Associations between prenatal exposure to polycyclic aromatic hydrocarbons and thyroid hormones in umbilical cord blood.

We explored the association between maternal urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid hormones in umbilical cord blood in 120 pairs of pregnant women and newborns. Maternal urinary PAH metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Thyroid hormones were measured using a flow fluorescence assay. The dose-response relationship between PAH metabolites and thyroid hormones was analyzed using the generalized linear model and restricted cubic spline model. Results showed that Æ©OH PAHs in maternal urine had a negative effect on triiodothyronine (T3). Associations between maternal urinary PAH metabolites and thyroid hormones in umbilical cord blood plasma were observed. Prenatal exposure to PAHs could affect neonatal thyroid hormones, thereby disrupting neonatal thyroid function.

Mitochondrial DNA copy number dynamics and associations with the prenatal environment from birth through adolescence in a population of Dominican and African American children.

Mitochondrial DNA copy number (mtDNAcn) dynamics throughout childhood are poorly understood. We profiled mtDNAcn from birth through adolescence and evaluated how the prenatal environment influences mtDNAcn across childhood. Data were collected from children from New York City followed through 18 years. Using duplexed qRT-PCR, we quantified mtDNAcn relative to nuclear DNA in blood collected from the umbilical cord (n = 450), children aged 5-7 (n = 510), and adolescents aged 15-18 (n = 278). We examined mtDNAcn across childhood with linear mixed-effects models (LMM). Relative mtDNAcn was lowest at birth (mean ± SD: 0.67 ± 0.35) and increased in childhood (1.24 ± 0.50) then slightly declined in adolescence (1.13 ± 0.44). We observed no differences in mtDNAcn by sex or race/ethnicity. mtDNAcn was positively associated with prenatal environmental tobacco smoke exposure (0.077 [ 0.01, 0.14] change in relative mtDNAcn) but negatively associated with maternal completion of high school (-0.066 [-0.13, 0.00]), with the receipt of public assistance at birth (-0.074 [-0.14, -0.01]), and when mother born outside the U.S (-0.061 [-0.13, 0.003]). Infant birth outcomes were not associated with mtDNAcn. MtDNAcn levels were dynamic through childhood and associated with some prenatal factors, underscoring the need for the investigation of longitudinal mtDNAcn for human health research.

Race Differences in Telomere Length in Benign Prostate Biopsies and Subsequent Risk of Prostate Cancer.

BACKGROUND: Telomere shortening is linked to aging and may be associated with increased risk for cancer. Most cancer studies have used telomere length in leukocytes rather than in the target tissue of cancer origin. METHODS: A case-control study of 524 case-control pairs with a benign prostate biopsy nested within a historical cohort of 10,478 men was conducted to determine whether premalignant prostate telomere length (assessed using a modified qRT-PCR) is associated with prostate cancer risk. RESULTS: Telomere lengths in benign prostate biopsies of cases versus controls were similar (1.46 ± 0.38 vs. 1.45 ± 0.42; P = 0.49). African American (AA) men had significantly shorter telomeres compared with White men (1.51 ± 0.38 vs. 1.63 ± 0.39; P < 0.0001). In race-stratified analyses, increasing telomere length was more strongly associated with prostate cancer risk in White men, wherein those with telomere length in the highest quartile had 1.9-fold greater adjusted risk of prostate cancer compared with men with prostate telomere lengths in the lowest quartile [OR = 1.90; 95% confidence interval (CI) = 1.08-3.36]. Men in the highest telomere length quartile also had a greater risk of aggressive prostate cancer compared with men with telomere lengths in the lowest quartile (OR = 2.78; 95% CI = 1.25-6.19). CONCLUSIONS: White men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease. IMPACT: Race-specific telomere length measures may be an early biomarker of aggressive prostate cancer.

Prenatal PM2.5 Exposure in Relation to Maternal and Newborn Telomere Length at Delivery.

Particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) is a ubiquitous air pollutant that is increasingly threatening the health of adults and children worldwide. One health impact of elevated PM2.5 exposure is alterations in telomere length (TL)-protective caps on chromosome ends that shorten with each cell division. Few analyses involve prenatal PM2.5 exposure, and paired maternal and cord TL measurements. Here, we analyzed the association between average and trimester-specific prenatal PM2.5 exposure, and maternal and newborn relative leukocyte TL measured at birth among 193 mothers and their newborns enrolled in a New-York-City-based birth cohort. Results indicated an overall negative relationship between prenatal PM2.5 and maternal TL at delivery, with a significant association observed in the second trimester (ß = -0.039, 95% CI: -0.074, -0.003). PM2.5 exposure in trimester two was also inversely related to cord TL; however, this result did not reach statistical significance (ß = -0.037, 95% CI: -0.114, 0.039), and no clear pattern emerged between PM2.5 and cord TL across the different exposure periods. Our analysis contributes to a limited body of research on ambient air pollution and human telomeres, and emphasizes the need for continued investigation into how PM2.5 exposure during pregnancy influences maternal and newborn health.

Racial differences in the systemic inflammatory response to prostate cancer.

Systemic inflammation may increase risk for prostate cancer progression, but the role it plays in prostate cancer susceptibility is unknown. From a cohort of over 10,000 men who had either a prostate biopsy or transurethral resection that yielded a benign finding, we analyzed 517 incident prostate cancer cases identified during follow-up and 373 controls with one or more white blood cell tests during a follow-up period between one and 18 years. Multilevel, multivariable longitudinal models were fit to two measures of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), to determine NLR and MLR trajectories associated with increased risk for prostate cancer. For both measures, we found no significant differences in the trajectories by case/control status, however in modeling NLR trajectories there was a significant interaction between race (white or Black and case-control status. In race specific models, NLR and MLR values were consistently higher over time among white controls than white cases while case-control differences in NLR and MLR trajectories were not apparent among Black men. When cases were classified as aggressive as compared to non-aggressive, the case-control differences in NLR and MLR values over time among white men were most apparent for non-aggressive cases. For NLR among white men, significant case-control differences were observed for the entire duration of observation for men who had inflammation in their initial prostate specimen. It is possible that, among white men, monitoring of NLR and MLR trajectories after an initial negative biopsy may be useful in monitoring prostate cancer risk.

Telomere dynamics across the early life course: Findings from a longitudinal study in children.

Telomeres are protective caps on chromosome ends that shorten with each cell division. Telomere length (TL) predicts the onset of cellular senescence and correlates with longevity and age-related disease risk. Previous research suggests that adults display fixed ranking and tracking of TL by age 20 years, supporting the importance of TL at birth and attrition during childhood. However, longitudinal research examining telomere dynamics during early life is sparse. Here, we used monochrome multiplex quantitative polymerase chain reaction to measure relative TL in leukocytes isolated from cord blood and child blood collected at ages 3, 5, 7, and 9 years among 224 minority children enrolled in a New York City-based birth cohort. We also measured maternal TL at delivery in a subset of 197 participants with a biobanked blood sample. TL decreased most rapidly in the first years of life (birth to 3 years), followed by a period of maintenance into the pre-puberty period. Mothers with longer telomeres gave birth to newborns with longer telomeres that remained longer across childhood, suggesting that the fixed ranking and tracking of TL observed among adults may extend to early childhood or even the prenatal period with a potential transgenerational basis. We did not find significant sex differences in the pattern of child TL change across development. These findings emphasize the need to understand factors and mechanisms that determine TL during early childhood.

Growth and differentiation factor 15 and NF-κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection.

Growth and differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1), may act as both a tumor suppressor and promotor and, by regulating NF-κB and macrophage signaling, promote early prostate carcinogenesis. To determine whether expression of these two inflammation-related proteins affect prostate cancer susceptibility, dual immunostaining of benign prostate biopsies for GDF-15 and NF-κB was done in a study of 503 case-control pairs matched on date, age, and race, nested within a historical cohort of 10,478 men. GDF-15 and NF-κB expression levels were positively correlated (r = 0.39; p < 0.0001), and both were significantly lower in African American (AA) compared with White men. In adjusted models that included both markers, the odds ratio (OR) for NF-κB expression was statistically significant, OR =0.87; p = 0.03; 95% confidence interval (CI) =0.77-0.99, while GDF-15 expression was associated with a nominally increased risk, OR =1.06; p = 0.27; 95% CI =0.96-1.17. When modeling expression levels by quartiles, the highest quartile of NF-κB expression was associated with almost a fifty percent reduction in prostate cancer risk (OR =0.51; p = 0.03; 95% CI =0.29-0.92). In stratified models, NF-κB had the strongest negative association with prostate cancer in non-aggressive cases (p = 0.03), older men (p = 0.03), and in case-control pairs with longer follow-up (p = 0.02). Risk associated with GDF-15 expression was best fit using nonlinear regression modeling where both first (p = 0.02) and second (p = 0.03) order GDF-15 risk terms were associated with significantly increased risk. This modeling approach also revealed significantly increased risk associated with GDF-15 expression for subsamples defined by AA race, aggressive disease, younger age, and in case-control pairs with longer follow-up. Therefore, although positively correlated in benign prostatic biopsies, NF-κB and GDF-15 expression appear to exert opposite effects on risk of prostate tumor development.

The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis.

M2 (tumor-supportive) macrophages may upregulate growth differentiation factor 15 (GDF15), which is highly expressed in prostate tumors, but the combined utility of these markers as prognostic biomarkers are unclear. We retrospectively studied 90 prostate cancer cases that underwent radical prostatectomy as their primary treatment and were followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least 1 year or more before their prostate cancer surgery. Using computer algorithms to analyze digitalized immunohistochemically stained slides, GDF15 expression and the presence of M2 macrophages based on the relative density of CD204- and CD68-positive macrophages were measured in prostate: (i) benign biopsy, (ii) cancer and (iii) tumor-adjacent benign (TAB) tissue. Both M2 macrophages (P = 0.0004) and GDF15 (P < 0.0001) showed significant inter-region expression differences. Based on a Cox proportional hazards model, GDF15 expression was not associated with BCR but, in men where GDF15 expression differences between cancer and TAB were highest, the risk of BCR was significantly reduced (hazard ratio = 0.26; 95% confidence interval = 0.09-0.94). In addition, cases with high levels of M2 macrophages in prostate cancer had almost a 5-fold increased risk of BCR (P = 0.01). Expression of GDF15 in prostate TAB was associated with M2 macrophage levels in both prostate cancer and TAB and appeared to moderate M2-macrophage-associated BCR risk. In summary, the relationship of GDF15 expression and CD204-positive M2 macrophage levels is different in a prostate tumor environment compared with an earlier benign biopsy and, collectively, these markers may predict aggressive disease.

The associations between prenatal exposure to polycyclic aromatic hydrocarbon metabolites, umbilical cord blood mitochondrial DNA copy number, and children's neurobehavioral development.

Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy is a risk factor for adverse neurobehavioral development outcomes. Mitochondrial DNA are sensitive to environmental toxicants due to the limited ability of repairing. The change of mitochondrial DNA copy number (mtDNAcn) might be a biologically mechanism linking PAH exposure and children's neurobehavioral impairment. Our aims are to explore whether PAH metabolites in maternal urine were associated with children's neurobehavioral development at 2 years old and umbilical cord blood mtDNAcn, and whether mtDNAcn was a mediator of PAH-related neurobehavioral development. We included 158 non-smoking pregnant women from Taiyuan City, Shanxi Province. Maternal urinary eleven PAH metabolites were detected by high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). MtDNAcn in cord blood was detected by real time quantitative polymerase chain reaction (RT-PCR). Children's neurodevelopment was measured by Gesell Developmental Schedules (GDS) when children were two years age. Generalized linear models and restricted cubic spline models were applied to assess the relationships between PAH metabolites in maternal urine and GDS scores and mtDNAcn. A mediation analysis was also conducted. Generalized linear models showed the relationships of sum of PAH metabolites (Σ-OHPAHs) in maternal urine with decreased motor score, and Σ-OHPAHs with increased mtDNAcn (p for trend < 0.05). Urinary levels of Ln (Σ-OHPAHs) increased one unit was related to a 2.08 decreased in motor scores, and Ln (Σ-OHPAHs) increased one unit was related to 0.15 increased in mtDNAcn. Mediation analysis did not find mtDNAcn can be a mediator between PAH metabolites and neurobehavioral development. Our results suggest that prenatal exposure to PAH decreased children's neurobehavioral development scores and increased mtDNAcn. And reducing exposure to PAH during pregnancy will benefit to improving neurobehavioral development in children. In our present cohort study, sum of PAH metabolites in urine of pregnant women were related with motor score and were positively associated with umbilical cord blood mtDNA copy number.

Prenatal exposure to polycyclic aromatic hydrocarbons modifies the effects of early life stress on attention and Thought Problems in late childhood.

BACKGROUND: Risk for childhood psychopathology is complex and multifactorial, implicating direct and interacting effects of familial and environmental factors. The role of environmental neurotoxicants in psychiatric risk is of growing concern, including polycyclic aromatic hydrocarbons (PAH), common in air pollution. Prenatal PAH exposure is linked to adverse physical, behavioral, and cognitive outcomes as well as increasing psychiatric risk. It is unclear whether environmental exposures, like PAH, magnify the effects of exposure to early life stress (ELS), a critical risk factor for psychopathology. The current work aimed to test potential interactions between prenatal PAH exposure and psychosocial/socioeconomic stress on psychiatric symptoms in school-age children. METHODS: Data were from the Columbia Center for Children's Environmental Health Mothers and Newborns longitudinal birth cohort study. Prenatal PAH exposure was ascertained though air monitoring during pregnancy and maternal PAH-DNA adducts at delivery. Mothers reported on ELS (child age 5) and on child psychiatric symptoms across childhood (child age 5, 7, 9, and 11) using the Child Behavior Checklist (CBCL). RESULTS: Significant prenatal airborne PAH × ELS interactions (FDR-corrected) predicted CBCL Attention (ß = 0.22, t(307) = 3.47, p < .001, pfdr  = .003) and Thought Problems T-scores (ß = 0.21, t(307) = 3.29, p = .001, pfdr  = .004) at age 11 (n = 319). Relative to those with lower exposure, children with higher prenatal PAH exposure exhibited stronger positive associations between ELS and CBCL Attention and Thought Problem T-scores. This interaction was also significant examining convergent ADHD measures (Conners, DuPaul) and examining maternal PAH-DNA adducts (ß = 0.29, t(261) = 2.48, p = .01; n = 273). A three-way interaction with assessment wave indicated that the PAH × ELS interaction on Attention Problems was stronger later in development (ß = 0.03, t(1,601) = 2.19, p = .03; n = 477). CONCLUSIONS: Prenatal exposure to PAH, a common neurotoxicant in air pollution, may magnify or sustain the effects of early life psychosocial/socioeconomic stress on psychiatric outcomes later in child development. This work highlights the critical role of air pollution exposure on child mental health.

A powerful and flexible weighted distance-based method incorporating interactions between DNA methylation and environmental factors on health outcomes.

MOTIVATION: Deoxyribonucleic acid (DNA) methylation plays a crucial role in human health. Studies have demonstrated associations between DNA methylation and environmental factors with evidence also supporting the idea that DNA methylation may modify the risk of environmental factors on health outcomes. However, due to high dimensionality and low study power, current studies usually focus on finding differential methylation on health outcomes at CpG level or gene level combining multiple CpGs and/or finding environmental effects on health outcomes but ignoring their interactions on health outcomes. Here we introduce the idea of a pseudo-data matrix constructed with cross-product terms between CpGs and environmental factors that are able to capture their interactions. We then develop a powerful and flexible weighted distance-based method with the pseudo-data matrix where association strength was used as weights on CpGs, environmental factors and their interactions to up-weight signals and down-weight noises in distance calculations. RESULTS: We compared the power of this novel approach and several comparison methods in simulated datasets and the Mothers and Newborns birth cohort of the Columbia Center for Children's Environmental Health to determine whether prenatal polycyclic aromatic hydrocarbons interacts with DNA methylation in association with Attention Deficit Hyperactivity Disorder and Mental Development Index at age 3. AVAILABILITY AND IMPLEMENTATION: An R code for the proposed method Dw-M-E-int together with a tutorial and a sample dataset is available for downloading from http://www.columbia.edu/∼sw2206/softwares.htm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Contemporary blood lead levels of children aged 0-84 months in China: A national cross-sectional study.

Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 µg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 µg/L) compared to girls (GM: 25.9 µg/L) (p < 0.001). Children at the age of 0-36 months had a lower PbB (GM 25.7 µg/L) level compared with those aged 36-84 months (GM 27.9 µg/L) (p < 0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27 µg/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27 µg/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.

Potential effect of anti-inflammatory drug use on PSA kinetics and subsequent prostate cancer diagnosis: Risk stratification in black and white men with benign prostate biopsy.

BACKGROUND: Rising prostate-specific antigen (PSA) levels are associated with both increased risk of prostate cancer and prostatic inflammation. The confounding effects of inflammation on the utility of PSA kinetics to predict prostate cancer may be partially mitigated by anti-inflammatory drug use. We investigated the influence of anti-inflammatory drug use on the association of PSA kinetics with prostate cancer risk. METHODS: We studied 488 prostate cancer case-control pairs (290 white, 198 African American (AA)) nested in a retrospective cohort of men with a benign prostate biopsy. A series of multivariable models estimated prostate cancer risk associated with PSA velocity (PSAV) at different levels of anti-inflammatory drug use while adjusting for the presence of both clinical and histologic prostatitis. RESULTS: In men with one, two, or three or more courses of anti-inflammatory drug use, for each ng/mL/year increase in PSAV, prostate cancer risk increased 1.21-fold, 1.83-fold, and 1.97-fold, respectively ( P < 0.0001). In controls with histologic prostatitis, anti-inflammatory drug use was associated with a significantly lower PSAV ( P < 0.0001). This association was not observed in men with histologic prostatitis who were subsequently diagnosed with prostate cancer. A positive interaction between anti-inflammatory drug use and PSAV-associated prostate cancer risk was only observed in AA men, as well as a strong positive association between any anti-inflammatory drug use and clinical prostatitis ( P = 0.004). CONCLUSIONS: In men with benign prostate biopsy, accounting for the presence of histologic prostatitis and anti-inflammatory drug use, particularly in AA men, may help distinguish between men with rising PSA because of prostatitis vs undiagnosed cancer.

Prenatal polycyclic aromatic hydrocarbons metabolites, cord blood telomere length, and neonatal neurobehavioral development.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbon (PAH) is a potential risk factor for child neurobehavioral development. Telomere length (TL) has important implications for health over the life course. OBJECTIVE: In this study, we aimed to investigate whether prenatal urinary PAH metabolites were associated with adverse neonatal neurobehavioral development and altered cord blood TL and to explore whether the change of TL was a predictor of neonatal neurobehavioral development. METHOD: We enrolled 283 nonsmoking pregnant women in Taiyuan city. Eleven PAH metabolites were measured in maternal urine samples. TL in cord blood was measured by real time quantitative polymerase chain reaction. Neonatal behavioral neurological assessment (NBNA) tests were conducted when the infants were three days old. Multiple linear regression models were used to analyze the associations of maternal urinary PAH metabolites with NBNA scores and cord blood TL, and restricted cubic spline models were further used to examine the shapes of dose-response relationships. A mediation analysis was also conducted. RESULT: We observed dose-response associations of maternal urinary 2-hydroxyfluorene (2-OHFlu) and 2-hydroxyphenanthrene (2-OH Phe) with decreased active tone scores, sum of NBNA scores, and cord blood TL (P for trend<0.05). Each 1 unit increase in urinary levels of Ln (2-OH Flu) or Ln (2-OH Phe) was associated with a 0.092 or 0.135 decrease in the active tone scores and a 0.174 or 0.199 decrease in the sum of NBNA scores. Mediation analysis showed TL could explained 21.74% of the effect of sum of NBNA scores change related to prenatal exposure to 2-OH Phe (P for mediator = 0.047). CONCLUSION: Our data indicates maternal urinary specific PAH metabolites are inversely associated with neonatal neurobehavioral development and cord blood TL. TL mediates the associations of 2-OH Phe with neonatal neurobehavioral development and partly explains the effect of 2-OH Phe on neonatal neurobehavioral development.

Maternal urinary 2-hydroxynaphthalene and birth outcomes in Taiyuan, China.

BACKGROUND: Naphthalene is the simplest polycyclic aromatic hydrocarbon (PAH). It is easily emitted into the atmosphere, posing a significant risk to human health. However, limited studies have described the impact of naphthalene exposure on birth outcomes. In this study, we investigated the association between the maternal urinary metabolites of naphthalene, 2-hydroxynaphthalene (2-OH NAP), and birth outcomes. METHOD: In the present study, four urinary PAH metabolites were measured in 263 pregnant women during late pregnancy. Multiple linear regression analysis was used to analyze the relationship between the concentrations of 2-OH NAP and birth outcomes, and restricted cubic spline models were further used to examine the shapes of the dose-response association. RESULT: General linear models showed that prenatal urinary 2-OH NAP was associated with lower birth weight (BW) (- 4.38% for the high vs. low exposure group of 2-OH NAP; p for trend = 0.049) and higher cephalization index (CI) (4.30% for the high vs. low exposure group of 2-OH NAP; p for trend = 0.038). These associations were linear and significant when 2-OH NAP was modeled as a continuous variable in restricted cubic spline models (P linear = 0.0293 for 2-OH NAP and BW; P linear = 0.0326 for 2-OH NAP and CI). Multiple linear regression data indicated that each 1 ln-unit increase in 2-OH NAP was significantly associated with a 2.09 g/cm increase in the CI. The associations among 2-OH NAP, BW, and CI were also observed in a subset of participants residing close to arterial traffic. CONCLUSION: Our data indicated that prenatal exposure to naphthalene had an adverse effect on fetal birth outcomes, especially the brain development index. Reduced exposure to naphthalene may improve newborn health outcomes. In Taiyuan, naphthalene may result from traffic pollution.

Using geographical semi-variogram method to quantify the difference between NO2 and PM2.5 spatial distribution characteristics in urban areas.

Urban air pollutant distribution is a concern in environmental and health studies. Particularly, the spatial distribution of NO2 and PM2.5, which represent photochemical smog and haze pollution in urban areas, is of concern. This paper presents a study quantifying the seasonal differences between urban NO2 and PM2.5 distributions in Foshan, China. A geographical semi-variogram analysis was conducted to delineate the spatial variation in daily NO2 and PM2.5 concentrations. The data were collected from 38 sites in the government-operated monitoring network. The results showed that the total spatial variance of NO2 is 38.5% higher than that of PM2.5. The random spatial variance of NO2 was 1.6 times than that of PM2.5. The nugget effect (i.e., random to total spatial variance ratio) values of NO2 and PM2.5 were 29.7 and 20.9%, respectively. This indicates that urban NO2 distribution was affected by both local and regional influencing factors, while urban PM2.5 distribution was dominated by regional influencing factors. NO2 had a larger seasonally averaged spatial autocorrelation distance (48km) than that of PM2.5 (33km). The spatial range of NO2 autocorrelation was larger in winter than the other seasons, and PM2.5 has a smaller range of spatial autocorrelation in winter than the other seasons. Overall, the geographical semi-variogram analysis is a very effective method to enrich the understanding of NO2 and PM2.5 distributions. It can provide scientific evidences for the buffering radius selection of spatial predictors for land use regression models. It will also be beneficial for developing the targeted policies and measures to reduce NO2 and PM2.5 pollution levels.

A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous air pollutants associated with negative impacts on growth, development and behavior in children. Source-specific biological markers of PAH exposure are needed for targeting interventions to protect children. Nitro-derivatives of PAH can act as markers of exposure to diesel exhaust, gasoline exhaust, or general combustion sources. Using a novel HPLC-APCI-MS/MS detection method, we examined four hemoglobin (Hb) adducts of nitro-PAH metabolites and the Hb adduct of a benzo[a]pyrene (BaP) metabolite in 22 umbilical cord blood samples. The samples were collected from a birth cohort with comprehensive data on prenatal PAH exposure, including prenatal personal air monitoring and DNA adducts in maternal and umbilical cord blood. Using non-parametric analyses, heat maps, and principal component analysis (PCA), we analyzed the relationship between the five Hb adducts and previous PAH measurements, with each measurement representing a different duration of exposure. We found that Hb adducts derived from several diesel-related nitro-PAHs (2-nitrofluorene and 1-nitropyrene) were significantly correlated (r = 0.77, p ≤ 0.0001) and grouped together in PCA. Nitro-PAH derived Hb adducts were largely unrelated to previously collected measures of exposure to a number of PAH parent compounds. These measures need to be validated in a larger sample.

Shorter telomere length in cord blood associated with prenatal air pollution exposure: Benefits of intervention.

BACKGROUND: To examine the molecular benefits of the government action to close the local coal burning power plant in Tongliang County, Chongqing Municipality, we compared biologic markers and health outcomes in two successive birth cohorts enrolled before and after the plant was shut down. In this city, polycyclic aromatic hydrocarbons (PAH) were primarily emitted by the coal burning facility. We previously reported that cord blood levels of PAH-DNA adducts (a biomarker of exposure) and various adverse health outcomes were reduced in the second cohort, whereas levels of brain-derived neurotrophic factor/BDNF (a protein involved in neuronal growth) were increased. Here we assessed telomere length (TL), which has been associated with risk of certain chronic diseases, early mortality, aging and cognitive decline in adults. OBJECTIVES: The goals of the present study were to determine whether TL differed between the two cohorts and whether prenatal PAH exposure, estimated by PAH-DNA adducts in cord white blood cells of newborns in China, were predictive of shorter TL in cord blood, suggesting the potential accrual of risk of certain chronic diseases during the prenatal period. We explored relationships of TL with BDNF and neurodevelopmental outcomes, each previously associated with PAH-DNA adducts in these cohorts, as well as the potential mediating role of TL in the associations between adducts and neurodevelopmental outcomes. METHODS: We analyzed TL in cord blood of 255 newborns who also had data on PAH-DNA adducts, BDNF, and relevant covariates. Multiple regression analysis was carried out to test associations between adducts and TL and between TL and BDNF, adjusting for relevant covariates. In the subset with developmental quotient (DQ) scores from Gesell testing at age 2 (N = 210), we explored whether TL was a mediator of the relationship between PAH-DNA adducts and DQ scores by first examining the associations between cord adducts and DQ, cord adducts and TL, and TL and DQ, adjusting for the same covariates. RESULTS: As hypothesized, the mean TL was significantly higher in the second cohort compared to the first cohort. Overall, PAH-DNA cord adducts were significantly and inversely correlated with TL. Multiple regression analysis showed a significant association between adducts and TL, after adjusting for key covariates: ß (effect size per standard deviation adducts) = -0.019, p = .003. The regression coefficient of TL on (Ln) BDNF was also significant (ß = 0.167, p < .001). Exploratory analysis, regressing TL on Gesell developmental scores, showed generally inverse, but not significant associations. TL was not, therefore, deemed to be a potential mediator of the association between adducts and developmental scores at age two. CONCLUSION: This study provides the first evidence that prenatal PAH exposure from coal burning may adversely affect TL, with potential implications for future risk of chronic diseases including cardiovascular disease. The improvement in TL in the second cohort and the observed correlation between increased TL and higher levels of BDNF indicate direct benefits to the health and development of children resulting from the government's closure of the power plant.

Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems.

IMPORTANCE: Polycyclic aromatic hydrocarbons (PAH) are carcinogenic and neurotoxic combustion by-products commonly found in urban air. Exposure to PAH is disproportionately high in low income communities of color who also experience chronic economic stress. OBJECTIVE: In a prospective cohort study in New York City (NYC) we previously found a significant association between prenatal PAH exposure and Attention Deficit Hyperactivity Disorder (ADHD) behavior problems at age 9. Here, we have evaluated the joint effects of prenatal exposure to PAH and prenatal/childhood material hardship on ADHD behavior problems. MATERIALS AND METHODS: We enrolled nonsmoking African-American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. As a biomarker of prenatal PAH exposure, PAH-DNA adducts were measured in maternal blood at delivery and were dichotomized at the limit of detection (to indicate high vs. low exposure). Maternal material hardship (lack of adequate food, housing, utilities, and clothing) was self-reported prenatally and at multiple time points through child age 9. Latent variable analysis identified four distinct patterns of hardship. ADHD behavior problems were assessed using the Conners Parent Rating Scale- Revised. Analyses adjusted for relevant covariates. RESULTS: Among 351 children in our sample, across all hardship groups, children with high prenatal PAH exposure (high adducts) generally had more symptoms of ADHD (higher scores) compared to those with low PAH exposure. The greatest difference was seen among the children with hardship persisting from pregnancy through childhood. Although the interactions between high PAH exposure and hardship experienced at either period ("persistent" hardship or "any" hardship) were not significant, we observed significant differences in the number of ADHD symptoms between children with high prenatal PAH exposure and either persistent hardship or any hardship compared to the others. These differences were most significant for combined high PAH and persistent hardship: ADHD Index (p < 0.008), DSM-IV Inattentive (p = 0.006), DSM-IV Hyperactive Impulsive problems (p = 0.033), and DSM-IV Index Total (p = 0.009). CONCLUSION: The present findings add to existing evidence that co-exposure to socioeconomic disadvantage and air pollution in early life significantly increases the risk of adverse neurodevelopmental outcomes. They suggest the need for multifaceted interventions to protect pregnant mothers and their children.

Environmental Pollutants and Neurodevelopment: Review of Benefits From Closure of a Coal-Burning Power Plant in Tongliang, China.

Background. Understanding preventable causes of neurodevelopmental disorders is a public health priority. Polycyclic aromatic hydrocarbons (PAH) from combustion of fossil fuel, lead, and mercury are among known neurodevelopmental toxicants. Method. For the first time, we comprehensively review the findings from a study by the Columbia Center for Children's Environmental Health and Chinese partners that followed 2 groups of mother-child pairs, one from 2002 and another from 2005, in Tongliang County, China. Pregnant mothers in the 2 cohorts experienced different exposure to PAH because a local coal-burning power plant was shut down in 2004. Investigators assessed change in prenatal PAH exposure, measured using a biomarker (benzo[a]pyrene [BaP]-DNA adducts in cord blood). Developmental quotients were measured using the Gesell Developmental Scales at age 2 and IQ was assessed using the Wechsler Intelligence Scale for Children at age 5. Biologic markers of preclinical response were measured in cord blood: methylation status of long interspersed nuclear elements (LINE1), an indicator of genomic stability, and brain-derived neurotrophic factor (BDNF), a neuronal growth promoter. Analyses accounted for co-exposure to lead and mercury. Results. BaP-DNA adducts were significantly inversely associated with Gesell Developmental Scales scores in the first cohort but not in the second cohort; and levels of BDNF and LINE1 methylation were higher in the second cohort. Conclusion. In this study, reduced exposure to PAH was associated with beneficial effects on neurodevelopment as well as molecular changes related to improved brain development and health. These benefits should encourage further efforts to limit exposure to these toxic pollutants.