulty of distinguishing spontaneous from induced pregnancy losses, particularly in countries with planning policies. OBJECTIVE: To examine the association between maternal PM2.5 exposure and spontaneous incident pregnancy loss in China. METHODS: A total of 18,513 women of reproductive age was recruited from Jiangsu Province, China, in 2007. Among them, 2451 women reported 2613 valid records of incident pregnancies from 2007 to 2010. We used Cox regression to link the outcomes (live birth, spontaneous pregnancy loss, or induced abortion) of those incident pregnancies with maternal PM2.5 exposures, assessed using well-developed estimates of historical concentrations at the county level. RESULTS: Among the 2613 incident pregnancies, 69 spontaneous pregnancy losses, 596 induced abortions, and 1948 live births occurred. According to the adjusted model, each 10-µg/m3 increment in the average PM2.5 concentration during pregnancy was associated with a 43.3% (95% confidence interval, 6.6-92.5%) increased probability of spontaneous pregnancy loss. Advanced maternal age, a potential competing risk factor, weakened the association between PM2.5 and spontaneous pregnancy loss. The association was nonsignificant for unintended pregnancies. CONCLUSION: Maternal PM2.5 exposure was associated significantly with incident spontaneous pregnancy loss. Our findings provide insight into the harmful effect of air pollution on human reproduction.

A novel strategy of identifying circRNA biomarkers in cardiovascular disease by meta-analysis.

Circular RNAs (circRNAs) are stable and abundantly expressed in vivo but are abnormally expressed in several diseases. This study aimed to identify circRNAs acting as potential biomarkers for cardiovascular disease (CVD). Research were retrieved from the articles published by September 2018 in eight databases to compare circRNA expression profiles between CVD and non-CVD in human and animal models. Meta-analysis under a random effects model was conducted. Subgroup analysis of tissue, species, and disease-specific circRNAs was examined. Sensitivity analysis was performed to explain the uncertainty among all studies. Diagnostic accuracy of circRNAs in CVD was analyzed to testify the discriminative ability. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted. Among 6,284 differentially expressed circRNAs from 32 original studies, only 322 circRNAs were reported in three or more studies. The meta-analysis identified 63 significantly dysregulated circRNAs, 44 upregulated and 19 downregulated. Among the tissue-specific or disease-specific circRNAs identified in the subgroup analysis, two circRNAs (circCDKN2BAS and circMACF1) showed the potential to be circulating biomarkers for CVD. Sensitivity analysis demonstrated 69% of circRNAs were in conformity with the overall analysis. The pooled diagnostic odds ratio was 2.94 (95% confidence interval [CI], 2.35-3.58), and the overall area under the curve value was 0.86 (95% CI, 0.83-0.89). GO and KEGG enrichment analyses indicated that the target genes of circRNAs participate in cardiogenesis-related processes and pathways. This study demonstrates circRNAs have a high diagnostic value as potential biomarkers for CVD, and two candidate circRNAs, circCDKN2BAS and circMACF1, are potential circulating biomarkers for CVD diagnosis and treatment.

Reduced human fecundity attributable to ambient fine particles in low- and middle-income countries.

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) has been associated with reduced human fecundity. However, the attributable burden has not been estimated for low- and middle-income countries (LMICs), where the exposure-response function between PM2.5 and the infertility rate has been insufficiently studied. OBJECTIVE: This study examined the associations between long-term exposure to PM2.5 and human fecundity indicators, namely the expected time to pregnancy (TTP) and 12-month infertility rate (IR), and then estimated PM2.5-attributable burden of infertility in LMICs. METHODS: We analyzed 164,593 eligible women from 100 Demographic and Health Surveys conducted in 49 LMICs between 1999 and 2021. We assessed PM2.5 exposures during the 12 months before a pregnancy attempt using the global satellite-derived PM2.5 estimates produced by Atmospheric Composition Analysis Group (ACAG). First, we created a series of pseudo-populations with balanced covariates, given different levels of PM2.5 exposure, using a matching approach based on the generalized propensity score. For each pseudo-population, we used 2-stage generalized Gamma models to derive TTP or IR from the probability distribution of the questionnaire-based duration time for the pregnancy attempt before the interview. Second, we used spline regressions to generate nonlinear PM2.5 exposure-response functions for each of the two fecundity indicators. Finally, we applied the exposure-response functions to estimate number of infertile couples attributable to PM2.5 exposure in 118 LMICs. RESULTS: Based on the Gamma models, each 10 µg/m3 increment in PM2.5 exposure was associated with a TTP increase by 1.7 % (95 % confidence interval [CI]: -2.3 %-6.0 %) and an IR increase by 2.3 % (95 %CI: 0.6 %-3.9 %). The nonlinear exposure-response function suggested a robust effect of an increased IR for high-concentration PM2.5 exposure (>75 µg/m3). Based on the PM2.5-IR function, across the 118 LMICs, the number of infertile couples attributable to PM2.5 exposure exceeding 35 µg/m3 (the first-stage interim target recommended by the World Health Organization global air quality guidelines) was 0.66 million (95 %CI: 0.061-1.43), accounting for 2.25 % (95 %CI: 0.20 %-4.84 %) of all couples affected by infertility. Among the 0.66 million, 66.5 % were within the top 10 % high-exposure infertile couples, mainly from South Asia, East Asia, and West Africa. CONCLUSION: PM2.5 contributes significantly to human infertility in places with high levels of air pollution. PM2.5-pollution control is imperative to protect human fecundity in LMICs.

Estimating the exposure-response function between long-term ozone exposure and under-5 mortality in 55 low-income and middle-income countries: a retrospective, multicentre, epidemiological study.

BACKGROUND: In 2021, WHO suggested new target concentration limits for long-term exposure to ambient ozone. However, the harmful effects of ozone on vulnerable children have not been sufficiently studied. We aimed to evaluate the association between long-term ozone exposure and mortality in children younger than 5 years (hereafter denoted under-5 mortality) in low-income and middle-income countries (LMICs) and to estimate this mortality burden for 97 LMICs. METHODS: By combining information from 128 Demographic and Health Surveys, we evaluated the association between the survival status of more than 1·2 million children younger than 5 years from 2457 sampling strata in 55 LMICs and the average peak-season ozone concentration during the life course, using a fixed-effects Cox model. A non-linear exposure-response function was developed by integrating the marginal effects of within-strata variation in exposure. We extrapolated the function obtained from the 55 LMICs to estimate the under-5 mortality burden attributable to ozone exposure in 97 LMICs, in which more than 95% of global deaths in this age group occur. FINDINGS: The fixed-effects model showed a robust association between ozone and under-5 mortality. According to the fully adjusted linear model, an increment of 10 ppb in the life-course average peak-season ozone concentration was associated with a 6·4% (95% CI 2·4-10·7) increase in the risk of under-5 mortality. The non-linear exposure-response function showed a sublinear curvature with a threshold, suggesting that the effect of ozone exposure was non-significant at concentrations lower than the first-stage interim target (100 µg/m3) recommended by WHO. Using this function, we estimate that, in 2010, long-term ozone exposure contributed to 153 361 (95% CI 17 077-276 768; 2·3% [0·3-4·1]) deaths of children younger than 5 years in 97 LMICs, which is equivalent to 56·8% of all ozone-related deaths in adults (269 785) in these countries. From 2003 to 2017, the ozone-related under-5 mortality burden decreased in most of the 97 LMICs. INTERPRETATION: Long-term exposure to ozone concentrations higher than the WHO first-stage interim target is a risk factor for under-5 mortality, and ozone exposure contributes substantially to mortality in this age group in LMICs. Increased efforts should be made to control ambient ozone pollution as this will lead to positive health benefits. FUNDING: Ministry of Science and Technology of the People's Republic of China and China National Natural Science Foundation.

Stillbirths attributable to open fires and their geographic disparities in non-Western countries.

Due to global warming, an increased number of open fires is becoming a major contributor to PM2.5 pollution and thus a threat to public health. However, the burden of stillbirths attributable to fire-sourced PM2.5 is unknown. In low- and middle-income countries (LMICs), there is a co-occurrence of high baseline stillbirth rates and frequent firestorms, which may lead to a geographic disparity. Across 54 LMICs, we conducted a self-matched case-control study, making stillbirths comparable to the corresponding livebirths in terms of time-invariant characteristics (e.g., genetics) and duration of gestational exposure. We established a joint-exposure-response function (JERF) by simultaneously associating stillbirth with fire- and non-fire-sourced PM2.5 concentrations, which were estimated by fusing multi-source data, such as chemical transport model simulations and satellite observations. During 2000-2014, 35,590 pregnancies were selected from multiple Demographic and Health Surveys. In each mother, a case of stillbirth was compared to her livebirth(s) based on gestational exposure to fire-sourced PM2.5. We further applied the JERF to assess stillbirths attributable to fire-sourced PM2.5 in 136 non-Western countries. The disparity was evaluated using the Gini index. The risk of stillbirth increased by 17.4% (95% confidence interval [CI]: 1.6-35.7%) per 10 µg/m3 increase in fire-sourced PM2.5. In 2014, referring to a minimum-risk exposure level of 10 µg/m3, total and fire-sourced PM2.5 contributed to 922,860 (95% CI: 578,451-1,183,720) and 49,951 (95% CI: 3,634-92,629) stillbirths, of which 10% were clustered within the 6.4% and 0.6% highest-exposure pregnancies, respectively. The Gini index of stillbirths attributable to fire-sourced PM2.5 was 0.65, much higher than for total PM2.5 (0.28). Protecting pregnant women against PM2.5 exposure during wildfires is critical to avoid stillbirths, as the burden of fire-associated stillbirths leads to a geographic disparity in maternal health.

Long-term exposure to the components of fine particulate matters and disability after stroke: Findings from the China National Stroke Screening Surveys.

BACKGROUND: Long-term exposure to ambient fine particulate matter (PM2.5) has been linked to an increased risk of stroke. However, the effect of long-term exposure to PM2.5 and its major components on the functional disability of stroke patients remains unclear. METHODS: Based on China National Stroke Screening Survey data obtained from 2013 to 2019, we conducted a national multicenter longitudinal study of the associations of long-term exposure to PM2.5 and its components with the risk of disability after stroke in China. Post-stroke disability was assessed using the modified Rankin scale (mRS), which ranges from 0 to 5, with higher scores indicating greater disability. Long-term exposure to PM2.5 and its five components [sulfate (SO42-), nitrate (NO3-), ammonium salt (NH4+), organic matter (OM), and black carbon (BC)] was determined based on average concentrations during the 3 years preceding mRS administration according to the geographic coordinates of residential communities, using state-of-the-art estimates from multiple sources. We used a fixed-effect model to evaluate the associations between mRS scores and PM2.5 exposure, with adjustment for multiple covariates. RESULTS: Every 10 µg/m3 increase in PM2.5 was associated with a 0.019 (95% confidence interval, 0.003, 0.036) increase in mRS score, but the effect was not significant after adjusting for all covariates [0.016 (95% CI, -0.003, 0.032)]. For PM2.5 components, each IQR (7.92 µg/m3) increment in OM exposure was associated significantly with 0.062 (95% CI, 0.013, 0.111) increment in the mRS score. A significant association was observed between SO42- exposure and the mRS score [0.057 (95% CI, 0.003, 0.112), per IQR: 6.28 µg/m3]. However, no significant association was found with BC, NO3-, or NH4+ exposure. Furthermore, the nonlinear curves were observed for the exposure-response relationship between PM2.5 exposure and the mRS score. CONCLUSION: Greater PM2.5 exposure increased the mRS score and was associated with post-stroke functional disability among stroke patients. However, different chemical components showed unequal neurotoxic effects, and long-term exposure to OM and SO42- may play a more important role. SYNOPSIS: This study reports fine particulate matter at higher concentrations damages the functional ability among specific stroke patients, and PM2.5 components have different neurotoxicities.

Landscape fire smoke enhances the association between fine particulate matter exposure and acute respiratory infection among children under 5 years of age: Findings of a case-crossover study for 48 low- and middle-income countries.

BACKGROUND: Fine particulate matter (PM2.5) produced by landscape fires is thought to be more toxic than that from non-fire sources. However, the effects of "fire-sourced" PM2.5 on acute respiratory infection (ARI) are unknown. METHODS: We combined Demographic and Health Survey (DHS) data from 48 countries with gridded global estimates of PM2.5 concentrations from 2003 to 2014. The proportions of fire-sourced PM2.5 were assessed by a chemical transport model using a variety of PM2.5 source data. We tested for associations between ARI and short-term exposure to fire- and "non-fire-sourced" PM2.5 using a bidirectional case-crossover analysis. The robustness and homogeneity of the associations were examined by sensitivity analyses. We also established a nonlinear exposure-response relationship between fire- and non-fire-sourced PM2.5 and ARI using a two-dimensional spline function. RESULTS: The study included 36,432 children under 5 years who reported ARI symptoms. Each 1 µg/m3 increment of fire-sourced PM2.5 was associated with a 3.2 % (95 % confidence interval [CI] 0.2, 6.2) increment in the risk of ARI. This effect was comparable to that of each ∼5 µg/m3 increment in PM2.5 from non-fire sources (3.1 %; 95 % CI 2.4, 3.7). The association between ARI and total PM2.5 concentration was significantly mediated by the proportion of fire-sourced particles. Nonlinear analysis showed that the risk of ARI was increased by both fire- and non-fire-sourced PM2.5, but especially by the former. CONCLUSIONS: PM2.5 produced by landscape fire was more strongly associated to ARI among children under 5 years than that from non-fire sources.

Estimating birthweight reduction attributable to maternal ozone exposure in low- and middle-income countries.

The effect of O3 on birthweight in low- and middle-income countries (LMICs) remains unknown. A multicenter epidemiological study was conducted to evaluate the association between maternal peak-season O3 exposure and birthweight, using 697,148 singleton newborns obtained in 54 LMICs between 2003 and 2019. We estimated the birthweight reduction attributable to peak-season O3 exposure in 123 LMICs based on a nonlinear exposure-response function (ERF). With every 10-part per billion increment in O3 concentration, we found a reduction in birthweight of 19.9 g [95% confidence interval (CI): 14.8 to 24.9 g]. The nonlinear ERF had a monotonic decreasing curve, and no safe O3 exposure threshold was identified. The mean reduction in birthweight reduction attributable to O3 across the 123 LMICs was 43.8 g (95% CI: 30.5 to 54.3 g) in 2019. The reduction in O3-related birthweight was greatest in countries in South Asia, the Middle East, and North Africa. Effective O3 pollution control policies have the potential to substantially improve infant health.

The PM2.5 concentration reduction improves survival rate of lung cancer in Beijing.

INTRODUCTION: Long-term exposure to ambient fine particulate matter (PM2.5) has been linked to increases in the incidence of lung cancer. However, more evidence is needed to conclude its effects on lung cancer survival. OBJECTIVES: The study aimed to explore the relationship between long-term PM2.5 exposure and lung cancer survival and evaluated the benefits of clean air actions in Beijing. METHODS: A whole-population cohort study was conducted on lung cancer patients diagnosed between 2001 and 2017. An atmospheric chemical transport model was used to estimate exposure under a counterfactual scenario without the policy and then quantified the effect of the policy. Cox regression models were used with the seasonality-adjusted PM2.5 as the main effect. RESULTS: A 10 µg/m3 increase in PM2.5 was estimated to be with a 6.5 % (95 % CI: 4.8 %, 8.2 %) increase in the mortality rates. The association was heterogeneous and modified by individual-level characteristics. The clean air actions were estimated to have prevented 3548 (95 % CI: 3280, 3825) premature deaths and to have prolonged survival time by 4.29 months (95 % CI: 0.01, 25.11). CONCLUSION: Our findings suggest that PM2.5 exposure lowers the survival rate for lung cancer. The clean air actions implemented in Beijing can protect lung cancer patients by increasing their survival time. SYNOPSIS: Long-term exposure to PM2.5 can lower lung patients' survival rates whereas the clean air actions in Beijing have prolonged these patients' survival time by reducing PM2.5 level.

Time-varying association between fetal death and gestational exposure to ambient fine particles: a nationwide epidemiological study of 49 million fetuses in the contiguous US from 1989 to 2004.

BACKGROUND: Gestational exposure to fine particulate matter (PM2.5) has been reported to be associated with an increased risk of fetal death in recent studies, but earlier studies in the past century have usually reported a non-significant association. As such, it remains unknown whether this adverse effect of PM2.5 exposure varies with time. METHODS: Nearly 49.2 million eligible birth and fetal death records from 1989 to 2004 were selected from the United States (US) birth and fetal death certificate datasets. For each record, the level of prenatal exposure to PM2.5 was taken as the average concentration in the mother's residential county during the entire gestational period, according to well-established estimates of monthly levels across the contiguous US. We first stratified the dataset by the month of the last menstrual period (LMP) and then independently evaluated the nationwide association between PM2.5 exposure and fetal death within each stratum using five typical logit models: unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models. Finally, we conducted a meta-analysis to pool estimated LMP-specific associations and explored how the overall association varied by LMP month. RESULTS: Different models showed temporal heterogeneity in the estimated association between PM2.5 exposure and fetal death. According to the meta-analysis, double robust model estimates were more homogeneous than the rest, and thus the model outcome was recognized as the main result. For each 1-µg/m3 increase in prenatal exposure to PM2.5, the pooled odds ratio (OR) of fetal death was estimated to be 1.08 [95% confidence interval (CI): 1.05, 1.10]. The LMP-specific ORs exhibited a slightly increasing trend and a significant seasonal pattern. Compared with the pooled OR among samples with the LMP in spring, the estimates for summer, fall and winter were higher by 11.1% (95% CI: 6.2%, 16.3%), 27.8% (95% CI: 22.1%, 33.8%) and 28.8% (95% CI: 23.7%, 34.1%), respectively. We also found that temporal patterns in the association between PM2.5 exposure and fetal death could be explained by several population-level indicators or modifiers (i.e. ethnicity, maternal age, gestational weight gain, previous pregnancy of abnormal termination and diabetes). CONCLUSIONS: Prenatal exposure to PM2.5 can increase the risk of fetal death. The effects of PM2.5 exposure may be modified by complex factors, which leads to a time-varying association.

Association Between Ambient Fine Particulate Matter and Physical Functioning in Middle-Aged and Older Chinese Adults: A Nationwide Longitudinal Study.

BACKGROUND: Exposure to air pollution is associated with several chronic diseases and subclinical processes that could subsequently contribute to physical disability. However, whether and to what extent air pollution exposure is associated with objective measures of physical functioning remains understudied. METHODS: We used longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) and included 10 823 participants who were surveyed at least twice. Annual average exposure to fine particulate matter (PM2.5) was assessed using a state-of-the-art estimator. Physical functioning was assessed with 4 objective tests covering hand-grip strength, balance, repeated chair stands, and gait speed. Mixed-effects models with participants as a random term were used to estimate associations with multiple adjustments. RESULTS: We found a significant and robust association between exposure to increased PM2.5 and the reduction in hand-grip strength and balance ability. Each 10 µg/m3 increase in annual averaged concentrations of PM2.5 was associated with a 220-g (95% confidence interval [CI]: 127, 312 g) reduction in hand-grip strength per 60 kg of body weight and a 5% risk (95% CI: 2, 7) of reduced balance ability. The estimated effect of each 10 µg/m3 increase in PM2.5 on hand-grip strength and balance ability was equivalent to the effect of aging (1.12 [95% CI: 0.76, 1.48] and 0.98 [95% CI: 0.50, 1.50] years, respectively). CONCLUSIONS: PM2.5 may be differentially associated with various dimensions of physical functioning. Improving air quality can prevent physical disability.

Estimation of stillbirths attributable to ambient fine particles in 137 countries.

Gestational exposure to ambient fine particles (PM2.5) increases the risk of stillbirth, but the related disease burden is unknown, particularly in low- and middle-income countries (LMICs). We combine state-of-the-art estimates on stillbirths, and multiple exposure-response functions obtained from previous meta-analyses or derived by a self-matched case-control study in 54 LMICs. 13,870 stillbirths and 32,449 livebirths are extracted from 113 geocoded surveys from the Demographic and Health Surveys. Each stillbirth is compared to livebirth(s) of the same mother using a conditional logit regression. We find that 10-µg/m3 increase of PM2.5 is associated with an 11.0% (95% confidence interval [CI] 6.4, 15.7) increase in the risk of stillbirth, and the association is significantly enhanced by maternal age. Based on age-specific nonlinear PM2.5-stillbirth curves, we evaluate the PM2.5-related stillbirths in 137 countries. In 2015, of 2.09 (95% CI: 1.98, 2.20) million stillbirths, 0.83 (0.54, 1.08) million or 39.7% (26.1, 50.8) are attributable to PM2.5 exposure exceeding the reference level of 10 µg/m3. In LMICs, preventing pregnant women from being exposed to PM2.5 can improve maternal health.

Association of PM 2.5 Reduction with Improved Kidney Function: A Nationwide Quasiexperiment among Chinese Adults.

Background. Increasing evidence from human studies has revealed the adverse impact of ambient fine particles (PM 2.5) on health outcomes related to metabolic disorders and distant organs. Whether exposure to ambient PM 2.5 leads to kidney impairment remains unclear. The rapid air quality improvement driven by the clean air actions in China since 2013 provides an opportunity for a quasiexperiment to investigate the beneficial effect of PM 2.5 reduction on kidney function.Methods. Based on two repeated nationwide surveys of the same population of 5115 adults in 2011 and 2015, we conducted a difference-in-difference study. Variations in long-term exposure to ambient PM 2.5 were associated with changes in kidney function biomarkers, including estimated glomerular filtration rate by serum creatinine (GFR scr) or cystatin C (GFR cys), blood urea nitrogen (BUN), and uric acid (UA).Results. For a 10 µg/m 3 reduction in PM 2.5, a significant improvement was observed for multiple kidney functional biomarkers, including GFR scr, BUN and UA, with a change of 0.42 (95% confidence interval [CI]: 0.06, 0.78) mL/min/1.73m 2, -0.38 (-0.64, -0.12) mg/dL, and -0.06 (-0.12, -0.00) mg/dL, respectively. A lower socioeconomic status, indicated by rural residence or low educational level, enhanced the adverse effect of PM 2.5 on kidney function.Conclusions. These results support a significant nephrotoxicity of PM 2.5 based on multiple serum biomarkers and indicate a beneficial effect of improved air quality on kidney function.

The effect of China's Clean Air Act on cognitive function in older adults: a population-based, quasi-experimental study.

BACKGROUND: Air pollution might accelerate cognitive ageing; it is unclear whether large-scale interventions, such as China's Clean Air Act (CCAA), can mitigate cognitive deterioration. We aimed to evaluate the effect of CCAA on changes in cognitive function in older adults. METHODS: In this population-based, quasi-experimental study, we did a difference-in-differences analysis of the data collected during the 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The study design used a counterfactual analysis feature by dividing CLHLS participants into two groups. The intervention group included participants who lived in areas where the provincial government set a target of reducing particulate matter (PM) by at least 5% annually from 2014 onward, whereas the control group consisted of individuals who lived in areas without a PM reduction target. Global cognitive function was measured using the Mini-Mental State Examination (MMSE). We used fixed-effects models to examine the between-group differences in MMSE score changes before and after CCAA implementation. We associated longitudinal changes in MMSE scores with changes in concentrations of PM with a diameter of less than 2·5 µm (PM2·5) concentration and other regulated pollutants. We used alternative models and sensitivity analyses to evaluate the robustness of the results from the main models. FINDINGS: 2812 individuals participated in the 2014 and 2018 surveys (mean age 81·0 years [SD 9·3] in 2014; 1408 [50·1%] female and 1404 [49·9%] male). 2251 (80·0%) were included in the intervention group and 561 (20·0%) in the control group. After controlling for potential confounders, the intervention group had a significantly smaller decline in MMSE scores from 2014 to 2018 compared with the control group: the mean between-group difference was 2·45 points (95% CI 1·32-3·57). Interquartile increases in PM2·5 were associated with a significant MMSE score decline of 0·83 points (95% CI 0·24-1·42); similarly, increases in SO2 were also associated with a significant MMSE score decline of 0·80 points (0·32-1·29). INTERPRETATION: Implementing stringent clean air policies might mitigate the risk of air pollutant-associated cognitive ageing in older people. FUNDING: National Natural Sciences Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation funded project, the Duke/Duke-National University of Singapore Collaboration Pilot Project, the National Institute on Aging and Peking University-Baidu Fund, Energy Foundation, and the Fundamental Research Funds for the Central Universities.

Long-Term Exposure to Ozone Increases Neurological Disability after Stroke: Findings from a Nationwide Longitudinal Study in China.

Exposure to ozone (O3) is associated with stroke incidence and mortality. However, whether long-term exposure to O3 is associated with post-stroke neurological disability remains unknown. This study investigated the relationship based on the longitudinal analysis of China National Stroke Screening Survey (CNSSS), which included 65,778 records of stroke patients. All of the analyzed patients were followed-up at least twice. Stroke disability was assessed using the modified Rankin scale (mRS). Long-term exposure was assessed by the peak-season or annual mean of maximum 8-h O3 concentrations for 365 days before the mRS measurement. We used fixed-effect models to evaluate the associations between O3 and mRS score, with adjustment for multiple confounders, and found a 10 µg/m3 increase in peak-season O3 concentration was associated with a 0.0186 (95% confidence interval [CI] 0.0115-0.0256) increment in the mRS score. The association was robust in various subpopulations. For secondary outcomes, for each 10 µg/m3 increment in peak-season O3, the odds ratio of an increased mRS score (vs. unchanged or decreased mRS score) increased by 23% (95% CI 9-37%). A nonlinear analysis showed a sublinear association between O3 exposure and risk for post-stroke disability. A saturation effect was observed at an O3 concentration of more than ~120 µg/m3. Our study adds to evidence that long-term exposure to O3 increases the risk of neurological disability after stroke.

Exposure to landscape fire smoke reduced birthweight in low- and middle-income countries: findings from a siblings-matched case-control study.

Background: Landscape fire smoke (LFS) has been associated with reduced birthweight, but evidence from low- and middle-income countries (LMICs) is rare. Methods: Here, we present a sibling-matched case-control study of 227,948 newborns to identify an association between fire-sourced fine particulate matter (PM2.5) and birthweight in 54 LMICs from 2000 to 2014. We selected mothers from the geocoded Demographic and Health Survey with at least two children and valid birthweight records. Newborns affiliated with the same mother were defined as a family group. Gestational exposure to LFS was assessed in each newborn using the concentration of fire-sourced PM2.5. We determined the associations of the within-group variations in LFS exposure with birthweight differences between matched siblings using a fixed-effects regression model. Additionally, we analyzed the binary outcomes of low birthweight (LBW) or very low birthweight (VLBW). Results: According to fully adjusted models, a 1 µg/m3 increase in the concentration of fire-sourced PM2.5 was significantly associated with a 2.17 g (95% confidence interval [CI] 0.56-3.77) reduction in birthweight, a 2.80% (95% CI 0.97-4.66) increase in LBW risk, and an 11.68% (95% CI 3.59-20.40) increase in VLBW risk. Conclusions: Our findings indicate that gestational exposure to LFS harms fetal health. Funding: PKU-Baidu Fund, National Natural Science Foundation of China, Peking University Health Science Centre, and CAMS Innovation Fund for Medical Sciences.