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Abstract Background Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. Methods This research involved 895 mother–child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath’s epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. Results The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), − 13.22 (− 23.21 to − 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), − 14.13 (− 21.59 to − 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than − 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than − 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than − 1.35, followed by a plateau between − 1.35 and − 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than − 0.67. Conclusions In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.

Abstract Background Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children’s neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children’s neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. Methods The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. Results Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P

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

Objectives: Environmental exposure may affect the telomere length (TL) of newborns, which is considered as an early biomarker indicating susceptibility for later life diseases. However, the effects of prenatal organochlorine pesticide (OCP) exposure on newborn TL remain unclear. This study aimed to investigate the association between prenatal exposure levels of OCPs during pregnancy and TL in neonatal cord blood. Methods: A total of 168 mother–infant pairs from a birth cohort in Wuhan, China, were included this study. The concentrations of hexachlorocyclohexanes (HCHs, including β-HCH, α-HCH, and γ-HCH), p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT) and its metabolites (p,p’-dichlorodiphenyldichloroethane, p,p’-DDD; p,p’-dichlorodiphenyldichloroethylene, p,p’-DDE) were measured in cord blood. The associations between the OCPs and the TL in newborns were analyzed by a generalized linear regression model. Stratified analyses by newborn sex, maternal gestational weight gain, and pregnancy body mass index (BMI) were performed to evaluate if the associations were modified by these factors. Results: The detection rates of various OCPs ranged from 50.9% to 100.0%. The median concentration of p,p’-DDE was the highest (33.90 ng/g lipid), followed by β-HCH (8.67 ng/g lipid), and the median concentrations of the other OCPs were between 0.12 and 0.33 ng/g lipid. Among the all newborns, a two-fold increase in the γ-HCH concentration in the cord blood was significantly associated with a 0.024 (95% CI: −0.041, −0.007) decrease in the TL. After stratification by newborn sex, the inverse association between γ-HCH and the TL was only statistically significant in boys, but not in girls (P for interaction Conclusions: Prenatal exposure to OCPs during pregnancy was associated with a decreased neonatal telomere length, which may be affected by the newborn sex and pre-pregnancy BMI. These findings may provide new insights into the mechanisms underlying OCP-induced adverse health effects.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6–19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend

Purpose: To investigate the effect of isometric prone trunk extension (IPTE) contraction intensity on the stiffness of erector spinae (ES), semitendinosus (ST), biceps femoris (BF), and gastrocnemius muscles to understand the overall muscle mechanical behavior during IPTE and to explore the mechanisms of oordinated contraction of the body kinetic chain.Methods: Twenty healthy females were recruited, and participants underwent IPTE at three contraction intensities, i.e., 0% maximum voluntary isometric contraction (MVIC), 30% MVIC, and 60% MVIC, and muscle stiffness was measured using MyotonPRO.Results: Muscle stiffness was moderately to strongly positively correlated with contraction intensity (r = 0.408–0.655, p < 0.001). The percentage increase in stiffness at low intensity was much greater in ES than in lower limb muscles and greater in ST and BF than in gastrocnemius, whereas at moderate intensity, the percentage increase in stiffness decreased in all muscles, and the percentage increase in stiffness in ES was lower than that in ST. There was a moderate to strong positive correlation between ES stiffness variation and ST (r = 0.758–0.902, p < 0.001), BF (r = 0.454–0.515, p < 0.05), MG (r = 0.643–0.652, p < 0.01), LG (r = 0.659–0.897, p < 0.01).Conclusion: IPTE significantly affected the stiffness of lumbar and lower limb muscles, and low-intensity IPTE activated the ES more efficiently. There were significant coordinated muscle contractions between ES, ST, and LG. This provides preliminary evidence for exploring the overall modulation pattern of the lumbar and lower limb muscles’ kinetic chains. In future studies, we will combine other stiffness assessment methods (such as Magnetic Resonance Elastography, Shear Wave Elastography, or electromyography) to corroborate our findings.

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

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

Background: Benzophenones (BPs), parabens, and triclosan (TCS) are widely used in personal care products and may be neurotoxic to children, but limited studies have estimated the associations between exposure to these potential endocrine disrupting chemicals during pregnancy and child neurocognitive development. Objective: Our aim was to evaluate the relationships of prenatal exposure to BPs, parabens and TCS with child neurocognitive development at age 2. Methods: From 2014 to 2015, 478 mother-child pairs from a longitudinal prenatal cohort in China were included in present study. We quantified BPs, parabens and TCS in three spot urine samples during pregnancy (in the first, second, and third trimester). The Bayley Scales of Infant Development (BSID) test to children was performed at 2 years. Multivariate linear regression models and generalized estimating equations were used to examine changes in mental developmental index (MDI) and psychomotor development index (PDI) per 2-fold increase in averaged and trimester-specific maternal urinary phenols, respectively. Results: In the adjusted models, each 2-fold increase in average prenatal paraben concentration was associated with lower MDI scores among girls [−1.08 (95% CI: −2.10, −0.06) and − 1.51 (95% CI: −2.69, −0.32) for methyl paraben (Mep) and Σparabens, respectively], but the association was not statistically significant among boys [−0.24 (95% CI: −1.46, 0.99), Psex-int = 0.37 and 0.18 (95% CI: −1.28, 1.64), Psex-int = 0.10 for Mep and Σparabens, respectively]. Increasing urinary 4-hydroxybenzophenone (4-OH-BP) concentration was associated with lower PDI scores among boys [−2.96 (95% CI: −4.48, −1.45)], not girls [−0.07 (95% CI: −1.57, 1.43)] and the association was significantly different in boys and girls (Psex-int = 0.01). No significant associations were observed between the average prenatal TCS exposure and BSID results. In trimester-specific analyses, increasing parabens was associated with lower girls' MDI only in the second trimester, while increasing 4-OH-BP was associated with lower boys' PDI in each trimester. Conclusion: Our results suggest that prenatal exposure to BPs and parabens may be associated with impairment in child cognitive abilities at 2 years. Further human and animal studies are needed to verify our results and elucidate the biological mechanisms involved in these associations. Keywords: Benzophenones, Parabens, Triclosan, Child neurocognitive development

Background: Widespread exposure to parabens has been a concern, especially among pregnant women. Only one study reported that parabens are associated with glucose levels among pregnant women. However, studies on parabens exposure and gestational diabetes mellitus (GDM) are lacking. Objectives: This study investigated whether exposure to parabens in early pregnancy is related to GDM. Methods: We conducted a prospective study of 1087 pregnant women from a single tertiary medical center between 2014 and 2015 in Wuhan, China. Parabens [methyl paraben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and benzylparaben (BzP)] concentrations were measured in spot urine samples collected between 8 and 16 gestational weeks. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations. We used the Poisson regression with a robust error variance with generalized estimating equations (GEE) estimation analyses to evaluate associations between parabens exposure and GDM risk. Results: A total of 103 (9.5%) women were diagnosed with GDM. We evaluated the associations of GDM risk with urinary MeP, EtP, and PrP (detection rate: >90%), but not with BuP and BzP due to the relatively low detection rate (

Endocrine-disrupting chemicals (EDCs) are widespread environmental chemicals that are often considered as risk factors with weak activity on the hormone-dependent process of pregnancy. However, the adverse effects of EDCs in the body of pregnant women were underestimated. The interaction between dynamic concentration of EDCs and endogenous hormones (EHs) on gestational age and delivery time remains unclear. To define a temporal interaction between the EDCs and EHs during pregnancy, comprehensive, unbiased, and quantitative analyses of 33 EDCs and 14 EHs were performed for a longitudinal cohort with 2317 pregnant women. We developed a machine learning model with the dynamic concentration information of EDCs and EHs to predict gestational age with high accuracy in the longitudinal cohort of pregnant women. The optimal combination of EHs and EDCs can identify when labor occurs (time to delivery within two and four weeks, AUROC of 0.82). Our results revealed that the bisphenols and phthalates are more potent than partial EHs for gestational age or delivery time. This study represents the use of machine learning methods for quantitative analysis of pregnancy-related EDCs and EHs for understanding the EDCs’ mixture effect on pregnancy with potential clinical utilities.

The rapid popularity of mobile shopping makes people’s lives more convenient, but it also makes it easier for customers to change providers. How to use marketing stimulus to retain customers has become an urgent concern for mobile sales companies. However, the theoretical researches in this field are not enough. For this reason, this study used the methods of literature review and structural equation to explore the effects of mobile marketing design factors on the continual intention of consumers in mobile shopping by using the S-O-R model and its extended theories. The conclusions of the research showed that interface quality of mobile sales terminal and integrity of mobile sales terminal had significant positive impacts on consumption emotion; sales promotion in mobile sales terminal had a significant positive impacts on continual intention of mobile shopping; consumption emotion had a significant positive effect on continual intention of consumers in mobile shopping; consumption emotion played a significant mediating role in the relationship between interface quality of mobile sales terminal and continual intention of mobile shopping and between integrity of mobile sales terminal and continual intention of mobile shopping. The conclusions could not only enrich the theories of mobile shopping behavior but also provide guidance for companies to carry out mobile marketing activities and allocate marketing resources rationally.

Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A1, phospholipase A2, and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival.

Background: Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional per-/polyfluoroalkyl substances (PFASs), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Other PFASs, used as the replacements of PFOS and PFOA, are widely and increasingly detected in humans. Whether these replacements influence glucocorticoids and progestogens in newborns remains unknown. Objective: To investigate the associations between exposures of PFOS, PFOA and their replacements and glucocorticoids and progestogens in newborns. Methods: We measured the concentrations of 13 PFASs, 3 glucocorticoids (11-deoxycortisol, cortisol and cortisone) and 2 progestogens [progesterone, 17-hydroxyprogesterone (17OHP)] in the cord sera of 374 neonates in a birth cohort from Wuhan, China, between 2013 and 2014. We evaluated the associations of each PFAS with glucocorticoids and progestogens using multiple linear regression models, and multiple comparisons were additionally corrected via false discovery rates (FDR). Results: Out of the 13 PFASs, 9 were detected in over 95% of cord sera. The Chinese specific PFOS replacement − 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA, trade name F-53B) was positively associated with 13.13% change in cortisol in girls (95% CI = 4.47%, 22.52%, for each IQR increase in 6:2 Cl-PFESA). Seven PFASs had positive associations with the precursor of cortisol, namely 11-deoxycortisol (percent change ranged from 6.41% to 11.24%, for each IQR increase in PFASs). Perfluorobutane sulfonate (PFBS) in cord sera was positively associated with progesterone in the linear model, whereas PFOS and perfluorohexane sulfonate (PFHxS) levels were associated with progesterone in the quartile models. No PFASs were related to 17OHP or cortisone. Conclusions: In this study, PFOS, PFOA and/or their replacements were positively associated with progesterone, cortisol and 11-deoxycortisol in newborns. These results suggested that not only PFOS and PFOA, but also other PFASs have potential impacts on glucocorticoids and progestogens in newborns.

Previous studies have proven the endocrine-disrupting properties and health hazards of parabens, triclosan, and benzophenones, but their relationship with blood pressure during pregnancy remains unknown. Therefore, we investigated the associations of repeated measures of urinary parabens, triclosan, and benzophenones with blood pressure during pregnancy and evaluated whether the associations were modified by fetal sex. From a prospective birth cohort in Wuhan, China, we collected urine samples from 644 pregnant women in the first, second, and third trimesters between 2014 and 2015. Five parabens, triclosan, and three benzophenones were quantified in all urine samples. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in each trimester after urine sampling. Mixed linear models were used to estimate the associations between urinary chemical levels and blood pressure during pregnancy among all pregnant women and subgroups stratified by fetal sex. In the women carrying male fetuses, urinary triclosan and selected benzophenone concentrations were associated with a slight change of SBP during pregnancy. In the women carrying female fetuses, no chemical was associated with SBP, while urinary concentration of triclosan was inversely associated with DBP, though the magnitude was small. Urinary paraben levels weren't associated with blood pressure during pregnancy. Our results suggest that triclosan and selected benzophenone exposure might be associated with blood pressure during pregnancy in a potential fetal sex-different manner. Replicated research studies in pregnant women with higher triclosan and benzophenone exposure levels are needed in the future.

Background: Previous studies have suggested that phthalates might disrupt fetal steroidogenesis. However, the evidence of the effects of prenatal phthalate exposure across pregnancy on fetal glucocorticoids was insufficient. Objective: We investigated the associations between urinary phthalate metabolites across pregnancy and cord blood glucocorticoids in a prospective birth cohort. Methods: Our study included 553 mother-infant pairs from a prospective birth cohort conducted in Wuhan, China. Maternal urine samples were collected at 14, 24 and 36 weeks of gestation (mean). Urinary phthalate metabolites and cord blood glucocorticoids (cortisol and cortisone) were measured. Generalized estimating equation models were conducted to explore the relationships of phthalate metabolite concentrations at each trimester and glucocorticoid levels. Results: Among the participants, mono‑benzyl phthalate (MBzP) in the first trimester was associated with higher cortisol/cortisone ratio concentrations, and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP) and mono‑(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP) measured in the third trimester were associated with decreased cortisone. Moreover, the associations between phthalates and glucocorticoids varied by sex. Among the female infants, each 10-fold increase in several maternal urinary phthalate metabolite concentrations in 1st and 3rd trimester was associated with the increased glucocorticoid levels with percent changes ranged from 16.2%–55.9%. However, among male infants, each 10-fold increase in maternal urinary MECPP, mono‑(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP) and MEOHP in 3rd trimester was associated with 20.8%–36.3% decreased cortisol and cortisone levels, respectively. Conclusion: We have shown that prenatal phthalate exposure during early and late trimester disrupted the infant steroidogenesis and these associations might be modified by infant sex. To the best of our knowledge, this is the first study to evaluate phthalate exposure at three trimesters during pregnancy in relation to infant glucocorticoids. Keywords: Phthalate, Glucocorticoid, Prenatal exposure, Trimester-specific

Background: Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with high production volume worldwide, which exhibit potential health risk to human. To date, little is known about the exposure of BTRs and BTHs (BTs) on human, especially in the context of pregnancy. Objectives: We aimed to characterize the exposure profiles, temporal variability, and potential predictors of urinary BTs during pregnancy. Methods: Between 2014 and 2015, we recruited 856 pregnant women in Wuhan who provided urine samples at three trimesters (13.1 ± 1.1, 23.7 ± 3.2, and 35.7 ± 3.4 gestational weeks). We measured the urinary concentrations of five BTRs (1‑H‑benzotriazole, 1‑hydroxy‑benzotriazole, xylyltriazole, tolyltriazole, 5‑chloro‑1‑H‑benzotriazole) and five BTHs (benzothiazole, 2‑hydroxy‑benzothiazole, 2‑methylthio‑benzothiazole, 2‑amino‑benzothiazole, 2‑thiocyanomethylthio‑benzothiazole) to characterize the exposure profiles of BTs. We calculated the intra-class correlation coefficients (ICCs) to assess the temporal variability and investigated potential predictors of urinary BTs by using the mixed models. Results: Most of the targeted BTs were detected in over 50% of urine samples, except for 5‑chloro‑1‑H‑benzotriazole (9.3%) and 2‑thiocyanomethylthio-benzothiazole (1.4%). The predominant BTRs in urine was 1‑hydroxy‑benzotriazole [Geometric Mean (GM): 0.77 ng/mL]. Benzothiazole was the major derivative in urine samples with a GM concentration of 1.6 ng/mL. Correlations among BTHs (r = 0.04–0.39) were higher than that among BTRs (r = 0.02–0.14). The exposure pattern was constant at low level and co-exposure to all the targeted compounds was infrequent during pregnancy. Urinary concentrations of BTRs exhibited considerable within-subject variation (ICCs: 0.12–0.56) during pregnancy. Relatively high temporal reliability was observed for urinary concentrations of BTHs with ICCs ranging from 0.42 to 0.85. It was found that parity, household income, pregnancy occupational status, sampling season and menstrual cycle were associated with urinary concentrations of BTs in pregnant women (P

Background: Evidence from animal and in vitro studies suggest that some metals interfere with normal platelet counts (PLT). However, limited human studies have investigated the association of metals and PLT, a marker of hematologic and hemostatic, particularly in susceptible populations such as pregnant women. Objectives: Our purpose was to investigate the associations of repeated measures of 13 urinary metals with PLT during pregnancy. Methods: The present study involved 3911 pregnant women participating in a prospective cohort study in Wuhan, China, from 2013 to 2016. We measured 13 metals in urine and PLT in blood samples collected in the first, second, and third trimester (median = 13, 24, and 35 weeks of gestation, respectively). Mixed linear models and general linear models were applied to analyze the associations between multiple metals and PLT during pregnancy. The odds ratio (OR) for gestational thrombocytopenia was examined using generalized estimating equations. Results: After adjusting for other metals and covariates, the repeated measure analyses showed that decreased levels of PLT were associated with a 10-fold increase in urinary concentration of cadmium (Cd) [percent difference (%Δ) = −5.02, 95%CI = −9.53, −0.29], manganese (Mn) [percent difference (%Δ) = −4.63, 95%CI = −7.50, −1.67], and arsenic (As) [percent difference (%Δ) = −4.56, 95%CI = −8.11, −0.86]. Cross-sectional analyses by trimesters revealed that Cd was inversely associated with PLT through the three trimesters. In addition, Cd was associated with an increased OR of 1.80 (95%CI: 1.26, 2.56), 1.65 (95%CI: 1.05, 2.59), 1.54 (95%CI: 1.02, 2.33) for gestational thrombocytopenia in the first, second, and third trimester, respectively. Conclusions: Our study suggested an association of Cd, Mn, and As with decreased PLT during pregnancy. Particularly, Cd may increase the risk of gestational thrombocytopenia. Keywords: Multiple metals, Platelet counts, Gestational thrombocytopenia, Pregnancy

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

Background: Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with potential insulin modulation activities. Pregnancy exposure to BTs (BTRs and BTHs) may be a risk factor for the development of gestational diabetes mellitus (GDM). However, epidemiological studies are limited. Objectives: We prospectively investigated the associations of exposure to BTs at early pregnancy with the blood glucose levels and the risks of GDM. Methods: A prospective cohort of 1770 pregnant women who were free of diabetes at baseline was established between 2013 and 2015 in Wuhan, China. Urine samples collected at 13.1 ± 1.1 weeks of gestation were analyzed to estimate the exposure level of BTs. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) conducted at 26.4 ± 2.4 weeks of gestation. We examined the associations between urinary concentration of BTs and blood glucose levels by linear regression models. The associations of urinary BTs concentrations with the relative risk (RR) of GDM were evaluated by generalized estimating equations with Poisson regression. Effect modifications by fetus sex and pre-pregnancy body mass index (BMI) were further evaluated in the sensitivity analysis. Results:A total of 147 (8.31%) pregnant women were diagnosed with GDM. Median concentrations of urinary BTs did not differ significantly between pregnant women with and without GDM. It was found that urinary levels of benzothiazole and 2-hydroxy-benzothiazole (2-OH-BTH) were positively associated with 2-hour blood glucose (p for trend

Background: 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. Objectives: 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. Method: 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). Results: 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. Conclusions: 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. Keywords: Phthalate metabolites, Child neurodevelopment, Prenatal exposure, Trimester-specific, Cumulative risk assessment

Background: Vanadium, an important pollutant produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in animal studies. However, little is known about its effects on humans. We aimed to assess the association of prenatal exposure to vanadium with the risk of adverse birth outcomes in babies born to women in China. Methods: For this population-based cohort study, the Healthy Baby Cohort, women were recruited from three cities in Hubei Province, China. Women included in this analysis were recruited from Wuhan Women and Children Medical Care Center, Wuhan. We measured urinary concentrations of vanadium and other metals simultaneously using inductively coupled plasma mass spectrometry. We used multivariable logistic regressions, with adjustment for potential confounders, to estimate the associations of natural logarithm transformed creatinine-corrected urinary vanadium (Ln-vanadium) concentrations as continuous variables and categorised into quartiles (Q; Q1: ≤0·84 μg/g creatinine, Q2: 0·84–1·40 μg/g creatinine, Q3: 1·40–2·96 μg/g creatinine, Q4: >2·96 μg/g creatinine, with the lowest quartile set as reference) with preterm delivery, early-term delivery, low birthweight, and being small for gestational age. We applied restricted cubic spline models to evaluate the dose-response relationships. Findings: Data from 7297 women recruited between Sept 22, 2012, and Oct 22, 2014, were included in this study. Urinary Ln-vanadium concentrations showed non-linear dose-response relationships with risk of preterm delivery (S-shaped, p