High-sensitivity liquid chromatography-tandem mass spectrometry quantitative for alkyl imidazolium ionic liquids in human serum: Advancing biomonitoring of human exposure concerns.

Alkyl imidazolium ionic liquids (Cn[MIM]), initially heralded as eco-friendly green solvents for diverse industrial applications, have increasingly been recognized fortheir biodegradability challenges and multiple biotoxicity. Despite potential health risks, research into the effects of Cn[MIM] on human health remains scarce, particularly regarding their detection in biological serum samples. This study validated a matrix-matched calibration quantitative method that utilizes solid-phase extraction (SPE) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was used to analyze the presence of 10 ionic liquids (ILs) with varying alkyl carbon chain lengths (C2-C12) across 300 human serum samples. Efficient separation was achieved using optimized SPE conditions and a BEH C18 column with an appropriate mobile phase. Results demonstrated a strong linear relationship (0.05-100 ng/mL; R2 = 0.995-0.999), with detection and quantification limits with detection and quantification limits ranging from 0.001 to 0.107 ng/mL and 0.003-0.355 ng/mL, respectively. Intraday and inter-day precisions were 0.85-6.99 % and 1.50-7.46 %, with recoveries between 82 and 113 %. The validated method detected C6MIM in 19 % of samples and C8MIM in 8.3 % of samples, with concentrations ranging from 0.02 to 111.70 µg/L and 0.09-16.99 µg/L, respectively, suggesting a potential risk of human exposure. This underscores the importance of robust detection methods in monitoring environmental and human health impacts of alkyl imidazolium compounds.

[Contamination levels of perfluorinated and polyfluoroalkyl compounds in breast milk and assessment of their exposure risk to infants].

The purposes of this study are to explore the contamination levels of perfluorinated and polyfluoroalkyl substances (PFASs) in breast milk and assess their exposure risk to infants. Based on data from a birth cohort study conducted in Yingcheng, Hubei Province, from 2018 to 2021, the contents of 23 types of PFASs in the breast milk of 324 pregnant women were determined using isotope dilution-high performance liquid chromatography-tandem mass spectrometry. Multiple linear regression was then performed to analyze the effects of various demographic characteristics and eating habits on the concentration of PFASs in breast milk. The daily PFASs intake of infants through breast milk was estimated, and the exposure risk of infants was also assessed. The results revealed that 23 types of PFASs in breast milk had good linear relationships in the range of 0.2-100 ng/mL, with correlation coefficients greater than 0.992. The limits of detection were 5-42 pg/mL, the limits of quantification were 15-126 pg/mL, the recoveries were 65.6%-108.1%, and the relative standard deviations were 1.6%-12.8%. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoate acid (PFOA), and perfluorohexanesulfonic acid (PFHxS), with median concentrations of 200.7, 63.5, and 25.2 pg/mL, respectively, were the main PFASs found in breast milk. The detection rates of these three contaminants were higher than 80%, whereas the detection rates of other compounds were lower than 45%. The results of multiple linear regression showed that older pregnant women and a higher frequency of pickled food intake may be related to increased PFAS levels in breast milk whereas a higher frequency of legume intake may be related to decreased PFAS levels in breast milk. The median estimated daily intakes (EDIs) of PFOS, PFOA, and PFHxS for infants were 25.1, 7.9, and 3.2 ng/(kg·d), respectively. In summary, this study found notable PFAS levels in breast milk in Yingcheng, Hubei Province. Among these PFASs, PFOS, PFOA, and PFHxS were the main contaminants. Maternal age as well as pickled food and legume intake may affect the PFAS level in breast milk. The health risk of PFAS intake through breast milk to some infants is worthy of attention and further study.

Prenatal exposure to per- and polyfluoroalkyl substances and DNA methylation in the placenta: A prospective cohort study.

Epidemiological studies regarding the relationship between per- and polyfluoroalkyl substances (PFAS) and DNA methylation were limited. We investigated the associations of maternal PFAS concentrations with placental DNA methylation and examined the mediating role of methylation changes between PFAS and infant development. We measured the concentrations of 11 PFAS in maternal plasma during early pregnancy and infant development at six months of age. We analyzed genome-wide DNA methylation in 16 placental samples using reduced representation bisulfite sequencing. Additionally, we measured DNA methylation levels using bisulfite amplicon sequencing in 345 mother-infant pairs for five candidate genes, including carbohydrate sulfotransferase 7 (CHST7), fibroblast growth factor 13 (FGF13), insulin receptor substrate 4 (IRS4), paired like homeobox 2Ap (PHOX2A), and plexin domain containing 1 (PLXDC1). We found that placental DNA methylation profiles related to PFOA mainly enriched in angiogenesis and neuronal signaling pathways. PFOA was associated with hypomethylation of IRS4 and PLXDC1, and PFNA was associated with PLXDC1 hypomethylation. There were positive associations of CHST7 methylation with PFTrDA and IRS4 methylation with PFDoA and PFTrDA. PLXDC1 hypomethylation mediated the association between PFOA and suspected developmental delay in infants. Future studies with larger sample sizes are warranted to confirm these findings.

Neuroprotective Effects of Vinpocetine Against Ischemia-Reperfusion Injury Via Inhibiting NLRP3 Inflammasome Signaling Pathway.

Ischemic stroke is one of the main causes of serious disability and death worldwide. NLRP3 inflammasome is an intracellular pattern recognition receptor composed of polyprotein complex, which participates in mediating a series of inflammatory responses and is considered as a potential target for the treatment of ischemic stroke. Vinpocetine, a derivative of vincamine, has been widely used in the prevention and treatment of ischemic stroke. However, the therapeutic mechanism of vinpocetine is not clear, and its effect on NLRP3 inflammasome remains to be determined. In this study, we used the mouse model of transient middle cerebral artery occlusion (tMCAO) to simulate the occurrence of ischemic stroke. Different doses of vinpocetine (5, 10, 15 mg/kg/d) were injected intraperitoneally for 3 days after ischemia-reperfusion in mice. The effects of different doses of vinpocetine on the degree of ischemia-reperfusion injury in mice were observed by TTC staining and modified neurological severity score scale, and the optimal dose was determined. Then, based on this optimal dose, we observed the effects of vinpocetine on apoptosis, microglial proliferation and NLRP3 inflammasome. In addition, we compared the effects of vinpocetine and MCC950 (a specific inhibitor of NLRP3 inflammasome) on NLRP3 inflammasome. Our results show that vinpocetine can effectively reduce the infarct volume and promote the recovery of behavioral function in stroke mice, and the maximal beneficial effects were observed at the dose of 10 mg/kg/d. Vinpocetine can effectively inhibit the apoptosis of peri-infarct neurons, promote the expression of Bcl-2, inhibit the expression of Bax and Cleaved Caspase-3, and reduce the proliferation of peri-infarct microglia. In addition, vinpocetine, like MCC950, can reduce the expression of NLRP3 inflammasome. Therefore, vinpocetine can effectively alleviate the ischemia-reperfusion injury in mice, and the inhibition of NLRP3 inflammasome may be an important therapeutic mechanism of vinpocetine.

Prenatal Exposure to Perfluoroalkyl Substances and Cognitive and Neurobehavioral Development in Children at 6 Years of Age.

Epidemiological evidence regarding the effects of prenatal exposure to perfluoroalkyl substances (PFASs) on neurodevelopment in children is inconclusive. In 449 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we measured the concentrations of 11 PFASs in maternal plasma samples obtained at 12-16 weeks of gestation. We assessed children's neurodevelopment at 6 years of age by the fourth edition of the Chinese Wechsler Intelligence Scale for Children and Child Behavior Checklist for ages 6-18. We evaluated the association between prenatal exposure to PFASs and children's neurodevelopment and the effect modification of maternal dietary factors during pregnancy and the child's sex. We found that prenatal exposure to multiple PFASs was associated with increased scores for attention problems, and the individual effect of perfluorooctanoic acid (PFOA) was statistically significant. However, no statistically significant association between PFASs and cognitive development was observed. Additionally, we found the effect modification of maternal nut intake and child's sex. In conclusion, this study suggests that prenatal exposure to PFASs was associated with more attention problems, and maternal nut intake during pregnancy may alter the potential effect of PFASs. However, these findings were exploratory because of multiple testing and the relatively small sample size.

Associations between Maternal Polychlorinated Dibenzo-p-dioxin and Dibenzofuran Serum Concentrations and Pulse Pressure in Early Pregnancy: A Cross-Sectional Study.

Pulse pressure (PP) is the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP), and an independent predictor of cardiovascular risk. Previous research suggests, with different conclusions, that exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) could affect blood pressure (BP). We conducted a cross-sectional study to determine the association of dioxin exposure with PP in early pregnancy. A total of 305 pregnant women in early pregnancy in Yingcheng, China, recruited from May 2018 to February 2021, were included in this study. We measured 17 congeners of PCDD/Fs in maternal serum via high-resolution gas chromatography tandem high-resolution mass spectrometry. A generalized linear regression model was used to analyze the influencing factors of dioxin exposure and their relationships with PP. The levels of total PCDD/Fs (∑PCDD/Fs) ranged from 163.52 pg/g lipid to 1,513,949.52 pg/g lipid, with a mean of 10,474.22 pg/g lipid. The mean toxicity equivalent (TEQ) of total PCDD/Fs (∑TEQ-PCDD/Fs) was 42.03 pg/g lipid. The ratio of tetrachlorinated to octa-chlorinated congeners in maternal serum was enriched with an increasing number of chlorines. Pregnant women with college and above education had higher concentrations of ∑PCDD/Fs than those with education levels of junior high school and below (ß = 0.34, 95% CI: 0.01, 0.67). The adjusted model for ∑TEQ-PCDD/Fs was significantly and negatively associated with PP (ß = -1.79, 95% CI: -2.91, -0.68). High levels of dioxins were found in this area, and exposure to dioxins may affect the PP of women in early pregnancy, with health risks.

Distribution and bioaccumulation of polychlorinated dibenzo-p-dioxins and dibenzofurans in the tissues of Yorkshire pig.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in various foods continuously concern the public. Pork and its byproducts, especially from Yorkshire pigs, are the largest meat food consumed by the general population in China. This study aims to investigate the distribution of PCDD/Fs in different tissues of Yorkshire pigs to understand their bioaccumulation. Yorkshire pigs were fed a known amount of PCDD/Fs through fly ash. PCDD/Fs were determined by isotope dilution method with a gas chromatography-high resolution mass spectrometer. The liver had the highest concentration levels (2041.33 pg/g lipid) and toxic equivalents values (69.14 pg/g lipid), followed by the spleen and lung, and the lowest ones in the brain. The liver also had the highest bioaccumulation of PCDD/Fs, and this level was considerably higher than that of other tissues. This study showed a strong accumulation capacity of the liver for polychlorinated dibenzo-p-dioxins and dibenzofurans under short-term exposure conditions, suggesting that the liver is a more sensitive tissue for monitoring PCDD/Fs in food safety risk monitoring. PRACTICAL APPLICATION: This paper may help the consumer in making food choices to minimize the exposure risk to Polychlorinated dibenzo-p-dioxins and dibenzofurans.

Association between prenatal exposure to perfluoroalkyl substances and anogenital distance in female neonates.

BACKGROUND: Perfluoroalkyl substances (PFASs) have been reported to exert reproductive toxicity. Anogenital distance (AGD) is a biomarker of intrauterine androgen exposure and an indicator of genital development. An animal study reported that female neonatal rats exposed to perfluorooctanoic acid or perfluorooctane sulfonate (PFOS) during postnatal days 1-5 exhibited a longer AGD, while epidemiological studies have shown inconsistent results. This study aimed to examine the effects of prenatal exposure to PFASs on the AGD in female neonates. METHODS: PFAS levels were measured in plasma samples obtained from pregnant women at 12-16 gestational weeks using high-performance liquid chromatography/mass spectrometry. The AGD of each female neonate was measured within 3 days after delivery. The anogenital index (AGI), calculated as AGD divided by weight, was also determined. A total of 362 motherinfant pairs were included in this study. A multivariate linear regression model was used to examine the association between prenatal ln-transformed concentrations of PFASs and AGD/AGI. In addition, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) models were used to assess the overall effects of a mixture of PFASs on the AGD/AGI and to identify important contributors to the overall effect. RESULTS: There was a consistent pattern of association between maternal PFAS concentrations and increased AGDanus to posterior fourchette (AF), AGDanus to clitoris (AC), and AGIAF lengths at birth. Statistical significance was found between maternal ln-transformed concentrations of perfluorohexane sulfonate (PFHxS), perfluorododecanoic acid, and perfluorotridecanoic acid and AGDAF, with ß values (95% confidence interval [CI]) of 0.83 (0.16, 1.51), 0.32 (0.05, 0.59), and 0.25 (0.00, 0.51) mm, respectively; between PFOS and AGDAC, with a ß value (95% CI) of 0.63 (0.04, 1.21) mm; and between PFHxS and AGIAF, with a ß value (95% CI) of 0.22 (0.02, 0.43) mm/kg. Similarly, the WQSR and BKMR models showed that an increase in the AGDAF/AGIAF at birth was associated with co-exposure to a mixture of PFASs. CONCLUSION: High maternal concentrations of PFASs were associated with increased AGD in female neonates, indicating that PFASs may impair reproductive development in female offspring in early life.

[Serum polychlorinated biphenyls levels in some reproductive aged men in Wuhan and the influencing factors in 2013].

OBJECTIVE: To measure polychlorinated biphenyls(PCBs) concentrations in serum of some reproductive aged men in Wuhan and explore the influencing factors of PCBs exposure. METHODS: Based on a cross-sectional study in 2013 on the association between exposure to environmental pollutants and adverse male reproductive health, which was conducted in Wuhan. Levels of dioxins-like PCBs(dl-PCBs) and non-dioxin-like PCBs(ndl-PCBs) in 101 serum samples of men with childbearing age were analyzed via high-resolution gas chromatograph tandem high-resolution mass spectrometer(HRGC-HRMS) method. Multiple linear regression models were used to analyze the associations between PCBs levels and influencing factors. RESULTS: Total concentrations of twelve dl-PCBs(Σdl-PCBs) were in range of 177.85-7271.48 pg/g lipid, the median value was 1530.71 pg/g lipid, and CB-118 was the predominant congener. For six ndl-PCBs, total concentrations(Σndl-PCBs) were in range of 1463.23-40561.47 pg/g lipid, the median value was 5498.37 pg/g lipid, and CB-153 was the predominant congener. The World Health Organization toxicity equivalent(WHO_(2005)-TEQ) of dl-PCBs(ΣTEQ_(dl-PCBs)) were 0.02-162.29 pg TEQ/g lipid, the median value was 1.77 pg TEQ/g lipid. The age was positively correlated with Σmono-ortho PCBs(ß=0.01, 95%CI 0.00-0.02), ΣTEQ_(mono-ortho PCBs)(ß=0.01, 95%CI 0.00-0.02) and Σndl-PCBs(ß=0.02, 95%CI 0.00-0.03). Men who drank alcohol tend to show higher exposure to ΣTEQ_(dl-PCBs)(ß=0.56, 95%CI 0.13-1.00) than those did not drink alcohol. And higher levels of Σndl-PCBs(ß=0.15, 95%CI 0.04-0.26) was found in the men who reside in urban areas as compared to rural one. CONCLUSION: There were PCBs exposure in some reproductive aged men in Wuhan. Age, drink alcohol status, and residence were influencing factors on PCBs.

Associations between prenatal exposure to perfluoroalkyl substances and neurobehavioral development in early childhood: A prospective cohort study.

Findings from epidemiological studies on the associations between prenatal perfluoroalkyl substances (PFASs) exposure and children's neurodevelopment were inconclusive, and most studies did not account for the co-exposure to multiple PFASs with strong inter-correlations. The present study aimed to assess the effects of prenatal multiple PFAS exposure on children's neurobehavioral development based on 614 mother-infant pairs in the Shanghai-Minhang Birth Cohort Study. Eight PFAS concentrations were measured in maternal plasma at 12-16 weeks of gestation. Children's neurobehavioral development at 2 and 4 years of age was assessed by the Child Behavior Checklist for Ages 1.5-5. In Bayesian kernel machine regression (BKMR) analyses that could address the inter-correlations between multiple PFASs, PFAS mixture appeared to be associated with fewer Somatic Complaints and more Externalizing Problems in boys, but more Somatic Complaints and Sleep Problems in girls. There were suggestive associations of PFNA and PFOS with decreased risk of Somatic Complaints and of PFUdA and PFTrDA with increased risk of Externalizing Problems in boys; trends of increased risk in girls were observed between PFUdA and Somatic Complaints and between PFTrDA and Sleep Problems. Overall, we found no clear evidence that prenatal exposure to PFASs had negative effects on neurobehavioral development in children. However, the modest associations still suggested the potential developmental neurotoxicity of prenatal PFAS exposure.

Association between prenatal exposure to polybrominated diphenyl ethers and anogenital distance in girls at ages 0-4 years.

Anogenital distance (AGD) is a sensitive marker for the effect of in utero hormonal disturbance. However, studies on the associations between prenatal exposure to polybrominated diphenyl ethers (PBDEs), a group of endocrine disruptors, and AGD are limited. We examined the associations between prenatal PBDE exposure and AGD in girls at ages 0-4 years in the Shanghai-Minhang Birth Cohort Study. We measured PBDE in cord plasma collected from 148 girls at birth. Of them, two AGD metrics (AGDAC: from the anterior surface of the clitoral hood to the center of the anus; AGDAF: from the posterior end of the fourchette to the center of the anus) were measured in 142, 114, 104 and 120 of girls at birth, 6, 12, and 48 months of age, respectively. Linear regression models and linear mixed models were used to evaluate the associations between PBDE exposure and AGD at ages 0-4 years. We found positive associations of PBDE exposure with AGDAF and AGDAC in linear regression models, although some associations only reached significance at 6 and 48 months of age. For AGDAF, the associations were statistically significant for BDE-47, -99, and -100 at 6 months of age (ß = 2.34, 95% CI (0.21, 4.48) for BDE-47; ß = 2.21, 95% CI (0.05, 4.36) for BDE-99; ß = 2.12, 95% CI (0.01, 4.23) for BDE-100), and for BDE-99 and -100 at 48 months of age (ß = 4.49, 95% CI (1.27, 7.71) for BDE-99; ß = 5.04, 95% CI (1.87, 8.22) for BDE-100), while statistically significant associations with AGDAC were only observed for BDE-99, -100, -153, and ∑5PBDEs at 48 months of age (ß = 7.62, 95% CI (2.59, 12.64) for BDE-99; ß = 7.04, 95% CI (2.01, 12.07) for BDE-100; ß = 5.41, 95% CI (0.45, 10.38) for BDE-153; ß = 5.05 mm, 95% CI (0.09, 10.01 for ∑5PBDEs). A consistent pattern of positive associations between prenatal exposure to PBDEs and AGD was also observed in linear mixed models. The finding provided further insights into the adverse effects of PBDEs on reproductive development at low dose exposure.

Sex-specific associations of prenatal exposure to bisphenol A and its alternatives with fetal growth parameters and gestational age.

BACKGROUND: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. OBJECTIVE: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. METHODS: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose-response associations between exposures and outcomes. RESULTS: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: -0.44, -0.15 and -0.21 cm, 95% CI: -0.36, -0.07 comparing the extreme exposure groups, respectively, both p for trends < 0.01). These associations were more pronounced in girls with inverted U-shaped dose-response relationships. Maternal urinary BPA and BPF were positively related to ponderal index (0.05 g/cm3 × 100, 95% CI: 0.01, 0.09 and 0.04 g/cm3 × 100, 95% CI: 0.01, 0.08 comparing the extreme exposure groups, respectively, both p for trends = 0.02), and maternal urinary BPS was associated with shorter gestational age (-0.20 weeks, 95% CI: -0.37, -0.03 comparing the extreme exposure groups, p for trend = 0.02). These associations were only observed in girls and exhibited a linear dose-response relationship. CONCLUSIONS: Prenatal BPA, BPF, and BPS exposures were associated with detrimental effects on fetal growth parameters, and stronger effects were noted in female infants.

Interannual variation and exposure risk assessment of lead in brick tea in Hubei, China.

Lead (Pb) exposure may cause severe health outcomes such as decreased fertility, joint pain and neurological disorders. It is important to know the Pb exposure level in tea and the risk assessment for local residents who drink brick tea daily. This study detected sixteen brick tea samples over 26 years and fifteen green tea samples in 2011 in a southeast city of Hubei province. The Pb content in brick tea was found to increase rapidly with the fast development of industrial activities represented by car sales from 1985 to 2011, which was less susceptible to gasoline. The concentrations of Pb in 16 brick tea were in the range of 1.77-17.8 mg/kg with a mean value of 11.1 mg/kg. Their percentiles P50, P90, and P95 were 13.22, 16.95, and 17.21 mg/kg. A regressional model was built, suggesting strong correlation between the Pb content in brick tea and the car sales. The concentrations of Pb in 15 green tea samples were between 0.36-1.30 mg/kg with a mean value of 0.66 mg/kg and the percentiles P50, P90, and P95 were 0.62, 1.05, and 1.23 mg/kg. The MOE values of brick tea and green tea were all greater than 1 just considering tea consumption which displayed low Pb exposure risk. By adding the Pb exposure by food, the MOE values for green tea were still greater than 1 while the MOE values of brick tea were less than 1 suggesting a potential risk of Pb exposure to the people drinking brick tea daily, who should pay more attention.

Urinary Biomarker of Prenatal Exposure to Disinfection Byproducts, Maternal Genetic Polymorphisms in CYP2E1 and GSTZ1, and Birth Outcomes.

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.

Polychlorinated Dibenzo-p-Dioxins, Polychlorinated Dibenzofurans, and Dioxin-Like Polychlorinated Biphenyls in Umbilical Cord Serum from Pregnant Women Living Near a Chemical Plant in Tianjin, China.

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (dl-PCBs) are bioaccumulative compounds that may affect fetal growth and infant development. The aim of this study was to determine whether the pregnant women living near a chemical plant in Tianjin had a risk of exposure to dioxins. Concentrations of PCDD/Fs and dl-PCBs in 24 umbilical cord serum samples collected from pregnant women were measured using a high-resolution gas chromatograph with a high-resolution mass spectrometer (HRGC-HRMS) and an isotopic dilution method. The levels of ∑(PCDD/Fs + dl-PCBs) were in the range 476-8307 pg·g-1 lipid, with a mean of 3037 pg·g-1. The mean World Health Organization toxicity equivalent (WHO-TEQ) for PCDD/Fs and dl-PCBs was 14.0 and 2.14 pg·g-1 lipid, respectively. The PCDD/Fs and dl-PCBs contributed 86.7% and 13.3%, respectively, to the total TEQ. The octa-CDFs and penta-CBs were predominant for the PCDD/Fs and dl-PCBs, accounting for 57.6% and 74.3%, respectively. Several PCDD/F and dl-PCB congeners were highly correlated, such as PCB 105 and PCB 118 (r = 0.982, p < 0.001). Although the results hint at decreasing trends for PCDD/F and dl-PCBs by comparison with a similar study in Tianjin, a total TEQ of 41.7% of study participants had a body burden that exceeded the biomonitoring equivalents for dioxins. It was shown that pregnant women and infants had a health risk of exposure to dioxins.

Maternal plasma concentrations of perfluoroalkyl and polyfluoroalkyl substances during pregnancy and anogenital distance in male infants.

STUDY QUESTION: Are maternal plasma concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFASs) during pregnancy associated with anogenital distance (AGD) in male infants at birth, 6, and 12 months of age? SUMMARY ANSWER: Higher maternal plasma concentrations of some PFASs were associated with shorter AGD in male infants at birth and 6 months of age. WHAT IS KNOWN ALREADY: Two animal studies have found that exposure to PFASs was associated with shorter AGD in male rat fetuses and wild male minks. There is only one human study on the topic that did not identify consistent patterns between maternal serum concentrations of PFASs during pregnancy and AGD in male infants. STUDY DESIGN, SIZE, DURATION: In the prospective cohort study, a total of 1292 eligible pregnant women were recruited at 12-16 weeks of gestation between April and December 2012 at the Maternal and Child Health Hospital of Minhang district in Shanghai, China. At delivery, 667 male singletons were born. They were then followed up at birth (n = 439) and at 6 (n = 411) and 12 months (n = 376) of age when anopenile distance (AGDAP) and anoscrotal distance (AGDAS) were measured. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 500 male infants who had both maternal plasma concentrations of PFASs and at least one AGD measurement of at three time points were included in the present study. Multiple linear regression models were used to evaluate the potential linear associations between maternal concentrations of PFASs and AGD. MAIN RESULTS AND THE ROLE OF CHANCE: Maternal plasma concentrations (ln-transformed) of perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA) were inversely associated with AGDAS or AGDAP at birth (AGDAS: per ln unit increase in PFAS concentrations: ß (95% CI): -0.65 (-1.27 to -0.02) mm for PFOS; -0.58 (-1.11 to -0.06) mm for PFDA; and -0.57 (-1.09 to -0.06) mm for PFUdA; AGDAP: per ln unit increase in PFAS concentrations: ß (95% CI): -0.63 (-1.24 to -0.01) mm for PFDA and - 0.76 (-1.36 to -0.16) mm for PFUdA). At 6 months of age, per unit increase in maternal ln concentrations of PFOS and perfluorotridecanoic acid (PFTrDA), AGDAS decreased on average by -2.21 (95% CI: -4.28 to -0.14) and -1.11 (95% CI: -2.17 to -0.06) mm, respectively. Additionally, ln-transformed perfluorooctanoic acid (PFOA) showed nonsignificant but inverse associations with both AGDAS and AGDAP at 6 months of age. We found no significant associations between ln-transformed maternal concentrations of PFASs and either AGDAS or AGDAP at 12 months of age. However, significantly inverse association of ln-transformed PFOA with AGDAP was observed in male infants who never or shortly breastfed (<3 months) at 12 months of age. LIMITATIONS, REASONS FOR CAUTION: AGD measurements were performed by different examiners at each follow-up visit, and the intra-examiner variation was not assessed, which might cause intra-rater and inter-rater measurement errors. Additionally, our study may have selection bias since a considerable number of participants withdrew from the cohort although the differences in demographic characteristics were not statistically significant between included mother-infant pairs and those excluded. No statistical correction was made for multiple comparisons. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may have important implications for the early development of genital health in male infants since PFASs can be detected in almost all pregnant women and infants worldwide. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development program of China (2018YFC1002801 and 2016YFC1000505), the Science and Technology Commission of Shanghai Municipality (16ZR1430100), the National Natural Science Foundation of China (81428011), and the Innovation-Oriented Science and Technology Grant from National Health Commission Key Laboratory of Reproduction Regulation (CX2017-06). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Urinary biomarker of late pregnancy exposure to drinking water disinfection by-products and ultrasound measures of fetal growth in Wuhan, China.

BACKGROUND: Disinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. OBJECTIVE: To investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. METHODS: We included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. RESULTS: We found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: -0.35, -0.07; P for trend = 0.003), 0.46 cm (95% CI: -0.81, -0.10; P for trend = 0.01) and 0.17 cm (95% CI: -0.30, -0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. CONCLUSION: The results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth.

Perfluoroalkyl substances in umbilical cord serum and gestational and postnatal growth in a Chinese birth cohort.

Although animal studies have found that perfluoroalkyl substances (PFASs) affect gestational and postnatal growth, the epidemiological findings are limited and not in agreement. We explored the associations of PFAS concentrations in umbilical cord blood with gestational and postnatal growth in China. Three hundred thirty-seven singleton newborns and their mothers were recruited from November 2013 to December 2015 in Zhoukou City, China. Umbilical cord blood was collected to measure eleven PFASs by liquid chromatography-mass spectrometry. The index of gestational and postnatal growth contained fetal weight, length, and head circumference. These were obtained at birth and at the follow-up investigation (mean 19 months). Exposed to higher perfluorooctanoic acid (PFOA) were connected with reduced length at birth (p for trend = 0.01) and decreased postnatal weight (ß = -429.2 g; 95% CI: -858.4, -0.121 for 2nd VS. 1st). Exposed to perfluoroundecanoic acid (PFUdA) were positively associated with indications of gestational growth and postnatal growth (p for trend = 0.02 for birth length; p for trend = 0.04 for postnatal length). Exposed to higher perfluorododecanoic acid (PFDoA) were associated with lower birth weight (ß = -122.9 g, 95% CI: -244.7 to -1.2 for 2nd VS. 1st), but higher postnatal length (p for trend = 0.03). Neonates in the highest exposure group of per-fluorohexanesulfonate (PFHxS) showed decreased birth length (ß = -0.33 cm, 95% CI: -0.68 to -0.01, for 2nd VS. 1st), but increased postnatal head circumference (p for trend = 0.04). Increased PFOA concentrations was associated with shorter birth length only in girls (p for trend = 0.04), suggesting that the effect of PFASs on gestational growth were different between boys and girls. In utero exposure to PFASs may affect gestational and postnatal growth.

Prenatal urinary polycyclic aromatic hydrocarbon metabolites, global DNA methylation in cord blood, and birth outcomes: A cohort study in China.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for adverse birth outcomes. Epigenetic mechanisms may play a key role in which PAHs exert its effects. OBJECTIVE: Our study aimed to examine whether prenatal PAH exposure was associated with adverse birth outcomes and altered DNA methylation and to explore potential mediating roles of DNA methylation. METHODS: Ten urinary PAH metabolites were measured from 106 pregnant women during late pregnancy in a Chinese cohort study. Cord blood DNA methylation in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements as surrogates of global DNA methylation was analyzed by bisulfite pyrosequencing. Multivariable linear regression was used to estimate the associations of urinary PAH metabolites with birth outcomes and DNA methylation, and a mediation analysis was also conducted. RESULTS: Prenatal urinary 2-hydroxynaphthalene (2-OHNa), ∑OHNa (sum of 1- and 2-OHNa), and sum of monohydroxy-PAH (∑OH-PAHs) were associated with lower birth length (e.g., -0.80%, 95% CI: -1.39%, -0.20% for the third vs. first tertile of 2-OHNa; p for trend = 0.01). Prenatal urinary 2-OHNa and 1-hydroxyphenanthrene (1-OHPh) were associated with lower Alu and LINE-1 methylation (e.g., -1.88%, 95% CI: -3.73%, -0.10% for the third vs. first tertile tertile of 2-OHNa in Alu methylation; p for trend = 0.04). Mediation analysis failed to show a mediator effect of global DNA methylation in the association between prenatal urinary OH-PAHs and birth outcomes. CONCLUSIONS: Prenatal specific PAH exposures are associated with decreased birth length and global DNA methylation. However, global DNA methylation does not mediate the associations of prenatal PAH exposure with birth outcomes. Further studies are needed to confirm the results.

Prenatal exposure to drinking water disinfection by-products and DNA methylation in cord blood.

Maternal exposure to drinking water disinfection by-products (DBPs) during pregnancy has been related to adverse birth outcomes. While experimental studies have shown that exposure to DBPs induce DNA hypomethylation, evidence from humans is limited. This study aimed to examine whether prenatal exposure to drinking water DBPs was associated with DNA methylation in cord blood. Maternal biomarkers of exposure to drinking water DBPs including blood trihalomethanes [THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary trichloroacetic acid (TCAA) were measured during late pregnancy. DNA methylation in Alu and long interspersed nucleotide element-1 (LINE-1) repetitive elements from cord blood samples (n=115) was measured by pyrosequencing. We used multivariable linear regression to estimate the associations of DNA methylation in cord blood with maternal blood THMs and urinary TCAA. We found no statistically significant association between urinary TCAA and DNA methylation. However, we found that blood TBM was associated with decreased Alu methylation (-0.39%; 95% CI: -0.83%, 0.05% for the highest versus lowest exposure group; p for trend=0.08) and decreased LINE-1 methylation (-1.27%; 95% CI: -2.91%, 0.36% for the highest versus lowest exposure group; p for trend=0.06). Our results suggest that prenatal exposure to drinking water TBM is associated with DNA hypomethylation in cord blood. However, further studies are needed to confirm our findings.