Gestational Weight Gain and Birth Outcome: A Comparison of Methods of Accounting for Gestational Age.

Cross-sectional studies of total gestational weight gain (GWG) and perinatal outcomes have used different approaches to operationalize GWG and adjust for duration of gestation. Using birth records from California (2007-2017), Nevada (2010-2017), and Oregon (2008-2017), we compared 3 commonly used approaches to estimate associations between GWG and cesarean delivery, small-for-gestational-age birth, and low birth weight (LBW): 1) the Institute of Medicine-recommended GWG ranges at a given gestational week, 2) total weight gain categories directly adjusting for gestational age as a covariate, and 3) weight-gain-for-gestational-age z scores derived from an external longitudinal reference population. Among 5,461,130 births, the 3 methods yielded similar conclusions for cesarean delivery and small-for-gestational-age birth. However, for LBW, some associations based on z scores were in the opposite direction of methods 1 and 2, paradoxically suggesting that higher GWG increases risk of LBW. This was due to a greater proportion of preterm births among those with high z scores, and controlling for gestational age in the z score model brought the results in line with the other methods. We conclude that the use of externally derived GWG z scores based on ongoing pregnancies can yield associations confounded by duration of pregnancy when the outcome is strongly associated with gestational age at delivery.

Short-term association between ambient temperature and homicide in South Africa: a case-crossover study.

BACKGROUND: Criminology research has traditionally investigated sociodemographic predictors of crime, such as sex, race, age, and socioeconomic status. However, evidence suggests that short-term fluctuations in crime often vary more than long-term trends, which sociodemographic factors cannot explain. This has redirected researchers to explore how environmental factors, such as meteorological variables, influence criminal behavior. In this study we investigate the association between daily ambient temperature and homicide incidence in South Africa, a country with one of the highest homicide rates in the world. METHODS: Mortality data was from South Africa's civil registration system and includes all recorded deaths in the country from 1997 to 2013 (17 years). Daily temperature was from the National Oceanographic and Atmospheric Association of the United States and South Africa's Agricultural Research Council. Data were analyzed using a time-stratified case-crossover design with conditional logistic regression. We delineated cases as either "definite" (ICD-10 codes X85-Y09, n = 68,356) or "probable" homicides (ICD-10 codes W25-W26, W32-W34, W50, Y22-Y24, Y28-Y29, n = 177,873). Case periods were defined as the day on which a death occurred. Control periods were selected using a day-of-week match within the same month and district. Analyses investigated same-day and lagged effects of maximum, mean and minimum temperature. RESULTS: A one-degree Celsius increase in same-day maximum temperature - our a priori metric of choice - was associated with a 1.5% (1.3-1.8%) increase in definite homicides and a 1.2% (1.1-1.3%) increase in total (definite + probable) homicides. Significant (p < 0.05) positive associations were also observed when applying other temperature metrics (mean, minimum) and lags (1, 0-1). The shape of the association did not display any clear non-linearities. There was no evidence of confounding by public holidays or air pollution. CONCLUSIONS: This study suggests a positive association between daily ambient temperature and homicide in South Africa. This temperature-health relationship may be of particular concern in the context of climate change. The ability to include meteorological variables as a predictor of criminal activity and violent behavior could prove valuable in resource allocation for crime prevention efforts.

Impact of fluid overload and infection on respiratory adverse event development during induction therapy for childhood acute myeloid leukemia.

BACKGROUND: Treatment-related morbidity and mortality occur frequently in childhood acute myeloid leukemia (AML) induction. Yet the contributions of respiratory adverse events (AEs) within this population are poorly understood. Furthermore, the roles of fluid overload (FO) and infection in AML pulmonary complications have been inadequately examined. OBJECTIVES: To describe the incidence, categories, and grades of respiratory AEs and to assess the associations of FO and infection on respiratory AE development in childhood AML induction. METHODS: We retrospectively examined the induction courses of a cohort of de novo pediatric AML patients for any NCI CTCAE grade 2 to 5 respiratory AE, FO, and systemic/pulmonary infection occurrence. Demographic, disease, and treatment-related data were abstracted. Descriptive, univariate, survival, and multivariable analyses were conducted. RESULTS: Among 105 eligible subjects from 2009 to 2016, 49.5% (n = 52) experienced 63 discrete respiratory AEs. FO occurred in 28.6% of subjects (n = 30), with half occurring within 24 hours of hospitalization. Positive FO status < 10 days (aHR 5.5, 95% CI 2.3-12.8), ≥ 10 days (aHR 13, 95% CI 4.1-41.8), and positive infection status ≥ 10 days into treatment (aHR 14.9, 5.4-41.6) were each independently associated with AE development. CONCLUSIONS: We describe a higher incidence of respiratory AEs during childhood AML induction than previously illustrated. FO occurs frequently and early in this course. Late infections and FO at any time frame were strongly associated with AE development. Interventions focused on the prevention and management of FO and infectious respiratory complications could be instrumental in reducing preventable treatment-related morbidity and mortality.

Source-Apportioned PM2.5 and Cardiorespiratory Emergency Department Visits: Accounting for Source Contribution Uncertainty.

BACKGROUND: Despite evidence suggesting that air pollution-related health effects differ by emissions source, epidemiologic studies on fine particulate matter (PM2.5) infrequently differentiate between particles from different sources. Those that do rarely account for the uncertainty of source apportionment methods. METHODS: For each day in a 12-year period (1998-2010) in Atlanta, GA, we estimated daily PM2.5 source contributions from a Bayesian ensemble model that combined four source apportionment methods including chemical transport and receptor-based models. We fit Poisson generalized linear models to estimate associations between source-specific PM2.5 concentrations and cardiorespiratory emergency department visits (n = 1,598,117). We propagated uncertainty in the source contribution estimates through analyses using multiple imputation. RESULTS: Respiratory emergency department visits were positively associated with biomass burning and secondary organic carbon. For a 1 µg/m increase in PM2.5 from biomass burning during the past 3 days, the rate of visits for all respiratory outcomes increased by 0.4% (95% CI 0.0%, 0.7%). There was less evidence for associations between PM2.5 sources and cardiovascular outcomes, with the exception of ischemic stroke, which was positively associated with most PM2.5 sources. Accounting for the uncertainty of source apportionment estimates resulted, on average, in an 18% increase in the standard error for rate ratio estimates for all respiratory and cardiovascular emergency department visits, but inflation varied across specific sources and outcomes, ranging from 2% to 39%. CONCLUSIONS: This study provides evidence of associations between PM2.5 sources and some cardiorespiratory outcomes and quantifies the impact of accounting for variability in source apportionment approaches.

Review of Acellular Assays of Ambient Particulate Matter Oxidative Potential: Methods and Relationships with Composition, Sources, and Health Effects.

Oxidative stress is a potential mechanism of action for particulate matter (PM) toxicity and can occur when the body's antioxidant capacity cannot counteract or detoxify harmful effects of reactive oxygen species (ROS) due to an excess presence of ROS. ROS are introduced to the body via inhalation of PM with these species present on and/or within the particles (particle-bound ROS) and/or through catalytic generation of ROS in vivo after inhaling redox-active PM species (oxidative potential, OP). The recent development of acellular OP measurement techniques has led to a surge in research across the globe. In this review, particle-bound ROS techniques are discussed briefly while OP measurements are the focus due to an increasing number of epidemiologic studies using OP measurements showing associations with adverse health effects in some studies. The most common OP measurement techniques, including the dithiothreitol assay, glutathione assay, and ascorbic acid assay, are discussed along with evidence for utility of OP measurements in epidemiologic studies and PM characteristics that drive different responses between assay types (such as species composition, emission source, and photochemistry). Overall, most OP assays respond to metals like copper than can be found in emission sources like vehicles. Some OP assays respond to organics, especially photochemically aged organics, from sources like biomass burning. Select OP measurements have significant associations with certain cardiorespiratory end points, such as asthma, congestive heart disease, and lung cancer. In fact, multiple studies have found that exposure to OP measured using the dithiothreitol and glutathione assays drives higher risk ratios for certain cardiorespiratory outcomes than PM mass, suggesting OP measurements may be integrating the health-relevant fraction of PM and will be useful tools for future health analyses. The compositional impacts, including species and emission sources, on OP could have serious implications for health-relevant PM exposure. Though more work is needed, OP assays show promise for health studies as they integrate the impacts of PM species and properties on catalytic redox reactions into one measurement, and current work highlights the importance of metals, organic carbon, vehicles, and biomass burning emissions to PM exposures that could impact health.

Impact of air pollution control policies on cardiorespiratory emergency department visits, Atlanta, GA, 1999-2013.

BACKGROUND: Air pollution control policies resulting from the 1990 Clean Air Act Amendments were aimed at reducing pollutant emissions, ambient concentrations, and ultimately adverse health outcomes. OBJECTIVES: As part of a comprehensive air pollution accountability study, we used a counterfactual study design to estimate the impact of mobile source and electricity generation control policies on health outcomes in the Atlanta, GA, metropolitan area from 1999 to 2013. METHODS: We identified nine sets of pollution control policies, estimated changes in emissions in the absence of these policies, and employed those changes to estimate counterfactual daily ambient pollutant concentrations at a central monitoring location. Using a multipollutant Poisson time-series model, we estimated associations between observed pollutant levels and daily counts of cardiorespiratory emergency department (ED) visits at Atlanta hospitals. These associations were then used to estimate the number of ED visits prevented due to control policies, comparing observed to counterfactual daily concentrations. RESULTS: Pollution control policies were estimated to substantially reduce ambient concentrations of the nine pollutants examined for the period 1999-2013. We estimated that pollutant concentration reductions resulting from the control policies led to the avoidance of over 55,000 cardiorespiratory disease ED visits in the five-county metropolitan Atlanta area, with greater proportions of visits prevented in later years as effects of policies became more fully realized. During the final two years of the study period, 2012-2013, the policies were estimated to prevent 16.5% of ED visits due to asthma (95% interval estimate: 7.5%, 25.1%), 5.9% (95% interval estimate: -0.4%, 12.3%) of respiratory ED visits, and 2.3% (95% interval estimate: -1.8%, 6.2%) of cardiovascular disease ED visits. DISCUSSION: Pollution control policies resulting from the 1990 Clean Air Act Amendments led to substantial estimated reductions in ambient pollutant concentrations and cardiorespiratory ED visits in the Atlanta area.

Characterization of the concentration-response curve for ambient ozone and acute respiratory morbidity in 5 US cities.

Although short-term exposure to ambient ozone (O3) can cause poor respiratory health outcomes, the shape of the concentration-response (C-R) between O3 and respiratory morbidity has not been widely investigated. We estimated the effect of daily O3 on emergency department (ED) visits for selected respiratory outcomes in 5 US cities under various model assumptions and assessed model fit. Population-weighted average 8-h maximum O3 concentrations were estimated in each city. Individual-level data on ED visits were obtained from hospitals or hospital associations. Poisson log-linear models were used to estimate city-specific associations between the daily number of respiratory ED visits and 3-day moving average O3 levels controlling for long-term trends and meteorology. Linear, linear-threshold, quadratic, cubic, categorical, and cubic spline O3 C-R models were considered. Using linear C-R models, O3 was significantly and positively associated with respiratory ED visits in each city with rate ratios of 1.02-1.07 per 25 ppb. Models suggested that O3-ED C-R shapes were linear until O3 concentrations of roughly 60 ppb at which point risk continued to increase linearly in some cities for certain outcomes while risk flattened in others. Assessing C-R shape is necessary to identify the most appropriate form of the exposure for each given study setting.

Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis.

BACKGROUND: Numerous studies indicate caesarean delivery is associated with childhood asthma. Sex-specific associations were reported in four of these studies, and in all four studies, the estimated association between caesarean delivery and asthma was of greater magnitude among girls, although most report a lack of evidence of multiplicative interaction. METHODS: We assessed potential effect modification by sex, on the additive and multiplicative scales, of the association between caesarean delivery and asthma by ages 2 through 6 in up to 17 075 racially diverse children from a retrospective birth cohort, the Kaiser Air Pollution and Pediatric Asthma (KAPPA) Study. We also conducted a random-effects meta-analysis, combining our sex-stratified results (using the odds ratio for compatibility with previous studies) with previously published results. RESULTS: Adjusted risk differences for caesarean delivery and asthma in the KAPPA cohort were higher among girls than boys at every follow-up age. By age 5, caesarean delivery was associated with an absolute 3.8% (95% confidence interval [CI] 0.4%, 7.3%) higher asthma risk among girls and a 1.9% (95% CI -1.7, 5.4) higher risk among boys. The summary odds ratio from the meta-analysis for caesarean delivery and asthma among girls was 1.26 (95% CI 1.14, 1.39) and 1.08 (95% CI 0.98, 1.20) among boys (P = 0.036). CONCLUSIONS: Higher, but imprecise, estimates for females across five studies should motivate investigators to estimate sex-specific associations for caesarean delivery and asthma and to explore biological mechanisms or sex-dependent biases that could explain this possible heterogeneity.

Associations of mobile source air pollution during the first year of life with childhood pneumonia, bronchiolitis, and otitis media.

BACKGROUND: Exposure to pollution from motor vehicles in early life may increase susceptibility to common pediatric infections. METHODS: We estimated associations between residential exposure to primary fine particulate matter (PM2.5), nitrogen oxides (NOx), and carbon monoxide (CO) from traffic during the first year of life and incident pneumonia, bronchiolitis, and otitis media events by age two years in 22,441 children from the Kaiser Air Pollution and Pediatric Asthma Study, a retrospective birth cohort of children born during 2000-2010 and insured by Kaiser Permanente Georgia. Time to first clinical diagnosis of each outcome was defined using medical records. Exposure to traffic pollutants was based on observation-calibrated estimates from A Research LINE-source dispersion model for near surface releases (RLINE) and child residential histories. Associations were modeled using Cox proportional hazards models, with exposure as a continuous linear variable, a natural-log transformed continuous variable, and categorized by quintiles. RESULTS: During follow-up 2,181 children were diagnosed with pneumonia, 5,533 with bronchiolitis, and 14,373 with otitis media. We observed positive associations between early-life traffic exposures and all three outcomes; confidence intervals were widest for pneumonia as it was the least common outcome. For example, adjusted hazard ratios for a 1-unit increase in NOx on the natural log scale (a 2.7-fold increase) were 1.19 (95% CI 1.12, 1.27) for bronchiolitis, 1.17 (1.12, 1.22) for otitis media, and 1.08 (0.97, 1.20) for pneumonia. CONCLUSIONS: Our results provide evidence for modest, positive associations between exposure to traffic emissions and common pediatric infections during early childhood.

A Long-term Safety Study of Latanoprost in Pediatric Patients With Glaucoma and Ocular Hypertension: A Prospective Cohort Study.

PURPOSE: The objective was to assess the long-term effect of treatment with latanoprost on ocular development and safety in pediatric patients with glaucoma and ocular hypertension. DESIGN: Prospective cohort study. METHODS: This was a prospective 3-year cohort study conducted in 14 countries in Europe and South America. Patients aged < 18 years with glaucoma or ocular hypertension were enrolled into either the latanoprost or non-prostaglandin (non-PG) group in this observational study. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline to 3 years. Several secondary endpoints were evaluated, including corneal thickness and ocular hyperpigmentation. For treatment comparison, analysis of covariance (ANCOVA) was used for continuous endpoints and Fisher exact test was applied for proportion of participants with clinically significant deterioration events. RESULTS: A total of 175 patients were enrolled: 102 in the latanoprost group (median follow-up: 36.7 months) and 73 in the non-PG group (median follow-up: 36.1 months). There was no statistically significant difference between the latanoprost and the non-PG groups (aged 5 to <18 years) in BCVA change from baseline (least square mean logMAR difference -0.03 [95% confidence interval: -0.12, 0.06]), corneal thickness, or ocular hyperpigmentation. CONCLUSIONS: Latanoprost had an acceptable safety profile with no evidence of inducing clinically meaningful or statistically significant changes in ocular development or ocular hyperpigmentation in pediatric patients with glaucoma and ocular hypertension.

Associations between birth outcomes and maternal PM2.5 exposure in Shanghai: A comparison of three exposure assessment approaches.

BACKGROUND: Few studies have estimated effects of maternal PM2.5 exposure on birth outcomes in China due to the lack of historical air pollution data. OBJECTIVES: We estimated the associations between maternal PM2.5 exposure and birth outcomes using gap-filled satellite estimates in Shanghai, China. METHODS: We obtained birth registration records of 132,783 singleton live births during 2011-2014 in Shanghai. PM2.5 exposures were assessed from satellite-derived estimates or central-site measurements. Linear and logistic regressions were used to estimate associations with term birth weight and term low birth weight (LBW), respectively. Logistic and discrete-time survival models were used to estimate associations with preterm birth. Effect modification by maternal age and parental education levels was investigated. RESULTS: A 10 µg/m3 increase in gap-filled satellite-based whole-pregnancy PM2.5 exposure was associated with a -12.85 g (95% CI: -18.44, -7.27) change in term birth weight, increased risk of preterm birth (OR 1.27, 95% CI: 1.20, 1.36), and increased risk of term LBW (OR 1.22, 95% CI: 1.06, 1.41). Sensitivity analyses during 2013-2014, when ground PM2.5 measurements were available, showed that the health associations using gap-filled satellite PM2.5 concentrations were higher than those obtained using satellite PM2.5 concentrations without accounting for missingness. The health associations using gap-filled satellite PM2.5 had similar magnitudes to those using central-site measurements, but with narrower confidence intervals. CONCLUSIONS: The magnitude of associations between maternal PM2.5 exposure and adverse birth outcomes in Shanghai was higher than previous findings. One reason could be reduced exposure error of the gap-filled high-resolution satellite PM2.5 estimates.

Effect of infant feeding practices on iron status in a cohort study of Bolivian infants.

BACKGROUND: Iron deficiency (ID) is the most common micronutrient deficiency worldwide, with potentially severe consequences on child neurodevelopment. Though exclusive breastfeeding (EBF) is recommended for 6 months, breast milk has low iron content. This study aimed to estimate the effect of the length of EBF on iron status at 6 - 8 months of age among a cohort of Bolivian infants. METHODS: Mother-infant pairs were recruited from 2 hospitals in El Alto, Bolivia, and followed from one through 6 - 8 months of age. Singleton infants > 34 weeks gestational age, iron-sufficient at baseline, and completing blood draws at 2 and 6 - 8 months of age were eligible for inclusion (N = 270). Ferritin was corrected for the effect of inflammation. ID was defined as inflammation-corrected ferritin < 12 µg/L, and anemia was defined as altitude-corrected hemoglobin < 11 g/dL; IDA was defined as ID plus anemia. The effect of length of EBF (infant received only breast milk with no other liquids or solids, categorized as < 4, 4 - 6, and > 6 months) was assessed for ID, IDA, and anemia (logistic regression) and ferritin (Fer) and hemoglobin (Hb, linear regression). RESULTS: Low iron status was common among infants at 6 - 8 months: 56% of infants were ID, 76% were anemic, and 46% had IDA. EBF of 4 months and above was significantly associated with ID as compared with EBF <  4 months (4 - 6 months: OR 2.0 [1.1 - 3.4]; > 6 months: 3.3 [1.0 - 12.3]), but not with IDA (4 - 6 months: OR 1.4 [0.8 - 2.4]; > 6 months: 2.2 [0.7 - 7.4]), or anemia (4 - 6 months: OR 1.4 [0.7 - 2.5]; > 6 months: 1.5 [0.7 - 7.2]). Fer and Hb concentrations were significantly lower with increasing months of EBF. CONCLUSIONS: Results suggest a relationship between prolonged EBF and ID, but are not sufficient to support changes to current breastfeeding recommendations. More research is needed in diverse populations, including exploration of early interventions to address infant IDA.

Estimating Acute Cardiovascular Effects of Ambient PM2.5 Metals.

BACKGROUND: Few epidemiologic studies have investigated health effects of water-soluble fractions of PM2.5 metals, the more biologically accessible fractions of metals, in their attempt to identify health-relevant components of ambient PM2.5. OBJECTIVES: In this study, we estimated acute cardiovascular effects of PM2.5 components in an urban population, including a suite of water-soluble metals that are not routinely measured at the ambient level. METHODS: Ambient concentrations of criteria gases, PM2.5, and PM2.5 components were measured at a central monitor in Atlanta, Georgia, during 1998-2013, with some PM2.5 components only measured during 2008-2013. In a time-series framework using Poisson regression, we estimated associations between these pollutants and daily counts of emergency department (ED) visits for cardiovascular diseases in the five-county Atlanta area. RESULTS: Among the PM2.5 components we examined during 1998-2013, water-soluble iron had the strongest estimated effect on cardiovascular outcomes [RÍ¡R=1.012 (95% CI: 1.005, 1.019), per interquartile range increase (20.46ng/m3)]. The associations for PM2.5 and other PM2.5 components were consistent with the null when controlling for water-soluble iron. Among PM2.5 components that were only measured during 2008-2013, water-soluble vanadium was associated with cardiovascular ED visits [RÍ¡R=1.012 (95% CI: 1.000, 1.025), per interquartile range increase (0.19ng/m3)]. CONCLUSIONS: Our study suggests cardiovascular effects of certain water-soluble metals, particularly water-soluble iron. The observed associations with water-soluble iron may also point to certain aspects of traffic pollution, when processed by acidifying sulfate, as a mixture harmful for cardiovascular health. https://doi.org/10.1289/EHP2182.

Exposure to Mobile Source Air Pollution in Early-life and Childhood Asthma Incidence: The Kaiser Air Pollution and Pediatric Asthma Study.

BACKGROUND: Early-life exposure to traffic-related air pollution exacerbates childhood asthma, but it is unclear what role it plays in asthma development. METHODS: The association between exposure to primary mobile source pollutants during pregnancy and during infancy and asthma incidence by ages 2 through 6 was examined in the Kaiser Air Pollution and Pediatric Asthma Study, a racially diverse birth cohort of 24,608 children born between 2000 and 2010 and insured by Kaiser Permanente Georgia. We estimated concentrations of mobile source fine particulate matter (PM2.5, µg/m), nitrogen oxides (NOX, ppb), and carbon monoxide (CO, ppm) at the maternal and child residence using a Research LINE source dispersion model for near-surface releases. Asthma was defined using diagnoses and medication dispensings from medical records. We used binomial generalized linear regression to model the impact of exposure continuously and by quintiles on asthma risk. RESULTS: Controlling for covariates and modeling log-transformed exposure, a 2.7-fold increase in first year of life PM2.5 was associated with an absolute 4.1% (95% confidence interval, 1.6%, 6.6%) increase in risk of asthma by age 5. Quintile analysis showed an increase in risk from the first to second quintile, but similar risk across quintiles 2-5. Risk differences increased with follow-up age. Results were similar for NOX and CO and for exposure during pregnancy and the first year of life owing to high correlation. CONCLUSIONS: Results provide limited evidence for an association of early-life mobile source air pollution with childhood asthma incidence with a steeper concentration-response relationship observed at lower levels of exposure.

Erratum: Associations between Ambient Fine Particulate Oxidative Potential and Cardiorespiratory Emergency Department Visits.

[This corrects the article DOI: 10.1289/EHP1545.].

Associations between Ambient Fine Particulate Oxidative Potential and Cardiorespiratory Emergency Department Visits.

BACKGROUND: Oxidative potential (OP) has been proposed as a measure of toxicity of ambient particulate matter (PM). OBJECTIVES: Our goal was to address an important research gap by using daily OP measurements to conduct population-level analysis of the health effects of measured ambient OP. METHODS: A semi-automated dithiothreitol (DTT) analytical system was used to measure daily average OP (OPDTT) in water-soluble fine PM at a central monitor site in Atlanta, Georgia, over eight sampling periods (a total of 196 d) during June 2012-April 2013. Data on emergency department (ED) visits for selected cardiorespiratory outcomes were obtained for the five-county Atlanta metropolitan area. Poisson log-linear regression models controlling for temporal confounders were used to conduct time-series analyses of the relationship between daily counts of ED visits and either the 3-d moving average (lag 0-2) of OPDTT or same-day OPDTT. Bipollutant regression models were run to estimate the health associations of OPDTT while controlling for other pollutants. RESULTS: OPDTT was measured for 196 d (mean=0.32 nmol/min/m3, interquartile range=0.21). Lag 0-2 OPDTT was associated with ED visits for respiratory disease (RR=1.03, 95% confidence interval (CI): 1.00, 1.05 per interquartile range increase in OPDTT), asthma (RR=1.12, 95% CI: 1.03, 1.22), and ischemic heart disease (RR=1.19, 95% CI: 1.03, 1.38). Same-day OPDTT was not associated with ED visits for any outcome. Lag 0-2 OPDTT remained a significant predictor of asthma and ischemic heart disease in most bipollutant models. CONCLUSIONS: Lag 0-2 OPDTT was associated with ED visits for multiple cardiorespiratory outcomes, providing support for the utility of OPDTT as a measure of fine particle toxicity. https://doi.org/10.1289/EHP1545.

A New Method for Partial Correction of Residual Confounding in Time-Series and Other Observational Studies.

Methods exist to detect residual confounding in epidemiologic studies. One requires a negative control exposure with 2 key properties: 1) conditional independence of the negative control and the outcome (given modeled variables) absent confounding and other model misspecification, and 2) associations of the negative control with uncontrolled confounders and the outcome. We present a new method to partially correct for residual confounding: When confounding is present and our assumptions hold, we argue that estimators from models that include a negative control exposure with these 2 properties tend to be less biased than those from models without it. Using regression theory, we provide theoretical arguments that support our claims. In simulations, we empirically evaluated the approach using a time-series study of ozone effects on asthma emergency department visits. In simulations, effect estimators from models that included the negative control exposure (ozone concentrations 1 day after the emergency department visit) had slightly or modestly less residual confounding than those from models without it. Theory and simulations show that including the negative control can reduce residual confounding, if our assumptions hold. Our method differs from available methods because it uses a regression approach involving an exposure-based indicator rather than a negative control outcome to partially correct for confounding.

A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

BACKGROUND: Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations. OBJECTIVE: We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations. METHODS: In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30-65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005-2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause. RESULTS: Menopause and eGFR were significantly associated with measured (trend tests: p = 0.013, p = 0.0005, respectively) but not with modeled serum PFOA (p = 0.50, p = 0.76, respectively). Measured PFOA levels increased for the first 7 years after menopause (trend test, p < 0.0001), providing further evidence that the observed association between measured PFOA and menopause is subject to reverse causation for this outcome. CONCLUSION: Our results support the conjecture that in previous studies, earlier menopause and reduced kidney function are the causes rather than the results of increased measured serum PFOA. These results suggest caution in using biomarkers in cross-sectional studies. Citation: Dhingra R, Winquist A, Darrow LA, Klein M, Steenland K. 2017. A study of reverse causation: examining the associations of perfluorooctanoic acid serum levels with two outcomes. Environ Health Perspect 125:416-421; http://dx.doi.org/10.1289/EHP273.

Estimating Acute Cardiorespiratory Effects of Ambient Volatile Organic Compounds.

BACKGROUND: The health effects of ambient volatile organic compounds (VOCs) have received less attention in epidemiologic studies than other commonly measured ambient pollutants. In this study, we estimated acute cardiorespiratory effects of ambient VOCs in an urban population. METHODS: Daily concentrations of 89 VOCs were measured at a centrally-located ambient monitoring site in Atlanta and daily counts of emergency department visits for cardiovascular diseases and asthma in the five-county Atlanta area were obtained for the 1998-2008 period. To understand the health effects of the large number of species, we grouped these VOCs a priori by chemical structure and estimated the associations between VOC groups and daily counts of emergency department visits in a time-series framework using Poisson regression. We applied three analytic approaches to estimate the VOC group effects: an indicator pollutant approach, a joint effect analysis, and a random effect meta-analysis, each with different assumptions. We performed sensitivity analyses to evaluate copollutant confounding. RESULTS: Hydrocarbon groups, particularly alkenes and alkynes, were associated with emergency department visits for cardiovascular diseases, while the ketone group was associated with emergency department visits for asthma. CONCLUSIONS: The associations observed between emergency department visits for cardiovascular diseases and alkenes and alkynes may reflect the role of traffic exhaust, while the association between asthma visits and ketones may reflect the role of secondary organic compounds. The different patterns of associations we observed for cardiovascular diseases and asthma suggest different modes of action of these pollutants or the mixtures they represent.

Measurement error in mobile source air pollution exposure estimates due to residential mobility during pregnancy.

Prenatal air pollution exposure is frequently estimated using maternal residential location at the time of delivery as a proxy for residence during pregnancy. We describe residential mobility during pregnancy among 19,951 children from the Kaiser Air Pollution and Pediatric Asthma Study, quantify measurement error in spatially resolved estimates of prenatal exposure to mobile source fine particulate matter (PM2.5) due to ignoring this mobility, and simulate the impact of this error on estimates of epidemiologic associations. Two exposure estimates were compared, one calculated using complete residential histories during pregnancy (weighted average based on time spent at each address) and the second calculated using only residence at birth. Estimates were computed using annual averages of primary PM2.5 from traffic emissions modeled using a Research LINE-source dispersion model for near-surface releases (RLINE) at 250 m resolution. In this cohort, 18.6% of children were born to mothers who moved at least once during pregnancy. Mobile source PM2.5 exposure estimates calculated using complete residential histories during pregnancy and only residence at birth were highly correlated (rS>0.9). Simulations indicated that ignoring residential mobility resulted in modest bias of epidemiologic associations toward the null, but varied by maternal characteristics and prenatal exposure windows of interest (ranging from -2% to -10% bias).