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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 (β; 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. [ABSTRACT FROM AUTHOR]

General population are concurrently and extensively exposed to many volatile organic compounds (VOCs), including some Group 1 human carcinogens, such as 1,3-butadiene. However, only a few studies assessed internal exposure levels of VOCs; particularly, very limited studies have examined associations between the urinary concentrations of multiple VOC metabolites (mVOCs) and oxidative stress biomarkers (OSBs) among the general population. In this study, 21 mVOCs and three OSBs including 8-hydroxy-2′-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA), and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid) were measured in 406 urine samples collected from 128 healthy adults during autumn and winter of 2018 in Wuhan, central China, including repeated samples taken in 3 d from 75 volunteers. Inter-day reproducibility for most mVOCs was good to excellent; urinary concentrations of mVOCs in winter were generally higher than those in autumn. Risk assessment was conducted by calculating hazard quotients for the parent compounds, and the results suggested that acrolein, 1,3-butadiene, and cyanide should be considered as high-priority hazardous ones for management. After false-discovery adjustment, 16 of the studied mVOCs were positively associated with 8-OHdG and 8-OHG (β values ranged from 0.04 to 0.48), and four mVOCs were positively associated with HNEMA (β values ranged from 0.21 to 0.78). Weighted quantile sum regression analyses were used to assess associations of mVOC mixture and OSBs, and we found significantly positive associations between the mixture index and OSBs, among which the strongest mVOC contributors for the associations were 2-methylhippuric acid for both DNA (20%) and RNA (17%) oxidative damage, and trans,trans -muconic acid (50%) for lipid peroxidation. This study firstly reported good to excellent short-term reproducibility, seasonal difference in autumn and winter, and possible health risk in urinary concentrations of multiple mVOCs among the general population. [Display omitted] • Inter-day reproducibility for most mVOCs was good to excellent. • Urinary concentrations of mVOCs in winter were generally higher than in autumn. • Most of the studied mVOCs were positively associated with 8-OHdG and 8-OHG. • Acrolein, 1,3-butadiene, and cyanide are high priority VOCs in Wuhan, central China. [ABSTRACT FROM AUTHOR]

Studies have shown that lead exposure affected the immune function, but few studies have examined the relationships between in utero lead exposure, a sensitive period that is important for immune development, and later immune responses. To investigate the effects of prenatal and childhood lead exposure on the preschool-aged children's immune responses, a prospective birth cohort study was established in Wuhan, China, in which lead concentrations were analyzed in maternal urine during the third trimester and in plasma samples from children aged about 3 years. We assessed immune responses by measuring immune cytokines in the children's plasma (n = 326) and peripheral blood T lymphocyte subsets (n = 394) at 3 years of age. Each unit increase in maternal urinary lead concentration (μg/g creatinine) was associated with reduced IL-10 (β = −5.93%, 95%CI: −11.82%, −0.03%) and reduced IL-4 levels (β = −5.62%, 95%CI: −10.44%, −0.80%). Lead in children's plasma (μg/L) was associated with significant increase in TNF-α (β = 10.78%, 95%CI: 3.97%, 17.59%). No statistically significant relationship of childhood lead exposure with T lymphocyte subsets was observed. The study suggested prenatal and childhood lead exposure was associated with changes in preschool children's plasma cytokine levels. • The associations between prenatal and postnatal exposure to lead and immune responses of preschool children were evaluated. • Prenatal lead exposure decreased plasma IL-10 and IL-4 levels in preschool children. • Postnatal lead exposure increased plasma TNF-α level in preschool children. [ABSTRACT FROM AUTHOR]

Concerns on minimizing health risks of phthalates have been raised due to their widespread exposure and well-documented endocrine disrupting properties, but the determinants of levels, metabolism, and health risks of phthalate exposures have not been thoroughly characterized among the Chinese population, particularly pregnant women. The metabolites of five phthalates were analyzed: diethyl (DEP), diisobutyl (DiBP), di-n-butyl (DnBP), di-(2-ethylhexyl) (DEHP), and benzyl butyl phthalate (BBzP) were analyzed in urine samples collected from 946 mothers in Wuhan during 2014–2015. We applied linear mixed models to investigate the relationships between biomarkers (e.g., urinary concentrations of phthalate metabolites, phthalates, and ratios of metabolites) and factors including sampling seasons and epidemiological characteristics. We calculated estimated daily intake (EDI) using average phthalate concentrations over three trimesters and hazard index (HI) by dividing EDI by tolerance daily intake. About 24.9% of participants were at health risks with HI > 1. The largest health risks were driven by one specific phthalate (DnBP or DEHP). We observed lower urinary levels of phthalate metabolites in winter. Elevated levels were found in mothers with higher education levels or those employed. Mothers who got pregnant on purpose had lower phthalate concentrations than those got pregnant by accident. More recent exposure to phthalates was observed among groups of mothers giving birth to girls, or those who got excessive gestational weight gain. Younger mothers were more susceptible to phthalate exposure. This repeated measurement study suggests that the intervention should be taken to limit application and production of DnBP and DEHP, and highlights that typical demographic factors should be taken into account in demographic studies. • Phthalate levels were associated with sampling seasons, education levels, and employment. • Mothers who got pregnant on purpose had lower phthalate concentrations. • More recent exposure was observed among mothers who gave birth to girls. • More recent exposure was observed among mothers who gained excessive weight. • Younger mothers were more susceptible to phthalate exposure. [ABSTRACT FROM AUTHOR]

Phthalates are a family of endocrine disruptors with short elimination half-lives in the human body. To date, few epidemiological studies have examined repeated measures of maternal urinary phthalates and the combined effects of prenatal exposure to multiple phthalates on children's neurocognitive development. We aimed to investigate the association between children's neurocognitive development at 2 years of age and prenatal phthalate exposure, as assessed by repeated measurements during pregnancy, and to further examine the effects of co-exposure to multiple phthalates using cumulative risk assessment. Within a prenatal cohort in Wuhan, China, we measured five high-molecular-weight (HMW) phthalates and three low-molecular-weight (LMW) phthalate metabolites' concentrations in three urine samples collected in the 1st, 2nd, and 3rd trimester of pregnancy from each mother. We assessed neurocognitive development by Bayley Scales of Infant and Toddler Development (BSID) at 2 years of age (n = 476) to obtain the children's mental development index (MDI) and psychomotor development index (PDI). Higher exposure levels to LMW phthalates compared to HMW phthalates were observed in our population. Ln-transformed averaged concentration of mono- n -butyl phthalate (MnBP), a metabolite of the LMW phthalate di- n -butyl phthalate (DnBP) during pregnancy, was associated with decreased PDI scores in all children (β = −1.90, 95% CI: −3.43, −0.37). Similarly, the averaged sum concentration of ∑dibutyl phthalate (∑DBP) was associated with decreased PDI scores in all children (β = −1.89, 95% CI: −3.63, −0.15). A negative trend of association between exposure to HMW phthalates and PDI scores was observed in girls, while a positive association was found in boys. In cumulative risk assessment analyses, we consistently observed that the hazard quotient of DnBP (the parent compound of MnBP) was inversely associated with PDI scores in all children, whereas the hazard quotient of di-2-ethylhexyl phthalate (DEHP), an HMW phthalate, was positively associated with PDI scores in boys only. This study is the first to use repeated measurement of maternal urinary phthalates in all three trimesters to assess prenatal exposure in relation to children's neurodevelopment. Our study suggested a negative association between prenatal exposure to MnBP and children's psychomotor development, and potentially sex-specific associations between HMW phthalates and neurocognitive development among boys and girls. These findings warrant further confirmation. • We first evaluated the effect of repeated measurements of maternal urinary phthalates on child neurocognitive development. • Prenatal exposure to mono-n-butyl phthalate was negatively associated with children's psychomotor development. • The sex-specific effect may exist between phthalates and neurocognitive development. [ABSTRACT FROM AUTHOR]

Human beings are extensively and concurrently exposed to multiple volatile organic compounds (VOCs, including some Class I human carcinogens), which may induce oxidative stress in human body. Data on urinary metabolites of VOCs (mVOCs) among young children are limited. No studies have examined their inter-day variability of mVOCs and their associations with oxidative stress biomarkers (OSBs) using repeated urine samples from children. In this study, we measured twenty one mVOCs and three OSBs [8-hydroxy-2′-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA], and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid)] in 390 urine samples of 130 children (three samples on three consecutive days provided by each participant) aged 0–7 years from September 2018 to January 2019 in Shenzhen, south China, and Wuhan, central China. HPMMA (3-hydroxypropyl-1-methyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl-1-methyl)- l -cysteine), 3HPMA (3-hydroxypropyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl)- l -cysteine), and ATCA (2-aminothiazoline-4-carboxylic acid) had higher specific gravity-adjusted median concentrations (1 383, 286, and 273 μg/L, respectively) than the others. Intraclass correlation coefficients of mVOCs ranged from 0.29 to 0.71. After false-discovery rate (FDR, defined as FDR q -value < 0.05) adjustment, linear mixed-effects models revealed that 14 mVOCs were positively associated with 8-OHdG (β range: 0.09–0.37), 11 mVOCs were positively associated with 8-OHG (β range: 0.08–0.30), and 11 mVOCs were positively associated with HNEMA (β range: 0.21–0.70) in urine. Considering the weight of the mVOC index accounted for the associations, based on the weighted quantile sum regression model, parent compounds of DHBMA (3,4-dihydroxybutyl mercapturic acid/N-Acetyl-S-(3,4-dihydroxybutyl)- l -cysteine) and t,t-MA (trans,trans -muconic acid) should be listed as priority VOCs for management to mitigate health risks. For the first time, this study characterized the inter-day variability of urinary mVOCs and their associations with selected OSBs (8-OHdG, 8-OHG, and NHEMA) in young, healthy Chinese children. [Display omitted] • First to characterize the profile of urinary mVOCs in Chinese infants and toddler. • Inter-day variability of the mVOCs among young children was evaluated. • Over ten mVOCs were positively associated with 8-OHdG, 8-OHG, and HNEMA. • DHBMA was the major contributor in elevated 8-OHdG and 8-OHG. • t,t-MA was the major contributor in elevated HNEMA. [ABSTRACT FROM AUTHOR]