Heavy metals and metalloids exposure and liver function in Chinese adults - A nationally representative cross-sectional study.

BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.

Serum per- and polyfluoroalkyl substances and abnormal lipid metabolism: A nationally representative cross-sectional study.

BACKGROUND: The associations of legacy per- and polyfluoroalkyl substances (PFAS) with lipid metabolism are controversial, and there is little information about the impact of emerging PFAS (6:2 Cl-PFESA) on lipid metabolism in China. OBJECTIVES: We aimed to explore the associations of legacy and emerging PFAS with lipid profiles and dyslipidemia in Chinese adults. METHODS: We included 10,855 Chinese participants aged 18 years and above in the China National Human Biomonitoring. The associations of 8 PFAS with 5 lipid profiles and 4 dyslipidemia were investigated using weighted multiple linear regression or weighted logistic regression, and the dose-response associations were investigated using restricted cubic spline model. RESULTS: Among the 8 PFAS, the concentration of PFOS was the highest, with a geometric mean of 5.15 ng/mL, followed by PFOA and 6:2 Cl-PFESA, which were 4.26 and 1.63 ng/mL, respectively. Legacy (PFOA, PFOS, PFUnDA) or emerging (6:2 Cl-PFESA) PFAS were associated with lipid profiles (TC, LDL-C, HDL-C, non HDL-C) and dyslipidemia (high LDL-C, high TC, low HDL-C), and their effects on TC were most obvious. TC concentration increased by 0.595 mmol/L in the highest quartile (Q4) of PFOS when compared with the lowest quartile (Q1), (95 % CI:0.396, 0.794). Restricted cubic spline models showed that PFAS are nonlinearly associated with TC, non HDL-C, LDL-C and HDL-C, and that the lipid concentrations tend to be stable when PFOS and PFOA were > 20 ng/mL well as when the 6:2 Cl-PFESA level was > 10 ng/mL. The positive associations between PFAS mixtures and lipid profiles were also significant. CONCLUSIONS: Single and mixed exposure to PFAS were positively associated with lipid profiles, and China's unique legacy PFAS substitutes (6:2 Cl-PFESA) contributed less to lipid profiles than legacy PFAS. In the future, cohort studies will be needed to confirm our findings.

Phthalate metabolite concentrations and effects on albuminuria in the US population.

BACKGROUND: The usage pattern of phthalates has changed with the introduction of new alternatives such as 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) and di-isodecyl phthalate (DiDP). However, the concentrations of these alternatives at the population level and their effects on endothelial function are under-studied. OBJECTIVES: We examined the concentrations of the new alternatives and their previous counterparts, as well as the associations between phthalate exposure and albuminuria in the general US population. METHODS: In total, 2672 participants from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were enrolled in this study, and we obtained data on 19 urinary phthalate metabolites, albumin, and creatinine. The distributions of urinary phthalates were studied by age and sex. Linear and logistic regressions were used to estimate the association between urinary phthalate metabolites and albumin. RESULTS: The geometric mean of the total phthalate concentrations in males and females was 124.97 and 113.09 ng/mL respectively. The detection rates of most urinary phthalate metabolites were greater than 95 %. The major phthalate metabolites found in the US population were MEP (24.20 %) and MECPTP (23.76 %). More positive relationships between phthalate and micro- plus albuminuria were found in females aged ≥ 60 years group（1.49 (95 % CI: 1.08-1.90), 1.44 (95 % CI: 1.06-1.81), 1.52 (95 % CI: 1.14-1.90), 1.41(95 % CI: 1.04-1.78), 1.29(95 % CI: 1.01-1.58), 1.60(95 % CI: 1.20-2.01), 1.45(95 % CI:1.14-1.77), and 1.55(95 % CI: 1.22-1.87) in MECPP, MEHHP, MEOHP, MEHP, MCPP, MHBP, MHNCH and MCOCH respectively）. In total population, logistic regression showed that all traditional phthalate metabolites were associated with an increased proportion of albuminuria (OR range from 1.19 to 1.40, all p < 0.05). However, three new alternatives were not associated with albuminuria (OR range from 1.01 to 1.05, all p > 0.05), and six new alternatives were associated with an increased proportion of albuminuria (OR range from 1.14 to 1.30, all p < 0.05). CONCLUSIONS: Children have higher metabolite concentrations than adults. Exposure to certain phthalates may disrupt albuminuria homeostasis, especially in older females. Alternative phthalates may have a lower impact on albuminuria than conventional phthalates. The safety of the new alternatives should be interpreted with caution, as more research is still required.

Cadmium exposure is associated with testosterone levels in men: A cross-sectional study from the China National Human Biomonitoring.

BACKGROUND: Sex hormone disorders can cause adverse health consequences. While experimental data suggests that cadmium (Cd) disrupts the endocrine system, little is known about the link between Cd exposure and sex hormones in men. METHODS: We measured blood cadmium (B-Cd), urine cadmium (U-Cd), serum testosterone and serum estradiol in men aged ≥18 years old participating in the China National Human Biomonitoring program, from 2017 to 2018. Urine cadmium adjusted for creatinine (Ucr-Cd) and the serum testosterone to serum estradiol ratio (T/E2) were calculated. The association of Cd exposure to serum testosterone and T/E2 in men was analyzed with multiple linear regression models. RESULTS: Among Chinese men ≥18 years old, the weighted geometric mean (95% CI) of B-Cd and Ucr-Cd levels were 1.23 (1.12-1.35) µg/L and 0.53 (0.47-0.59) µg/g, respectively. The geometric means (95% CI) of serum testosterone and T/E2 were 18.56 (17.92-19.22) nmol/L and 143.86 (137.24-150.80). After adjusting for all covariates, each doubling of B-Cd level was associated with a 5.04% increase in serum testosterone levels (ß = 0.071; 95%CI: 0.057-0.086) and a 4.03% increase in T/E2 (ß = 0.057; 95%CI: 0.040-0.075); similar findings were found in Ucr-Cd. CONCLUSIONS: In Chinese men, Cd may be an endocrine disruptor, which is positively associated with serum testosterone and T/E2.

Effect of the phthalates exposure on sex steroid hormones in the US population.

BACKGROUND: New alternative phthalates have been increasingly substituted for certain phthalates in some consumer products due to safety concerns. However, research on the steroidal effect of exposure to the newer replacement phthalates in the general adult population is lacking. OBJECTIVES: This study aimed to examine the associations of exposure to the older generation and newer replacement phthalates with sex hormone levels in the U.S. general population. METHODS: The current cross-sectional study was based on the National Health and Nutrition Examination Survey (NHANES) 2015-2016. Sixteen urinary phthalates metabolites and three serum sex hormones were measured in 1768 adults. Gender-specific associations between urinary phthalate concentrations and sex hormones were estimated by using adjusted multiple linear regression. Logistic regression was performed to calculate the risk of phthalates exposure on hormones dysfunction. RESULTS: Most phthalates metabolites concentrations were lower than 50 ng/mL. MEP, MBP, MiBP, MECPP, MCOP, MEHHP, MEOHP were higher than others, suggesting that new alternative DEP, DBP, and DiNP were exposed at high levels in daily life while DINCH was at a low level. Phthalates exposure was associated with decreased testosterone levels and increased estradiol and SHBG in total samples. Testosterone level was negatively associated with MnBP (ß: -0.05, 95% CI: -0.09, 0), MEOHP (ß:-0.05, 95% CI:-0.09,-0.01), MEHHP (ß:-0.04, 95% CI:-0.08,0), MECPP (ß:-0.07, 95% CI:-0.11,-0.03), MEP (ß: -0.03, 95% CI: -0.06, 0), MiBP (ß: -0.05, 95% CI: -0.10, -0.01) in males; ln-transformed estradiol were increased by 0.18 pg/mL (95% CI: 0.05,0.31), 0.15 pg/mL (95% CI: 0.01,0.29) with each 1 ln-concentration increase in MEHP and MNP, respectively, in females. CONCLUSIONS: Our results suggest that phthalates exposure may disturb the hormone homeostasis in adults. The safe alternative should be used with caution in industrial production in the future and the need for further research into the safety of the new alternative replacements is necessary.

Characteristics, distribution, and children exposure assessment of 13 metals in household dust in China: A big data pilot study.

To explore the pollution characteristics of metals in household dust in China and their exposure to children, this study searched peer-reviewed papers published during 1980-2020 and analyzed 30 eligible papers screened under the per-decided strategy. We evaluated the sample-weighted concentration (SWC) of each metal, explored the sources of metals, and presented the quantitative description of spatial-temporary characteristics and children exposure to 13 metals with multi-route under a general living scenario. The results showed the concentrations of 13 metals with a range of 0.89-29 090.19 mg/kg. The SWC of Cd in household dust from rural areas was 3.29 times of that from urban areas, while the SWC of Ni from urban areas was 3.71 times of that from rural areas. The results showed that four principal components were extracted, and the cumulative contribution rate reached 79.127%. The exposure dose of 13 metals to children aged 2-3 years was presented with the highest by ingestion. Metals such as Fe, Zn, and Mn posed inevitable health risk to children with high exposure. Countermeasures should be carried out to minimize the children exposure to metals in household dust urgently, such as the establishment of environmental health standard for household dust.

Prenatal serum thallium exposure and cognitive development among preschool-aged children: A prospective cohort study in China.

Thallium, a highly toxic heavy metal and priority pollutant, has been widely reported to cause neurodevelopmental toxicity in animals. However, accessible epidemiological studies concerning the neurodevelopmental toxicity of early-life thallium exposure in humans are limited. In a prospective birth cohort including 2164 mother-child pairs, we explored the effect of prenatal serum thallium exposure on cognitive development among preschool-aged children born in Ma'anshan, Anhui, China. Serum thallium concentrations were measured in the first trimester, second trimester, third trimester, and cord blood by inductively coupled plasma mass spectrometry (ICP-MS). Child cognitive development was appraised by the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) at 4.5 years old. Multiple informants generalized estimating equations (GEEs) were fit to jointly estimate the association between the four repeated measurements of thallium concentrations and the preschool-aged children's cognitive test scores. After adjusting for potential confounders, the visual spatial index (VSI) was 1.45 points lower in the highest tertile of serum thallium during the first trimester than in the lowest tertile (p for trend = 0.04). Moreover, children in the highest tertile of serum thallium during the third trimester had a significantly lower full-scale intelligence quotient (FSIQ) (ß = -1.51, 95% CI: -2.68, -0.35), VSI (ß = -1.79, 95% CI: -3.16, -0.42), fluid reasoning index (FRI) (ß = -1.41, 95% CI: -2.73, -0.10), and processing speed index (PSI) (ß = -1.47, 95% CI: -2.71, -0.24) scores than the children in the lowest tertile. When performing stratified analysis by child sex, the associations of first- and third-trimester thallium concentrations with cognitive test scores were more prominent in boys than in girls. Our findings revealed that maternal serum thallium exposure during the first and third trimesters, but not other periods, had detrimental effects on preschoolers' cognitive development, and these effects showed sex differences.

Declines in Blood Lead Levels Among General Population - China, 2000-2018.

What is already known about this topic?: Environmental and occupational lead exposure has generally declined in the past two decades. However, there is no large-scale monitoring of blood lead levels (BLLs) in the Chinese general population. What is added by this report?: This nationally representative study showed declines of BLLs in all ages of participants; for children aged 3-5 years, down from 78.1 µg/L to 16.9 µg/L, corresponding to 78.4% decrease in the past two decades (2000-2018). What are the implications for public health practice?: Recommendations for elevated BLLs on screening children at high risk now need to be revisited and updated from 100 µg/L to 50 µg/L in guidelines to conform with the substantial declines in China.

Indoor air quality in the primary school of China-results from CIEHS 2018 study.

Indoor air quality ((IAQ) in classrooms was associated with the daily exposure of school-age children who are particularly vulnerable to air pollutants exposure, while few data exist to evaluate classroom indoor air quality nationwide in China. The subsample of the CIEHS 2018 study was performed in 66 classrooms of 22 primary schools nationwide in China. Temperature, relative humidity, PM2.5, PM10, CO2, CO, formaldehyde concentrations, bacteria and fungi were detected in all classrooms by using the instruments that meet the specified accuracy. The ratios of indoor to outdoor (I/O) of PM2.5 were calculated in each classroom to identify whether the indoor environment the pollutants comes from outdoors. The indoor PM2.5, PM10, CO, HCHO, bacteria and fungi GM concentration are 47.40 µg/m3, 72.91 µg/m3, 0.37 mg/m3, 0.02 mg/m3, 347.51 CFU/m3 and 362.76 CFU/m3, respectively. We observed that there were 66.5%, 52.6%, 22.4%, 1.8%, and 9.6% of the classrooms that exceeded the guideline values of PM2.5, PM10, CO2, HCHO, and bacteria, respectively. It should be attention that all of the classroom's PM2.5 concentrations in Shijiazhuang and Nanning, PM10 concentrations in Nanning, CO2 concentration in Lanzhou were exceeded the suggested values. Bacteria contamination in Shijiazhuang's classrooms is also serious. All classroom CO concentrations meet the requirement. The results indicated that classroom indoor PM2.5 was significantly positively correlated with indoor PM10 and CO2, while was negative correlated with temperature, CO, and fungi. Our results suggest that indoor air pollution in classrooms was a severe problem in Chinese primary schools. It is necessary to strengthen ventilation in the classroom to improve indoor air quality. What's more, a healthy learning environment should be created for primary school students.

Spatiotemporal variation in residential PM2.5 and PM10 concentrations in China: National on-site survey.

BACKGROUND: Significant efforts have been directed toward addressing the adverse health effects of particulate matter, while few data exist to evaluate indoor exposure nationwide in China. OBJECTIVES: This study aimed to investigate dwellings particulate matter levels in the twelve cities in China and provide large data support for policymakers to accelerate the legislative process. METHODS: The current study was based on the CIEHS 2018 study and conducted in 12 cities of China. A total of 2128 air samples were collected from 610 residential households during the summer and winter. Both PM10 and PM2.5 were detected with a light-scattering dust meter in both the living room and bedroom. The Wilcoxon rank-sum test was performed to evaluate the correlations between PM2.5 and PM10 concentrations and both sampling season and site. Ratios of the living room to bedroom were calculated to evaluate the particulate matter variation between rooms. Hierarchical clustering was used to probe the question of whether the concentration varies between cities throughout China. RESULTS: The geometric means of the PM2.5 in living rooms and bedrooms were 39.80 and 36.55 µg/m3 in the summer, and 70.97 and 67.99 µg/m3 in the winter, respectively. In the summer, approximately 70 % of indoor dwelling PM2.5 exceeded the limit of 25 µg/m3, and for PM10 approximately 60 % of dwellings demonstrated levels higher than 50 µg/m3; the corresponding values were over 90 % and 80 % in winter, respectively. In Shijiazhuang, Lanzhou, Luoyang and Qingdao, the geometric means of the PM2.5 concentrations were observed to be 1.5 to 4.3 times higher during winter than during summer; similar concentrations in summer and winter were observed in Harbin, Wuxi, and Shenzhen, while the PM2.5 concentrations in Panjin were approximately 1.5 times higher in summer than in winter. There was no significant difference in particulate matter concentrations between the living rooms and bedrooms. Scatter plots showed that cities with low GDP and a small population had higher concentrations, while Shenzhen, which has a higher GDP and a large permanent population, had a relatively low concentration of particulate matter. CONCLUSIONS: Our results suggest that indoor air pollution is a severe problem in China. It is necessary to continue monitoring indoor air quality to observe the changing trend under the tremendous effort of the Chinese government.

Effects of single and combined gestational phthalate exposure on blood pressure, blood glucose and gestational weight gain: A longitudinal analysis.

Few studies have investigated the association of gestational exposure to phthalate with metabolic risk and have reached inconsistent conclusions. Based on the Ma'anshan Birth Cohort, 3273 women were included in the present study. All participants provided up to three urine samples for 7 phthalate metabolite measurements. The hazard index (HI) was used to evaluate the cumulative risk of multiple phthalate coexposures. The outcomes of interest included hypertensive disorders of pregnancy (HDOP), gestational diabetes mellitus (GDM), and gestational weight gain (GWG). The incidences of HDOP, GDM, and excessive GWG were 5.93%, 13.09%, and 28.95%, respectively. Exposure to a single phthalate metabolite or a specific diester during the first trimester of pregnancy elevated blood pressure (BP) and fasting plasma glucose (FPG) in the third trimester and body weight gain throughout pregnancy. However, inverse relationships were revealed for some phthalate metabolites, which were inconsistent with the results of their diesters. The HI value during the first trimester was positively associated with subsequent BP, FPG, and GWG. In addition, HI during the first trimester increased the risks of GDM [odds ratio (OR) = 1.34, 95% confidence intervals (CIs) = 1.02-1.75)] and excessive GWG (OR = 1.76, 95% CIs = 1.41-2.19) in a linear manner thereafter. Notably, phthalates might directly increase maternal blood glucose and pressure, and these changes were secondary effects of the obesiogenic effects of certain phthalates. In conclusion, exposure to single and multiple phthalates during the first trimester of pregnancy increased the risks of maternal metabolic syndrome components. However, the conflicting findings between phthalates and their metabolites need to be interpreted carefully.

Residential airborne culturable fungi under general living scenario: On-site investigation in 12 typical cities, China.

BACKGROUND: Residential airborne fungi may present obvious risk to human health. However, many countries do not recognize the necessarily need to control residential airborne culturable fungi (RAF). In China, few systemic investigations have been conducted to illustrate the distribution of residential airborne fungi and identify the association between indoor influencing variables and RAF under general living scenario in China. OBJECTIVE: This study aimed to investigate RAF with the on-site research of 12 typical cities in China, and provided the latest characteristics and potential influencing factors of RAF under general living scenario. METHODS: We measured RAF and investigated residential characteristics in 12 typical cities in China, 2018. At least 50 resident families were randomly selected both from downwind and upwind districts in each city with pre-proposed requirements. The RAF were sampled by the six-stage Anderson impactor. PM2.5 and PM10 were monitored by calibrated light-scattering dust meters. CO and CO2 were monitored by non-dispersive infrared analyzer method. NO2 was determined by Saltzman method. General linear model was used to evaluate the association between RAF exposure and residential characteristics with adjustment for potential confounders. RESULTS: The RAF concentrations ranged from 0 to 9371 CFU/m3 with a median concentration of 396 CFU/m3. The median concentrations of RAF in the warm season were statistically higher than the cold season in Panjin, Qingdao, Lanzhou and Luoyang, but lower than the cold season in Shijiazhuang, Ningbo and Nanning. RAF in the bedrooms were more than the living rooms in all cities except Xi'an. Temperature and humidity had an interactive effect on the RAF (OR = 1.0006, 95% CI: 1.0005, 1.0006). Some residential environmental pollutants, including PM2.5 (OR = 0.9989, 95% CI: 0.9988, 0.9989), PM10 (OR = 0.9993, 95% CI: 0.9993, 0.9993), and CO2 (OR = 0.0236, 95% CI: 0.0230, 0.0243), were negatively correlated with RAF. CO (OR = 1.1450, 95% CI: 1.1433, 1.1467) and NO2 (OR = 1.0026, 95% CI: 1.0024, 1.0028) were positively correlated with RAF. Architectural characteristics (sunlight exposure, building history, longitude, latitude, total living area, living floor, distance from the road, house type, the layers of window glass and decoration), family-related information (income) and lifestyle behaviors (keeping pets, growing plants, cooking, using insecticide, burning incense, heating, using air conditioner and cleaning frequencies) were also significantly related with RAF. CONCLUSIONS: This study reported nation-wide baseline condition of RAF and related influencing factors under general living scenario with quantitative details, which are exceedingly promising for evidence-driven standard and reasonable control strategy of residential airborne culturable in China.

Characterization and exposure assessment of household fine particulate matter pollution in China.

Household fine particulate matter (PM2.5 ) pollution greatly impacts residents' health. To explore the current national situation of household PM2.5 pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM2.5 (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 µg/m3 . HPL in the rural area (164.3 ± 104.5 µg/m3 ) was higher than that in the urban area (123.9 ± 122.3 µg/m3 ). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM2.5 among school-age children differed from provinces with the highest dose up to 5.9 µg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.

Source, Characterization of Indoor Dust PAHs and the Health Risk on Chinese Children.

Polycyclic aromatic hydrocarbons (PAHs) in indoor dust are one of the common exposure sources for children worldwide. The aim of this study is to explore PAHs pollution status in indoor dust and estimate health risk on Chinese children with big data. Weighted average concentration was used to analyze source and characterization of PAHs in indoor dust based on peer-reviewed literature. According to specific inclusion criteria, 17 studies were included finally to analyze weighted average concentration. The national average concentration of Σ16PAHs was approximately 25.696 µg/g. The highest concentration of Σ16PAHs was in Shanxi (2111.667 µg/g), and the lowest was in Hong Kong (1.505 µg/g). The concentrations in Shanxi and Guangdong were higher than national level and the over standard rate was 18.18%. The concentrations of individual PAHs varied greatly across the country, and Flu in Shanxi was the highest (189.400 µg/g). The sources of PAHs varied in different regions and combustion processes played a leading role. PAHs exposure through ingestion and dermal contact was more carcinogenic than inhalation. The incremental lifetime cancer risk model indicated that children lived in Shanxi were found in the highest health risk coupled with the highest BaPE concentration (54.074 µg/g). Although PAHs concentrations of indoor dust showed a downward trend from 2005 to 2018, indoor environmental sanitation should be improved with multidisciplinary efforts. Health standard should be possibly established to minimize children exposure to PAHs in indoor dust in China.

Domain- and trimester-specific effect of prenatal phthalate exposure on preschooler cognitive development in the Ma'anshan Birth Cohort (MABC) study.

BACKGROUND: Phthalates are a group of heavily produced endocrine disruptors that are widely used in personal care products, food packaging, building materials, and medical device. Few epidemiological studies have examined the effect of repeated prenatal exposure to multiple phthalates on preschooler cognitive development. OBJECTIVES: This study aimed to examine the association between prenatal phthalate exposure measured at multiple time points and the intelligent quotient (IQ) scores of preschoolers, and to further identify the critical windows and specific intelligence domains in which phthalate exposure would affect preschooler cognitive development. METHODS: The current study was based on the Ma'anshan Birth Cohort (MABC) study. Seven phthalate metabolites were measured in 2128 maternal urine samples collected during the first, second, and third trimesters of pregnancy. The IQ score of preschool-aged children were assessed with the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth edition (WPPSI-Ⅳ CN). Linear mixed models (LMMs) were used to assess the longitudinal effects of repeated prenatal phthalate exposure on children's IQ score. Multiple linear regression models were fitted to determine whether critical window phthalate exposure would affect cognitive development of children. RESULTS: Overall, the repeated measures analysis indicated that the verbal comprehension index (VCI), visual space index (VSI) and full-scale intelligence quotient (FSIQ) decreased by 0.30 (95% CI: -0.60, 0; p = 0.05), 0.32 (95% CI: -0.62, -0.01; p = 0.04), and 0.31 (95% CI:-0.57, -0.04; p = 0.02) points, respectively, with each ln-transformed increase in the metabolite concentration of MBP. The fluid reasoning index (FRI) and processing speed index (PSI) increased by 0.30 (95% CI: 0.07, 0.54; p = 0.01) and 0.28 (95% CI: 0.06, 0.51; p = 0.01) points, respectively, with each ln-concentration increase in MEP. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. In the first trimester, each ln-transformed MBP increase was associated with reductions in VCI, VSI and FSIQ of 0.56 (95% CI:-1.09, -0.02; p = 0.04), 0.60 (95% CI:-1.15, -0.05; p = 0.03) and 0.49 (95% CI:-0.97, -0.01; p = 0.04) points, respectively. In the third trimester, we observed that only MBzP exposure was associated with an increase in VCI (ß: 0.48, 95% CI: 0.03, 0.92; p = 0.04). The gender-stratified analyses revealed that boys drove these associations. CONCLUSIONS: Our results suggest that prenatal phthalate exposure impairs the cognitive development of preschoolers. The first trimester of pregnancy might be the most vulnerable period in terms of neurotoxicitydue to phthalate exposure. These findings warrant further confirmation.

Repeated measures of prenatal thallium exposure and placental inflammatory cytokine mRNA expression: The Ma'anshan birth cohort (MABC) study.

Thallium (Tl), a ubiquitous environmental toxicant, can cross the placental barrier during pregnancy. However, the effects of prenatal Tl exposure on placental function are currently unclear. Based on the Ma'anshan Birth Cohort study, we examined whether long-term prenatal Tl exposure was associated with placental inflammation. Tl concentrations were quantified in serum samples (n = 7050) from 2515 pregnancy during each trimester, placental inflammatory cytokine mRNA expression was assessed in 2519 placenta tissues. Geometric mean values of serum Tl concentrations were 63.57, 63.63 and 48.71 ng/L for the first, second and third trimesters, respectively. After adjustment for potential confounders, serum Tl concentration was positively associated with CD68 (ß: 0.30; 95% CI: 0.05, 0.56) in the first trimester and TNF-α (ß: 0.12; 95% CI: 0.01, 0.23), IL-6 (ß: 0.15; 95% CI: 0.05, 0.25) and CD68 (ß: 0.25; 95% CI: 0.10, 0.39) in the third trimester, however was negatively associated with IL-4 (ß: -0.21; 95% CI: -0.41, -0.01) and CD206 (ß: -0.23; 95% CI: -0.45, -0.02) in the first trimester. Repeated measures analysis showed that TNF-α, IL-6 and CD68 increased by 0.11 (95% CI: 0.01, 0.21), 0.12 (0.15, 95% CI: 0.05, 0.25), 0.22 (95% CI: 0.10, 0.39), respectively, with each 1ln-transformed Tl increase in total samples. Gender-specific analyses revealed that these associations were largely driven by male offspring. In addition, immunohistochemistry revealed that nuclear NF-κB p65 expression increased in placenta tissue. The results of this prospective cohort study provide longitudinal evidence that prenatal Tl exposure induces a placental inflammatory response in the Chinese population.

Prenatal phthalate exposure in relation to gestational age and preterm birth in a prospective cohort study.

This study enrolled 3266 pregnant women, to explore the relationship of prenatal phthalate exposure with the risk of preterm birth and gestational age. All participants filled questionnaires and provided with up to three urine samples during three trimesters. Seven phthalate metabolites in urines were measured. The incidences of very preterm, late preterm, early-term, late-term and postterm births were 0.58%, 3.52%, 24.22%, 10.53%, and 0.34%, respectively. Non-linear relationships were shown between phthalate metabolites and gestational age. Except for monomethyl phthalate (OR = 1.65, 95%CI = 1.17-2.34), the average concentrations of phthalate metabolites were associated with a slightly and insignificantly increased risk of overall preterm birth (<37+0 gestational weeks). Through a restricted cubic spline regression, phthalate metabolites were found to be related to the risk of overall preterm birth in a linear manner (p-value >0.05) or a non-linear manner (p-value <0.05). All curves indicated the overall preterm birth risk rose with the increase of phthalate metabolite concentrations. Finally, compared with full-term birth (39+0 to 40+6 gestational weeks), phthalate metabolites were associated with the elevated risks of very preterm, late preterm and postterm births, although some relationships were not statistically significant. In conclusion, these findings suggested non-linear associations between phthalate metabolites and gestational age. Exposure to some phthalate metabolites was associated with increased risks of overall preterm birth and postterm birth.

Repeated measures of prenatal phthalate exposure and maternal hemoglobin concentration trends: The Ma'anshan birth cohort (MABC) study.

A prospective cohort study of a Chinese population was conducted to investigate the relationship between prenatal phthalates exposure and maternal hemoglobin or anemia. Based on the Ma'anshan Birth Cohort study, 7 phthalate metabolites were quantified in spot pregnancy urine samples (n = 9263) from 3269 pregnant women during each trimester. The maternal hemoglobin concentrations were obtained from electronic medical records at the same three time points for each participant during pregnancy. Anemia was defined as a hemoglobin concentration below 110 g/L in pregnant women. Repeated measures and trimester-specific analyses were used to estimate the effects of phthalates exposure on maternal hemoglobin and anemia. The prevalence of anemia was 3.6%, 27.0%, and 26.5% during the first, second and third trimester, respectively. Repeated measures analysis showed that hemoglobin concentrations decreased by 0.55, 0.19, 0.57, 0.49, and 0.54 g/L with each 1 ln-transformed concentration increase of MBP, MBzP, MEHP, MEOHP, and MEHHP, respectively. Exposure to MMP, MBP, MEHP, MEOHP, and MEHHP increased the risk of anemia by 1.11-fold, 1.21-fold, 1.20-fold, 1.13-fold, and 1.16-fold, respectively. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. This is the first study focusing on the effect of prenatal phthalate exposures on hemoglobin or anemia in pregnant Chinese women. We found that prenatal phthalates exposure not only decreased the concentrations of hemoglobin but also showed associations with the prevalence of anemia. Associations appeared stronger for the subsample representing women pregnant with a male fetus than those pregnant with a female fetus. Anemia remains a moderate public health problem in China, and effective measures should be implemented.

Temporal Variability of Cumulative Risk Assessment on Phthalates in Chinese Pregnant Women: Repeated Measurement Analysis.

The assessment of the combined effects of multiple phthalate exposures at low levels is a newly developed concept to avoid underestimating their actual cumulative health risk. A previous study included 3455 Chinese pregnant women. Each woman provided up to three urine samples (in total 9529). This previous study characterized the concentrations of phthalate metabolites. In the present study, the data from 9529 samples was reanalyzed to examine the cumulative risk assessment (CRA) with two models: (1) the creatinine-based and (2) the volume-based. Hazard index (HI) values for three phthalates, dibutyl phthalate, butyl benzyl phthalate, and di(2-ethylhexyl) phthalate, in the first, second, and third trimesters of pregnancy, were calculated, respectively. In creatinine-based model, 3.43%, 14.63%, and 17.28% of women showed HI based on the European Food Safety Authority tolerable daily intake exceeding 1 in the first, second, and third trimester of pregnancy, respectively. The intraclass correlation coefficient of HI was 0.49 (95% confidence interval: 0.46-0.53). Spearman correlations between HI of the creatinine model and ∑androgen disruptor (a developed potency weighted approach) ranged from 0.824 to 0.984. In summary, this study suggested a considerable risk of cumulative exposure to phthalates during the whole gestation in Chinese pregnant women. In addition, moderate temporal reproducibility indicated that single HI, estimated by the phthalate concentration in single spot of urine, seemed representative to describe the throughout pregnancy CRA. Finally, strong correlation between HI of the creatinine model and ∑androgen disruptor revealed that the creatinine-based model was more appropriate to evaluate the CRA.

Prenatal phthalate exposure and placental size and shape at birth: A birth cohort study.

OBJECTIVE: There is concern over the potential placental effects of prenatal phthalate exposure, and the potential adverse effects of prenatal phthalate exposure require further study; however, few data are available in humans. We investigated the associations between phthalate exposure in each trimester and both placental size and shape at birth. METHODS: We measured the urinary concentrations of phthalate metabolites among 2725 pregnant women in the Ma'anshan Birth Cohort. Before collecting urine samples from each of the three trimesters, the pregnant women were interviewed via questionnaires. Placental information was obtained from hospital records. We estimated the sex-specific associations between urinary phthalate concentrations in each trimester and both placental size and shape at birth using adjusted multiple regression. A linear mixed model was used for the repeated measures analysis with subject-specific random intercepts and slopes for gestational age at sample collection to test the effect of phthalate levels on placental size and shape and to estimate the effect sizes. RESULTS: Overall, placental breadth increased by 0.148cm (95% CI: 0.078, 0.218) with each 1 ln-concentration increase in MBP in the first trimester. The difference between placental length and breadth (length-breadth) decreased by 0.086cm (95% CI: -0.159, -0.012) and 0.149cm (95% CI: -0.221, -0.076) with each 1 ln-concentration increase in MMP and MBP, respectively, in the first trimester. In the second trimester, placental thickness increased by 0.017cm (95% CI: 0.006, 0.027), 0.020cm (95% CI: 0.004, 0.036), 0.028cm (95% CI: 0.007, 0.048), and 0.035cm (95% CI: 0.018, 0.053) with each 1 ln-concentration increase in MMP, MBP, MEOHP, and MEHHP, respectively. In the third trimester, placental thickness increased by 0.037cm (95% CI: 0.019, 0.056) and 0.019cm (95% CI: 0, 0.037) with each 1 ln-concentration increase in MBP and MEHP, respectively. Multiple linear regression for each offspring sex indicated that prenatal phthalate exposure increased placental thickness in both the first and second trimesters in males, whereas the corresponding relationship was close to null in females. Linear mixed models (LMMs) yielded similar results. CONCLUSION: Our results suggest the presence of associations between prenatal phthalate exposure and placental size and shape. Exposure to certain phthalates may cause the placenta to become thicker and more circular. Associations appeared stronger for the subsample representing male offspring than those for the subsample representing female offspring. Given the few studies on this topic, additional research is warranted.