Establishment and validation of a prediction model for gestational diabetes.

AIM: To develop a visual prediction model for gestational diabetes (GD) in pregnant women and to establish an effective and practical tool for clinical application. METHODS: To establish a prediction model, the modelling set included 1756 women enrolled in the Zunyi birth cohort, the internal validation set included 1234 enrolled women, and pregnant women in the Wuhan cohort were included in the external validation set. We established a demographic-lifestyle factor model (DLFM) and a demographic-lifestyle-environmental pollution factor model (DLEFM) based on whether the women were exposed to environmental pollutants. The least absolute shrinkage and selection lasso-logistic regression analyses were used to identify the independent predictors of GD and construct a nomogram for predicting its occurrence. RESULTS: The DLEFM regression analysis showed that a family history of diabetes (odd ratio [OR] 2.28; 95% confidence interval [CI] 1.05-4.71), a history of GD in pregnant women (OR 4.22; 95% CI 1.89-9.41), being overweight or obese before pregnancy (OR 1.71; 95% CI 1.27-2.29), a history of hypertension (OR 2.61; 95% CI 1.41-4.72), sedentary time (h/day) (OR 1.16; 95% CI 1.08-1.24), monobenzyl phthalate (OR 1.95; 95% CI 1.45-2.67) and Q4 mono-ethyl phthalate concentration (OR 1.85; 95% CI 1.26-2.73) were independent predictors. The area under the receiver operating curves for the internal validation of the DLEFM and the DLFM constructed using these seven factors was 0.827 and 0.783, respectively. The calibration curve of the DLEFM was close to the diagonal line. The DLEFM was thus the more optimal model, and the one which we chose. CONCLUSIONS: A nomogram based on preconception factors was constructed to predict the occurrence of GD in the second and third trimesters. It provided an effective tool for the early prediction and timely management of GD.

Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. METHODS: The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. RESULTS: Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. CONCLUSION: The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.

Association of urinary polycyclic aromatic hydrocarbon metabolites with gestational diabetes mellitus and gestational hypertension among pregnant women in Southwest China: A cross-sectional study.

The association of polycyclic aromatic hydrocarbons (PAHs) with gestational diabetes mellitus (GDM) and gestational hypertension during pregnancy has not yet been established. To investigate the association between PAH exposure and GDM and gestational hypertension, we conducted a cross-sectional study of 4206 pregnant women from the Zunyi birth cohort in southwestern China. Gas chromatography/mass spectrometry was used to detect the urinary levels of 10 monohydroxylated PAHs (OH-PAHs). GDM and gestational hypertension were diagnosed and the relevant information was documented by specialist obstetricians and gynecologists. Logistic regression and restricted cubic spline regression were employed to investigate their single and nonlinear associations. Stratified analyses of pregnancy and body mass index data were conducted to determine their moderating effects on the abovementioned associations. Compared with the first quartile of urinary ∑OH-PAHs, the third or fourth quartile in all study participants was associated with an increased risk of GDM (quartile 3: odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.03-1.77) and gestational hypertension (quartile 3: OR = 1.88, 95% CI: 1.26-2.81; quartile 4: OR = 1.58, 95% CI: 1.04-2.39), respectively. Nonlinear associations of 1-OH-PYR with GDM (cutoff level: 0.02 µg/g creatinine [Cr]) and 1-OH-PHE with gestational hypertension (cutoff level: 0.06 µg/g Cr) were also observed. In pregnant women with overweight or obesity, 1-OH-PHE and 3-OH-PHE were more strongly associated with gestational hypertension. Our results indicate that exposure to PAH during pregnancy may significantly increase the maternal risks of GDM and gestational hypertension; however, this finding still needs to be confirmed through larger-scale prospective studies and biological evidence.

Single and joint associations of exposure to polycyclic aromatic hydrocarbons with blood coagulation function during pregnancy: A cross-sectional study.

Association linking polycyclic aromatic hydrocarbons (PAHs) to blood coagulation function during pregnancy remains absent. Hence, we conducted a cross-sectional study including 679 late pregnant women (27.2 ± 5.1 years old) drawn from Zunyi birth cohort, Southwest China. During late pregnancy, ten urinary PAHs metabolites and four clinical blood coagulation parameters were measured, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB). Multiple linear regression, Restricted cubic spline (RCS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (Q-g) regression were used to investigate their single, nonlinear, and mixed associations. Each 2.7-fold increment in 2-hydroxyfluorene (2-OHFlu), 9-hydroxyfluorene (9-OHFlu), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyphenanthrene (2-OHPhe), and 3-hydroxyphenanthrene (3-OHPhe) were associated with 0.287 s, 0.190 s, 0.487 s, and 0.396 s shorter APTT, respectively; each 2.7-fold increment in 2-OHPhe was associated with a 0.047 s longer PT; each 2.7-fold increment in 9-hydroxyphenanthrene (9-OHPhe) and 1-hydroxypyrene (1-OHPyr) were associated with 0.087 s and 0.031 s shorter TT, respectively; and each 2.7-fold increment in 1-hydroxynaphthalene (1-OHNap) was associated with 0.032 g/L higher FIB level. The nonlinear association of 2-OHPhe with APTT and 1-OHNap with FIB were also observed. Furthermore, the shortened APTT and TT associated with PAHs mixture were indicated by BKMR and Q-g model. BKMR also revealed a nonlinear association of 2-OHPhe with PT and an interaction effect of 2-OHPhe and 3-OHPhe on APTT. Our results indicate that urinary PAHs was associated with shortened coagulation time and increased FIB. Therefore, more attention should be paid for late pregnant women to prevent PAHs-associated risk of thrombosis. Future perspective studies to confirm our findings and explore the underlying biological mechanism are warranted.

Risk assessment and environmental determinants of urinary phthalate metabolites in pregnant women in Southwest China.

Pregnant women are widely exposed to phthalic acid esters (PAEs) that are commonly used in most aspects of modern life. However, few studies have examined the cumulative exposure of pregnant women to a variety of PAEs derived from the living environmental conditions in China. Therefore, this study aimed to determine the urinary concentrations of nine PAE metabolites in pregnant women, examine the relationship between urinary concentrations and residential characteristics, and conduct a risk assessment analysis. We included 1,888 women who were in their third trimester of pregnancy, and we determined their urinary concentrations of nine PAE metabolites using high-performance gas chromatography-mass spectrometry. The risk assessment of exposure to PAEs was calculated based on the estimated daily intake. A linear regression model was used to analyze the relationship between creatinine-adjusted PAE metabolite concentrations and residential characteristics. The detection rate of five PAE metabolites in the study population was > 90%. Among the PAE metabolites adjusted by creatinine, the urinary metabolite concentration of monobutyl phthalate was found to be the highest. Residential factors, such as housing type, proximity to streets, recent decorations, lack of ventilation in the kitchen, less than equal to three rooms, and the use of coal/kerosene/wood/wheat straw fuels, were all significantly associated with high PAE metabolite concentrations. Due to PAE exposure, ~ 42% (n = 793) of the participants faced potential health risks, particularly attributed to dibutyl phthalate, diisobutyl phthalate, and di(2-ethyl)hexyl phthalate exposure. Living in buildings and using coal/kerosene/wood/wheat straw as domestic fuel can further increase the risks.

The association between genital mycoplasma infection and spontaneous abortion: A systematic review and meta-analysis.

Epidemiological findings on the association between genital mycoplasma infection (GMI) and spontaneous abortion are inconsistent. Therefore, this meta-analysis aims to determine whether mycoplasma infection during pregnancy increases the risk of spontaneous abortion. An electronic database search was conducted using China National Knowledge Infrastructure, Elsevier, PubMed, SinoMed, The Cochrane Library, and Wanfang Database from database establishment to October 2021. Sixteen case-controls and 3 prospective cohorts were included. The meta-analysis showed that GMI was positively associated with spontaneous abortion (odds ratio (OR) 2.35, 95% confidence interval (CI) 1.50, 3.67). Of them, case-control studies showed that the GMI proportion in the spontaneous abortion group was higher than that in the normal group (OR 2.13, 95% CI 1.33, 3.43); the cohort study showed that the spontaneous abortion rate in the GMI group was higher than those in non-infected groups (relative risk 5.17, 95% CI 2.07, 12.95; risk difference 0.18, 95% CI 0.09, 0.27). Each outcome indicator was relatively robust in the sensitivity analysis, and no significant publication bias was found in the funnel plots. Our data support that GMI during pregnancy increases the risk of spontaneous abortion. Thus, the monitoring and timely treatment of GMI before pregnancy of GMI are essential to decrease the risk of spontaneous abortion.

Characteristics of exposure to 10 polycyclic aromatic hydrocarbon metabolites among pregnant women: cohort of pregnant women in Zunyi, southwest China.

OBJECTIVE: Our aim was to elucidate the polycyclic aromatic hydrocarbon (PAH) metabolites exposure levels of pregnant women in the underdeveloped region of Zunyi, southwest China. METHODS: Sociodemographic information was collected via questionnaires, and urine samples were collected at the same time. A total of 3047 pregnant women participated in the study. Gas chromatography/mass spectrometry was used to detect the urine concentrations of 10 PAH metabolites. A generalised linear model (GLM) was used to identify predictive factors of PAH metabolites. RESULTS: All PAH metabolites had a detection rate greater than 60% (67.21%-90.57%) except for 4-OH-PHE at 55.54%. The median concentrations were 0.02-0.11 µg/g Cre except for 1-OH-NAP, 2-OH-NAP, 2-OH-FLU and 9-OH-FLU (0.36-0.50 µg/g Cre). The cluster analysis identified the phenanthrene and fluorene metabolite clusters (containing no other metabolites), while naphthalene metabolites (1-OH-NAP, 2-OH-NAP) could not be clustered without other metabolites. GLM analysis identified that pregnant women with the following characteristics have high urinary concentration of PAH metabolites: overweight, in the last trimester of pregnancy, distance between their house and main traffic lines as <5 m, use fuel for cooking, passive smoking, renovated their residence for less than 3 years, middle family income and office workers. CONCLUSION: The results clarified pregnant women from the economically underdeveloped area could be the victims of PAHs. In addition, PAHs present a demographic and seasonal differential distribution, which will aid in the development of targeted interventions and reduce exposure to PAHs during pregnancy.

Maternal urine phthalate metabolite exposure and miscarriage risk: a nested case-control study of the Zunyi Birth Cohort.

Phthalates (PAEs) are widespread persistent organic pollutants and endocrine disruptors. However, the associations between PAE exposure and the risk of miscarriage in humans are unclear, and an insufficient number of studies have evaluated the possible threshold or dose-dependent effects of first trimester PAE exposure on miscarriage risk. Our research measured the levels of mono-methyl phthalate (MMP), mono-ethyl phthalate, mono-isobutyl phthalate, MiBP mono-butyl phthalate (MBP), mono-octyl phthalate, mono-benzyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in maternal urine collected in early gestation between 150 pregnancies ending in miscarriage and 150 pregnancies with live birth. We also estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PAE as a continuous variable or quartile. A restrictive cubic splines was used to assess dose-dependent effects after controlling for maternal characteristics (e.g., age, educational level). we identified monotonically increasing dose-dependent effects of MEHHP and MMP on the risk of miscarriage. The largest effect estimates were approximately threefold higher for the highest MBP (OR = 2.57; 95% CI = 1.32-5.01) or MMP quartile (OR = 3.57; 95% CI = 1.82-7.00) and two-fold higher for the highest MEHHP quartile (OR = 2.12; 95% CI = 1.10-4.11). Our research preliminarily obtained possible thresholds of MBP, MEHHP, and MMP which were 18.07, 2.38, and 0.80 µg/g Cr for the risk of miscarriage, respectively. First-trimester exposure to MBP, MEHHP, and MMP exceeding certain thresholds increases the risk of miscarriage.

Effects of exposure to phthalate during early pregnancy on gestational diabetes mellitus: a nested case-control study with propensity score matching.

Owing to the complexity of phthalates (PAEs) components and the diversity of their sources, the health hazards of their metabolites to pregnant women remain unclear. This study aimed to explore the relationship between exposure to PAEs during early pregnancy and gestational diabetes mellitus (GDM) in rural pregnant women. We assessed pregnant women with (n = 338) or without (n = 3082) GDM from the ongoing Zunyi Birth Cohort. Participants' urine samples were collected to measure the levels of 10 metabolites of PAEs. GDM was diagnosed using the 75-g oral glucose tolerance test at 24-28 weeks of gestation. We adopted propensity score matching based on GDM-related factors and pregnant women's backgrounds to establish two groups of 338 patients: those with or without GDM. In the cohort, we included 5734 pregnant women; 519 of them developed GDM, yielding a GDM incidence rate of 9.05%. Urinary concentrations of monooctyl phthalate (MOP), mono-benzyl phthalate (MBzP), mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) during early pregnancy were significantly associated with GDM (P < 0.05). Logistic regression models revealed that MEOHP in the urine was positively associated with GDM (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.00-2.39). Furthermore, restricted cubic spline models revealed that urine MEOHP concentrations greater than 15.6 µg/L were positively associated with GDM, and approximately 23.5% pregnant women had urine MEOHP concentrations greater than 15.6 µg/L. Thus, approximately 23.5% of pregnant women were at the risk of developing GDM due to MEOHP, which suggested that pregnant women should reduce the use of packaged food and cosmetics to reduce the risk of GDM. However, further molecular biology experiments are required to confirm these findings and to elucidate the underlying mechanisms.

Association between exposures to phthalate metabolites and preterm birth and spontaneous preterm birth: A systematic review and meta-analysis.

Emerging evidence from observational studies proves the association between preterm birth (PTB) and phthalate metabolites; however, such findings are inconsistent and inconclusive. This meta-analysis aimed to clarify this association by accessing the connection between 11 phthalate metabolites and PTB, and 6 phthalate metabolites and spontaneous PTB. The PubMed, Embase, and WOS (Web of Science) databases were searched up to July 2020. Seven prospective studies met the inclusion criteria. Pooled odds ratios (OR) with 95 % confidence intervals (CIs) were calculated for risk estimation. Our results indicated that mono-n-butyl phthalate (MBP), sum of di-2-ethylhexyl phthalate (ΣDEHP), and mono 3-carboxypropyl phthalate (MCPP) significantly correlated with the risk of PTB (MBP: OR = 1.23, 95 % CI = 1.05-1.45; ΣDEHP: OR = 1.21, 95 % CI =1.01-1.44; MCPP: OR = 1.09, 95 % CI = 1.00-1.19). Pooled results showed that spontaneous PTB was associated with higher urinary levels of mono-ethyl phthalate (MEP), MCPP, mono-isobutyl phthalate (MIBP), and MBP (MBP: OR = 1.27, 95 % CI = 1.02-1.58; MEP: OR = 1.19, 95 % CI = 1.01-1.40; MCPP: OR = 1.15, 95 % CI = 1.02-1.30; MIBP: OR = 1.38, 95 % CI = 1.12-1.71). Overall, we conclude that during pregnancy, MBP, ΣDEHP, and MCPP levels are associated positively with PTB. MBP, MEP, MCPP, and MIBP levels had increased odds of spontaneous PTB. No significant associations were observed between other phthalate metabolites and PTB or spontaneous PTB. Further research is needed to verify these findings and elucidate the association of phthalate levels and PTB.

Chlorinated Polyfluorinated Ether Sulfonates and Thyroid Hormone Levels in Adults: Isomers of C8 Health Project in China.

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

Exposure characteristics of phthalate metabolites among the Zunyi cohort of pregnant women in Southwest China.

Reported evidence has increasingly indicated that exposure to phthalates can cause adverse pregnancy outcomes. However, phthalate exposure levels among pregnant women remains unclear. We aimed to evaluate the concentrations and predictors of phthalate metabolites in urine samples of the ongoing Zunyi cohort of pregnant women from Southwest China. The urine samples were collected from 1003 pregnant women during their third trimester of pregnancy. The concentrations of nine phthalate metabolites in urine samples were then determined. Data on socio-demographic profiles of the participants, lifestyle during pregnancy, parity, and sampling season were collected using questionnaires. The detectable rate of phthalate metabolites ranged from 76 to 100%. On average, mono-butyl phthalate exhibited the highest median concentration (62.45 µg/L), while mono-benzyl phthalate exhibited the lowest median concentration (0.04 µg/L). Urine concentrations of phthalate metabolites were significantly higher in older, multiparous, higher body mass index, higher income, and passive smoking during pregnancy participants. The levels of low-molecular-weight phthalate metabolites were highest during the summer. The findings indicate the health of pregnant women and fetuses in Zunyi may be generally harmed by the high exposure of phthalate metabolites, especially by mono-n-butyl phthalate. In addition, phthalate metabolites present a demographic and seasonal differential distribution among the study population. Targeted measures to reduce phthalate exposure for high-risk pregnant women and during high-exposure seasons may have potential benefits for maternal and fetal health protection.

Nickel nanoparticles affect the migration and invasion of HTR-8/SVneo cells by downregulating MMP2 through the PI3K/AKT pathway.

Proper migration and invasion of extravillous trophoblast cells into the endometrium in early gestation is essential for successful embryo implantation. The development of nanotechnology has led to the emergence of nickel nanoparticles (Ni NPs), for which attendant health concerns are widespread. Ni NPs are known to affect reproduction and be embryotoxic, but whether they affect the migration and invasion functions of trophoblast cells is unclear. We investigated the effects of Ni NPs on the migration and invasion of HTR-8/SVneo in extravillous trophoblast cells and explored the possible role of the PI3K/AKT/MMP2 signaling pathway in this regard. Results showed that the migration and invasion of cells was significantly inhibited by the exposure of Ni NPs. The protein and mRNA levels of PI3K/AKT/MMP2 signaling pathway were significantly reduced with the increase in Ni NPs concentration. The presence of the PI3K activator 740Y-P partially attenuated the inhibition of cell migration and invasion by Ni NPs, confirming the involvement of this pathway. Thus, Ni NPs inhibit migration and invasion of human trophoblast HTR-8/SVneo cells by downregulating the PI3K/AKT/MMP2 signaling pathway. This study is important for the development of safety evaluation criteria for Ni NPs.

The associations between exposure to trihalomethanes during pregnancy and adverse birth outcomes: A systematic review and meta-analysis.

The study aimed to examine the associations between the level of trihalomethanes and its metabolites in pregnancy and the risks of adverse birth outcomes. We searched the databases of the China National Knowledge Infrastructure, WanFang, Vip, PubMed, and Elsevier Science Direct from database establishment to July 14, 2021 and performed a systematic review and meta-analysis of observational studies reporting associations between trihalomethanes level and abnormally low birth weight and preterm birth. The pooled odds ratio (OR), pooled risk ratio, and pooled risk difference with their 95% confidence interval (CI) were calculated for risk estimates. A total of 24 studies involving 1,118,037 pregnant women were finally enrolled in the present systematic review and meta-analysis. Our research found that abnormally low birth weight was associated with higher levels of total trihalomethanes (OR = 2.45, 95% CI: 1.28, 4.68; P = 0.007). Unexpectedly, the meta-analysis indicated that higher total trihalomethanes level was associated with lower odds of preterm birth (OR = 0.90, 95% CI: 0.81, 0.99; P = 0.03). Our findings indicate that trihalomethanes exposure might be a risk factor for abnormally low birth weight and that it would be prudent to minimize exposure to trihalomethanes during pregnancy because of the risk of abnormally low birth weight. Given some limitations of the systematic review and meta-analysis, our results should be interpreted with caution.

Associations between both legacy and alternative per- and polyfluoroalkyl substances and glucose-homeostasis: The Isomers of C8 health project in China.

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.

The effects of Cl-PFESAs exposure on blood lipids - A community-based large population study in Guangzhou.

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.

Associations between metabolic syndrome and anthropogenic heat emissions in northeastern China.

BACKGROUND: Recent research attention has been paid to anthropogenic heat emissions (AE), temperature increase generated by human activity such as lighting, transportation, manufacturing, construction, and building climate controls. However, there is no epidemiological data available to investigate the association between anthropogenic heat emissions and metabolic syndrome (MetS), a cluster of conditions that increase risk of stroke, heart disease and diabetes. OBJECTIVE: To explore the relationships between AE and MetS in China. METHODS: We recruited 15,477 adults from the 33 Communities Chinese Health Study, a cross-sectional study in northeastern China. We retrieved anthropogenic heat flux by collecting socio-economic and energy consumption data as well as satellite-based nighttime light and Normalized Difference Vegetation Index datasets, including emissions from buildings, transportation, human metabolism, and industries. We also measured MetS components consisting of triglycerides, high density lipoprotein cholesterol, fasting glucose, systolic blood pressure, and diastolic blood pressure, and waist circumference. Restricted cubic spline models were applied to assess the associations between AE and MetS. RESULTS: The median flux of total AE was 30.98 W/m2 and industrial AE was the dominant contributor (87.64%). The adjusted odds ratio and 95% confidence interval (CI) of MetS for the 75th and 95th percentiles of the total AE against the threshold were 1.29 (95% CI: 1.21, 1.38) and 1.65 (95% CI: 1.47, 1.85). Greater AE was associated with higher odds of MetS in a dose-response pattern, and the lowest point of U-shape curve indicated the threshold effect. Participants who are young and middle-aged exhibited stronger associations between AE and MetS. CONCLUSIONS: Our novel findings reveal that AE are positively associated with MetS and that associations are modified by age. Further investigations into the mechanisms of the effects are needed.

Exposure to second-hand smoke during early life and subsequent sleep problems in children: a population-based cross-sectional study.

BACKGROUND: Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children. METHODS: In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems. RESULTS: We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (ß = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses. CONCLUSIONS: Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6-18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life.

The Asthma Family Tree: Evaluating Associations Between Childhood, Parental, and Grandparental Asthma in Seven Chinese Cities.

Objective: To evaluate the associations between childhood, parental, and grandparental asthma. Methods: We studied 59,484 children randomly selected from 94 kindergartens, elementary, and middle schools in seven Chinese cities from 2012 to 2013, using a cross-sectional survey-based study design. Information on their and their family members' (parents, paternal grandparents, and maternal grandparents) asthma status were reported by children's parents or guardians. Mixed effects logistic regressions were used to assess hereditary patterns of asthma and mediation analysis was performed to estimate the potential mediation effect of parents on the association between grandparental asthma and childhood asthma. Results: The magnitude of ORs for childhood asthma increased as the number of family members affected by asthma increased. Among children who had one family member with asthma, childhood asthma was associated with asthma in maternal grandmothers (OR: 2.08, 95% CI: 1.67-2.59), maternal grandfathers (OR: 2.08, 95% CI: 1.71-2.53), paternal grandmothers (OR: 2.40, 95% CI: 1.93-2.99), and paternal grandfathers (OR: 2.59, 95% CI: 2.14-3.13). Among children who had two family members with asthma, the highest asthma risk was found when both parents had asthma (OR: 15.92, 95% CI: 4.66-54.45). Parents had a small proportion of mediation effect (9-12%) on the association between grandparental asthma and childhood asthma. Conclusions: Grandparents with asthma were associated with childhood asthma and parents with asthma partially mediated the association.

Association between eye-level greenness and lung function in urban Chinese children.

BACKGROUND: Health effects of greenness perceived by residents at eye level has received increasing attention. However, the associations between eye-level greenness and respiratory health are unknown. The aim of the study was to investigate the associations between exposure to eye-level greenness and lung function in children. METHODS: From 2012 to 2013, a total of 6740 school children in seven cities in northeast China were recruited into this cross-sectional study. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEF), and maximum mid expiratory flow rate (MMEF) were measured to evaluate lung function and to define lung impairment. Eye-level greenness was extracted from segmented Tencent Map street view images, and a corresponding green view index (GVI) was calculated. Higher GVIs mean more greenness coverage. Mixed-effects logistic regressions were used to estimate the health effects on lung impairment per interquartile range (IQR) increase in GVI. Linear regressions were used to estimate the associations between GVI and lung function. The health effects of ambient air pollutants were also assessed, including particulate matter with an aerodynamic diameter <1.0 µm (PM1), <2.5 µm (PM2.5), <10 µm (PM10) as well as nitrogen dioxide (NO2). RESULTS: An increase of GVI800m was associated with lung impairment in FEV1, FVC, PEF and MMEF, with ORs ranging from 0.68 (95% CI: 0.59, 0.79) to 0.83 (95% CI: 0.74, 0.93). The associations between an IQR increase of GVI800m and FEV1 (48.15 ml, 95% CI: 30.33-65.97 ml), FVC (50.57 ml, 95% CI: 30.65-70.48 ml), PEF (149.59 ml/s, 95% CI: 109.79-189.38 ml/s), and MMEF (61.18 ml/s, 95% CI: 31.07-91.29 ml/s) were significant, and PM1, PM2.5, and PM10 were found to be mediators of this relationship. CONCLUSION: More eye-level greenness was associated with better lung function and reduced impairment. However, eye-level greenness associations with lung function became non-significant once lower particulate matter air pollution exposures were considered.