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.

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.

Association of maternal folic acid supplementation during pregnancy with newborn telomere length.

This study aimed to explore the associations between maternal folic acid (FA) supplementation during different trimesters of pregnancy and newborn telomere length (TL). Data were collected from a birth cohort study of 746 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. After adjustment for potential confounders, maternal FA supplementation after the first trimester and throughout pregnancy were associated with longer newborn TL [ß = 0.29, 95 % confidence interval (CI): 0.20, 0.38 and ß = 0.24, 95 % CI: 0.16, 0.32, respectively]. No significant association was found between maternal FA supplementation in the first trimester and newborn TL. In conclusion, a possible association between maternal FA supplementation during pregnancy with longer newborn TL was suggested in the present study. This study provides insight into the benefit of newborn TL by maternal FA supplementation during pregnancy.

Association of exposure to per- and polyfluoroalkyl substances with hemoglobin and hematocrit during pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear. OBJECTIVES: We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy. METHODS: The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy. RESULTS: In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively. CONCLUSION: Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.

Associations between Maternal Selenium Status and Cord Serum Vitamin D Levels: A Birth Cohort Study in Wuhan, China.

Serum selenium (Se) has been reported to be associated with serum 25-hydroxyvitamin D [25(OH)D], but epidemiological findings are limited in pregnant women. We aimed to assess the associations between maternal urinary Se concentrations and cord serum 25(OH)D levels. We measured urinary concentrations of Se in the first, second, and third trimesters and cord serum 25(OH)D of 1695 mother-infant pairs from a prospective cohort study in Wuhan, China. The results showed that each doubling of urinary Se concentrations in the first, second, third trimester, and whole pregnancy (average SG-adjusted concentrations across three trimesters) were associated with 8.76% (95% confidence interval (CI): 4.30%, 13.41%), 15.44% (95% CI: 9.18%, 22.06%), 11.84% (95% CI: 6.09%, 17.89%), and 21.14% (95% CI: 8.69%, 35.02%) increases in 25(OH)D levels. Newborns whose mothers with low (<10 µg/L) or medium (10.92−14.34 µg/L) tertiles of urinary Se concentrations in whole pregnancy were more likely to be vitamin D deficient (<20 ng/mL) compared with those with the highest tertile (>14.34 µg/L). Our study provides evidence that maternal Se levels were positively associated with cord serum vitamin D status.

Association between maternal urinary selenium during pregnancy and newborn telomere length: results from a birth cohort study.

BACKGROUND: Newborn telomere length is considered as an effective predictor of lifespan and health outcomes in later life. Selenium is an essential trace element for human health, and its antioxidation is of great significance for the prevention of telomere erosion. METHODS: We recruited 746 mother-newborn pairs in Wuhan Children's Hospital between 2013 and 2015. Urine samples were repeatedly collected at three time points during pregnancy, and umbilical cord blood samples were collected right after parturition. Urinary selenium concentration was detected using inductively coupled plasma mass spectrometry, and newborn telomere length was measured using quantitative real-time polymerase chain reaction. We applied general estimating equations to examine the trimester-specific association between maternal urinary selenium during pregnancy and newborn telomere length. RESULTS: The median of creatinine-corrected selenium concentrations during pregnancy were 16.29, 18.08, and 18.35 µg/g·creatinine in the first, second, and third trimesters, respectively. Selenium concentrations in all the three trimesters were significantly associated with newborn telomere length. Per doubling of maternal urinary selenium concentrations was associated with 6.44% (95% CI: 0.92, 12.25), 6.54% (95% CI: 0.17, 13.31), and 6.02% (95% CI: 0.29, 12.09) longer newborn telomere length in the first, second, and third trimesters, respectively, after adjusting for potential confounders. CONCLUSIONS: This is the first study to provide evidence for the effect of maternal selenium levels on fetal telomere erosion. Findings from our study suggested that maternal urinary selenium was positively associated with newborn telomere length, indicating that intrauterine selenium exposure might have effect on initial setting of human telomere length.

Circulating fatty acids and risk of gestational diabetes mellitus: prospective analyses in China.

OBJECTIVE: We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women. METHODS: Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24-28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment. RESULTS: Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles. CONCLUSIONS: We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.

Low level prenatal exposure to a mixture of Sr, Se and Mn and neurocognitive development of 2-year-old children.

The excess or deficiency of trace metals can cause adverse neurocognitive development. Evidence of health effect of trace metal mixtures on neurocognitive development is limited in children. We evaluated associations of prenatal exposure to trace metals and metal mixtures with neurocognitive development of 2-year-old children. A total of 544 mother-child pairs were included in the study. The concentrations of 10 trace metals in maternal urine were monitored before delivery. Neurocognitive development indexes, including mental development index (MDI) and psychomotor development index (PDI), were assessed using the Bayley Scales of Infant Development. Linear regression analysis was performed to explore the effects of single-metal and multi-metal exposures. Bayesian Kernel Machine regression (BKMR) was used to investigate overall effect of exposure to metal mixtures and potential interactions among mixture components. We found positive associations of urinary strontium (Sr) and Selenium (Se) levels with MDI scores among all children in the single-metal model. Sr was positively related to MDI, while Manganese (Mn) was negatively associated with PDI in the multi-metal model. The results from BKMR model in girls revealed that MDI scores were improved with the increasing concentrations of Sr, Se and Mn mixture until the concentrations reached their 30th percentiles (Sr: 149.49 µg/g creatinine, Se:18.38 µg/g creatinine, Mn:1.96 µg/g creatinine), with no effect after that threshold level. Sr played a positive role in mental development among mixture components, which was consistent with the results of Sr in the multi-metal models. No signification association of mixture with MDI/PDI was found in boys. The study suggested potential sex-specific association of Sr, Se and Mn mixture levels (at or below their 30th percentiles) with improved mental development, and beneficial role of Sr.

Association of adverse birth outcomes with prenatal uranium exposure: A population-based cohort study.

Uranium (U) is a well-recognized hazardous heavy metal with embryotoxicity and fetotoxicity. However, little is known about its association with adverse birth outcomes. We aimed to investigate the potential correlation between prenatal U exposure and birth outcomes. Urine samples of 8500 women were collected before delivery from a birth cohort in Wuhan, China. Concentrations of urinary U and other metals were measured by inductively coupled plasma mass spectrometry. We used multivariable logistic regressions to evaluate the associations between urinary U concentrations and adverse birth outcomes, such as preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Associations of urinary U concentrations with gestational age, birth weight, and birth length were investigated by linear regressions. The geometric mean of U concentration was 0.03 µg/L. After adjustment for potential confounders, we found each Log2-unit increase in U concentration was associated with a significant decrease in gestational age [adjusted ß = -0.32 day; 95% confidence interval (CI): -0.44, -0.20] and a significant increased likelihood of PTB (adjusted OR = 1.18, 95% CI: 1.07, 1.29). This birth cohort uncovered an association of maternal exposure to U during pregnancy with decreased gestational age and increased risk of PTB. Our findings reveal an association of maternal exposure to U during pregnancy with decreased gestational age and increased risk of PTB.

Urinary concentrations of environmental metals and associating factors in pregnant women.

Pregnant women, a vulnerable population, can be exposed to a variety of environmental metals that may adversely affect their health at elevated concentrations. Moreover, environmental exposure and risk disparities are associated with several factors such as sociodemographic characteristics, pregnancy complications, and nutritional supplementation indicators. Our aim was to investigate whether and how the urinary metal concentrations vary according to these factors in a large pregnancy and birth cohort. Urinary levels of seven metals including manganese, zinc, selenium, arsenic, cadmium, thallium, and lead were assessed in 7359 participants across Wuhan City in China. In all, 7359 urine samples from the third trimester were analyzed and 15 sociodemographic characteristics, pregnancy complications, and nutritional supplementation indicators were assessed: maternal age, household income, multivitamin supplements during pregnancy, etc. Concentrations of Zn, As, and Cd were detected in all urine samples; Mn, Se, Tl, and Pb were detected in 95.3%, 99.8%, 99.8%, and 99.9% urine samples, respectively. The geometric mean (GM) of creatinine-adjusted urinary Mn, Zn, Se, As, Cd, Tl, and Pb concentrations were 1.42, 505.44, 18.24, 30.49, 0.64, 0.55, and 3.69 µg/g. Factors that associated with environmental metals concentration were as follows: (1) Urinary Zn and Cd concentrations increased with maternal age. (2) Pregnant women with higher education had lower Cd concentrations. (3) Pregnant women with folic acid supplementation had lower Mn and with multivitamin supplementation had higher Se and lower Tl. Our results demonstrated that the maternal age, education level, folic acid supplementation, and multivitamin supplementation were significantly associated with environmental metal concentrations. Furthermore, studies are recommended to explore the influence of diet on biological metals concentrations in more detail.

Association between prenatal nickel exposure and preterm low birth weight: possible effect of selenium.

There is a proposed link between prenatal nickel (Ni) exposure and preterm low birth weight (PLBW); however, this association remains unclear. Selenium (Se) may modify this relationship by protecting against Ni toxicity. Concentrations of Ni and Se were measured in urine samples collected from 408 pregnant women (102 PLBW cases and 306 matched controls) in China. Conditional logistic regression was utilized to explore the association between Ni levels and PLBW, as well as the effect modification by Se on this association. A significant association was observed between higher maternal urinary Ni levels and risk of PLBW [adjusted odds ratio (OR) = 2.80 (95% confidence interval (CI): 1.44, 5.44) for the highest tertile], and this association was more apparent among female infants than that among male infants. Further analyses showed that mothers with high urinary Ni and low urinary Se levels had a significantly increased risk for PLBW [adjusted OR = 2.87 (95% CI: 1.09, 7.56)] compared with the mothers with low urinary Ni and high urinary Se levels. Our study indicates that prenatal exposure to Ni was a risk factor for PLBW. Se might provide protection against the toxicity of Ni.

Predictors of thallium exposure and its relation with preterm birth.

Thallium (Tl) is a well-recognized hazardous toxic heavy metal that has been reported to have embryotoxicity and fetotoxicity. However, little is known about its association with preterm birth (PTB) in humans. We aimed to evaluate the predictors of Tl exposure and assessed its relation with PTB. The study population included 7173 mother-infant pairs from a birth cohort in Wuhan, China. Predictors of Tl concentrations were explored using linear regression analyses, and associations of Tl exposure with risk of PTB or gestational age at birth were estimated using logistic regression or generalized linear models. The geometric mean and median values of urinary Tl concentrations were 0.28 µg/L (0.55 µg/g creatinine) and 0.29 µg/L (0.53 µg/g creatinine). We found that maternal urinary Tl concentrations varied by gestational weight gain, educational attainment, multivitamin and iron supplementations. Women with Tl concentrations higher than 0.80 µg/g creatinine were at higher risk of giving birth prematurely versus those with Tl concentrations lower than 0.36 µg/g creatinine [adjusted odds ratio (95% confidence interval (CI)): 1.55 (1.05, 2.27)], and the association was more pronounced in PTB with premature rupture of membranes (PROM) rather than in PTB without PROM. About 3-fold increase in creatinine-corrected Tl concentrations were associated with 0.99-day decrease in gestational length (95% CI: -1.36, -0.63). This is the first report on the associations between maternal Tl exposure and the risk of PTB.

Pancreatic impairment and Igf2 hypermethylation induced by developmental exposure to bisphenol A can be counteracted by maternal folate supplementation.

Increasing evidence indicates that bisphenol A (BPA), a widely manufactured environmental pollutant, can induce changes in DNA methylation paatterns, which is a potential mechanism linking this environmental exposure to disease development. We investigated the influence of developmental exposure to BPA on pancreatic DNA methylation patterns and whether maternal folate supplementation can modify the epigenetic status and pancreatic impairment induced by BPA. Our results showed that maternal dietary folate supplementation in rats exposed to BPA counteracted the observed BPA-induced pancreatic impairments in the offspring, which included disrupted insulin secretion and glucose intolerance, and impaired morphology and ultrastructure of ß cells. Moreover, these pancreatic dysfunctions were shown to be associated with low expression and DNA hypermethylation of insulin-like growth factor-2 (Igf2) in islets induced by exposure to BPA during the developmental period. Importantly, maternal dietary folate supplementation was demonstrated to negate this Igf2 DNA hypermethylation in the offspring, which was consistent with the upregulation of Igf2 expression. Overall, our results suggest that early developmental exposure to BPA alters the DNA methylation of Igf2, that these altered methylation patterns are associated with impaired ß-cell function in the offspring and that these effects can be counteracted by maternal folate supplementation. Copyright © 2017 John Wiley & Sons, Ltd.

Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brains.

With the wide application of nanoscaled particles, the risk of human exposure to these particles has been markedly increased. However, knowledge about their safety falls far behind the utility of these nanoparticles. Here we have analyzed the activation of brain microglia and astrocytes, which are sensitive to changes of brain environment after peripheral exposure to nanoscaled aluminum oxide suspension. Sprague-Dawley rats (six rats per treatment) were intraperitoneally injected once every second day for 30 or 60 days with nanoscaled aluminum oxide (NSAO; 1 mg/kg or 50 mg/kg), non-nanoscaled aluminum oxide (nNSAO, 1 mg/kg), or vehicle (saline). After 60 days' exposure the numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, compared with nNSAO, NSAO has potential effects on the innate immune system of rat brain. This should be considered when evaluating the toxicological effects of nanosized particles. FROM THE CLINICAL EDITOR: Sprague-Dawley rats were intraperitoneally injected with nanosized aluminum oxide, (NSAO); non-nanoscaled aluminum oxide, or vehicle (saline). The numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, NSAO has potential effects on the innate immune system of rat brain.

[Effects of benzene and selenium on telomerase in mouse lymphocytes in vivo].

OBJECTIVE: To study the effects of benzene and selenium on telomerase in mouse lymphocytes in vivo and evaluate telomerase activity as an early marker of benzene effects on lymphocytes. METHODS: Male Kunming mice were divided randomly into 8 groups, including negative control group, reagent control group, 100 mg/kg benzene group, 200 mg/kg benzene group, 400 mg/kg benzene group, 200 mg/kg benzene + 0.75 mg/kg selenium group, 200 mg/kg benzene + 1.50 mg/kg selenium group and 200 mg/kg benzene + 3.00 mg/kg selenium group, 5 mice in each group. The mice in different groups were treated with different methods, once daily for 5 days. After 48 hours of the final exposure, lymphocytes were separated and the telomerase activities were detected with TRAPELISA. RESULTS: Compared with negative and reagent control groups, the telomerase activity was increased after treatment with different dose of benzene and at the dose of 100 mg/kg benzene group it was significantly increased (P < 0.01). At the dose of 200 mg/kg benzene + 0.75 mg/kg selenium group, it was significantly increased (P < 0.01). Compared with the counterpart treated with 200 mg/kg benzene group, the expression of telomerase was increased at the different concentrations after treatment with benzene combined with selenium and it was significantly increased at the dose of 200 mg/kg benzene + 0.75 mg/kg selenium group (P < 0.05). CONCLUSION: Increased telomerase activity in lymphocytes stimulated by benzene at different concentrations indicates activation and proliferation of these lymphocytes of mice in vivo. Telomerase activity is probably a sensitive early marker of lymphocyte proliferation by benzene. Selenium can upregulate the telomerase activity.

[Effects of sodium selenite on telomerase activity and telomere length].

To study the biological basis of selenium in resisting senescence through its effects on cellular telomerase activity and telomere length. In the experiments, the cell line of hepatocytes L-02 was divided into three groups supplemented with sodium selenite at final concentrations of 0, 0.5 and 2.5 micromol/L, respectively. Cellular telomerase activity was measured by telomeric repeat amplification protocol and enzymatic luminometric inorganic pyrophosphate detection assay. RT-PCR was used to semi-quantitatively detect human telomerase reverse transcriptase (hTERT) gene expression. The change of telomere length was assayed through flow cytometry and fluorescence in situ hybridization. Results showed that L-02 cells had low telomerase activity and hTERT gene expression level when cultured in the normal way. The cells grew well after 3-week-cultivation in the media supplemented with 0.5 or 2.5 micromol/L sodium selenite. Besides, sodium selenite significantly increased cellular telomerase activity and hTERT gene expression level. The telomere length of L-02 cells was also extended after 4-week-cultivation with sodium selenite. Thus, sodium selenite at nutritional doses could prolong the life span of hepatocytes L-02 through increasing telomerase activity and telomere length. This result provides a possible mechanism for explaining the anti-senescence function of selenium.