Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Residential proximity to greenspace is associated with various health outcomes. OBJECTIVES: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors. METHODS: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income. RESULTS: After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81). DISCUSSION: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods.

Effect measure modification of the association between short-term exposures to PM2.5 and hospitalizations by longs-term PM2.5 exposure among a cohort of people with Chronic Obstructive Pulmonary Disease (COPD) in North Carolina, 2002-2015.

BACKGROUND: Approximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM2.5 exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD. METHODS: In a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004-2016 (n = 520), and estimated ambient PM2.5 concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0-2 and 0-3 day lags of PM2.5 concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM2.5 concentration at the median value. RESULTS: We observed generally null or low-magnitude negative associations with short-term PM2.5 exposure and respiratory-related (OR per 5 µg/m3 increase in 3-day lag PM2.5: 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM2.5 exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 0.914 (0.804, 1.039)). CONCLUISONS: Differences in associations demonstrate that people in areas with higher annual PM2.5 exposure may be associated with higher risk of hospitalization during short-term increases in PM2.5 exposure.

North Carolina's Changing Energy Generation Profile and Reductions in Key Air Pollutants, 2000-2019.

BACKGROUND Coal combustion releases a number of airborne toxins. The North Carolina Clean Smokestacks Act (CSA) of 2002 required North Carolina coal-fired power plants (CFPP) to reduce nitrogen oxides (NOX) emissions by 2009 and sulfur dioxide (SO2) emissions to 2 benchmarks by 2009 and 2013.METHODS We utilized publicly available databases from the Energy Information Administration and the Environmental Protection Agency to characterize North Carolina's electricity generation profile from 2000 until 2019 and evaluate corresponding NOx and SO2 emissions by sector over the same time period.RESULTS Between 2000 and 2008 in North Carolina, approximately 60% of electric power was generated by CFPPs. Since then, North Carolina's electric power generation has transformed from predominant dependence on coal to approximately equal dependence on natural gas and nuclear power (each at ~ 30%), with coal close behind (~ 25%). Renewables have increased, although marginally relative to the rapid increase in natural gas. Despite the stark drop in reliance on CFPPs for energy in North Carolina and subsequent drop in emissions, CFPPs still contribute ~ 60% of SO2 air pollution as of 2017.LIMITATIONS This analysis relies upon electricity generation and emissions data self-reported by utilities and publicly available from federal agenciesCONCLUSION North Carolina's electric utilities met the 2009 and 2013 regulatory benchmarks set by the CSA, which resulted in substantial reductions in SO2 emissions from the fuel combustion electric generation sector. Still, CFPPs remain the primary utility-related and overall anthropogenic contributor of SO2 air pollution in North Carolina.

Critical window variable selection: estimating the impact of air pollution on very preterm birth.

Understanding the impact that environmental exposure during different stages of pregnancy has on the risk of adverse birth outcomes is vital for protection of the fetus and for the development of mechanistic explanations of exposure-disease relationships. As a result, statistical models to estimate critical windows of susceptibility have been developed for several different reproductive outcomes and pollutants. However, these current methods fail to adequately address the primary objective of this line of research; how to statistically identify a critical window of susceptibility. In this article, we introduce critical window variable selection (CWVS), a hierarchical Bayesian framework that directly addresses this question while simultaneously providing improved estimation of the risk parameters. Through simulation, we show that CWVS outperforms existing competing techniques in the setting of highly temporally correlated exposures in terms of (i) correctly identifying critical windows and (ii) accurately estimating risk parameters. We apply all competing methods to a case/control analysis of pregnant women in North Carolina, 2005-2008, with respect to the development of very preterm birth and exposure to ambient ozone and particulate matter $<$ 2.5 $\mu$m in aerodynamic diameter, and identify/estimate the critical windows of susceptibility. The newly developed method is implemented in the R package CWVS.

Ozone exposure during early pregnancy and preterm birth: A systematic review and meta-analysis.

Exposure to ozone has been linked to reproductive outcomes, including preterm birth. In this systematic review, we summarize published epidemiologic cohort and case-control studies examining ozone exposures (estimated on a continuous scale) in early pregnancy (1st and 2nd trimesters (T1, T2)) and preterm birth using ratio measures, and perform a meta-analysis to evaluate the potential relationship between them. Studies were identified by searching PubMed and Web of Science, screened according to predefined inclusion/exclusion criteria, and evaluated for study quality. We extracted study data including effect estimates, confidence limits, study location, study years, ozone exposure assessment method, and mean or median ozone concentrations. Nineteen studies were identified and included, of which 18 examined T1 exposure (17 reported effect estimates), and 15 examined T2 exposure. Random effects meta-analysis was performed in the metafor package, R 3.5.3. The pooled OR (95% CI) for a 10 ppb increase in ozone exposure in T1 was 1.06 (1.03, 1.10) with a 95% prediction interval of 0.95, 1.19; for T2 it was 1.05 (1.02, 1.08) with a 95% prediction interval of 0.95, 1.16. Effect estimates for both exposure periods showed high heterogeneity. In meta-regression analyses of study characteristics, study location (continent) explained some (~20%) heterogeneity for T1 exposure studies, but no characteristic explained a substantial amount of heterogeneity for T2 exposure studies. Increased ozone exposure during early pregnancy is associated with preterm birth across studies.

Disparities in Distribution of Particulate Matter Emissions from US Coal-Fired Power Plants by Race and Poverty Status After Accounting for Reductions in Operations Between 2015 and 2017.

Objectives. To investigate potential changes in burdens from coal-fired electricity-generating units (EGUcfs) that emit fine particulate matter (PM2.5, defined as matter with a nominal mean aerodynamic diameter of ≤ 2.5 µm) among racial/ethnic and economic groups after reduction of operations in 92 US EGUcfs.Methods. PM2.5 burdens calculated for EGUs listed in the 2008, 2011, and 2014 National Emissions Inventory were recalculated for 2017 after omitting emissions from 92 EGUcfs. The combined influence of race/ethnicity and poverty on burden estimates was characterized.Results. Omission of 92 EGUcfs decreased PM2.5 burdens attributable to EGUs by 8.6% for the entire population and to varying degrees for every population subgroup. Although the burden decreased across all subgroups, the decline was not equitable. After omission of the 92 EGUcfs, burdens were highest for the below-poverty and non-White subgroups. Proportional disparities between White and non-White subgroups increased. In our combined analysis, the burden was highest for the non-White-high-poverty subgroup.Conclusions. Our results indicate that subgroups living in poverty experience the greatest absolute burdens from EGUcfs. Changes as a result of EGUcf closures suggest a shift in burden from White to non-White subgroups. Policymakers could use burden analyses to jointly promote equity and reduce emissions.

Maternal exposure to outdoor air pollution and congenital limb deficiencies in the National Birth Defects Prevention Study.

BACKGROUND: Congenital limb deficiencies (CLDs) are a relatively common group of birth defects whose etiology is mostly unknown. Recent studies suggest maternal air pollution exposure as a potential risk factor. AIM: To investigate the relationship between ambient air pollution exposure during early pregnancy and offspring CLDs. METHODS: The study population was identified from the National Birth Defects Prevention Study, a population-based multi-center case-control study, and consisted of 615 CLD cases and 5,701 controls with due dates during 1997 through 2006. Daily averages and/or maxima of six criteria air pollutants (particulate matter <2.5 µm [PM2.5], particulate matter <10 µm [PM10], nitrogen dioxide [NO2], sulfur dioxide [SO2], carbon monoxide [CO], and ozone [O3]) were averaged over gestational weeks 2-8, as well as for individual weeks during this period, using data from EPA air monitors nearest to the maternal address. Logistic regression was used to estimate odds ratios (aORs) and 95% confidence intervals (CIs) adjusted for maternal age, race/ethnicity, education, and study center. We estimated aORs for any CLD and CLD subtypes (i.e., transverse, longitudinal, and preaxial). Potential confounding by co-pollutant was assessed by adjusting for one additional air pollutant. Using the single pollutant model, we further investigated effect measure modification by body mass index, cigarette smoking, and folic acid use. Sensitivity analyses were conducted restricting to those with a residence closer to an air monitor. RESULTS: We observed near-null aORs for CLDs per interquartile range (IQR) increase in PM10, PM2.5, and O3. However, weekly averages of the daily average NO2 and SO2, and daily max NO2, SO2, and CO concentrations were associated with increased odds of CLDs. The crude ORs ranged from 1.03 to 1.12 per IQR increase in these air pollution concentrations, and consistently elevated aORs were observed for CO. Stronger associations were observed for SO2 and O3 in subtype analysis (preaxial). In co-pollutant adjusted models, associations with CO remained elevated (aORs: 1.02-1.30); but aORs for SO2 and NO2 became near-null. The aORs for CO remained elevated among mothers who lived within 20 km of an air monitor. The aORs varied by maternal BMI, smoking status, and folic acid use. CONCLUSION: We observed modest associations between CLDs and air pollution exposures during pregnancy, including CO, SO2, and NO2, though replication through further epidemiologic research is warranted.

Disparities in Distribution of Particulate Matter Emission Sources by Race and Poverty Status.

OBJECTIVES: To quantify nationwide disparities in the location of particulate matter (PM)-emitting facilities by the characteristics of the surrounding residential population and to illustrate various spatial scales at which to consider such disparities. METHODS: We assigned facilities emitting PM in the 2011 National Emissions Inventory to nearby block groups across the 2009 to 2013 American Community Survey population. We calculated the burden from these emissions for racial/ethnic groups and by poverty status. We quantified disparities nationally and for each state and county in the country. RESULTS: For PM of 2.5 micrometers in diameter or less, those in poverty had 1.35 times higher burden than did the overall population, and non-Whites had 1.28 times higher burden. Blacks, specifically, had 1.54 times higher burden than did the overall population. These patterns were relatively unaffected by sensitivity analyses, and disparities held not only nationally but within most states and counties as well. CONCLUSIONS: Disparities in burden from PM-emitting facilities exist at multiple geographic scales. Disparities for Blacks are more pronounced than are disparities on the basis of poverty status. Strictly socioeconomic considerations may be insufficient to reduce PM burdens equitably across populations.

A cross-disciplinary evaluation of evidence for multipollutant effects on cardiovascular disease.

BACKGROUND: The current single-pollutant approach to regulating ambient air pollutants is effective at protecting public health, but efficiencies may be gained by addressing issues in a multipollutant context since multiple pollutants often have common sources and individuals are exposed to more than one pollutant at a time. OBJECTIVE: We performed a cross-disciplinary review of the effects of multipollutant exposures on cardiovascular effects. METHODS: A broad literature search for references including at least two criteria air pollutants (particulate matter [PM], ozone [O3], oxides of nitrogen, sulfur oxides, carbon monoxide) was conducted. References were culled based on scientific discipline then searched for terms related to cardiovascular disease. Most multipollutant epidemiologic and experimental (i.e., controlled human exposure, animal toxicology) studies examined PM and O3 together. DISCUSSION: Epidemiologic and experimental studies provide some evidence for O3 concentration modifying the effect of PM, although PM did not modify O3 risk estimates. Experimental studies of combined exposure to PM and O3 provided evidence for additivity, synergism, and/or antagonism depending on the specific health endpoint. Evidence for other pollutant pairs was more limited. CONCLUSIONS: Overall, the evidence for multipollutant effects was often heterogeneous, and the limited number of studies inhibited making a conclusion about the nature of the relationship between pollutant combinations and cardiovascular disease.

Maternal Exposure to Nitrogen Dioxide, Intake of Methyl Nutrients, and Congenital Heart Defects in Offspring.

Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study (United States, 1997-2006) were used to estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients, and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across postconception weeks 2-8, were assigned to 6,160 nondiabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residences. Intakes of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed, and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (odds ratio = 3.23, 95% confidence interval: 1.74, 6.01; relative excess risk due to interaction = 2.15, 95% confidence interval: 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy.

Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects.

Epidemiologic studies suggest that maternal ambient air pollution exposure during critical periods of pregnancy is associated with adverse effects on fetal development. In this work, we introduce new methodology for identifying critical periods of development during post-conception gestational weeks 2-8 where elevated exposure to particulate matter less than 2.5 µm (PM2.5 ) adversely impacts development of the heart. Past studies have focused on highly aggregated temporal levels of exposure during the pregnancy and have failed to account for anatomical similarities between the considered congenital heart defects. We introduce a multinomial probit model in the Bayesian setting that allows for joint identification of susceptible daily periods during pregnancy for 12 types of congenital heart defects with respect to maternal PM2.5 exposure. We apply the model to a dataset of mothers from the National Birth Defect Prevention Study where daily PM2.5 exposures from post-conception gestational weeks 2-8 are assigned using predictions from the downscaler pollution model. This approach is compared with two aggregated exposure models that define exposure as the average value over post-conception gestational weeks 2-8 and the average over individual weeks, respectively. Results suggest an association between increased PM2.5 exposure on post-conception gestational day 53 with the development of pulmonary valve stenosis and exposures during days 50 and 51 with tetralogy of Fallot. Significant associations are masked when using the aggregated exposure models. Simulation study results suggest that the findings are robust to multiple sources of error. The general form of the model allows for different exposures and health outcomes to be considered in future applications. Copyright © 2016 John Wiley & Sons, Ltd.

Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.

BACKGROUND: Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. METHODS: We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. RESULTS: We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). CONCLUSION: Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc.

Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study.

BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of hypospadias by interrupting normal urethral development. METHODS: Using data from the National Birth Defects Prevention Study, a population-based case-control study, we considered the role of maternal exposure to atrazine, a widely used herbicide and potential endocrine disruptor, via drinking water in the etiology of 2nd and 3rd degree hypospadias. We used data on 343 hypospadias cases and 1,422 male controls in North Carolina, Arkansas, Iowa, and Texas from 1998-2005. Using catchment level stream and groundwater contaminant models from the US Geological Survey, we estimated atrazine concentrations in public water supplies and in private wells. We assigned case and control mothers to public water supplies based on geocoded maternal address during the critical window of exposure for hypospadias (i.e., gestational weeks 6-16). Using maternal questionnaire data about water consumption and drinking water, we estimated a surrogate for total maternal consumption of atrazine via drinking water. We then included additional maternal covariates, including age, race/ethnicity, parity, and plurality, in logistic regression analyses to consider an association between atrazine and hypospadias. RESULTS: When controlling for maternal characteristics, any association between hypospadias and daily maternal atrazine exposure during the critical window of genitourinary development was found to be weak or null (odds ratio for atrazine in drinking water = 1. 00, 95 % CI = 0.97 to 1.03 per 0.04 µg/day increase; odds ratio for maternal consumption = 1.02, 95 % CI = 0.99 to 1.05; per 0.05 µg/day increase). CONCLUSIONS: While the association that we observed was weak, our results suggest that additional research into a possible association between atrazine and hypospadias occurrence, using a more sensitive exposure metric, would be useful.

Associations between prenatal exposure to air pollution, small for gestational age, and term low birthweight in a state-wide birth cohort.

A range of health effects, including adverse pregnancy outcomes, have been associated with exposure to ambient concentrations of particulate matter (PM) and ozone (O3). The objective of this study was to determine whether maternal exposure to fine particulate matter (PM2.5) and O3 during pregnancy is associated with the risk of term low birthweight and small for gestational age infants in both single and co-pollutant models. Term low birthweight and small for gestational age were determined using all birth certificates from North Carolina from 2003 to 2005. Ambient air concentrations of PM2.5 and O3 were predicted using a hierarchical Bayesian model of air pollution that combined modeled air pollution estimates from the EPA׳s Community Multi-Scale Air Quality (CMAQ) model with air monitor data measured by the EPA׳s Air Quality System. Binomial regression, adjusted for multiple potential confounders, was performed. In adjusted single-pollutant models for the third trimester, O3 concentration was positively associated with small for gestational age and term low birthweight births [risk ratios for an interquartile range increase in O3: 1.16 (95% CI 1.11, 1.22) for small for gestational age and 2.03 (95% CI 1.80, 2.30) for term low birthweight]; however, inverse or null associations were observed for PM2.5 [risk ratios for an interquartile range increase in PM2.5: 0.97 (95% CI 0.95, 0.99) for small for gestational age and 1.01 (95% CI 0.97, 1.06) for term low birthweight]. Findings were similar in co-pollutant models and linear models of birthweight. These results suggest that O3 concentrations in both urban and rural areas may be associated with an increased risk of term low birthweight and small for gestational age births.

Comparison of Trihalomethane exposure assessment metrics in epidemiologic analyses of reproductive and developmental outcomes.

BACKGROUND: Researchers have developed exposure assessment metrics for disinfection by-products (DBPs) utilizing drinking water monitoring data and accounting for spatial and temporal variability, water consumption, and showering and bathing time with an expectation of decreasing exposure misclassification compared to the use of measured concentrations at public water supply (PWS) monitoring locations alone. OBJECTIVE: We used exposure data collected for a previous study of DBPs to evaluate how different sources of information impact trihalomethane (THM) exposure estimates. METHODS: We compared gestational exposure estimates to THMs based on water utility monitoring data alone, statistical imputation of daily concentrations to incorporate temporal variability, and personal water consumption and use (bathing and showering). We used Spearman correlation coefficients and ranked kappa statistics to compare exposure classifications. RESULTS: Exposure estimates based on measured or imputed daily THM concentrations, self-reported consumption, or bathing and showering differed substantially from estimates based solely on concentrations from PWS quarterly monitoring reports. Ranked exposure classifications, high to low quartiles or deciles, were generally consistent across each exposure metric (i.e., a subject with "high" exposure based on measured or imputed THM concentrations generally remained in the "high" category across exposure metrics.) The measured concentrations and imputed daily (i.e., spline regression) concentrations were highly correlated (r = 0.98). The weighted kappa statistics comparing exposure estimates using different exposure metrics ranged from 0.27 to 0.89, with the highest values for the ingestion + bathing/showering metrics compared to metrics for bathing/showering only (0.76 and 0.89). Bathing and showering contributed the most to "total" THM exposure estimates. IMPACT STATEMENT: We compare exposure metrics capturing temporal variability and multiple estimates of personal THM exposure with THM concentrations from PWS monitoring data. Our results show exposure estimates based on imputed daily concentrations accounting for temporal variability were very similar to the measured THM concentrations. We observed low agreement between imputed daily concentrations and ingestion-based estimates. Considering additional routes of exposure (e.g., inhalation and dermal) slightly increased agreement with the measured PWS exposure estimate in this population. Overall, the comparison of exposure assessment metrics allows researchers to understand the added value of additional data collection for future epidemiologic analyses of DBPs.

Examining modification of the associations between air pollution and birth outcomes by neighborhood deprivation in a North Carolina birth cohort, 2011-2015.

Background: Evidence from studies of air pollutants and birth outcomes suggests an association, but uncertainties around geographical variability and modifying factors still remain. As neighborhood-level social characteristics are associated with birth outcomes, we assess whether neighborhood deprivation level is an effect measure modifier on the association between air pollution and birth outcomes in a North Carolina birth cohort. Methods: Using birth certificate data, all North Carolina residential singleton live births from 1 January 2011 to 31 December 2015 with gestational ages of 20-44 weeks (n = 566,799) were examined for birth defect diagnoses and preterm birth. Exposures were daily average fine particulate matter (PM2.5), daily 8-h maximum nitrogen dioxide (NO2), and daily 8-h maximum ozone (O3) modeled concentrations, and the modifier of interest was the neighborhood deprivation index (NDI). Linear binomial models were used to estimate the prevalence differences and 95% confidence intervals (CI) for the association between ambient air pollution and birth defect diagnoses. Modified Poisson regression models were used to estimate risk differences (RDs) and 95% CIs for air pollution and preterm birth. Models were stratified by the neighborhood deprivation index group (low, medium, or high) to assess potential modification by NDI. Results: Approximately 3.1% of the study population had at least one birth defect and 8.18% were born preterm. For preterm birth, associations with PM2.5 and O3 did not follow a conclusive pattern and there was no evidence of modification by NDI. The associations between NO2 and preterm birth were generally negative across exposure windows except for a positive association with NO2 and preterm birth for high NDI [RD: 34.70 (95% CI 4.84-64.56)] for entire pregnancy exposure. There was no evidence of associations between pollutants examined and birth defects. Conclusions: There may be differences in the association between NO2 exposure and preterm birth by NDI but we did not observe any evidence of associations for birth defects. Our results support the public health protection afforded by reductions in air pollution, even in areas of neighborhood deprivation, but future research conducted in areas with higher levels of air pollution and evaluating the potential for modification by neighborhood deprivation level would be informative.

Early prenatal exposure to air pollution and its associations with birth defects in a state-wide birth cohort from North Carolina.

BACKGROUND: Few studies have examined the potential relationship between air pollution and birth defects. The objective of this study was to investigate whether maternal exposure to particulate matter (PM2.5 ) and ozone (O3 ) during pregnancy is associated with birth defects among women living throughout North Carolina. METHODS: Information on maternal and infant characteristics was obtained from North Carolina birth certificates and health service data (2003-2005) and linked with information on birth defects from the North Carolina Birth Defects Monitoring Program. The 24-hr PM2.5 and O3 concentrations were estimated using a hierarchical Bayesian model of air pollution generated by combining modeled air pollution predictions from the U.S. Environmental Protection Agency's Community Multi-Scale Air Quality model with air monitor data from the Environmental Protection Agency's Air Quality System. Maternal residence was geocoded and assigned pollutant concentrations averaged over weeks 3 to 8 of gestation. Binomial regression was performed and adjusted for potential confounders. RESULTS: No association was observed between either PM2.5 or O3 concentrations and most birth defects. Positive effect estimates were observed between air pollution and microtia/anotia and lower limb deficiency defects, but the 95% confidence intervals were wide and included the null. CONCLUSION: Overall, this study suggested a possible relationship between air pollution concentration during early pregnancy and certain birth defects (e.g., microtia/anotia, lower limb deficiency defects), although this study did not have the power to detect such an association. The risk for most birth defects does not appear to be affected by ambient air pollution.

Associations between weekly gestational exposure of fine particulate matter, ozone, and nitrogen dioxide and preterm birth in a North Carolina Birth Cohort, 2003-2015.

Background: Preterm birth (PTB; <37 weeks completed gestation) is associated with exposure to air pollution, though variability in association magnitude and direction across exposure windows exists. We evaluated associations between weekly gestational exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) with PTB in a North Carolina Birth Cohort from 2003 to 2015 (N = 1,367,517). Methods: Daily average PM2.5 and daily 8-hour maximum NO2 concentration estimates were obtained from a hybrid ensemble model with a spatial resolution of 1 km2. Daily 8-hour maximum census tract-level concentration estimates for O3 were obtained from the EPA's Fused Air Quality Surface Using Downscaling model. Air pollutant concentrations were linked by census tract to residential address at delivery and averaged across each week of pregnancy. Modified Poisson regression models with robust errors were used to estimate risk differences (RD [95% confidence intervals (CI)]) for an interquartile range increase in pollutants per 10,000 births, adjusted for potential confounders. Results: Associations were similar in magnitude across weeks. We observed positive associations for PM2.5 and O3 exposures, but generally null associations with NO2. RDs ranged from 15 (95% CI = 11, 18) to 32 (27, 37) per 10,000 births for PM2.5; from -7 (-14, -1) to 0 (-5, 4) for NO2; and from 4 (1, 7) to 13 (10, 16) for O3. Conclusion: Our results show that increased PM2.5 exposure is associated with an increased risk of PTB across gestational weeks, and these associations persist in multipollutant models with NO2 and/or O3.

Is residential proximity to polluted sites during pregnancy associated with preterm birth or low birth weight? Results from an integrated exposure database in North Carolina (2003-2015).

BACKGROUND: Preterm birth (PTB) and term low birth weight (LBW) have been associated with pollution and other environmental exposures, but the relationship between these adverse outcomes and specific characteristics of polluted sites is not well studied. OBJECTIVES: We conducted a retrospective cohort study to examine relationships between residential proximity to polluted sites in North Carolina (NC) and PTB and LBW. We further stratified exposure to polluted sites by route of contaminant emissions and specific contaminants released at each site. METHODS: We created an integrated exposure geodatabase of polluted sites in NC from 2002 to 2015 including all landfills, Superfund sites, and industrial sites. Using birth certificates, we assembled a cohort of 1,494,651 singleton births in NC from 2003 to 2015. We geocoded the gestational parent residential address on the birth certificate, and defined exposure to polluted sites as residence within one mile of a site. We used log-binomial regression models to estimate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Binomial models were used to estimate adjusted risk differences (aRD) per 10,000 births and 95% CIs for associations between exposure to polluted sites and PTB or LBW. RESULTS: We observed weak associations between residential proximity to polluted sites and PTB [aRR(95% CI): 1.07(1.06,1.09); aRD(95% CI): 61(48,74)] and LBW [aRR(95% CI): 1.09(1.06,1.12); aRD(95% CI): 24(17,31)]. Secondary analyses showed increased risk of both PTB and LBW among births exposed to sites characterized by water emissions, air emissions, and land impoundment. In analyses of specific contaminants, increased risk of PTB was associated with proximity to sites containing arsenic, benzene, cadmium, lead, mercury, and polycyclic aromatic hydrocarbons. LBW was associated with exposure to arsenic, benzene, cadmium, lead, and mercury. SIGNIFICANCE: This study provides evidence for potential reproductive health effects of polluted sites, and underscores the importance of accounting for heterogeneity between polluted sites when considering these exposures. IMPACT STATEMENT: We documented an overall increased risk of both PTB and LBW in births with gestational exposure to polluted sites using a harmonized geodatabase of three site types, and further examined exposures stratified by site characteristics (route of emission, specific contaminants present). We observed increased risk of both PTB and LBW among births exposed to sites with water emissions or air emissions, across site types. Increased risk of PTB was associated with gestational proximity to sites containing arsenic, benzene, cadmium, lead, mercury, and polycyclic aromatic hydrocarbons; increased risk of LBW was associated with exposure to arsenic, benzene, cadmium, lead, and mercury.

Short-term exposure to air pollution and infant mortality: A systematic review and meta-analysis.

BACKGROUND AND AIM: Infant mortality is a widely reported indicator of population health and a leading public health concern. In this systematic review and meta-analysis, we review the available literature for epidemiologic evidence of the association between short-term air pollution exposure and infant mortality. METHODS: Relevant publications were identified through PubMed and Web of Science databases using comprehensive search terms and screened using predefined inclusion/exclusion criteria. We extracted data from included studies and applied a systematic rubric for evaluating study quality across domains including participant selection, outcome, exposure, confounding, analysis, selective reporting, sensitivity, and overall quality. We performed meta-analyses, using both fixed and random-effect methods, and estimated pooled odds ratios (ORs) and 95 % confidence intervals (95%CI) for pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), coarse particulate matter (PM10), fine particulate matter (PM2.5), ozone (O3), carbon monoxide (CO)) and infant mortality, neonatal mortality, or postneonatal mortality. RESULTS: Our search returned 549 studies. We excluded 490 studies in the abstract screening phase and an additional 37 studies in the full text screening phase, leaving 22 studies for inclusion. Among these 22 studies, 14 included effect estimates for PM10, 13 for O3, 11 for both NO2 and CO, 8 for SO2, and 3 for PM2.5. We did not calculate a pooled OR for PM2.5 due to the limited number of studies available and demonstrated heterogeneity in the effect estimates. The pooled ORs (95%CI) with the greatest magnitudes were for a 10-ppb increase in SO2 or NO2 concentration in the days before death (1.07 [95%CI: 1.02, 1.12], 1.04 [95%CI: 1.01, 1.08], respectively). The pooled OR for PM10 was 1.02 (95%CI: 1.00, 1.03), and the pooled ORs for CO and O3 were 1.01 (95%CI: 1.00, 1.02) and 0.99 (95%CI: 0.97, 1.01). CONCLUSIONS: Increased exposure to SO2, NO2, PM10, or CO is associated with infant mortality across studies.