solid volume ratio in predicting pathological features of cT1 lung adenocarcinoma.

BACKGROUND: More effective methods are urgently needed for predicting the pathological grade and lymph node metastasis of cT1-stage lung adenocarcinoma. METHODS: We analyzed the relationships between CT quantitative parameters (including three-dimensional parameters) and pathological grade and lymph node metastasis in cT1-stage lung adenocarcinoma patients of our center between January 2015 and December 2023. RESULTS: A total of 343 patients were included, of which there were 233 males and 110 females, aged 61.8 ± 9.4 (30-82) years. The area under the receiver operating characteristic (ROC) curve for predicting the pathological grade of lung adenocarcinoma using the consolidation tumor ratio (CTR) and the solid volume ratio (SVR) were 0.761 and 0.777, respectively. The areas under the ROC curves (AUCs) for predicting lymph node metastasis were 0.804 and 0.873, respectively. Multivariate logistic regression analysis suggested that the SVR is an independent predictor of highly malignant lung adenocarcinoma pathology, while the SVR and pathological grade are independent predictors of lymph node metastasis. The sensitivity of predicting the pathological grading of lung adenocarcinoma based on SVR>5% is 97.2%, with a negative predictive value of 96%. The sensitivity of predicting lymph node metastasis based on SVR>47.1% is 97.3%, and the negative predictive value is 99.5%. CONCLUSIONS: The SVR has greater diagnostic value than the CTR in the preoperative prediction of pathologic grade and lymph node metastasis in stage cT1-stage lung adenocarcinoma patients, and the SVR may replace the diameter and CTR as better criteria for guiding surgical implementation.

Low-grade systemic inflammation links heavy metal exposures to mortality: A multi-metal inflammatory index approach.

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (ß = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Prenatal exposure to metal mixtures, body mass index trajectories in early life and effect modifiers: Insights from a prospective birth cohort study.

Current scientific knowledge is insufficient on the effects of metal mixtures on early life growth trajectories. This study included 7118 mother-infant pairs from a Chinese birth cohort. Concentrations of 18 maternal urinary metals were quantified, and growth trajectories were conducted based on standardized body mass index (BMI) for up to eight times from 0 to 2 years. A three-phase analytical framework was applied to explore the risk ratios (RR) and 95 % confidence intervals (95 % CI) of co-exposure to metals on dynamic growth, along with potential modifiers. Five growth trajectory groups were identified. Exposure to metal mixtures driven by thallium (Tl, 34.8 %) and aluminum (Al, 16.2 %) was associated with an increased risk of low-rising trajectory (RR=1.58, 95 % CI: 1.25, 2.00); however, exposure to mixtures driven by strontium (Sr, 49.5 %) exhibited an inverse correlation (RR = 0.81, 95 % CI: 0.67, 0.97). Furthermore, infants with varying levels of Tl, Al and Sr, as well as modifiers including pre-pregnancy BMI and infant sex faced distinct risks of low-rising trajectory. Our findings highlighted the Tl, Al, and Sr as key metals in relation to the low-rising trajectory in early life characterized as catch-up growth, with pre-pregnancy BMI and infant sex exerting as potential modifiers.

Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study.

BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. OBJECTIVE: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). METHOD: This study included 285 mother-child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. RESULTS: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P < 0.05). CONCLUSION: Our results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.

Intrauterine chromium exposure and cognitive developmental delay: The modifying effect of genetic predisposition.

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children's cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child's cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one's adverse genetic background jointly contribute to an increased risk of CDD in children.

Associations of glyphosate exposure and serum sex steroid hormones among 6-19-year-old children and adolescents.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.

First-trimester fetal size, accelerated growth in utero, and child neurodevelopment in a cohort study.

BACKGROUND: Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children's neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children's neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. METHODS: The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. RESULTS: Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P < 0.01) at age 2 years, respectively. No significant association was observed between fetal growth rate and PDI. For children with restricted first-trimester fetal size (the lowest tertile of first-trimester CRL), those with "intrauterine accelerated growth" pattern (higher growth rates) had significantly higher MDI (adjusted beta estimate = 6.14, (95% CI: 3.80, 8.49), P < 0.001) but indistinguishable PDI compared to those with "intrauterine faltering growth" pattern (lower growth rates). Main limitations of this study included potential misclassification of gestational age due to recall bias of the last menstrual period and residual confounding. CONCLUSIONS: The current study suggests that restricted first-trimester fetal size is associated with mental and psychomotor developmental delay in childhood. However, in children with restricted first-trimester fetal size, intrauterine accelerated growth was associated with improved mental development but had little effect on psychomotor development. Additional studies are needed to validate the results in diverse populations.

Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Associations of intrauterine exposure to manganese with fetal and early-childhood growth: a prospective prenatal cohort study.

Prenatal manganese (Mn) exposure may be related to poor birth outcomes; however, there are few relevant epidemiological reports on the effects of intrauterine Mn levels on intrauterine fetal and early childhood growth. From 2013 to 2016, 2082 pairs of mothers and infants were recruited in Wuhan, China, who provided an entire set of urine samples during their first, second, and third trimesters. Fetal head circumference (HC), abdominal circumference (AC), femoral length (FL), and estimated fetal weight (EFW) were obtained by ultrasound at the 16, 24, and 31 weeks of pregnancy. When the children were born, 6 months old, 12 months old, and 24 months old, their weight, height, weight-for-height, and BMI were measured. We used generalized linear models, generalized estimated equations, and restricted cubic spline curves (RCS) to investigate the linear and nonlinear relationships between antenatal Mn levels and fetal and early childhood growth. In all fetuses, Mn exposure during the 1st and 2nd gestation was associated with decreased fetal AC, FL, and EFW at 24 weeks (e.g., for each doubling of urinary Mn concentrations during the 1st and 2nd gestation, the SD score of EFW at 24 weeks decreased by - 4.16% (95% CI, - 6.22%, - 2.10%) and - 3.78% (95% CI, - 5.86%, - 1.70%)). Mn concentrations in the highest tertile group of the 1st and 2nd gestation were related to decreased fetus growth parameters compared to the lowest tertile group. For each doubling of the average Mn concentrations during pregnancy, the z-scores of weight, weight-for-height, and BMI at 12 months decreased, with percentage changes of - 2.93% (95% CI, - 5.08%, - 0.79%), - 3.25% (95% CI, - 5.56%, - 0.94%), and - 3.09% (95% CI, - 5.44%, - 0.73%). In the RCS model, we found a reverse U-shaped association between 1st trimester Mn concentration and fetal FL at 16 weeks and HC at 31 weeks in male fetuses and a non-linear association between mean Mn concentration during pregnancy and girls' weight-for-height and BMI at 6 months. Intrauterine exposure to Mn may be related to restricted growth in the fetus and early childhood, especially in fetuses at 24 weeks of gestation and children at 12 months of age. Also, meaningful curvilinear relationships were found in the sex stratification.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [ß = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 µg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 µg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

Prenatal phthalate exposure and fetal penile length and width.

BACKGROUND: Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS: Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS: 57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS: In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT: First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

Prenatal Lead Exposure, Genetic Factors, and Cognitive Developmental Delay.

Importance: Although the effects of lead (Pb) exposure on neurocognition in children have been confirmed, the individual associations of prenatal Pb exposure and its interaction with genetic factors on cognitive developmental delay (CDD) in children remain unclear. Objective: To investigate the association of prenatal Pb exposure and its interaction with genetic factors with CDD risk. Design, Setting, and Participants: Women in Wuhan, China, who had an expected delivery date between March 2014 and December 2017, were recruited for this prospective cohort study. Children were assessed for cognitive development at approximately 2 years of age (March 2016 to December 2019). Maternal venous blood, cord blood, and venous blood from children were collected in a longitudinal follow-up. Data analysis was performed from March 2022 to February 2023. Exposure: Prenatal Pb exposure, and genetic risk for cognitive ability evaluated by polygenic risk score constructed with 58 genetic variations. Main Outcomes and Measures: Cognitive developmental delay of children aged approximately 2 years was assessed using the Chinese revision of the Bayley Scale of Infant Development. A series of multivariable logistic regressions was estimated to determine associations between prenatal Pb exposure and CDD among children with various genetic backgrounds, adjusting for confounding variables. Results: This analysis included 2361 eligible mother-child pairs (1240 boys [52.5%] and 1121 girls [47.5%]; mean [SD] ages of mothers and children, 28.9 [3.6] years and 24.8 [1.0] months, respectively), with 292 children (12.4%) having CDD. Higher maternal Pb levels were significantly associated with increased risk of CDD (highest vs lowest tertile: odds ratio, 1.55; 95% CI, 1.13-2.13), adjusting for demographic confounders. The association of CDD with maternal Pb levels was more evident among children with higher genetic risk (highest vs lowest tertile: odds ratio, 2.59; 95% CI, 1.48-4.55), adjusting for demographic confounders. Conclusions and Relevance: In this cohort study, prenatal Pb exposure was associated with an increased risk of CDD in children, especially in those with a high genetic risk. These findings suggest that prenatal Pb exposure and genetic background may jointly contribute to an increased risk of CDD for children and indicate the possibility for an integrated strategy to assess CDD risk and improve children's cognitive ability.

Measuring semi-volatile organic compound exposures during pregnancy using silicone wristbands.

Silicone wristbands were utilized as personal passive samplers in a sub-cohort of 92 women, who participated in New York University Children's Health and Environment Study, to assess exposure to semi-volatile organic compounds (SVOCs). Wristbands were analyzed for 77 SVOCs, including halogenated and non-halogenated organophosphate esters (OPEs), polychlorinated biphenyls (PCBs), pesticides, phthalates, and brominated flame retardants (BFRs) (e.g. polybrominated diphenyl ethers (PBDEs)). This study aimed to look for patterns in chemical exposure utilizing participant demographics gathered from a questionnaire, and chemical exposure data across multiple timepoints during pregnancy. Analysis focused on 27 compounds detected in at least 80% of the wristbands examined. The chemicals detected most frequently included two pesticides, eight phthalates, one phthalate alternative, seven BFRs, and nine OPEs, including isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs). Co-exposure to different SVOCs was most prominent in compounds that were within the same chemical class or were used in similar consumer applications such as phthalates and OPEs, which are often used as plasticizers. Pre-pregnancy BMI was positively associated with multiple compounds, and there were both positive and negative associations between women's parity and SVOC exposure. Outdoor temperature was not correlated with the wristband concentrations over a five-day sampling period. Lastly, significant and moderately high Intraclass Correlation Coefficient (ICC) (0.66-0.84) values for phthalate measurementsacross pregnancy indicate chronic exposure and suggest that using wristbands during one sampling period may reliably predict exposure. However, multiple sampling periods may be necessary to accurately determine indoor exposure to other SVOCs including OPEs and BFRs.

Low level of urinary cotinine in pregnant women also matters: variability, exposure characteristics, and association with oxidative stress markers.

China has relatively high indoor contamination of nicotine, according to recent publications. Therefore, nicotine exposure risks for sensitive populations such as pregnant women in China are of concern. The variability of its internal exposure levels across three trimesters among pregnant women is not well documented. Factors related with nicotine exposure across pregnancy and its associations with oxidative stress markers are also understudied. Based on a birth cohort, we measured concentrations of cotinine (a major metabolite of nicotine) and oxidative stress markers including 8-OHdG, 8-OHG, and HNE-MA in urine samples collected at three trimesters from 1,155 pregnant women enrolled between January 2014 and June 2017 in Wuhan, China. The variability of urinary cotinine across the trimesters, potential factors associated with it, as well as the relationships between urinary cotinine and oxidative stress markers were assessed in pregnant women with cotinine concentrations of < 50 ng/mL (the cutoff value to distinguish smokers and non-smokers). Urinary specific gravity adjusted median concentrations of cotinine (ng/mL) in the entire pregnancy, first, second, and third trimester were 3.04, 3.32, 3.36, and 2.50, respectively, which exhibited fair reliability (intraclass correlation coefficient: 0.47) across pregnancy. Most participants had an estimated daily intake of nicotine higher than the acceptable value (100 ng/kg-bw/day) recommended by the UK and the USA. Maternal age, education level, pre-pregnancy body mass index, and sampling seasons were related to urinary concentrations of cotinine. After adjusting for confounding factors, significant positive relationships (ß; 95% confidence interval) were observed between urinary cotinine concentrations and 8-OHdG (0.28; 0.25, 0.30), 8-OHG (0.27; 0.25, 0.29), and HNE-MA (0.27; 0.21, 0.32), respectively (p < 0.01). These results lend insight into the major factors associated with nicotine exposure of pregnant women at environmentally relevant levels and its potential effect on oxidative stress with a large sample size, and warrant the necessity of reducing the exposure in sensitive populations.

Multiple metal exposure and metabolic syndrome in elderly individuals: A case-control study in an active mining district, Northwest China.

The prevalence of metabolic syndrome (MetS) is increasing at an alarming rate worldwide, particularly among elderly individuals. Exposure to various metals has been linked to the development of MetS. However, limited studies have focused attention on the elderly population living in active mining districts. Participants with MetS (N = 292) were matched for age (±2 years old) and sex with a healthy subject (N = 292). We measured the serum levels of 14 metals in older people aged 65-85 years. Conditional logistic regression, restricted cubic spline model, multiple linear regression, and Bayesian Kernel Machine Regression (BKMR) were applied to estimate potential associations between multiple metals and the risk of MetS. Serum levels of Sb and Fe were significantly higher than the controls (0.58 µg/L vs 0.46 µg/L, 2167 µg/L vs 2042 µg/L, p < 0.05), while Mg was significantly lower (20035 µg/L vs 20,394 µg/L, p < 0.05). An increased risk of MetS was associated with higher serum Sb levels (adjusted odds ratio (OR) = 1.61 for the highest tertile vs. the lowest tertile, 95% CI = 1.08-2.40, p-trend = 0.018) and serum Fe levels (adjusted OR = 1.55 for the highest tertile, 95% CI = 1.04-2.33, p-trend = 0.032). Higher Mg levels in serum may have potential protective effects on the development of MetS (adjusted OR = 0.61 for the highest tertile, 95% CI = 0.41-0.91, p-trend = 0.013). A joint exposure analysis by the BKMR model revealed that the mixture of 12 metals (except Tl and Cd) was associated with increased risk of MetS. Our results indicated that exposure to Sb and Fe might increase the risk of MetS in an elderly population living in mining-intensive areas. Further work is needed to confirm the protective effect of Mg on MetS.

Association of arsenic exposure and clinical hematological changes during pregnancy: Findings from a prospective Wuhan birth cohort study.

BACKGROUND: Animal studies have reported arsenic-induced disturbed erythropoiesis parameters. However, the effects of exposure to arsenic on hematological parameters among pregnant women are unclear. OBJECTIVES: We aimed to evaluate trimester-specific associations between arsenic metabolites and erythropoietic parameters measured repeatedly during pregnancy. METHODS: A total of 1945 pregnant women from a birth cohort study were included. We detected arsenic species in urine sampled at each trimester and extracted erythropoietic parameters in different trimesters from the medical records. We used linear regressions with generalized estimating equations (GEEs) to examine the relationship between arsenic metabolites concentrations at different trimesters and erythropoietic parameters. We utilized GEEs to calculate the odds ratio (OR) for anemia during pregnancy. RESULTS: Adjusted trimester-specific analysis showed that higher monomethylated arsenic (MMA) and %MMA were related to remarkably reduced hemoglobin (Hb) and mean corpuscular hemoglobin (MCH). Additionally, elevated urinary MMA concentration and %MMA in the early trimester were associated with an increased risk of microcytic anemias in the late trimester. CONCLUSIONS: Our study demonstrated a significant inverse relationship between gestational arsenic exposure and Hb and MCH. Notably, higher MMA and lower methylation capacity to metabolize inorganic arsenic (iAs) in early pregnancy might increase the likelihood of microcytic anemia among pregnant women in late pregnancy.

Associations between per and polyfluoroalkyl ether sulfonic acids and vitamin D biomarker levels in Chinese newborns.

Skeleton develops extremely fast during fetal and neonatal stages; thus, fetuses and newborns exhibit unique vulnerabilities to vitamin D metabolism dysregulation, giving vitamin D's principal role in calcium homeostasis. Previous studies linked legacy per and polyfluoroalkyl ether sulfonic acids (PFAS) with vitamin D biomarker status in adults and children; however, how PFAS, especially emerging CI-PFESAs, influence vitamin D among newborns is unknown. This study focused on the epidemiological linkages between PFAS and vitamin D biomarkers. Eleven PFAS, including legacy PFAS and emerging CI-PFESAs, as well as two vitamin D metabolites [25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3)], were determined in cord sera of 992 newborns from a birth cohort in Wuhan, China. The cord serum levels of 25(OH)D2 and 25(OH)D3 were summed as total 25(OH)D, which is a reliable biomarker of vitamin D status. The associations of separated PFAS with vitamin D biomarker levels were analyzed via multiple linear models, whereas the mixture effect was estimated by utilizing the weighted quantile sum (WQS) regression. We observed that per doubling changes in perfluorotridecanoate (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were associated with a 6.04 to 9.05 % change in total 25(OH)D levels. PFHxS contributed over half of the PFAS mixture effect on total 25(OH)D. Stratified analysis indicated that the associations of certain PFAS with vitamin D biomarkers were more pronounced among boys. The emerging CI-PFESAs were not robustly related to vitamin D biomarker levels. The results suggested that exposure to legacy PFAS might disturb vitamin D status in newborns. Future epidemiological studies are required to confirm the association and to determine healthy implications at a later age.

Associations of arsenic exposure with blood pressure and platelet indices in pregnant women: A cross-sectional study in Wuhan, China.

BACKGROUND: Environmental inorganic arsenic (iAs) exposure is potentially related to abnormal blood pressure (BP) changes and abnormal platelet activation. However, limited epidemiological studies have explored the impacts of iAs exposure on platelet change mediated by BP, especially for pregnant women. OBJECTIVES: Our purpose was to investigate the associations of arsenic exposure with blood pressure and platelet indices among pregnant women. METHODS: The present study population included 765 pregnant women drawn from a prospective birth cohort study in Wuhan, China, recruited between October 2013 and April 2016. Urine sampled in the second trimester were used to assess arsenic species concentrations. The relative distribution of urinary arsenic species was used to measure human methylation capacity. BP parameters and platelet indices originated from the medical record. We applied multivariable linear regression models to explore the cross-sectional relationships between urinary arsenic metabolites, BP parameters, and platelet indices. We utilized mediation analysis to investigate the impacts of arsenic exposure on platelet indices through BP as mediator variables. RESULTS: We observed significant positive correlations between iAs and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Pregnant women with higher methylation capacity to metabolize iAs characterized by higher secondary methylation index (SMI) and total methylation index (TMI) had a more significant reduction in SBP, DBP, and MAP. Pregnant women with higher DBP and MAP had higher platelet counts (PLC). A decreased PLC was found in subjects wither higher SMI. Additionally, SMI was negatively linked to PLC mediated through MAP. CONCLUSIONS: Obtained results suggested that higher methylation capacity to metabolize iAs might contribute to decreased PLC among pregnant women, and MAP might mediate the influence of SMI on PLC.

Sex-specific associations between legacy and novel per- and polyfluoroalkyl substances and telomere length in newborns in Wuhan, China: Mixture and single pollutant associations.

Telomere length (TL) at birth predicts later life TL and is related to health. Prenatal exposure to environmental pollutants might affect TL, but the associations between intrauterine per- and polyfluoroalkyl substances (PFASs) exposure and neonatal TL remained inconclusive. This study aimed to explore the single pollutant and mixture associations between legacy and novel PFASs and TL in newborns. In 908 mother-newborn pairs from Wuhan, China, thirteen PFASs were measured in cord serum, and TL was determined in cord leukocytes. Weighted quantile sum (WQS) regression and generalized linear model (GLM) were utilized to analyze the associations between PFASs mixture and single PFASs and TL in newborns. Furthermore, stratified and interaction analyses were performed to evaluate if there were sex-specific associations. The concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) ranked the highest (geometric mean, 4.12, 1.61, and 0.77 ng/mL, respectively) among the 13 measured PFASs. Each unit increase in WQS index of PFASs mixture was associated with -5.19 % change (95% CI, -9.44, -0.73) of neonatal TL, and 8:2 Cl-PFESA contributed most (32.59 %) to the mixture association. In stratified analyses by neonatal sex, PFOS (-4.73 % change, 95% CI, -8.40, -0.93 for per doubling concentration) and 8:2 Cl-PFESA (-4.52 % change, 95% CI, -8.20, -0.70) were negatively associated with neonatal TL in male newborns, but no significant association appeared in females. In summary, intrauterine exposure to PFASs in mixture was associated with shorter neonatal TL, and the negative associations of 8:2 Cl-PFESA and PFOS with neonatal TL were observed only in boys. Future risk assessments are needed to pay more attention to the health effects of novel PFASs.