Should we adjust for delivery hospital in studies of air pollution and pregnancy outcomes? Background: In conducting a study of ambient air pollution and pregnancy outcome in New York City, we identified delivery hospital as a potential confounder, given its association with both maternal residence and therefore air pollution exposure, and with clinical practices and as a potential marker of outcome misclassification in the coding of pregnancy complications. Motivated by evidence that adjustment for delivery hospital affected associations between air pollution and pregnancy outcome, we undertook a detailed empirical examination of the role of delivery hospital that warrants consideration by others addressing this topic. Methods: In a study of air pollution and pregnancy outcome, we identified births from 2008 to 2010 to residents of New York City and, after restrictions, included 238,960 in the analysis. Air pollution exposure estimates for ambient fine particles (PM2.5) and nitrogen dioxide (NO2) were derived from a community-wide exposure study and assigned based on geocoded maternal residence. We examined the impact of adjusting for delivery hospital and explored the relationship between delivery hospital and both exposure and pregnancy outcomes. Results: Statistical adjustment for delivery hospital markedly attenuated the relationship of air pollution with birth weight and gestational hypertension, with smaller effects on preterm birth and preeclampsia. Delivery hospital was associated with estimated maternal air pollution levels after adjusting for individual-level patient characteristics, more strongly for PM2.5 than for NO2. Delivery hospital predicted pregnancy outcome after adjustment for individual attributes, with larger hospitals and those that managed a greater volume of complicated cases having lower birth weight, more medically indicated preterm births, and more diagnosed gestational hypertension. Evaluation through the use of directed acyclic graphs illustrates the potential for adjustment for hospital to reduce residual spatial confounding, but also indicates the possibility of introducing bias through adjustment of a mediator. Conclusions: Based on these results, delivery hospital warrants closer consideration in studies of air pollution and other spatial factors in relation to pregnancy outcomes. The possibility of confounding by delivery hospital needs to be balanced with the risk of adjusting for a mediator of the air pollution—pregnancy outcome association in studies of this type.

Joint and independent neurotoxic effects of early life exposures to a chemical mixture: A multi-pollutant approach combining ensemble learning and G-computation Background: Exposure to mercury (Hg) is associated with adverse developmental effects. However, Hg occurs with a multitude of chemicals. We assessed the associations of developmental exposure to multiple pollutants with children’s neurodevelopment using a novel approach. Methods: Hg, polychlorinated biphenyls (PCBs), and perfluoroalkyl substances (PFASs) were measured in maternal and children’s blood at 5 years (n = 449 and 419). At 7 years, children were administered Boston Naming Test (BNT) and the Strengths and Difficulties Questionnaire (SDQ). We used the G-formula combined with SuperLearner to estimate independent and joint effects of chemicals at both ages. We constructed flexible exposure-response relationships and assessed interactions. Results: Most chemicals showed negative relationships with BNT scores. An interquartile range (IQR) increase in maternal Hg and perfluorooctanoic acid (PFOA) was associated with 0.15 standard deviation (SD) (95% confidence interval [CI] = –0.29, –0.03) and 0.14 SD (95% CI = –0.26, –0.05) lower scores in BNT, whereas a joint IQR increase in the mixture of chemicals was associated with 0.48 SD (95% CI = –0.69, –0.25) lower scores in BNT. An IQR increase in PFOA was associated with 0.11 SD (95% CI = 0.02, 0.26) higher total SDQ difficulties scores. Maternal ∑PCBs concentrations were associated with lower SDQ scores (β = –0.09 SD; 95% CI = –0.19, 0), whereas 5 years ∑PCBs showed a negative association (β = –0.09 SD; 95% CI = –0.21, 0). Finally, a joint IQR increase in the mixture was associated with 0.22 SD (95% CI = 0.04, 0.4) higher SDQ scores. Conclusions: Using a novel statistical approach, we confirmed associations between prenatal mercury exposure and lower cognitive function. The potential developmental effects of PFASs need additional attention.

Air pollution, maternal hypertensive disorders, and preterm birth Background: Air pollution has been associated with hypertension and preterm birth. We examined if prenatal exposure to air pollutants was associated with gestational hypertension and if its association with preterm birth was modified by maternal hypertension. Methods: Data were from birth certificates and hospital discharge records of 252,205 women in San Joaquin Valley of California from 2000 to 2006. Air quality data were assigned from 24-hour averages of nitrogen dioxide (NO2), particulate matter <10µm (PM10) and <2.5µm (PM2.5), and carbon monoxide (CO) for different averaging periods over pregnancy. We estimated odds of preterm birth and multiplicative interaction between each pollutant and hypertensive disorder. Results: Among normotensive women, odds of preterm birth were slightly higher for higher exposure to all pollutants over the entire pregnancy. Patterns were similar among women with a hypertensive disorder. Among 32–36 week births, there was effect modification for exposure to NO2 and CO during the first trimester with higher odds among hypertensive women, and PM2.5 and CO during the last 6 weeks with higher odds among normotensive women. For 28–31 week births, there was effect modification by hypertensive status for PM10 exposure for the entire pregnancy, first, and second trimester with hypertensive women consistently having lower odds of preterm birth than normotensive. Conclusion: There was some evidence of effect modification in the direction counter to our hypothesis for exposure to PM10 and early preterm birth, and CO and PM2.5 at the end of pregnancy, but overall, hypertension did not modify the relationship between pollution and preterm birth.

Early-life exposure to traffic-related air pollution and child anthropometry Background: Early-life exposure to traffic-related air pollution may decrease fetal growth and increase childhood obesity risk. Our objective was to evaluate the relationship of early-life exposure to traffic-related air pollution with birthweight in term newborns and obesity at age 7–8 years in two prospective birth cohorts in Cincinnati, OH (the Health Outcomes and Measures of the Environment [HOME] Study and Cincinnati Childhood Allergy and Air Pollution Study [CCAAPS]). Methods: We estimated elemental carbon attributable to traffic (ECAT) exposure at residential addresses during pregnancy with a validated land use regression model. We assessed birthweight among term infants using birth records or parent report (HOME Study n = 333 and CCAAPS n = 590). We measured children’s weight and height at 7–8 years and calculated age- and sex-specific body mass index (BMI) z-scores (HOME Study n = 198 and CCAAPS n = 459). Using multivariable linear regression, we estimated the difference in term birthweight and BMI z-score per interquartile range (IQR) increase in ECAT concentrations in each cohort separately and in the pooled sample. Results: In adjusted models, ECAT exposure was not associated with lower birthweight (pooled sample β: 30 g; 95% CI = −6, 66) or with higher BMI z-score (pooled sample β: −0.04; 95% CI = −0.15, 0.08). Infant sex modified the association between ECAT and birthweight (P = 0.05). Among male newborns, higher ECAT concentrations were associated with higher birthweight (β: 61 g; 95% CI = 9, 113), but we observed no association among female newborns (β: −9 g; 95% CI = −58, 41). Conclusions: In contrast to some prior studies, early-life traffic-related air pollution exposure was not associated with lower birthweight or increased childhood adiposity in these two cohorts.

A randomized, double-blind, crossover intervention study of traffic-related air pollution and airway inflammation in healthy adults Background: Traffic-related air pollution (TRAP) may increase the risk of respiratory disease. The components of TRAP that are responsible for its respiratory toxicity are largely unknown. The objective was to identify the component(s) of TRAP that cause airways inflammation using fractional exhaled nitric oxide (FENO) and randomized interventions. Methods: A randomized, double-blind, crossover intervention study was conducted in which 39 healthy university students spent 2 hours next to a busy road. During exposure, participants wore either a powered air-purifying respirator (PAPR) or an N95 facemask. PAPRs were fitted with a fine particle (PM2.5) filter, a PM2.5 and volatile organic carbon (VOC) filter, or a sham filter, and were blinded to filter type. The four interventions (three PAPR filters and N95) were assigned randomly for each participant and separated by at least 1 week. FENO was measured before and immediately after each roadside exposure, and at 1, 2, 4, and 6 hours after exposure. Results: With the sham PAPR filter, the mean postexposure FENO increased an average of 2.3 ppb (±4.4) compared with the pre-exposure level. Similar increases in FENO were seen with both the PM2.5 PAPR filter and the N95 mask, but no increase was seen with the combination PM2.5 and VOC PAPR filter. Conclusions: Because PAPR filters do not filter inorganic gases (e.g., NO2 or carbon monoxide), it is concluded that the VOC component of TRAP rather than either the particulate matter or the inorganic gases component is responsible for the airway inflammation caused by TRAP exposure.

Residential greenness, activities of daily living, and instrumental activities of daily living: A longitudinal cohort study of older adults in China Background: We aimed to explore whether higher levels of residential greenness were related to lower odds of disabilities in activities of daily living (ADL) and instrumental activities of daily living (IADL). Methods: We included older adults 65 years of age or older from the Chinese Longitudinal Healthy Longevity Survey. Our exposure was Normalized Difference Vegetation Index in 500 m radius around residence. Our outcome was ADL and IADL. We used binary logistic regression and mixed-effects logistic regression to estimate the odds of ADL and IADL disabilities. Results: A total of 36,803 and 32,316 participants were included for the analysis of ADL and IADL, with 71.6% free of ADL disability and 47.3% free of IADL disability. In the logistic regression model, compared with the participants living in the lowest quartile of residential greenness, those in the highest quartile had a 28% (odds ratio [OR] = 0.72; 95% confidence interval [CI] = 0.65, 0.79) lower odds of ADL disability and a 14% (OR = 0.86; 95% CI = 0.77, 0.95) lower odds of IADL disability. A similar association was found in the mixed-effects logistic regression models. During the follow-up period, 5,004 and 4,880 healthy participants developed ADL and IADL disabilities. Per 0.1-unit increase in baseline annual average Normalized Difference Vegetation Index (NDVI) was related to an OR of 0.95 of developing ADL disability (95% CI = 0.93, 0.98) and IADL disability (95% CI = 0.91, 0.98). Conclusions: Our study suggests that increasing green space is associated with lower odds of ADL and IADL disabilities, which may reduce caregiver burden of long-term care for Chinese older adults.

Prenatal exposure to metal mixture and sex-specific birth outcomes in the New Hampshire Birth Cohort Study Background: In utero exposure to individual metals may impact fetal growth, though little is known about the effects of exposure to metal mixtures. Therefore, we investigated joint effects of in utero exposure to a mixture of As (arsenic), Mn (manganese), and Pb (lead) on newborn outcomes in a United States population. Methods: Concentrations of As, Mn, and Pb were determined in maternal postpartum toenail samples, a biomarker of in utero exposure, from 989 maternal-infant pairs (492 females and 497 males). Newborns’ anthropometric characteristics, including head circumference, length, and weight, were obtained from medical records. The joint effects of the three metals were modeled using Bayesian kernel machine regression and linear regression. Both sex-combined and sex-stratified statistical analyses were performed. Results: We observed an inverted-U-shape association between maternal toenail Mn concentrations and newborn head circumference, particularly among female infants. Concentrations of Pb were related to reduced head circumference, weight, and length, especially among females at lower concentrations of the other metals. Overall, toenail As concentrations were related to reduced head circumference, especially among males, and an increase in birth length and weight among females. We found little evidence of As interactions with other metals within the mixture. Conclusions: Our findings suggest that in utero metal mixture exposures may influence birth outcomes, and that such relations may differ by infant sex.

Air pollution, neighborhood deprivation, and autism spectrum disorder in the Study to Explore Early Development Background: To examine whether neighborhood deprivation modifies the association between early life air pollution exposure and autism spectrum disorder (ASD), we used resources from a multisite case–control study, the Study to Explore Early Development. Methods: Cases were 674 children with confirmed ASD born in 2003–2006; controls were 855 randomly sampled children born during the same time period and residents of the same geographic areas as cases. Air pollution was assessed by roadway proximity and particulate matter <2.5 µm (PM2.5) exposure during pregnancy and first year of life. To characterize neighborhood deprivation, an index was created based on eight census tract-level socioeconomic status-related parameters. The continuous index was categorized into tertiles, representing low, moderate, and high deprivation. Logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: Neighborhood deprivation modified (Pfor interaction = 0.08) the association between PM2.5 exposure during the first year of life and ASD, with a stronger association for those living in high (OR = 2.42, 95% CI = 1.20, 4.86) rather than moderate (OR=1.21, 95% CI = 0.67, 2.17) or low (OR=1.46, 95% CI = 0.80, 2.65) deprivation neighborhoods. Departure from additivity or multiplicativity was not observed for roadway proximity or exposures during pregnancy. Conclusion: These results provide suggestive evidence of interaction between neighborhood deprivation and PM2.5 exposure during the first year of life in association with ASD.

A case–control study of breast cancer risk and ambient exposure to pesticides Background: While the estrogenic properties of certain pesticides have been established, associations between pesticide exposure and risk of breast cancer have been inconsistently observed. We investigated the relation between pesticide exposure and breast cancer risk using methods capable of objectively assessing exposure to specific pesticides occurring decades before diagnosis. Methods: A case–control study was conducted to evaluate the risk of postmenopausal breast cancer associated with historic pesticide exposure in California’s Central Valley, the most agriculturally productive region in the United States where pesticide drift poses a major source of nonoccupational exposure. Residential and occupational histories were linked to commercial pesticide reports and land use data to determine exposure to specific chemicals. Cases (N = 155) were recruited from a population-based cancer registry, and controls (N = 150) were obtained from tax assessor and Medicare list mailings. Results: There was no association between breast cancer and exposure to a selected group of organochlorine pesticides thought to have synergistic endocrine-disrupting potential; however, breast cancer was three times as likely to occur among women exposed to chlorpyrifos compared with those not exposed, after adjusting for exposure to other pesticides including organochlorines (OR = 3.22; 95% CI = 1.38, 7.53). Conclusions: Organophosphate pesticides, such as chlorpyrifos, have rarely been evaluated in studies of breast cancer risk. Additional research is needed to confirm these findings and to better understand the underlying mechanisms given that chlorpyrifos has been detected in local air monitoring at levels of concern for residents living in the agricultural regions where it is used.

Associations between ambient air pollution and noise from road traffic with blood pressure and insulin resistance in children from Denmark Background: Road traffic is a major source of air pollution and noise. Both exposures may contribute to increased blood pressure and metabolic disease; however, few studies have examined these relationships in children. Objectives: We aimed to investigate whether long-term exposures to air pollution and noise from road traffic were associated with increased blood pressure and insulin resistance in children. Methods: Cardiometabolic outcomes were derived from a follow-up examination of 629 children (10–15 years old) enrolled in the Danish National Birth Cohort. We evaluated associations with prenatal and postnatal residential exposure to nitrogen dioxide (NO2) and noise from road traffic (Lden) using historical addresses and linear regression models. Results: A 10-unit increase in postnatal exposure to NO2 and Lden was associated with a 0.31 (−0.87, 1.48) and 0.18 (−0.61, 0.96) mmHg changes in diastolic blood pressure, respectively. In contrast, both exposures were associated with decreased systolic blood pressure. After adjustment and mutual adjustment for NO2, exposure to Lden was associated with a statistical significant decrease in systolic blood pressure both during prenatal and postnatal life, but the majority of the associations evaluated did not reach statistical significance. Inverse associations were observed for plasma fasting glucose, insulin, and HOMA of insulin resistance for both exposures, exposure windows, before and after adjustment. Conclusions: The findings do not support evidence of associations between long-term exposures to air pollution and road traffic noise, increased blood pressure, and a metabolic profile characteristic of increased risk for glucose intolerance or type 2 diabetes later in life.