Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Association of Antepartum and Postpartum Air Pollution Exposure With Postpartum Depression in Southern California.

Importance: Women are especially vulnerable to mental health matters post partum because of biological, emotional, and social changes during this period. However, epidemiologic evidence of an association between air pollution exposure and postpartum depression (PPD) is limited. Objective: To examine the associations between antepartum and postpartum maternal air pollution exposure and PPD. Design, Setting, and Participants: This retrospective cohort study used data from Kaiser Permanente Southern California (KPSC) electronic health records and included women who had singleton live births at KPSC facilities between January 1, 2008, and December 31, 2016. Data were analyzed between January 1 and May 10, 2023. Exposures: Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter less than or equal to 2.5 µm (PM2.5), particulate matter less than or equal to 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) from spatial interpolation of monitoring station measurements. Constituents of PM2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from fine-resolution geoscience-derived models based on satellite, ground-based monitor, and chemical transport modeling data. Main Outcomes and Measures: Participants with an Edinburgh Postnatal Depression Scale score of 10 or higher during the 6 months after giving birth were referred to a clinical interview for further assessment and diagnosis. Ascertainment of PPD was defined using a combination of diagnostic codes and prescription medications. Results: The study included 340 679 participants (mean [SD] age, 30.05 [5.81] years), with 25 674 having PPD (7.54%). Increased risks for PPD were observed to be associated with per-IQR increases in antepartum and postpartum exposures to O3 (adjusted odds ratio [AOR], 1.09; 95% CI, 1.06-1.12), PM10 (AOR, 1.02; 95% CI, 1.00-1.04), and PM2.5 (AOR, 1.02; 95% CI, 1. 00-1.03) but not with NO2; PPD risks were mainly associated with PM2.5 organic matter and black carbon. Overall, a higher risk of PPD was associated with O3 during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods. Conclusions and Relevance: The study findings suggest that long-term exposure to antepartum and postpartum air pollution was associated with higher PPD risks. Identifying the modifiable environmental risk factors and developing interventions are important public health issues to improve maternal mental health and alleviate the disease burden of PPD.

Analysis of Heat Exposure During Pregnancy and Severe Maternal Morbidity.

Importance: The rate of severe maternal morbidity (SMM) is continuously increasing in the US. Evidence regarding the associations of climate-related exposure, such as environmental heat, with SMM is lacking. Objective: To examine associations between long- and short-term maternal heat exposure and SMM. Design, Setting, and Participants: This retrospective population-based epidemiological cohort study took place at a large integrated health care organization, Kaiser Permanente Southern California, between January 1, 2008, and December 31, 2018. Data were analyzed from February to April 2023. Singleton pregnancies with data on SMM diagnosis status were included. Exposures: Moderate, high, and extreme heat days, defined as daily maximum temperatures exceeding the 75th, 90th, and 95th percentiles of the time series data from May through September 2007 to 2018 in Southern California, respectively. Long-term exposures were measured by the proportions of different heat days during pregnancy and by trimester. Short-term exposures were represented by binary variables of heatwaves with 9 different definitions (combining percentile thresholds with 3 durations; ie, ≥2, ≥3, and ≥4 consecutive days) during the last gestational week. Main Outcomes and Measures: The primary outcome was SMM during delivery hospitalization, measured by 20 subconditions excluding blood transfusion. Discrete-time logistic regression was used to estimate associations with long- and short-term heat exposure. Effect modification by maternal characteristics and green space exposure was examined using interaction terms. Results: There were 3446 SMM cases (0.9%) among 403 602 pregnancies (mean [SD] age, 30.3 [5.7] years). Significant associations were observed with long-term heat exposure during pregnancy and during the third trimester. High exposure (≥80th percentile of the proportions) to extreme heat days during pregnancy and during the third trimester were associated with a 27% (95% CI, 17%-37%; P < .001) and 28% (95% CI, 17%-41%; P < .001) increase in risk of SMM, respectively. Elevated SMM risks were significantly associated with short-term heatwave exposure under all heatwave definitions. The magnitude of associations generally increased from the least severe (HWD1: daily maximum temperature >75th percentile lasting for ≥2 days; odds ratio [OR], 1.32; 95% CI, 1.17-1.48; P < .001) to the most severe heatwave exposure (HWD9: daily maximum temperature >95th percentile lasting for ≥4 days; OR, 2.39; 95% CI, 1.62-3.54; P < .001). Greater associations were observed among mothers with lower educational attainment (OR for high exposure to extreme heat days during pregnancy, 1.43; 95% CI, 1.26-1.63; P < .001) or whose pregnancies started in the cold season (November through April; OR, 1.37; 95% CI, 1.24-1.53; P < .001). Conclusions and Relevance: In this retrospective cohort study, long- and short-term heat exposure during pregnancy was associated with higher risk of SMM. These results might have important implications for SMM prevention, particularly in a changing climate.

Maternal exposure to ambient air pollution mixture and premature rupture of membranes: Evidence from a large cohort in Southern California (2008-2018).

BACKGROUND: There is minimal evidence of relationships between maternal air pollution exposure and spontaneous premature rupture of membranes (SPROM), a critical obstetrical problem that can significantly increase maternal and fetal mortality and morbidity. No prior study has explored the PROM risk related to specific components of particulate matter with aerodynamic diameters of ≤ 2.5 µm (PM2.5). We examined associations between maternal exposure to nitrogen dioxide (NO2), ozone (O3), PM2.5, PM10, and PM2.5 constituents and SPROM. METHODS: A large retrospective cohort study was conducted and included 427,870 singleton live births from Kaiser Permanente Southern California during 2008-2018. Monthly averages of NO2, O3 (8-h daily maximum), PM2.5, and PM10 were measured using empirical Bayesian kriging based on measurements from monitoring stations. Data on PM2.5 sulfate, nitrate, ammonium, organic matter, and black carbon were obtained from a fine-resolution model. A discrete time approach with pooled logistic regressions was used to estimate associations throughout the pregnancy and based on trimesters and gestational months. The quantile-based g-computation models were fitted to examine the effects of 1) the air pollution mixture of four pollutants of interest and 2) the mixture of PM2.5 components. RESULTS: There were 37,857 SPROM cases (8.8%) in our study population. We observed relationships between SPROM and maternal exposure to NO2, O3, and PM2.5. PM2.5 sulfate, nitrate, ammonium, and organic matter were associated with higher SPROM risks in the single-pollutant model. Mixture analyses demonstrated that the overall effects of the air pollution mixture and PM2.5 mixture in this study were mainly driven by O3 and PM2.5 nitrate, respectively. Underweight mothers had a significantly higher risk of SPROM associated with NO2. CONCLUSION: Our findings add to the literature on associations between air pollution exposure and SPROM. This is the first study reporting the impact of PM2.5 constituents on SPROM.

Examining the Relationship Between Extreme Temperature, Microclimate Indicators, and Gestational Diabetes Mellitus in Pregnant Women Living in Southern California.

Few studies have assessed extreme temperatures' impact on gestational diabetes mellitus (GDM). We examined the relation between GDM risk with weekly exposure to extreme high and low temperatures during the first 24 weeks of gestation and assessed potential effect modification by microclimate indicators. Methods: We utilized 2008-2018 data for pregnant women from Kaiser Permanente Southern California electronic health records. GDM screening occurred between 24 and 28 gestational weeks for most women using the Carpenter-Coustan criteria or the International Association of Diabetes and Pregnancy Study Groups criteria. Daily maximum, minimum, and mean temperature data were linked to participants' residential address. We utilized distributed lag models, which assessed the lag from the first to the corresponding week, with logistic regression models to examine the exposure-lag-response associations between the 12 weekly extreme temperature exposures and GDM risk. We used the relative risk due to interaction (RERI) to estimate the additive modification of microclimate indicators on the relation between extreme temperature and GDM risk. Results: GDM risks increased with extreme low temperature during gestational weeks 20--24 and with extreme high temperature at weeks 11-16. Microclimate indicators modified the influence of extreme temperatures on GDM risk. For example, there were positive RERIs for high-temperature extremes and less greenness, and a negative RERI for low-temperature extremes and increased impervious surface percentage. Discussion: Susceptibility windows to extreme temperatures during pregnancy were observed. Modifiable microclimate indicators were identified that may attenuate temperature exposures during these windows, which could in turn reduce the health burden from GDM.

Modeling spatially varying compliance effects of PM2.5 exposure reductions on gestational diabetes mellitus in southern California: Results from electronic health record data of a large pregnancy cohort.

Gestational diabetes mellitus (GDM) is a major pregnancy complication affecting approximately 14.0% of pregnancies around the world. Air pollution exposure, particularly exposure to PM2.5, has become a major environmental issue affecting health, especially for vulnerable pregnant women. Associations between PM2.5 exposure and adverse birth outcomes are generally assumed to be the same throughout a large geographical area. However, the effects of air pollution on health can very spatially in subpopulations. Such spatially varying effects are likely due to a wide range of contextual neighborhood and individual factors that are spatially correlated, including SES, demographics, exposure to housing characteristics and due to different composition of particulate matter from different emission sources. This combination of elevated environmental hazards in conjunction with socioeconomic-based disparities forms what has been described as a "double jeopardy" for marginalized sub-populations. In this manuscript our analysis combines both an examination of spatially varying effects of a) unit-changes in exposure and examines effects of b) changes from current exposure levels down to a fixed compliance level, where compliance levels correspond to the Air Quality Standards (AQS) set by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality guideline values. Results suggest that exposure reduction policies should target certain "hotspot" areas where size and effects of potential reductions will reap the greatest rewards in terms of health benefits, such as areas of southeast Los Angeles County which experiences high levels of PM2.5 exposures and consist of individuals who may be particularly vulnerable to the effects of air pollution on the risk of GDM.

Association between urban green space and postpartum depression, and the role of physical activity: a retrospective cohort study in Southern California.

Background: Little research exists regarding the relationships between green space and postpartum depression (PPD). We aimed to investigate the relationships between PPD and green space exposure, and the mediating role of physical activity (PA). Methods: Clinical data were obtained from Kaiser Permanente Southern California electronic health records in 2008-2018. PPD ascertainment was based on both diagnostic codes and prescription medications. Maternal residential green space exposures were assessed using street view-based measures and vegetation types (i.e., street tree, low-lying vegetation, and grass), satellite-based measures [i.e., Normalized Difference Vegetation Index (NDVI), land-cover green space, and tree canopy cover], and proximity to the nearest park. Multilevel logistic regression was applied to estimate the association between green space and PPD. A causal mediation analysis was performed to estimate the proportion mediated by PA during pregnancy in the total effects of green space on PPD. Findings: In total, we included 415,020 participants (30.2 ± 5.8 years) with 43,399 (10.5%) PPD cases. Hispanic mothers accounted for about half of the total population. A reduced risk for PPD was associated with total green space exposure based on street-view measure [500 m buffer, adjusted odds ratio (OR) per interquartile range: 0.98, 95% CI: 0.97-0.99], but not NDVI, land-cover greenness, or proximity to a park. Compared to other types of green space, tree coverage showed stronger protective effects (500 m buffer, OR = 0.98, 95% CI: 0.97-0.99). The proportions of mediation effects attributable to PA during pregnancy ranged from 2.7% to 7.2% across green space indicators. Interpretation: Street view-based green space and tree coverage were associated with a decreased risk of PPD. The observed association was primarily due to increased tree coverage, rather than low-lying vegetation or grass. Increased PA was a plausible pathway linking green space to lower risk for PPD. Funding: National Institute of Environmental Health Sciences (NIEHS; R01ES030353).

The role of extreme heat exposure on premature rupture of membranes in Southern California: A study from a large pregnancy cohort.

BACKGROUND: Significant mortality and morbidity in pregnant women and their offspring are linked to premature rupture of membranes (PROM). Epidemiological evidence for heat-related PROM risk is extremely limited. We investigated associations between acute heatwave exposure and spontaneous PROM. METHODS: We conducted this retrospective cohort study among mothers in Kaiser Permanente Southern California who experienced membrane ruptures during the warm season (May-September) from 2008 to 2018. Twelve definitions of heatwaves with different cut-off percentiles (75th, 90th, 95th, and 98th) and durations (≥ 2, 3, and 4 consecutive days) were developed using the daily maximum heat index, which incorporates both daily maximum temperature and minimum relative humidity in the last gestational week. Cox proportional hazards models were fitted separately for spontaneous PROM, term PROM (TPROM), and preterm PROM (PPROM) with zip codes as the random effect and gestational week as the temporal unit. Effect modification by air pollution (i.e., PM2.5 and NO2), climate adaptation measures (i.e., green space and air conditioning [AC] penetration), sociodemographic factors, and smoking behavior was examined. RESULTS: In total, we included 190,767 subjects with 16,490 (8.6%) spontaneous PROMs. We identified a 9-14% increase in PROM risks associated with less intense heatwaves. Similar patterns as PROM were found for TPROM and PPROM. The heat-related PROM risks were greater among mothers exposed to a higher level of PM2.5 during pregnancy, under 25 years old, with lower education and household income level, and who smoked. Even though climate adaptation factors were not statistically significant effect modifiers, mothers living with lower green space or lower AC penetration were at consistently higher heat-related PROM risks compared to their counterparts. CONCLUSION: Using a rich and high-quality clinical database, we detected harmful heat exposure for spontaneous PROM in preterm and term deliveries. Some subgroups with specific characteristics were more susceptible to heat-related PROM risk.

Bayesian profile regression to study the ecologic associations of correlated environmental exposures with excess mortality risk during the first year of the Covid-19 epidemic in lombardy, Italy.

Many countries, including Italy, have experienced significant social and spatial inequalities in mortality during the Covid-19 pandemic. This study applies a multiple exposures framework to investigate how joint place-based factors influence spatial inequalities of excess mortality during the first year of the Covid -19 pandemic in the Lombardy region of Italy. For the Lombardy region, we integrated municipality-level data on all-cause mortality between 2015 and 2020 with 13 spatial covariates, including 5-year average concentrations of six air pollutants, the average temperature in 2020, and multiple socio-demographic factors, and health facilities per capita. Using the clustering algorithm Bayesian profile regression, we fit spatial covariates jointly to identify clusters of municipalities with similar exposure profiles and estimated associations between clusters and excess mortality in 2020. Cluster analysis resulted in 13 clusters. Controlling for spatial autocorrelation of excess mortality and health-protective agency, two clusters had significantly elevated excess mortality than the rest of Lombardy. Municipalities in these highest-risk clusters are in Bergamo, Brescia, and Cremona provinces. The highest risk cluster (C11) had the highest long-term particulate matter air pollution levels (PM2.5 and PM10) and significantly elevated NO2 and CO air pollutants, temperature, proportion ≤18 years, and male-to-female ratio. This cluster is significantly lower for income and ≥65 years. The other high-risk cluster, Cluster 10 (C10), is elevated significantly for ozone but significantly lower for other air pollutants. Covariates with elevated levels for C10 include proportion 65 years or older and a male-to-female ratio. Cluster 10 is significantly lower for income, temperature, per capita health facilities, ≤18 years, and population density. Our results suggest that joint built, natural, and socio-demographic factors influenced spatial inequalities of excess mortality in Lombardy in 2020. Studies must apply a multiple exposures framework to guide policy decisions addressing the complex and multi-dimensional nature of spatial inequalities of Covid-19-related mortality.

Reductions in NO2 and emergency room visits associated with California's goods movement policies: A quasi-experimental study.

INTRODUCTION: This study examines whether the "Emission Reduction Plan for Ports and Goods Movement" in California reduced air pollution exposures and emergency room visits among California Medicaid enrollees with asthma and/or chronic obstructive pulmonary disease. METHOD: We created a retrospective cohort of 5608 Medicaid enrollees from ten counties in California with data from 2004 to 2010. We grouped the patients into two groups: those living within 500 m of goods movement corridors (ports and truck-permitted freeways), and control areas (away from the busy truck or car permitted highways). We created annual air pollution surfaces for nitrogen dioxide and assigned them to enrollees' home addresses. We used a quasi-experimental design with a difference-in-differences method to examine changes before and after the policy for cohort beneficiaries in the two groups. RESULTS: The reductions in nitrogen dioxide exposures and emergency room visits were greater for enrollees in goods movement corridors than those in control areas in post-policy years. We found that the goods movement actions were associated with 14.8% (95% CI, -24.0% to -4.4%; P = 0.006) and 11.8% (95% CI, -21.2% to -1.2%; P = 0.030) greater reduction in emergency room visits for the beneficiaries with asthma and chronic obstructive pulmonary disease, respectively, in the third year after California's emission reduction plan. CONCLUSION: These findings indicate remarkable health benefits via reduced emergency room visits from the significantly improved air quality due to public policy interventions for disadvantaged and susceptible populations.

Exposure to air pollutant mixture and gestational diabetes mellitus in Southern California: Results from electronic health record data of a large pregnancy cohort.

BACKGROUND: Epidemiological findings are inconsistent regarding the associations between air pollution exposure during pregnancy and gestational diabetes mellitus (GDM). Several limitations exist in previous studies, including potential outcome and exposure misclassification, unassessed confounding, and lack of simultaneous consideration of air pollution mixtures and particulate matter (PM) constituents. OBJECTIVES: To assess the association between GDM and maternal residential exposure to air pollution, and the joint effect of the mixture of air pollutants and PM constituents. METHODS: Detailed clinical data were obtained for 395,927 pregnancies in southern California (2008-2018) from Kaiser Permanente Southern California (KPSC) electronic health records. GDM diagnosis was based on KPSC laboratory tests. Monthly average concentrations of fine particulate matter < 2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using kriging interpolation of Environmental Protection Agency's routine monitoring station data, while PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon) were estimated using a fine-resolution geoscience-derived model. A multilevel logistic regression was used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of air pollution and PM component mixtures. Main analyses adjusted for maternal age, race/ethnicity, education, median family household income, pre-pregnancy BMI, smoking during pregnancy, insurance type, season of conception and year of delivery. RESULTS: The incidence of GDM was 10.9% in the study population. In single-pollutant models, we observed an increased odds for GDM associated with exposures to PM2.5, PM10, NO2 and PM2.5 constituents. The association was strongest for NO2 [adjusted odds ratio (OR) per interquartile range: 1.176, 95% confidence interval (CI): 1.147-1.205)]. In multi-pollutant models, increased ORs for GDM in association with one quartile increase in air pollution mixtures were found for both kriging-based regional air pollutants (NO2, PM2.5, and PM10, OR = 1.095, 95% CI: 1.082-1.108) and PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon, OR = 1.258, 95% CI: 1.206-1.314); NO2 (78%) and black carbon (48%) contributed the most to the overall mixture effects among all krigged air pollutants and all PM2.5 constituents, respectively. The risk of GDM associated with air pollution exposure were significantly higher among Hispanic mothers, and overweight/obese mothers. CONCLUSION: This study found that exposure to a mixture of ambient PM2.5, PM10, NO2, and PM2.5 chemical constituents was associated with an increased risk of GDM. NO2 and black carbon PM2.5 contributed most to GDM risk.

A spatial joint analysis of metal constituents of ambient particulate matter and mortality in England.

Few studies have investigated associations between metal components of particulate matter on mortality due to well-known issues of multicollinearity. Here, we analyze these exposures jointly to evaluate their associations with mortality on small area data. We fit a Bayesian profile regression (BPR) to account for the multicollinearity in the elemental components (iron, copper, and zinc) of PM10 and PM2.5. The models are developed in relation to mortality from cardiovascular and respiratory disease and lung cancer incidence in 2008-2011 at a small area level, for a population of 13.6 million in the London-Oxford area of England. From the BPR, we identified higher risks in the PM10 fraction cluster likely to represent the study area, excluding London, for cardiovascular mortality relative risk (RR) 1.07 (95% credible interval [CI] 1.02, 1.12) and for respiratory mortality RR 1.06 (95%CI 0.99, 1.31), compared with the study mean. For PM2.5 fraction, higher risks were seen for cardiovascular mortality RR 1.55 (CI 95% 1.38, 1.71) and respiratory mortality RR 1.51 (CI 95% 1.33, 1.72), likely to represent the "highways" cluster. We did not find relevant associations for lung cancer incidence. Our analysis showed small but not fully consistent adverse associations between health outcomes and particulate metal exposures. The BPR approach identified subpopulations with unique exposure profiles and provided information about the geographical location of these to help interpret findings.

Predicting differential improvements in annual pollutant concentrations and exposures for regulatory policy assessment.

Over the past decade, researchers and policy-makers have become increasingly interested in regulatory and policy interventions to reduce air pollution concentrations and improve human health. Studies have typically relied on relatively sparse environmental monitoring data that lack the spatial resolution to assess small-area improvements in air quality and health. Few studies have integrated multiple types of measures of an air pollutant into one single modeling framework that combines spatially- and temporally-rich monitoring data. In this paper, we investigated the differential effects of California emissions reduction plan on reducing air pollution between those living in the goods movement corridors (GMC) that are within 500 m of major highways that serve as truck routes to those farther away or adjacent to routes that prohibit trucks. A mixed effects Deletion/Substitution/Addition (D/S/A) machine learning algorithm was developed to model annual pollutant concentrations of nitrogen dioxide (NO2) by taking repeated measures into consideration and by integrating multiple types of NO2 measurements, including those through government regulatory and research-oriented saturation monitoring into a single modeling framework. Difference-in-difference analysis was conducted to identify whether those living in GMC demonstrated statistically larger reductions in air pollution exposure. The mixed effects D/S/A machine learning modeling result indicated that GMC had 2 ppb greater reductions in NO2 concentrations from pre- to post-policy period than far away areas. The difference-in-difference analysis demonstrated that the subjects living in GMC experienced statistically significant greater reductions in NO2 exposure than those living in the far away areas. This study contributes to scientific knowledge by providing empirical evidence that improvements in air quality via the emissions reductions plan policies impacted traffic-related air pollutant concentrations and associated exposures most among low-income Californians with chronic conditions living in GMC. The identified differences in pollutant reductions across different location domains may be applicable to other states or other countries if similar policies are enacted.

Associations between green space and preterm birth: Windows of susceptibility and interaction with air pollution.

BACKGROUND: Recent studies have reported inconsistent associations between maternal residential green space and preterm birth (PTB, born < 37 completed gestational weeks). In addition, windows of susceptibility during pregnancy have not been explored and potential interactions of green space with air pollution exposures during pregnancy are still unclear. OBJECTIVES: To evaluate the relationships between green space and PTB, identify windows of susceptibility, and explore potential interactions between green space and air pollution. METHODS: Birth certificate records for all births in California (2001-2008) were obtained. The Normalized Difference Vegetation Index (NDVI) was used to characterized green space exposure. Gestational age was treated as a time-to-event outcome; Cox proportional hazard models were applied to estimate the association between green space exposure and PTB, moderately PTB (MPTB, gestational age < 35 weeks), and very PTB (VPTB, gestational age < 30 weeks), after controlling for maternal age, race/ethnicity, education, and median household income. Month-specific green space exposure was used to identify potential windows of susceptibility. Potential interactions between green space and air pollution [fine particulate matter < 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3)] were examined on both additive and multiplicative scales. RESULTS: In total, 3,753,799 eligible births were identified, including 341,123 (9.09%) PTBs, 124,631 (3.32%) MPTBs, and 22,313 (0.59%) VPTBs. A reduced risk of PTB was associated with increases in residential NDVI exposure in 250 m, 500 m, 1000 m, and 2000 m buffers. In the 2000 m buffer, the association was strongest for VPTB [adjusted hazard ratio (HR) per interquartile range increase in NDVI: 0.959, 95% confidence interval (CI): 0.942-0.976)], followed by MPTB (HR = 0.970, 95% CI: 0.962-0.978) and overall PTB (HR = 0.972, 95% CI: 0.966-0.978). For PTB, green space during the 3rd - 5th gestational months had stronger associations than those in the other time periods, especially during the 4th gestational month (NDVI 2000 m: HR = 0.970, 95% CI: 0.965-0.975). We identified consistent positive additive and multiplicative interactions between decreasing green space and higher air pollution. CONCLUSION: This large study found that maternal exposure to residential green space was associated with decreased risk of PTB, MPTB, and VPTB, especially in the second trimester. There is a synergistic effect between low green space and high air pollution levels on PTB, indicating that increasing exposure to green space may be more beneficial for women with higher air pollution exposures during pregnancy.

Associations between metal constituents of ambient particulate matter and mortality in England: an ecological study.

OBJECTIVES: To investigate long-term associations between metal components of particulate matter (PM) and mortality and lung cancer incidence. DESIGN: Small area (ecological) study. SETTING: Population living in all wards (~9000 individuals per ward) in the London and Oxford area of England, comprising 13.6 million individuals. EXPOSURE AND OUTCOME MEASURES: We used land use regression models originally used in the Transport related Air Pollution and Health Impacts-Integrated Methodologies for Assessing Particulate Matter study to estimate exposure to copper, iron and zinc in ambient air PM. We examined associations of metal exposure with Office for National Statistics mortality data from cardiovascular disease (CVD) and respiratory causes and with lung cancer incidence during 2008-2011. RESULTS: There were 108 478 CVD deaths, 48 483 respiratory deaths and 24 849 incident cases of lung cancer in the study period and area. Using Poisson regression models adjusted for area-level deprivation, tobacco sales and ethnicity, we found associations between cardiovascular mortality and PM2.5 copper with interdecile range (IDR 2.6-5.7 ng/m3) and IDR relative risk (RR) 1.005 (95%CI 1.001 to 1.009) and between respiratory mortality and PM10 zinc (IDR 1135-153 ng/m3) and IDR RR 1.136 (95%CI 1.010 to 1.277). We did not find relevant associations for lung cancer incidence. Metal elements were highly correlated. CONCLUSION: Our analysis showed small but not fully consistent adverse associations between mortality and particulate metal exposures likely derived from non-tailpipe road traffic emissions (brake and tyre wear), which have previously been associated with increases in inflammatory markers in the blood.

Multi-pollutant Modeling Through Examination of Susceptible Subpopulations Using Profile Regression.

PURPOSE OF REVIEW: The inter-correlated nature of exposure-based risk factors in environmental health studies makes it a challenge to determine their combined effect on health outcomes. As such, there has been much research of late regarding the development and utilization of methods in the field of multi-pollutant modeling. However, much of this work has focused on issues related to variable selection in a regression context, with the goal of identifying which exposures are the "bad actors" most responsible for affecting the health outcome of interest. However, the question addressed by these approaches does not necessarily represent the only or most important questions of interest in a multi-pollutant modeling context, where researchers may be interested in health effects from co-exposure patterns and in identifying subpopulations associated with patterns defined by different levels of constituent exposures. RECENT FINDINGS: One approach to analyzing multi-pollutant data is to use a method known as Bayesian profile regression, which aids in identifying susceptible subpopulations associated with exposure mixtures defined by different levels of each exposure. Identification of exposure-level patterns that correspond to a location may provide a starting point for policy-based exposure reduction. Also, in a spatial context, identification of locations with the most health-relevant exposure-mixture profiles might provide further policy relevant information. In this brief report, we review and describe an approach that can be used to identify exposures in subpopulations or locations known as Bayesian profile regression. An example is provided in which we examine associations between air pollutants, an indicator of healthy food retailer availability, and indicators of poverty in Los Angeles County. A general tread suggesting that vulnerable individuals are more highly exposed and have limited access to healthy food retailers is observed, though the associations are complex and non-linear.

Association between Pesticide Profiles Used on Agricultural Fields near Maternal Residences during Pregnancy and IQ at Age 7 Years.

We previously showed that potential prenatal exposure to agricultural pesticides was associated with adverse neurodevelopmental outcomes in children, yet the effects of joint exposure to multiple pesticides is poorly understood. In this paper, we investigate associations between the joint distribution of agricultural use patterns of multiple pesticides (denoted as "pesticide profiles") applied near maternal residences during pregnancy and Full-Scale Intelligence Quotient (FSIQ) at 7 years of age. Among a cohort of children residing in California's Salinas Valley, we used Pesticide Use Report (PUR) data to characterize potential exposure from use within 1 km of maternal residences during pregnancy for 15 potentially neurotoxic pesticides from five different chemical classes. We used Bayesian profile regression (BPR) to examine associations between clustered pesticide profiles and deficits in childhood FSIQ. BPR identified eight distinct clusters of prenatal pesticide profiles. Two of the pesticide profile clusters exhibited some of the highest cumulative pesticide use levels and were associated with deficits in adjusted FSIQ of -6.9 (95% credible interval: -11.3, -2.2) and -6.4 (95% credible interval: -13.1, 0.49), respectively, when compared with the pesticide profile cluster that showed the lowest level of pesticides use. Although maternal residence during pregnancy near high agricultural use of multiple neurotoxic pesticides was associated with FSIQ deficit, the magnitude of the associations showed potential for sub-additive effects. Epidemiologic analysis of pesticides and their potential health effects can benefit from a multi-pollutant approach to analysis.

Part 3. Modeling of Multipollutant Profiles and Spatially Varying Health Effects with Applications to Indicators of Adverse Birth Outcomes.

The highly intercorrelated nature of air pollutants makes it difficult to examine their combined effects on health. As such, epidemiological studies have traditionally focused on single-pollutant models that use regression-based techniques to examine the marginal association between a pollutant and a health outcome. These relatively simple, additive models are useful for discerning the effect of a single pollutant on a health outcome with all other pollutants held to fixed values. However, pollutants occur in complex mixtures consisting of highly correlated combinations of individual exposures. For example, evidence for synergy among pollutants in causing health effects has been recently reviewed by Mauderly and Samet (2009). Also, studies cited in the Ozone Criteria Document (U.S. Environmental Protection Agency [U.S. EPA*] 2006) confirmed that synergisms between ozone and other pollutants have been demonstrated in laboratory studies involving humans and animals. Thus, the highly correlated nature of air pollution exposures makes marginal, single-pollutant models inadequate. This issue was raised in a report by the National Research Council (NRC 2004), which called for a multipollutant approach to air quality management. Here we present and apply a series of statistical approaches that treat patterns of covariates as a whole unit, stochastically grouping pollutant patterns into clusters and then using these cluster assignments as random effects in a regression model. Using this approach, the effect of a multipollutant pattern, or profile, is determined in a manner that takes into account the uncertainty in the clustering process. The models are set in a Bayesian framework, and in general, Markov chain Monte Carlo (MCMC) techniques (Gilks et al. 1998). For interpretation purposes, a best clustering is derived, and the uncertainty related to this best clustering is determined by utilizing model averaging techniques, in a manner such that consistent clustering obtained by the estimation process generally yields smaller standard errors while inconsistent clustering is generally associated with larger errors. These multivariate methods are applied to a range of different problems related to air pollution exposures, namely an association of multipollutant profiles with indicators of poverty and to an assessment of the association between measures of various air pollutants, patterns of socioeconomic status (SES), and birth outcomes. All of these studies involve an examination of regional-level exposures, at the census tract (CT) and census block group (CBG) levels, and individual-level outcomes throughout Los Angeles (LA) County. Results indicate that effects of pollutants vary spatially and vary in a complex interconnected manner that cannot be discerned using standard additive line ar models. Results obtaine d from these studies can be used to efficiently use limited resources to inform policies in targeting are as where air pollution reductions result in maximum health benefits.

Multi-pollutant exposure profiles associated with term low birth weight in Los Angeles County.

Research indicates that multiple outdoor air pollutants and adverse neighborhood conditions are spatially correlated. Yet health risks associated with concurrent exposure to air pollution mixtures and clustered neighborhood factors remain underexplored. Statistical models to assess the health effects from pollutant mixtures remain limited, due to problems of collinearity between pollutants and area-level covariates, and increases in covariate dimensionality. Here we identify pollutant exposure profiles and neighborhood contextual profiles within Los Angeles (LA) County. We then relate these profiles with term low birth weight (TLBW). We used land use regression to estimate NO2, NO, and PM2.5 concentrations averaged over census block groups to generate pollutant exposure profile clusters and census block group-level contextual profile clusters, using a Bayesian profile regression method. Pollutant profile cluster risk estimation was implemented using a multilevel hierarchical model, adjusting for individual-level covariates, contextual profile cluster random effects, and modeling of spatially structured and unstructured residual error. Our analysis found 13 clusters of pollutant exposure profiles. Correlations between study pollutants varied widely across the 13 pollutant clusters. Pollutant clusters with elevated NO2, NO, and PM2.5 concentrations exhibited increased log odds of TLBW, and those with low PM2.5, NO2, and NO concentrations showed lower log odds of TLBW. The spatial patterning of pollutant cluster effects on TLBW, combined with between-pollutant correlations within pollutant clusters, imply that traffic-related primary pollutants influence pollutant cluster TLBW risks. Furthermore, contextual clusters with the greatest log odds of TLBW had more adverse neighborhood socioeconomic, demographic, and housing conditions. Our data indicate that, while the spatial patterning of high-risk multiple pollutant clusters largely overlaps with adverse contextual neighborhood cluster, both contribute to TLBW while controlling for the other.