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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.

Background Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. Objectives To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. Methods We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. Results After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. Conclusions Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

Previous investigations on the associations of polyfluoroalkyl substances (PFASs) with overweight/obesity are mixed. Moreover, little information has been reported about the association between isomers of PFASs with body mass index (BMI), waist circumference (WC) or overweight. To address this shortcoming in the literature, we conducted a study involving 1612 Chinese adults (1204 men and 408 women), ages 22–96 years old, from Shenyang, China, to analyze serum isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other PFASs. Height, weight and WC were measured by a standardized protocol of WHO. Results indicated that increased serum concentrations of all (both branched and linear) isomers of PFASs were associated with a higher prevalence of overweight, and these associations were more pronounced in women. The adjusted odds ratios (ORs) from logistic regression analyses among women were 1.45 (95% confidence interval [CI]: 1.06, 1.99) for linear PFOS isomers, 1.33 (95% CI: 1.00, 1.77) for branched PFOS isomers, 1.39 (95% CI: 1.06, 1.81) for 3 + 4 + 5m PFOS, 1.54 (95% CI: 1.08, 2.21) for linear PFOA isomers, and 1.62 (95% CI: 1.05, 2.51) for branched PFOA isomers, respectively. Associations with increased WC were yielded a similar pattern. Linear regression models also showed positive associations between PFASs and BMI or WC. In conclusion, this study suggests that PFASs and their isomers are positively associated with overweight or increased WC, and the associations are stronger in women. Furthermore, PFOA and its isomers displayed the most robust obesogenic associations. Keywords: Perfluoroalkyl substances (PFASs), PFASs isomers, Overweight, Anthropometry, Obesity, Isomers of C8 Health Project

Backgrounds: Evidence on the association between long-term exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) and cardiovascular disease (CVD) is scarce in developing countries. Moreover, few studies assessed the role of the PM1 (≤1.0 μm) size fraction and CVD. We investigated the associations between PM1 and PM2.5 and CVD prevalence in Chinese adults. Methods: In 2009, we randomly recruited 24,845 adults at the age of 18–74 years from 33 communities in Northeastern China. CVD status was determined by self-report of doctor-diagnosed CVD. Three-year (2006–08) average concentrations of PM1 and PM2.5 were assigned using a satellite-based exposure. We used spatial Generalized Linear Mixed Models to evaluate the associations between air pollutants and CVD prevalence, adjusting for multiple covariates. Stratified and interaction analyses and sensitivity analyses were also performed. Results: A 10 μg/m3 increase in long-term exposure to ambient PM1 levels was associated a 12% higher odds for having CVD (OR = 1.12; 95% CI = 1.05–1.20). Compared to PM1, association between PM2.5 and CVD was lower (OR = 1.06; 95% CI = 1.01–1.11). No significant association was observed for PM1–2.5 (1–2.5 μm) size fraction (OR = 0.98; 95% CI = 0.85–1.13). Stratified analyses showed greater effect estimates in men and the elder. Conclusions: Long-term PM1 exposure was positively related to CVD, especially in men and the elder. In addition, PM1 may play a greater role than PM2.5 in associations with CVD. Further longitudinal studies are warranted to confirm our findings. Keywords: Particulate matter, Cardiovascular disease, Adults, Chinese, Cross-sectional study

Background: There is increasing interest in the effect of residential greenness on respiratory health in children with inconsistent results. However, there are no studies investigating the association between greenness around schools, a representative environment for children and childhood asthma. Objectives: To investigate the association between greenness surrounding schools and asthma in schoolchildren. Methods: We recruited 59,754 schoolchildren from 94 schools in 2012–2013 from the Seven Northeast Cities Study, China. Greenness surrounding schools was measured using the normalized difference vegetation index (NDVI) and soil adjusted vegetation index (SAVI) at buffers from 30 to 1000 m. Asthma symptoms were collected from validated self-reported questionnaires. Logistic mixed-effects regression models were used to estimate the associations between greenness surrounding school and childhood asthma after adjustment for covariates. Results: We found that greenness surrounding schools in all buffered sizes was negatively associated with the prevalence of asthmatic symptoms in schoolchildren. A 0.1-unit increase in NDVI1000m was associated with lower odds of current asthma (odds ratio: 0.81, 95% confidential interval: 0.75, 0.86) and current wheeze (OR: 0.89, 95% CI: 0.84, 0.94) in children after covariate adjustments. Higher greenness was associated with less asthma symptoms in a dose-response pattern (P for trend < 0.05). The estimated associations appeared to be stronger in children exposure to higher air pollution level. The observed associations varied across seven cities. Conclusion: Our findings suggest beneficial associations of greenness surrounding schools with childhood asthma. Further studies are needed to confirm our results.

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 (PM1), ≤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/m3] increase in PM1 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.

Experimental data suggests that PM

The detrimental effects of perfluoroalkyl substances (PFASs) on several physiological systems have been reported, but the association of PFASs with eye, one of the most sensitive and exposed organ, has never been explored. To investigate the association between eye diseases including visual impairment (VI) and PFASs isomers, a cross-sectional stratified study was conducted in 1202 Chinese population, aged 22–96 years, from Shenyang, China. A standard protocol including Snellen vision chart, slit-lamp microscopy and direct ophthalmoscopy was used to examine eye diseases/conditions relating to anterior and posterior segment of eyes. In addition, we measured the blood concentrations of 19 linear and branched PFASs at one-time point. Results indicated that blood levels of PFASs were significantly higher in eye disease group than normal group. PFASs exposure were positively associated with both combined eye diseases and individual eye diseases. Among other PFASs, linear perfluorooctane sulfonate (n-PFOS; odds ratio [OR] = 3.37, 95% confidence interval [CI]: 2.50, 4.56), branched perfluorooctane sulfonate (Br-PFOS; OR = 2.25, 95% CI: 1.72, 2.93) and linear perfluorooctanoic acid (n-PFOA; OR = 1.79, 95% CI: 1.36, 2.37) significantly increases the odds of VI. Vitreous disorder was adversely associated with long-chain PFASs exposure. For example, perfluorotridecanoic acid (PFTrDA; OR = 1.86, 95% CI: 1.51, 2.29) and perfluorodecanoic acid (PFDA; OR = 1.79, 95% CI: 1.36, 2.36) showed the most significant association. In conclusion, this study suggests higher serum PFASs levels were associated with increase odds of VI and vitreous disorder in Chinese adults. Keywords: Perfluoroalkyl substances (PFASs), PFASs isomers, Eye diseases, Visual impairment, Vitreous disorder

Background and objectives: Little is known about PM1 effects on respiratory health, relative to larger size fractions (PM2.5). To address this literature gap, we assessed associations between PM1 exposure and asthmatic symptoms in Chinese children and adolescents, compared with PM2.5. Methods: A total of 59,754 children, aged 2–17 years, were recruited from 94 kindergartens, elementary and middle schools in the Seven Northeast Cities (SNEC) study, during 2012–2013. We obtained information on asthma and asthma-related symptoms including wheeze, persistent phlegm, and persistent cough using a standardized questionnaire developed by the American Thoracic Society. PM1 and PM2.5 concentrations were estimated using a spatial statistical model matched to the children's geocoded home addresses. To examine the associations, mixed models with school/kindergarten as random intercept were used, controlling for covariates. Results: Odds ratios (ORs) of doctor-diagnosed asthma associated with a 10-μg/m3 increase for PM1 and PM2.5 were 1.56 (95% CI: 1.46–1.66) and 1.50 (1.41–1.59), respectively, and similar pattern were observed for other outcomes. Interaction analyses indicated that boys and the individuals with an allergic predisposition may be vulnerable subgroups. For example, among children with allergic predisposition, the ORs for doctor diagnosed asthma per 10 μg/m3 increase in PM1 was 1.71 (95% CI: 1.60–1.83), which was stronger than in their counterparts (1.46; 1.37–1.56) (p for interaction

Background Little information exists on the lipidemic effects of air pollution, particularly in developing countries. We aimed to investigate the associations of long-term exposure to ambient air pollutants with lipid levels and dyslipidemias in China. Methods In 2009, a total of 15,477 participants aged 18–74 years were recruited from the 33 Communities Chinese Health Study conducted in three Northeastern China cities. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured in participants' blood specimens. Three year (2006–08) average air pollution concentrations were assessed using data from 33 communities (particles with diameters ≤1.0 μm (PM 1 ) and ≤2.5 μm (PM 2.5 ) were predicted using a spatial statistical model) or 11 air monitoring stations (particles with diameters ≤10 μm (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and ozone (O 3 )). Associations were evaluated by two-level logistic and generalized linear regression models. Results We detected many significant associations between exposure to air pollutants (especially for PM 1 and PM 2.5 ) and blood lipid levels. Most of the associations suggested deleterious effects on blood lipid markers (e.g., a 10 μg/m 3 increase in PM 1 was associated with 1.6% (95% confidence interval (CI): 1.1, 2.0), 2.9% (95% CI: −3.3, 9.3), and 3.2% (95% CI: 2.6, 3.9) higher levels of TC, TG, and LDL-C, respectively, but 1.4% (95% CI: −1.8, −0.9) lower HDL-C levels), although beneficial associations were found for O 3 . In analysis with dyslipidemias, all the observed associations suggested deleterious lipidemic effects of air pollutants, and no significant beneficial association was observed for O 3 . Stratified analyses showed that the associations were stronger in overweight or obese participants; sex and age modified the associations, but the pattern of effects was mixed. Conclusions Long-term ambient air pollution was associated with both altered lipid profiles and dyslipidemias, especially among overweight or obese participants.

Background Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), a group of perfluorooctane sulfonate (PFOS) alternatives, can be widely observed in humans and environmental matrices. However, associations between exposure to Cl-PFESAs and serum lipid levels in adults are unknown. Objective To explore the relationships between Cl-PFESA levels and serum lipid levels in adults. Methods We analyzed 1238 adults from the Isomers of C8 Health Project, a cross-sectional study conducted in China from July 2015 to October 2016. The average age of the participants was 61.98 ± 14.40 years. We quantified two select legacy per- and perfluoroalkyl substances [perfluorooctanoic acid (PFOA) and PFOS] and their alternatives (6:2 and 8:2 Cl-PFESAs). We also measured four serum lipids: low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). We used generalized linear models to estimate the associations between PFASs and serum lipids, with PFASs defined as either a categorical variable divided into quartiles or as a continuous variable. Results We found that 6:2 Cl-PFESA was positively associated with serum TC and LDL-C. For instance, LDL-C levels in the highest quartile of 6:2 Cl-PFESA exposure (Q4) were significantly higher than those in the lowest quartile (Q1) [β: 0.19, 95% confidence interval (CI): 0.08, 0.30]. Further analysis showed that one ln-ng/mL increase in 6:2 Cl-PFESA exposure corresponded to a 0.10 mmol/L (95% CI: 0.05, 0.16) LDL-C increase, and that exposure to 8:2 Cl-PFESA was negatively correlated with HDL-C (β: −0.03, 95% CI: −0.05, −0.01). TC had a similar relationship with both 6:2 Cl-PFESA and legacy PFASs. Participants with a BMI ≥ 25 kg/m2 exhibited a stronger association between 6:2 Cl-PFESA and TC. Conclusions Our findings make the novel suggestion that exposure to Cl-PFESAs are adversely associated with serum lipid levels, and that such associations are also observed in legacy PFASs. Increased investigation into the effects of Cl-PFESAs exposure on human health is warranted.

Prior investigations on the associations of polyfluoroalkyl substances (PFASs) with fetal growth are mixed. Moreover, little research has accrued pertaining to the association between isomers of PFASs with gestational age and birth weight. To address this gap and present novel information, we conducted a study including 321 pairs of mothers and their infants recruited from Guangzhou, China. High performance liquid chromatography-mass spectrometry was utilized to analyze isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) along with other PFAS levels in cord serum samples. Mothers' and infants' characteristics were gathered from medical records. The resulting data revealed that higher PFOS, PFOA and isomers of PFOS were associated with lower birth weight. Per ln-unit (ng/mL) increase in cord serum total branched PFOS isomers was associated with a 126.3 g (95% CI: −195.9, −56.8) reduction in the weight of infants at birth, while an ln-unit (ng/mL) increase of serum linear PFOS isomers (n-PFOS) was associated with a 57.2 g (95% CI: −103.1, −11.3) reduction in the weight of infants at birth upon the subsequent adjustment for potential confounding variables. Notably, the association between cord PFAS level and birth weight was more pronounced in male infants. Furthermore, a positive association among branched PFOS isomers (1m-PFOS and 3 + 4 + 5m-PFOS) and gestational age was found. No associations could be found among other PFASs in conjunction with gestational age or birth weight. In conclusion, this investigation suggests that higher PFAS concentrations are associated with lower birth weight, and branched PFOS isomers show greater impact on infant birth weight than linear PFOS. Keywords: Polyfluoroalkyl substances (PFASs), Isomers, Birth weight, Gestational age

Background: Living in greener areas has many health benefits, but evidence concerning the effects on blood pressure remains mixed. We sought to assess associations between community greenness and both blood pressure and hypertension in Chinese urban dwellers, and whether the associations were mediated by air pollution, body mass index, and physical activity. Methods: We analyzed data from 24,845 adults participating in the 33 Communities Chinese Health Study, which was conducted in Northeastern China during 2009. We measured each participant's blood pressure according to a standardized protocol. We assessed community greenness using two satellite-derived vegetation indexes – the Normalized Difference Vegetation Index (NDVI) and the Soil Adjusted Vegetation Index (SAVI). Particulate matter ≤2.5 μm and nitrogen dioxide were used as proxies of ambient air pollution. We applied generalized linear mixed models to investigate the association between greenness and blood pressure. We also performed mediation analyses. Results: Living in greener areas was associated with lower blood pressure and hypertension prevalence; an interquartile range increase in both NDVI500-m and SAVI500-m were significantly associated with reductions in systolic blood pressure of 0.82 mm Hg (95% CI: −1.13, −0.51) and 0.89 mm Hg (95% CI: −1.21, −0.57), respectively. The same increases in greenness were also significantly associated with a 5% (95% CI: 1%, 8%) and 5% (95% CI: 1%, 9%) lower odds of having hypertension, respectively. These associations remained consistent in sensitivity analyses. The associations were stronger among women than men. Air pollutants and body mass index partly mediated the associations, but there was no evidence of mediation effects for physical activity. Conclusions: Our findings indicate beneficial associations between community greenness and blood pressure in Chinese adults, especially for women. Air pollution and body mass index only partly mediated the associations. Keywords: Greenness, Hypertension, Blood pressure, Mediation, Cross-sectional study, Chinese adults

Background: Greater levels of serum per- and polyfluoroalkyl substances (PFAS) are known to be associated with higher uric acid which itself leads to a number of chronic diseases. However, whether this association varies across PFAS isomers which recently have been found to be associated with human health remains unknown. Objectives: To address this research gap, we explored isomer-specific associations between serum PFAS and uric acid in Chinese adults. Methods: We conducted a cross-sectional study of associations between serum PFAS isomer and serum uric acid in 1612 participants from the Isomer of C8 Health Project. We used multivariable linear and logistic regression models to analyze serum isomers of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and other PFASs as continuous and categorical predictors of uric acid, adjusted for confounders. The association was also stratified by kidney function stage based on estimated glomerular filtration rate (GF-1, GF-2, GF-3a, and GF-3b/4). Results: We found positive associations between serum PFAS isomer concentrations and uric acid. Uric acid levels were greater for each log-unit increase in branched PFOA (β = 0.30, 95% CI: 0.21, 0.40), linear PFOA (β = 0.18, 95% CI: 0.09, 0.26), branched PFOS (β = 0.09, 95% CI: 0.02, 0.17) and linear PFOS (β = 0.06, 95% CI: −0.01, 0.14) concentration. The associations between PFAS and uric acid showed an inverted ‘U' shaped pattern across kidney function stages. For example, uric acid level was greater with each log-unit increase in total-PFOA among GF-1 (β = 0.21, 95% CI: 0.06, 0.37), this relationship was greater in GF-3a (β = 0.49, 95% CI: 0.09, 0.89) and decreased in GF-3b/4 (β = −0.22, 95% CI: −0.83, 0.39). We also found the odds of hyperuricemia increased linearly with increasing branched PFOA in quartiles (odds ratio = 2.67, 95% CI: 1.86, 3.85 at the highest quartile). Conclusion: We report novel results in which PFAS associations with uric acid varied according to isomer and adult kidney function. Besides, our findings are consistent with previous epidemiologic studies in finding a positive association between serum PFAS concentrations and serum uric acid, especially for PFOA. Our results indicate that more research is needed to more clearly assess the impact of PFAS isomers on human health, which will help to refine regulation policies for PFAS. Keywords: Per- and polyfluoroalkyl substances, Uric acid, Hyperuricemia, Adult, Isomers of C8 Health Project in China

Evidence on the association between long-term exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PMIn 2009, we randomly recruited 24,845 adults at the age of 18-74 years from 33 communities in Northeastern China. CVD status was determined by self-report of doctor-diagnosed CVD. Three-year (2006-08) average concentrations of PMA 10 μg/mLong-term PM

Little is known about PMA total of 59,754 children, aged 2-17 years, were recruited from 94 kindergartens, elementary and middle schools in the Seven Northeast Cities (SNEC) study, during 2012-2013. We obtained information on asthma and asthma-related symptoms including wheeze, persistent phlegm, and persistent cough using a standardized questionnaire developed by the American Thoracic Society. PMOdds ratios (ORs) of doctor-diagnosed asthma associated with a 10-μg/mThis study indicated that long-term exposure to PM