Publications by authors named "Michael S Bloom"

144 Publications

Gestational exposure to perfluoroalkyl substances and congenital heart defects: A nested case-control pilot study.

Environ Int 2021 Apr 23;154:106567. Epub 2021 Apr 23.

Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, #96 Dongchuan Road, Guangzhou 510080, China. Electronic address:

Background: Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs.

Methods: A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables.

Results: Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood.

Conclusion: These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.
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http://dx.doi.org/10.1016/j.envint.2021.106567DOI Listing
April 2021

Trace element analysis of human seminal plasma: A cautionary tale of preanalytical variation and use of non-traditional matrices in human biomonitoring studies.

Int J Hyg Environ Health 2021 May 18;234:113751. Epub 2021 Apr 18.

Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New York State Department of Health, Albany, NY, USA; Department of Environmental Health Sciences, School of Public Health, The University at Albany, State University of New York, Albany, NY, USA. Electronic address:

Ensuring harmonization of (ultra-)trace element measurements in non-traditional matrices is a particular analytical challenge that is highlighted in this work for seminal plasma as part of the developmental core at the Wadsworth Center Human Health Exposure Analysis Resource Targeted Laboratory. Seminal plasma was collected from 39 male partners of women undergoing in vitro fertilization and analyzed by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) following deproteinization with concentrated HNO. Validation was accomplished using: 1) two aqueous NIST SRMs; 2) a seminal plasma QC pool, characterized via standard additions; 3) standard additions on a subset of samples; and 4) sample duplicates. Agreement with NIST certified or reference values were obtained to within ±15% for the SRMs, and agreement between aqueous calibration values and standard additions values agreed to within ±10-20% for all elements. Standard additions of seminal plasma samples revealed varying matrix effects for Cu and Cr that were not found for the pooled samples. Duplicate analyses agreed to within ±10-30% depending on element. A potential source of contamination in colloidal silica used for processing seminal plasma was identified that requires further study. Comparisons with literature indicate lack of consensus for As, Cd, Cr, Mn, Pb, and V content in seminal plasma. Further work is needed to improve harmonization of future studies.
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http://dx.doi.org/10.1016/j.ijheh.2021.113751DOI Listing
May 2021

Perfluorooctane sulfonate alternatives and metabolic syndrome in adults: New evidence from the Isomers of C8 Health Project in China.

Environ Pollut 2021 Apr 3;283:117078. Epub 2021 Apr 3.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives.
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http://dx.doi.org/10.1016/j.envpol.2021.117078DOI Listing
April 2021

Maternal exposure to ambient air pollution and congenital heart defects in China.

Environ Int 2021 Apr 7;153:106548. Epub 2021 Apr 7.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China.

Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes.

Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m] increase in PM was associated with 1.09-fold ([95% confidence interval, 1.01-1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed.

Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings.
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http://dx.doi.org/10.1016/j.envint.2021.106548DOI Listing
April 2021

Maternal Food and Beverage Consumption Behaviors and Discrepant Phthalate Exposure by Race.

Int J Environ Res Public Health 2021 02 23;18(4). Epub 2021 Feb 23.

Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC 29425, USA.

: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women's reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. : We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. : Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%; < 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%; < 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%; < 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%; 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. : Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.
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http://dx.doi.org/10.3390/ijerph18042190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927108PMC
February 2021

Greenness may improve lung health in low-moderate but not high air pollution areas: Seven Northeastern Cities' study.

Thorax 2021 Feb 25. Epub 2021 Feb 25.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China

Introduction: There is growing interest in the impact of greenness exposure on airway diseases, but the impact of greenness on lung function in children is limited. We aimed to investigate the associations between greenness surrounding schools and lung function in children and whether these associations are modified by air pollution exposure.

Methods: Between 2012 and 2013, a cross-sectional survey and spirometry were performed among 6740 school children. Lung function patterns were determined as obstructive forced expiratory volume 1 s/forced vital capacity (FEV/FVC <0.8) or restrictive (FEV/FVC ≥0.8 but FVC <80% of predicted). School greenness was defined by Normalized difference vegetation index (NDVI) and soil-adjusted vegetation index. Nitrogen dioxide, sulphur dioxide and particular matter concentrations were assessed using a spatiotemporal model and national monitoring data. Two-level generalised linear models were used to investigate associations and interactions.

Results: Overall, an IQR in NDVI within 500 m was associated with higher FEV (+57 mL 95% CI 44 to 70) and FVC (+58 mL 95% CI 43 to 73). NDVI was similarly associated with 25% reduced odds of spirometric restriction (OR: 0.75, 95% CI 0.65 to 0.86). However, among children exposed to the highest compared with the lowest quartile of particulate matter, increasing NDVI was paradoxically associated with lower -40 mL FVC (95% CI -47 to -33, p <0.05).

Discussion: Our findings suggest that, in this study population, greening urban areas may promote lung health in low-moderate pollution areas but not in high air pollution areas. If the findings are replicated in other moderate-to-high pollution settings, this highlights a need to have a flexible green policy.
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http://dx.doi.org/10.1136/thoraxjnl-2020-214767DOI Listing
February 2021

Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro.

Sci Total Environ 2021 Apr 19;766:142365. Epub 2020 Sep 19.

Guangzhou Key Laboratory of Otorhinolaryngology, Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Emerging evidence suggests associations between Perfluoroalkyl substances (PFASs) exposure and asthma, but the findings are inconsistent. The current study sought to investigate whether perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) could contribute to asthma exacerbation and to clarify the underlying biological mechanisms. The objectives are a) to determine whether PFOS or PFOA could aggravate the mouse asthma and pulmonary inflammation b) to investigate whether PFOS and PFOA regulate the balance of Th1/Th2 through the JAK-STAT signaling pathway and aggravated asthma. Ovalbumin (OVA) induced asthmatic mice were exposed to PFOS or PFOA by gavage. PFOS and PFOA serum level and toxicity in organs were assessed; and the impacts on respiratory symptoms, lung tissue pathology, T helper cell (Th2) response, and STAT6 pathway activity were also evaluated. In vitro Jurkat cells were used to study the mechanisms of PFOS and PFOA mediated Th1 and Th2 responses. Both PFOS and PFOA exacerbated lung tissue inflammation (greater number of eosinophils and mucus hyperproduction), upregulated Th2 cytokine production (IL-4 and IL-13), and promoted Th2 cells and STAT6 activation. Furthermore, PFOS and PFOA enhanced the Th2 response in Jurkat cells via STAT6 activation; and the effect of PFOS exposure on GATA-3, IL-4 and IFN-γ was blocked after the expression of STAT6 was suppressed in Jurkat cells, however, the effects of PFOA exposure were only partially blocked. PFOS and PFOA aggravated inflammation among OVA-induced asthmatic mice, by promoting the Th2 response in lymphocytes and disturbing the balance of Th1/Th2 through the JAK-STAT signaling pathway.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142365DOI Listing
April 2021

Temperature variation and preterm birth among live singleton deliveries in Shenzhen, China: A time-to-event analysis.

Environ Res 2021 04 3;195:110834. Epub 2021 Feb 3.

Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, No.74 Zhongshan Road #2, Guangzhou, 510080, China; Shanghai Key Laboratory of Meteorology and Health, Shanghai Meteorological Service, Shanghai, 200030, China; School of Public Health, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:

Objective: Ambient temperature extremes due to heat exposure was an established risk factor for preterm birth (<37 gestational weeks). However, there is insufficient epidemiological evidence on the effects of temperature variation(TV), although TV is also associated with heat exposure and can influence human health risk. This study aimed to investigate the relationship between inter- and intraday TV and preterm birth (PTB).

Method: A total of 1,388,994 live singleton births were collected from January 2003 to December 2012, from the Shenzhen Birth registry system. Daily temperature range (DTR) was defined as the difference between the highest and lowest recorded daily temperature. Intraday TV was defined as the maximum daily diurnal temperature range in a given week (Max-DTR). Inter-day TV was defined as the maximum increase or decrease in daily mean temperature between days t and t-1in a given week; either an increase (Temp-inc) or a decrease (Temp-dec). We used Cox proportional hazards models to estimate TV-related PTB risks during the first trimester, the second trimester, and in late pregnancy.

Results: The maximum values for DTR, Temp-inc, and Temp-dec were 17 °C, 8 °C and 11 °C, respectively. The greatest TV-related PTB risk occurred in the second trimester, with 5.8% (95%CI: 3.3%, 8.3%), 23.7% (95%CI: 19.6%, 27.9%), and 4.4% (95%CI: 1.8%, 7.1%) differences per 1 °C increase in Max-DTR, Temp-inc, and Temp-dec, respectively. Greater TV was associated with elevated PTB risk during the warm season. The association between TV and PTB was modified by seasons, maternal education and chronic conditions.

Conclusions: Sharp TV is a likely risk factor for PTB. Policy makers and clinicians should recognize the potential role of TV in the etiology of PTB so that interventions can be designed to protect pregnant women and their fetuses against extreme temperatures.
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http://dx.doi.org/10.1016/j.envres.2021.110834DOI Listing
April 2021

Association between gestational phthalate exposure and newborn head circumference; impacts by race and sex.

Environ Res 2021 04 29;195:110763. Epub 2021 Jan 29.

Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA.

Observational and experimental studies report associations between gestational phthalate exposure and fetal development, yet few data exist to characterize phthalate effects on head circumference (HC) or to estimate the impact of race or sex. To address this data gap, we enrolled 152 African American and 158 white mothers with uncomplicated singleton pregnancies from the Charleston, South Carolina (USA) metropolitan area in a prospective birth cohort. Study participants provided up to two urine specimens during mid and late gestation, completed a study questionnaire, and allowed access to hospital birth records. We measured eight phthalate monoester metabolites using liquid chromatography with tandem mass spectrometry, and calculated molar sums of phthalate parent diesters. After specific gravity correction, we tested for associations between phthalates and neonatal HC (cm) and cephalization index (cm/g) using multiple informant linear regression with inverse probability weighting to account for selection bias between repeated urine sampling, adjusted for maternal race, age, body mass index, education, and smoking. We explored interactions by maternal race and infant sex. A doubling of urinary monoethyl phthalate (MEP) concentration was associated with a -0.49% (95%CI: -0.95%, -0.02%) smaller head circumference, although seven other phthalate metabolites were null. There were no statistically significant associations with cephalization index. HC was larger for whites than African American newborns (p < 0.0001) but similar for males and females (p = 0.16). We detected interactions for maternal race with urinary monobutyl phthalate (MBP; p = 0.03), monobenzyl phthalate (MBzP; p = 0.01), monoethylhexyl phthalate (MEHP; p = 0.05), monomethyl phthalate (MMP; p = 0.02), and the sum of dibutyl phthalate metabolites (∑DBP; p = 0.05), in which reduced HC circumference associations were stronger among whites than African Americans, and interactions for sex with MBP (p = 0.08) and MiBP (p = 0.03), in which associations were stronger for females than males. Our results suggest that gestational phthalate exposure is associated with smaller neonatal HC and that white mothers and female newborns have greater susceptibility.
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http://dx.doi.org/10.1016/j.envres.2021.110763DOI Listing
April 2021

Reported Neighborhood Traffic and the Odds of Asthma/Asthma-Like Symptoms: A Cross-Sectional Analysis of a Multi-Racial Cohort of Children.

Int J Environ Res Public Health 2020 12 31;18(1). Epub 2020 Dec 31.

Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4-8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child's race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.
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http://dx.doi.org/10.3390/ijerph18010243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794885PMC
December 2020

Variability of essential and non-essential trace elements in the follicular fluid of women undergoing in vitro fertilization (IVF).

Ecotoxicol Environ Saf 2021 Feb 29;209:111733. Epub 2020 Dec 29.

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, CA 94158, United States.

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n = 34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845532PMC
February 2021

A pilot investigation of couple-level phthalates exposure and in vitro fertilization (IVF) outcomes.

Reprod Toxicol 2021 01 30;99:56-64. Epub 2020 Nov 30.

Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY, United States; Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY, United States; Department of Global and Community Health, George Mason University, Fairfax, VA, United States. Electronic address:

Phthalates are reproductive toxicants in experimental animal studies and exposure has been associated with infertility in human populations, although the results have been inconsistent. To help to address the data gap, we conducted a hypothesis-generating investigation of associations between urinary phthalate metabolites and reproductive outcomes among women (n = 56) and their male partners (n = 43) undergoing in vitro fertilization (IVF). Urine was collected from participants on the day of oocyte retrieval. Samples were analyzed for a series of phthalates, MEP, MBP, MPP, MHxP, MEHP, MEHHP, MECPP, MiNP, MiDP, MCHP, and MBzP, using liquid chromatography-tandem mass spectrometry. We employed Poisson regression with robust variance estimation to estimate associations between urinary phthalate levels and biochemical pregnancy and live birth, adjusted for partner's concentration and confounding factors. Doublings in women's MBP (relative risk (RR) = 0.32, 95 % CI: 0.13, 0.78), and men's MEHP (RR = 0.28, 95 % CI: 0.09, 0.83), were associated with a lower likelihood for pregnancy. Doublings in women's (RR = 0.08, 95 % CI: 0.01, 0.67) and men's (RR = 0.13, 95 % CI: 0.02, 0.92) MHxP were associated with a lower likelihood of live birth. Our results suggest that phthalate exposure may impact IVF outcomes, and underscore the importance of including male partners when investigating the impact of phthalate exposure on IVF. These results also suggest that clinical recommendations should include male partners for limiting phthalate exposure. Still, a larger and more comprehensive investigation is necessary to more definitively assess the risks.
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http://dx.doi.org/10.1016/j.reprotox.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897280PMC
January 2021

Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring.

Prev Med 2021 Feb 7;143:106319. Epub 2020 Nov 7.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment <12 years, household individual income <3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.
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http://dx.doi.org/10.1016/j.ypmed.2020.106319DOI Listing
February 2021

Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study.

Paediatr Perinat Epidemiol 2021 Mar 26;35(2):174-183. Epub 2020 Oct 26.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.

Background: Obesity, a body mass index (BMI) ≥30 kg/m , is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous studies have not directly assessed the impact of adiposity, or body fat, on anovulation in the absence of clinical infertility.

Objective: To characterise the associations between adiposity and anovulation among women menstruating on a regular basis.

Methods: Women from the EAGeR trial (n = 1200), a randomised controlled trial of low-dose aspirin and pregnancy loss among women trying to conceive, were used to estimate associations between adiposity and incident anovulation. Participants completed baseline questionnaires and anthropometry, and provided blood specimens. Women used fertility monitors for up to six consecutive menstrual cycles, with collection of daily first morning voids for hormone analysis in the first two menstrual cycles for prospective assessment of anovulation. Anovulation was assessed by urine pregnanediol glucuronide or luteinising hormone concentration or the fertility monitor. Weighted mixed-effects log-binomial regression was used to estimate associations between measures of adiposity and incident anovulation, adjusted for free (bioavailable) testosterone, anti-Mullerian hormone (AMH), serum lipids, and demographic and life style factors.

Results: 343 (28.3%) women experienced at least one anovulatory cycle. Anovulation risk was higher per kg/m greater BMI (relative risk [RR] 1.03, 95% confidence interval (CI) 1.01, 1.04), cm waist circumference (RR 1.01, 95% CI 1.00, 1.02), mm subscapular skinfold (RR 1.02, 95% CI 1.01, 1.03), and mm middle upper arm circumference (RR 1.04, 95% CI 1.01, 1.06) adjusted for serum free testosterone, AMH, lipids, and other factors.

Conclusions: Adiposity may be associated with anovulation through pathways other than testosterone among regularly menstruating women. This may account in part for reported associations between greater adiposity and infertility among women having menstrual cycles regularly. Understanding the association between adiposity and anovulation might lead to targeted interventions for preventing infertility.
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http://dx.doi.org/10.1111/ppe.12726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878298PMC
March 2021

Association Between Residential Greenness, Cardiometabolic Disorders, and Cardiovascular Disease Among Adults in China.

JAMA Netw Open 2020 09 1;3(9):e2017507. Epub 2020 Sep 1.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, Sun Yat-sen University School of Public Health, Guangzhou, China.

Importance: Living in areas with more vegetation (referred to as residential greenness) may be associated with cardiovascular disease (CVD), but little data are available from low- and middle-income countries. In addition, it remains unclear whether the presence of cardiometabolic disorders modifies or mediates the association between residential greenness and CVD.

Objective: To evaluate the associations between residential greenness, cardiometabolic disorders, and CVD prevalence among adults in China.

Design, Setting, And Participants: This analysis was performed as part of the 33 Communities Chinese Health Study, a large population-based cross-sectional study that was conducted in 33 communities (ranging from 0.25-0.64 km2) in 3 cities within the Liaoning province of northeastern China between April 1 and December 31, 2009. Participants included adults aged 18 to 74 years who had resided in the study area for 5 years or more. Greenness levels surrounding each participant's residential community were assessed using the normalized difference vegetation index and the soil-adjusted vegetation index from 2010. Lifetime CVD status (including myocardial infarction, heart failure, coronary heart disease, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, and subarachnoid hemorrhage) was defined as a self-report of a physician diagnosis of CVD at the time of the survey. Cardiometabolic disorders, including hypertension, diabetes, dyslipidemia, and overweight or obese status, were measured and defined clinically. Generalized linear mixed models were used to evaluate the association between residential greenness levels and CVD prevalence. A 3-way decomposition method was used to explore whether the presence of cardiometabolic disorders mediated or modified the association between residential greenness and CVD. Data were analyzed from October 10 to May 30, 2020.

Main Outcomes And Measures: Lifetime CVD status, the presence of cardiometabolic disorders, and residential greenness level.

Results: Among 24 845 participants, the mean (SD) age was 45.6 (13.3) years, and 12 661 participants (51.0%) were men. A total of 1006 participants (4.1%) reported having a diagnosis of CVD. An interquartile range (1-IQR) increase in the normalized difference vegetation index within 500 m of a community was associated with a 27% lower likelihood (odds ratio [OR], 0.73; 95% CI, 0.65-0.83; P < .001) of CVD prevalence, and an IQR increase in the soil-adjusted vegetation index within 500 m of a community was associated with a 26% lower likelihood (OR, 0.74; 95% CI, 0.66-0.84; P < .001) of CVD prevalence. The presence of cardiometabolic disorders was found to mediate the association between residential greenness and CVD, with mediation effects of 4.5% for hypertension, 4.1% for type 2 diabetes, 3.1% for overweight or obese status, 12.7% for hypercholesterolemia, 8.7% for hypertriglyceridemia, and 11.1% for high low-density lipoprotein cholesterol levels.

Conclusions And Relevance: In this cross-sectional study, higher residential greenness levels were associated with lower CVD prevalence, and this association may be partially mediated by the presence of cardiometabolic disorders. Further studies, preferably longitudinal, are warranted to confirm these findings.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.17507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506516PMC
September 2020

Is PM similar to PM? A new insight into the association of PM and PM with children's lung function.

Environ Int 2020 12 8;145:106092. Epub 2020 Sep 8.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Experimental data suggests that PM is more toxic than PM although the epidemiologic evidence suggests that the health associations are similar. However, few objective exposure data are available to compare the associations of PM and PM with children lung function. Our objectives are a) to evaluate associations between long-term exposure to PM, PM and children's lung function, and b) to compare the associations between PM and PM. From 2012 to 2013, we enrolled 6,740 children (7-14 years), randomly recruited from primary and middle schools located in seven cities in northeast China. We measured lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) utilizing two portable electronic spirometers. We dichotomized continuous lung function measures according the expected values for gender and age. The spatial resolution at which PM and PM estimated were estimated using a machine learning method and the temporal average concentrations were averaged from 2009 to 2012. A multilevel regression model was used to estimate the associations of PM, PM exposure and lung function measures, adjusted for confounding factors. Associations with lower lung function were consistently larger for PM than for PM. Adjusted odds ratios (OR) per interquartile range greater PM ranged from 1.53 for MMEF (95% confidence interval [CI]: 1.20-1.96) to 2.14 for FEV1 (95% CI: 1.66-2.76) and ORs for PM ranged from 1.36 for MMEF (95%CI: 1.12-1.66) to 1.82 for FEV1 (95%CI: 1.49-2.22), respectively. PM and PM had significant associations with FVC and FEV1 in primary school children, and on PEF and MMEF in middle school children. Long-term PM and PM exposure can lead to decreased lung function in children, and the associations of PM are stronger than PM. Therefore, PM may be more hazardous to children's respiratory health than PM exposure.
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http://dx.doi.org/10.1016/j.envint.2020.106092DOI Listing
December 2020

Greenspace with overweight and obesity: A systematic review and meta-analysis of epidemiological studies up to 2020.

Obes Rev 2020 11 16;21(11):e13078. Epub 2020 Jul 16.

Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Several reviews have been conducted to assess the association between greenspace and overweight or obesity, but the conclusions were inconsistent. However, an updated comprehensive review and meta-analysis is warranted, because several high-quality papers have been published more recently. The objectives of this study are to systematically and quantitatively assess the evidence for a link between greenspace with overweight/obesity and to make specific recommendations for further research. We searched three English language databases, four Chinese language databases and the reference lists of previously published reviews for epidemiological studies on greenspace and overweight/obesity published before January 2020. We developed inclusion criteria, screened the literature and extracted key data from selected papers. We assessed methodological quality and risk of bias, and we graded the credibility of the pooled evidence. We also performed sensitivity analyses. Fifty-seven records met our inclusion criteria and were included in the study. Most studies were cross-sectional designs (81%) and were from developed nations (88%). More than half (55%) of the included studies found beneficial associations between greenspace and overweight/obesity in overall or subpopulations. Our meta-analytical results showed that greater normalized difference vegetation index was associated with lower odds of overweight/obesity in a statistically significant fashion (odds ratio [OR]: 0.88; 95% CI: 0.84, 0.91) but not residential proximity to greenspace (OR: 0.99; 95% CI: 0.99, 1.00), proportion of greenspace (OR: 0.96; 95% CI: 0.85, 1.08) or number of parks in an area (OR: 0.99; 95% CI: 0.97, 1.01). However, we detected high between-study heterogeneity in two of the four meta-analyses, which reduced the credibility of the pooled evidence. Current evidence indicates that there might be an association between greater access to greenspace and lower odds of overweight/obesity. However, additional high-quality studies are needed to more definitively assess the evidence for a causal association.
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http://dx.doi.org/10.1111/obr.13078DOI Listing
November 2020

Associations of greenness with gestational diabetes mellitus: The Guangdong Registry of Congenital Heart Disease (GRCHD) study.

Environ Pollut 2020 Nov 29;266(Pt 2):115127. Epub 2020 Jun 29.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China. Electronic address:

Gestational diabetes mellitus (GDM) is associated with adverse short- and long-term health outcomes among mothers and their offspring. GDM affects 0.6%-15% of pregnancies worldwide and its incidence is increasing. However, intervention strategies are lacking for GDM. Previous studies indicated a protective association between greenspace and type 2 diabetes mellitus (T2DM), while few studies have explored the association between greenness and GDM. This study aimed to investigate the association between residential greenness and GDM among women from 40 clinical centers in Guangdong province, south China. The study population comprised 5237 pregnant mothers of fetuses and infants without birth defects, from 2004 to 2016. There were n = 157 diagnosed with GDM according to World Health Organization criteria. We estimated residential greenness using the Normalized Difference Vegetation Index (NDVI), derived from satellite imagery using a spatial-statistical model. Associations between greenness during pregnancy and GDM were assessed by confounder-adjusted random effects log-binomial regression models, with participating centers as the random effect. One interquartile increments of NDVI, NDVI and NDVI were associated with 13% (RR = 0.87, 95%CI: 0.87-0.87), 8% (RR = 0.92, 95%CI: 0.91-0.92) and 3% (RR = 0.97, 95%CI: 0.97-0.97) lower risks for GDM, respectively. However, NDVI was not significantly associated with GDM (RR = 0.96, 95%CI: 0.78-1.19). The risk for GDM decreased monotonically with greater NDVI. The protective effect of greenness on GDM was stronger among women with lower socioeconomic status and in environments with a lower level air pollutants. Our results suggest that greenness might provide an effective intervention to decrease GDM. Greenness and residential proximity to greenspace should be considered in community planning to improve maternal health outcomes.
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http://dx.doi.org/10.1016/j.envpol.2020.115127DOI Listing
November 2020

First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

J Am Heart Assoc 2020 07 2;9(13):e015652. Epub 2020 Jul 2.

Guangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong China.

Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first-trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case-control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong Province, China. Adjusted odds ratios (aORs) of FAS and multivitamin use between CHD cases (overall and specific CHD phenotypes) and controls were calculated by controlling for parental confounders. The multiplicative interaction effect of FAS and multivitamin use on CHDs was estimated. A significantly protective association was detected between first-trimester maternal FAS and CHDs among offspring (aOR, 0.69; 95% CI, 0.62-0.76), but not for multivitamin use alone (aOR, 1.42; 95% CI, 0.73-2.78). There was no interaction between FAS and multivitamin use on CHDs (=0.292). Most CHD phenotypes benefited from FAS (aORs ranged from 0.03-0.85), especially the most severe categories (ie, multiple critical CHDs [aOR, 0.16; 95% CI, 0.12-0.22]) and phenotypes (ie, single ventricle [aOR, 0.03; 95% CI, 0.004-0.21]). Conclusions First-trimester maternal FAS, but not multivitamin use, was substantially associated with lower risk of CHDs, and the association was strongest for the most severe CHD phenotypes. We recommend that women of childbearing age should supplement with folic acid as early as possible, ensuring coverage of the critical window for fetal heart development to prevent CHDs.
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http://dx.doi.org/10.1161/JAHA.119.015652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670504PMC
July 2020

Sources of exposure to urinary phthalates among couples undergoing infertility treatment.

Int J Hyg Environ Health 2020 08 26;229:113567. Epub 2020 Jun 26.

Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY, USA; Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY, USA. Electronic address:

Phthalates have been implicated as reproductive toxicants in animal models and in human populations. This study examined associations between potential exposure sources and urinary phthalate metabolite concentrations among women (n = 56) and their male partners (n = 43) undergoing in vitro fertilization (IVF). On the day of oocyte retrieval, participants provided urine samples and completed questionnaires detailing use of personal care products (PCPs), and consumption of medications, foods, and beverages in the preceding 24 h. Urine was analyzed for MEP, MBP, MPP, MHxP, MEHP, MEHHP, MECPP, MiNP, MiDP, MCHP, and MBzP, via liquid chromatography-tandem mass spectrometry. We employed principal component analysis (PCA) to summarize exposure sources and regression models to estimate associations between exposure patterns and urinary phthalate metabolites, adjusted for confounding variables. Among women, application of more body washes and eye creams, and consumption of more supplements, was associated with greater urinary MECPP [relative difference = 1.36 (95% CI: 1.28, 1.45)] and the molar sum of DEHP metabolites, including MEHP, MEHHP, and MECPP [∑DEHP; 1.26 (95% CI: 1.17, 1.34)]. Among men, consumption of more supplements and allergy medications was associated with greater urinary MECPP, MEHHP, and ∑DEHP [relative difference = 1.13 (95% CI: 1.02, 1.23)] concentrations. Identifying differences in sources of phthalate exposure may help clinicians to intervene to reduce exposure as part of a comprehensive strategy to help improve IVF outcomes.
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http://dx.doi.org/10.1016/j.ijheh.2020.113567DOI Listing
August 2020

Maternal residential greenness and congenital heart defects in infants: A large case-control study in Southern China.

Environ Int 2020 09 25;142:105859. Epub 2020 Jun 25.

Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou 510080, Guangdong, China. Electronic address:

Background: Proximity to greenness has shown protective effects on coronary heart diseases by limiting exposure to environmental hazards, encouraging physical activity, and reducing mental stress. However, no studies have previously evaluated the impacts of greenness on congenital heart defects (CHDs). We examined the association between maternal residential greenness and the risks of CHDs.

Methods: We conducted a case-control study (8042 children with major CHDs and 6887 controls without malformations) in 21 cities in Southern China, 2004 - 2016. CHDs cases were diagnosed and verified by obstetrician, pediatrician, or pediatric cardiologists, within one year. We estimated maternal residential greenness using satellite-derived normalized difference vegetation index (NDVI) in zones of 500 meters (m) and 1000 m surrounding participants' residences. Logistic regression models were used to assess NDVI-CHD relationships adjusting for confounders.

Results: Interquartile range NDVI increases within 500 m or 1000 m were associated with odds ratios (OR) of 0.95 (95% confidence interval (CI): 0.92, 0.98) and 0.94 (95%CI: 0.91, 0.97) for total CHDs respectively. Air pollutants mediated 52.1% of the association. We also identified a protective threshold at 0.21 NDVI on CHD. Similar protective effects from greenness were found in most CHDs subtypes. The protective associations were stronger for fall, urban or permanent residents, higher household income maternal age ≤35 years of age, and high maternal education (ORs: ranged from 0.85 to 0.96).

Conclusion: Our findings suggest a beneficial effect of maternal residential greenness on CHDs. Further studies are needed to confirm our findings, which will help to refine preventive health and urban design strategies.
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http://dx.doi.org/10.1016/j.envint.2020.105859DOI Listing
September 2020

Seafood consumption is associated with higher follicular fluid arsenic (As) and mercury (Hg) concentrations in women undergoing in vitro fertilization (IVF).

Environ Res 2020 09 1;188:109753. Epub 2020 Jun 1.

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, CA, 94158, United States.

Human exposure to non-essential toxic metals such as cadmium (Cd), mercury (Hg), and lead (Pb), and metalloids such as arsenic (As) commonly occurs through diet. Toxic trace element exposures have been reported in association with fertility and fecundity in epidemiologic studies even at low to moderate levels. While most previous studies employed blood and urine biomarkers of exposure, few have assessed toxic trace elements in ovarian follicular fluid (FF), which surrounds the developing oocyte and hence may better reflect concentrations potentially affecting reproductive outcomes. Our objective was to identify dietary predictors of FF toxic trace elements in n = 56 women (mean age: 38.3 years) undergoing in vitro fertilization (IVF) at the University of California at San Francisco. We determined As, Hg, Cd, and Pb in 197 FF specimens, collected on the day of oocyte retrieval, using inductively coupled plasma tandem mass spectrometry. A comprehensive food frequency questionnaire was used to assess the weekly and annual dietary "patterns" of participants. Consumption of specific seafood items and turkey were correlated with individual FF toxic trace elements. We also found that each unit higher seafood consumption in the past week dominated by mollusks, shrimp, and bass was associated with 60% higher FF As (95% confidence interval (CI): 25%, 105%) and FF Hg (95%CI: 7%, 136%) concentrations. Higher annual seafood consumption dominated by urchin, crab, and trout was associated with 16% higher FF As (95%CI: -2%, 38%) and 31% higher FF Hg (95%CI: 7%, 60%) concentrations per unit intake. No associations were noted between diet and Cd and Pb levels in FF. Overall, our results suggest that higher seafood consumption contributes to elevated levels of As and Hg in FF. These findings are consistent with previous IVF studies that assessed toxic trace element exposures in blood and urine. To our knowledge, this is the first study to report that diet might be a source of As, Hg, Cd, and Pb in FF.
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http://dx.doi.org/10.1016/j.envres.2020.109753DOI Listing
September 2020

Assessing the vaccine effectiveness for hand, foot, and mouth disease in Guangzhou, China: a time-series analysis.

Hum Vaccin Immunother 2021 Jan 12;17(1):217-223. Epub 2020 Jun 12.

Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University , Guangzhou, China.

: Hand, foot, and mouth disease (HFMD) is an important public health issue in China. Although efficacy has been demonstrated by randomized controlled trials, the evidence for effectiveness of the monovalent Enterovirus 71 (EV71) vaccine against HFMD remains unknown. This study aimed to assess the vaccine effectiveness for HFMD in Guangzhou, China. : Routinely collected vaccination and HFMD surveillance data were captured from the China Information System for Disease Control and Prevention. We estimated the EV71 vaccine effectiveness using spatial ecologic and time-series analysis approaches. : A total of 174,002 HFMD cases under 5 years of age were reported to the Guangzhou, China surveillance system from January 2016 to December 2018. A total of 408,664 children completed a two-dose EV71 vaccination series. In an ecologic analysis, a two-dose EV71 vaccination rate above the median conferred lower HFMD risk relative to a vaccination rate below the median (ratio ratio = 0.955, 95% confidence interval (CI): 0.949, 0.962; < .001). In the time-series approach, 0.9% fewer HFMD cases were associated with a 1% increase in the two-dose EV71 vaccination rate, but without statistical significance ( = .094). However, we detected statistically significant protective associations for HFMD among children 3 years of age (0.9% fewer HFMD cases with a 1% increased vaccination rate; = .046), and for EV71 (1.4%; = .012) and "other viruses" (1.3%; = .002), although not for Coxsackievirus A16 (CVA16). : Our findings, based on real-world data, provide evidence of EV71 vaccine effectiveness for preventing EV71 and "other" viruses associated with HFMD. An expanded program of EV71 vaccination is urgently needed.
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http://dx.doi.org/10.1080/21645515.2020.1763076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872061PMC
January 2021

Ambient air pollution and homocysteine: Current epidemiological evidence and a call for further research.

Environ Res 2020 08 16;187:109679. Epub 2020 May 16.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Elevated blood homocysteine (Hcy) is an independent risk factor for cardiovascular disease. A growing number of studies have evaluated the link between air pollution and blood Hcy levels, but the results are inconsistent. To date, no systematic review of the published studies has been conducted yet. We aimed to provide a comprehensive overview of these studies. We systematically searched three international databases (PubMed, Web of Science, and Embase) and four Chinese databases (Wanfang, CNKI, CBM, and VIP) for peer-reviewed epidemiological studies investigating associations between ambient air pollutants and Hcy levels published before December 2019. We screened literature, extracted data, assessed methodological quality, and evaluated the risk of bias of the included studies. Of 1157 identified articles, 10 were finally included in this systematic review. Most were cross-sectional studies and were performed in developed countries. Particulate matter with aerodynamic diameters less than 2.5 μm (PM) and/or 10 μm (PM) were investigated in all of the included studies. Overall, the evidence generally supports a positive association between higher PM concentrations and elevated Hcy levels. However, high heterogeneity in terms of study participants, study design, exposure duration, and particle components and sources, low methodological quality and probable high risk of bias in some studies, and limited literature number precluded us from drawing a robust conclusion. Associations between Hcy and gaseous pollutants were explored in only one or two studies, and the results were inconclusive. Additional, well-designed studies remain required to validate the association between air pollution and Hcy.
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http://dx.doi.org/10.1016/j.envres.2020.109679DOI Listing
August 2020

The role of influenza vaccination in mitigating the adverse impact of ambient air pollution on lung function in children: New insights from the Seven Northeastern Cities Study in China.

Environ Res 2020 08 7;187:109624. Epub 2020 May 7.

Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Guangdong Provincial Key Laboratory of Environmental Protection and Resources Utilization, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Background: Ambient air pollution exposure and influenza virus infection have been documented to be independently associated with reduced lung function previously. Influenza vaccination plays an important role in protecting against influenza-induced severe diseases. However, no study to date has focused on whether influenza vaccination may modify the associations between ambient air pollution exposure and lung function.

Methods: We undertook a cross-sectional study of 6740 children aged 7-14 years into Seven Northeast Cities (SNEC) Study in China during 2012-2013. We collected information from parents/guardians about sociodemographic factors and influenza vaccination status in the past three years. Lung function was measured using portable electronic spirometers. Machine learning methods were used to predict 4-year average ambient air pollutant exposures to nitrogen dioxide (NO) and particulate matter with an aerodynamic diameter <1 μm (PM), <2.5 μm (PM) and <10 μm (PM). Two-level linear and logistic regression models were used to assess interactions between influenza vaccination and long-term ambient air pollutants exposure on lung function reduction, controlling for potential confounding factors.

Results: Ambient air pollution were observed significantly associated with reductions in lung function among children. We found significant interactions between influenza vaccination and air pollutants on lung function, suggesting greater vulnerability to air pollution among unvaccinated children. For example, an interaction (p = 0.002) indicated a -283.44 mL (95% CI: -327.04, -239.83) reduction in forced vital capacity (FVC) per interquartile range (IQR) increase in PM concentrations among unvaccinated children, compared with the -108.24 mL (95%CI: -174.88, -41.60) reduction in FVC observed among vaccinated children. Results from logistic regression models also showed stronger associations between per IQR increase in PM and lung function reduction measured by FVC and peak expiratory flow (PEF) among unvaccinated children than the according ORs among vaccinated children [i.e., Odds Ratio (OR) for PM and impaired FVC: 2.33 (95%CI: 1.79, 3.03) vs 1.65 (95%CI: 1.20, 2.28); OR for PM and impaired PEF: 1.45 (95%CI: 1.12,1.87) vs 1.04 (95%CI: 0.76,1.43)]. The heterogeneity of the modification by influenza vaccination of the associations between air pollution exposure and lung function reduction appeared to be more substantial in girls than in boys.

Conclusion: Our results suggest that influenza vaccination may moderate the detrimental effects of ambient air pollution on lung function among children. This study provides new insights into the possible co-benefits of strengthening and promoting global influenza vaccination programs among children.
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http://dx.doi.org/10.1016/j.envres.2020.109624DOI Listing
August 2020

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program.

J Expo Sci Environ Epidemiol 2020 05 17;30(3):397-419. Epub 2020 Feb 17.

Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.
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http://dx.doi.org/10.1038/s41370-020-0211-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183426PMC
May 2020

SFPQ is involved in regulating arsenic-induced oxidative stress by interacting with the miRNA-induced silencing complexes.

Environ Pollut 2020 Jun 10;261:114160. Epub 2020 Feb 10.

The Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Arsenic exposure contributed to the development of human diseases. Arsenic exerted multiple organ toxicities mainly by triggering oxidative stress. However, the signaling pathway underlying oxidative stress is unclear. We previously found that the expression of SFPQ, a splicing factor, was positively associated with urinary arsenic concentration in an arsenic-exposed population, suggesting an oxidative stress regulatory role for SFPQ. To test this hypothesis, we established cell models of oxidative stress in human hepatocyte cells (L02) treated with NaAsO. Reactive oxygen species (ROS) synthesis displayed a time- and dose-dependent increase with NaAsO treatment. SFPQ suppression resulted in a 36%-53% decrease in ROS generation, leading to enhanced cellular damage determined by 8-OHdG, comet tail moment, and micronucleus analysis. Particularly, SFPQ deficiency attenuated expression of the oxidase genes DUOX1, DUOX2, NCF2, and NOX2. A fluorescent-based RNA electrophoretic mobility shift assay (FREMSA) and dual-luciferase reporter system revealed that miR-92b-5p targeted DUOX2 mRNA degradation. An RNA immunoprecipitation assay showed an interaction between SFPQ and miR-92b-5p of the miRNA-induced silencing complex (miRISC). Notably, NaAsO treatment diminished the interaction between SFPQ and miR92b-5p, accompanied by decreased binding between miR-92b-5p and 3'-UTR of DUOX2. However, SFPQ deficiency suppressed the dissociation of miR-92b-5p from 3'-UTR of DUOX2, indicating that miR-92b-5p regulated the SFPQ-dependent DUOX2 expression. Taken together, we reveal that SFPQ responds to arsenic-induced oxidative stress by interacting with the miRISC. These findings offer new insight into the potential role of SFPQ in regulating cellular stress response.
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http://dx.doi.org/10.1016/j.envpol.2020.114160DOI Listing
June 2020

The time window of pet ownership exposure modifies the relationship of Environmental Tobacco Smoke with lung function: A large population-based cohort study.

Environ Res 2020 04 30;183:109197. Epub 2020 Jan 30.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

There is a large body of evidence linking Environmental Tobacco Smoke (ETS) exposure with impaired lung function. However, it is not known whether exposure to pets modifies this relationship. To investigate if pet ownership changes the association between ETS exposure and lung function, a population-based sample of 7326 children, 7-14 years old, were randomly recruited from 24 districts in northeast China. Lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) was measured by spirometry, while pet ownership time periods and ETS exposure were collected by questionnaire. Two-level regression analysis was done, with covariates controlled for. The results showed pet exposure in certain early lifetime windows modified the associations of ETS exposure on decreased lung function in children. Among children exposed to current ETS, those exposed to pets in utero had greater reductions in lung function (for instance: OR for reduced FVC (<85% predicted) = 10.86; 95% CI: 3.80-30.97) than those not exposed to pets in utero (OR = 2.32; 95% CI: 1.76-3.05) (p = 0.005). While, children exposed to current pet ownership reduced the lung function impairment induced by ETS exposure during the first 2 years of life and/or ETS exposure during pregnancy, especially for FVC impairment. For instance, OR (95%CI) for reduced FVC (<85% predicted) was 0.81 (0.56, 1.18) and 1.42 (1.15, 1.74), respectively, for children with or without current pet ownership exposed to ETS during the first 2 years of life (p = 0.010). Furthermore, pet type or number of pets did not significantly modify associations between ETS exposure and lung function. In conclusion, the timing of pet ownership modified associations between ETS exposure and lung function, pet ownership in utero and during the first 2 years of life significantly worsened the adverse impacts of passive smoking on lung function.
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http://dx.doi.org/10.1016/j.envres.2020.109197DOI Listing
April 2020

Pet ownership in utero and in childhood decreases the effects of environmental tobacco smoke exposure on hypertension in children: A large population based cohort study.

Sci Total Environ 2020 May 22;715:136859. Epub 2020 Jan 22.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Background: Little is known about whether exposure to pets influences the association between hypertension and environmental tobacco smoke (ETS). The current study aims to examine the interaction of pet ownership on ETS exposure and the development of hypertension in children.

Methods: From 2012 to 2013, a total of 9354 children, 5 to 17 years of age, were recruited from 62 schools in seven northeastern cities. BP in children was measured and hypertension was defined as an average diastolic blood pressure (DBP) or systolic blood pressure (SBP) at or above the 95th percentile for that child's age, sex, and height. Pet ownership in three different time periods (in utero, past 2 years, and currently) and ETS exposure data were collected from parents via a questionnaire. Two-level regressions were used for the data analyses.

Results: The data show consistent, significant interactions between exposure to pets and effects from ETS. Children who were not exposed to pets experienced stronger effects from ETS on hypertension when compared to those exposed to pets, and the protective effect of pet ownership became stronger with a greater number of pets in the home. Exposure to in utero ETS was associated with hypertension [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI): 1.13-1.54] only for those children without pet exposure in utero but not for those with pets (aOR = 0.75; 95% CI: 0.49-1.15) (p < 0.05). Moreover, household dog ownership was related to significantly lower effects of current ETS on hypertension (aOR = 0.80, 95% CI: 0.61-1.05) compared with children without dogs (aOR = 1.26, 95% CI: 1.11-1.44) (p = 0.001). Interaction associations between ETS and pet ownership were more robust for girls than for boys and for younger than older children.

Conclusion: This study indicates an inverse relationship between pet ownership and ETS, potentially pointing to pet ownership as protecting against the development of hypertension in children.
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http://dx.doi.org/10.1016/j.scitotenv.2020.136859DOI Listing
May 2020

Residential greenness, air pollution and psychological well-being among urban residents in Guangzhou, China.

Sci Total Environ 2020 Apr 18;711:134843. Epub 2019 Nov 18.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

China's rapid urbanization has led to an increasing level of exposure to air pollution and a decreasing level of exposure to vegetation among urban populations. Both trends may pose threats to psychological well-being. Previous studies on the interrelationships among greenness, air pollution and psychological well-being rely on exposure measures from remote sensing data, which may fail to accurately capture how people perceive vegetation on the ground. To address this research gap, this study aimed to explore relationships among neighbourhood greenness, air pollution exposure and psychological well-being, using survey data on 1029 adults residing in 35 neighbourhoods in Guangzhou, China. We used the Normalized Difference Vegetation Index (NDVI) and streetscape greenery (SVG) to assess greenery exposure at the neighbourhood level, and we distinguished between trees (SVG-tree) and grasses (SVG-grass) when generating streetscape greenery exposure metrics. We used two objective (PM and NO concentrations) measures and one subjective (perceived air pollution) measure to quantify air pollution exposure. We quantified psychological well-being using the World Health Organization Well-Being Index (WHO-5). Results from multilevel structural equation models (SEM) showed that, for parallel mediation models, while the association between SVG-grass and psychological well-being was completely mediated by perceived air pollution and NO, the relationship between SVG-tree and psychological well-being was completely mediated by ambient PM, NO and perceived air pollution. None of three air pollution indicators mediated the association between psychological well-being and NDVI. For serial mediation models, measures of air pollution did not mediate the relationship between NDVI and psychological well-being. While the linkage between SVG-grass and psychological well-being scores was partially mediated by NO-perceived air pollution, SVG-tree was partially mediated by both ambient PM-perceived air pollution and NO-perceived air pollution. Our results suggest that street trees may be more related to lower air pollution levels and better mental health than grasses are.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134843DOI Listing
April 2020