Sex-specific associations of per- and polyfluoroalkyl substances with brain-derived neurotrophic factors (BDNF) in cord serum.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration. OBJECTIVE: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum. METHODS: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis. RESULTS: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 µg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (ß: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches. CONCLUSIONS: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific.

Associations of prenatal and concurrent exposure to phenols mixture with anthropometric measures and blood pressure during childhood: A time-varying mixture approach.

BACKGROUND: Environmental phenols were recognized as endocrine disrupting chemicals (EDCs). However, their impact on childhood anthropometric measures and blood pressure (BP) is still inconclusive. Limited studies have simultaneously considered prenatal and childhood exposures in analyzing mixtures of phenols. OBJECTIVE: We investigated the relationships between combined prenatal and childhood exposures (two periodic exposures) to phenol mixtures and anthropometric measure and BP, to further identify the vulnerable periods of phenol exposure and to explore the important individual contribution of each phenol. METHODS: We analyzed 434 mother-child dyads from the Sheyang Mini Birth Cohort Study (SMBCS). The urinary concentrations of 11 phenolic compounds were measured using gas chromatography tandem mass spectrometry. Generalized linear regression models (GLMs) and hierarchical Bayesian Kernel Machine Regression (hBKMR) were used to examine the effects of individual phenolic compounds at each period and of two periodic exposures. RESULTS: In the single-chemical analysis, prenatal or childhood exposure to specific phenols, especially Benzopheone-3 (BP3), 4-tert-Octylphenol (4-tOP), and Benzyl paraben (BePB) were associated with BMI z-scores (BAZ), Waist-to-height ratio (WHtR), and BP. In the hBKMR models, two periodic exposures to phenol mixtures had a U-shaped association with WHtR, primarily driven by childhood BePB exposure. Moreover, among the phenol mixtures analysis, childhood 4-tOP exposure was identified as the primary contributor to the positive association with diastolic BP. Concurrent exposure to phenol mixtures resulted in greater susceptibility. CONCLUSIONS: We found that prenatal and childhood exposure to phenol mixtures might influence childhood obesity and elevate blood pressure levels. Concurrent exposure to 4-tOP may be the primary driver of the positive associations with BP.

Quantitative PCR-based high-sensitivity detection of HBV-DNA levels reflects liver function deterioration in patients with hepatitis B virus-related cirrhosis.

OBJECTIVES: To investigate the clinical implication of quantitative polymerase chain reaction (PCR)-based high-sensitivity detection of hepatitis B virus (HBV)-DNA levels in patients with HBV-related liver cirrhosis (LC). METHODS: From January 2020 to December 2022, 100 fasting serum samples were collected and retrospectively analyzed from patients with treated HBV-related LC attending the Suzhou Hospital of Integrated Traditional Chinese and Western Medicine and Suzhou Guangci Cancer Hospital. Patients were divided into a negative group (HBV-DNA < 20 IU/mL) and a positive group (HBV-DNA ≥ 20 IU/mL) according to their high-sensitivity HBV-DNA test results. The clinical characteristics and serological indicators of the two groups were compared, mainly including gender, age, liver function [total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL)], lipids [total cholesterol (TC) and triglycerides (TG)], platelets (PLT), five serum liver fibrosis markers [cholyglycine (CG), hyaluronic acid (HA), laminin (LN), precollagen type III (PCIII), and type IV collagen (IV-C)], serum gastrointestinal tumor markers [α-fetoprotein (AFP) and carcinoembryonic antigen (CEA)], and hepatitis B surface antigen (HBsAg). The differences between the two groups in terms of liver function Child-Pugh grades and the incidence of hepatocellular carcinoma (HCC) were also compared. RESULTS: There were 39 patients in the positive group, including 29 males and 10 females, and 61 patients in the negative group, including 38 males and 23 females, with no statistically significant differences in gender and age distribution between the two groups (P > 0.05). The levels of serological indicators (TP, ALB, AST, GGT, ALP, TBIL, DBIL, IBIL, TC, TG, PLT, CG, HA, LN, PCIII, IV-C, AFP, CEA, and HBsAg) in both groups showed no significant differences (P > 0.05), but the ALT level in the positive group was higher than that in the negative group (P < 0.0001). The positive group had worse Child-Pugh grades and higher HCC incidence compared to the negative group (P < 0.0001, P = 0.028). CONCLUSIONS: Patients with HBV-related LC and HBV-DNA ≥ 20 IU/mL have higher serum ALT levels, worse liver function Child-Pugh grades, and higher HCC incidence than those with HBV-DNA < 20 IU/mL. High-sensitivity HBV-DNA quantification can reflect the deterioration of liver function in patients with HBV-related LC to some extent.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. OBJECTIVES: This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. METHODS: The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. RESULTS: The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (ß = -6.21, 95 % confidence interval [CI]: -12.21, -0.21), with more pronounced associations observed among girls (ß = -9.57, 95 % CI: -18.33, -0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. CONCLUSIONS: Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

Simultaneous determination of twelve neonicotinoids and six metabolites in human urine with isotope-dilution UPLC-Q-Orbitrap HRMS.

The extensive global use of neonicotinoid insecticides (NNIs) has led to widespread human exposure, necessitating the development of effective methods for large-scale biomonitoring. However, current methods are inadequate in simultaneously and accurately detecting various NNIs or their metabolites (m-NNIs). In this study, we aimed to establish a robust method using solid-phase extraction (SPE)-ultra high performance liquid chromatography tandem Q-Orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) for the simultaneous determination of 12 NNIs and 6 m-NNIs in human urine. Samples were prepared using Oasis HLB 96 well plate with Isopropanol: methanol (7:3, v/v) as the elution solvent. The target compounds were separated using the Accucore RP-MS column and subsequently analyzed under parallel reaction monitoring mode. NTN32692 (m/z = 255.06433) was confirmed to be the specific metabolite of cycloxaprid for the further detection. Satisfactory recoveries (81.6-122.4 %) of the NNIs and m-NNIs were observed, with intra- (n = 3) and inter-day (n = 9) relative standard deviation (RSD) ranging from 0.8 % to 13.7 % and from 1.1 % to 18.6 %, respectively. Good linearity (R2 > 0.99) was achieved for all analytes. The limits of detection (LODs) for all target analytes ranged from 0.01 ng/mL to 0.65 ng/mL. This method was applied to urine samples collected from 10 children recruited from an agricultural area in China. Our study provides an effective method to identify and assess human exposure to NNIs and their metabolites.

Sex-specific associations of maternal and childhood urinary arsenic levels with emotional problems among 6-year-age children: Evidence from a longitudinal cohort study in China.

BACKGROUND: Arsenic exposure has been linked to neurobehavior development disorders among children in cross-sectional studies, but there is little information on the effects of prenatal and childhood arsenic exposure on childhood behavior problem, especially emotional problems. OBJECTIVE: To explore the relationship between prenatal and childhood arsenic exposure and behavior problems among six-year-old children. METHODS: 389 mother-child pairs from a longitudinal birth cohort were enrolled in the study. The concentrations of arsenic in maternal and 6-year-old children's urine were measured using inductively coupled plasma mass spectrometry (ICP-MS). Neurobehavioral development in 6-year-old children was assessed by Child Behavior Checklist (CBCL). Generalized linear regression models were used to relate arsenic exposure to the score of different domains in CBCL. RESULTS: The median concentrations of maternal and 6-year-old children's urinary arsenic were 22.22 and 33.86 µg/L, respectively. After adjusting for potential covariates, natural logarithm transformed concurrent urinary arsenic levels were significantly associated with scores of anxious and depressed problems in 6-year-old girls (ß = 0.71, 95% CI: 0.12-1.31, p = 0.018). Furthermore, in terms of the trajectory of arsenic exposure, compared with the "consistently low" group, the "low to high" group (ß = 2.73, 95% CI: -3.99 to 9.45, p = 0.425) had a greater effect on total score of CBCL than "high to low" group (ß = -0.93, 95% CI: -7.22 to 5.36, p = 0.771) in girls, although insignificant. CONCLUSIONS: Our results suggested that concurrent arsenic exposure might have an adverse effect of emotional status in girls. Further studies are needed to verify the findings and explore the mechanisms of the sex-specific association.

Per- and polyfluoroalkyl substances in umbilical cord serum and body mass index trajectories from birth to age 10 years: Findings from a longitudinal birth cohort (SMBCS).

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to low birth weight but higher childhood weight and obesity. However, little is known regarding the associations between PFAS exposure and dynamic body mass index (BMI) trajectories, particularly from birth through preadolescence. OBJECTIVE: To evaluate the associations of cord serum PFAS concentrations with BMI trajectories from birth to age 10 years and longitudinal BMI in different periods. METHODS: Based on 887 mother-child pairs in the longitudinal prospective birth cohort, we measured 12 PFAS congeners in cord serum and calculated BMI with anthropometric indicators at 9 follow-up time points from birth to age 10 years. The BMI trajectories were identified using group-based trajectory model (GBTM). To estimate the associations of cord serum PFAS levels with BMI trajectories and longitudinal changes in BMI, logistic regression models, linear mixed models, Bayesian kernel machine regression, and quantile-based g-computation models (QGC) were used. RESULTS: The median concentrations of 10 PFAS congeners included in statistical analysis ranged from 0.047 to 3.623 µg/L. Two BMI trajectory classes were identified by GBTM, characterized by high group and low group. In logistic regression models, five PFAS congeners (PFBA, PFHpA, PFHxS, PFHpS, and PFDoDA) were associated with the higher probability of being in high BMI trajectory group (odds ratio, OR: 1.21 to 1.74, p < 0.05). Meanwhile, higher PFAS mixture were related to elevated odds for the high group in both BKMR models and QGC models, with PFHpA and PFHpS being the two most important drivers jointly. In the sex-stratified analysis, the positive associations remained significant exclusively among males. In the longitudinal analysis, PFUnDA and PFDoDA were associated with increased BMI from birth to age 10 years. Furthermore, PFBS and PFHpA were negatively related to BMI throughout infancy and toddlerhood (from birth to age 3 years), whereas PFDoDA confirmed a positive association with mid-childhood (from age 6 to 10 years) BMI. CONCLUSIONS: Prenatal PFAS exposure was positively associated with BMI trajectories from birth to preadolescence and longitudinal BMI in various periods. Future research could use better trajectory modeling strategies to shape more complete growth trajectories and explore the relationship between BMI trajectories and adulthood health.

Associations of perfluoroalkyl substances with adipocytokines in umbilical cord serum: A mixtures approach.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), a kind of emerging environmental endocrine disruptors, may interfere with the secretion of adipokines and affect fetal metabolic function and intrauterine development. However, the epidemiological evidence is limited and inconsistent. We examined the associations of single and multiple PFAS exposures in utero with adipocytokine concentrations in umbilical cord serum. METHODS: This study included 1111 mother-infant pairs from Sheyang Mini Birth Cohort Study (SMBCS), and quantified 12 PFAS and two adipokine in umbilical cord serum. Generalized linear models (GLMs) and Bayesian Kernel Machine Regression (BKMR) models were applied to estimate the associations of single- and mixed- PFAS exposure with adipokines, respectively. Furthermore, sex-stratification was done in each model to assess the sexually dimorphic effects of PFAS. RESULTS: 10 PFAS were detected with median concentrations (µg/L) ranging from 0.04 to 3.97, (except 2.7% for PFOSA and 1.7% for PFDS, which were excluded). In GLMs, for each doubling increase in PFBS, PFHpA, PFHxS, PFHpS, PFUnDA and PFDoDA, leptin decreased between 14.04% for PFBS and 22.69% for PFHpS (P < 0.05). PFAS, except for PFNA, were positively associated with adiponectin, and for each doubling of PFAS, adiponectin increased between 3.27% for PFBS and 12.28% for PFHxS (P < 0.05). In addition, infant gender modified the associations of PFAS with adipokines, especially the associations of PFBS, PFOA and PFHxS with adiponectin. Similarly, significant associations of PFAS mixtures with leptin and adiponectin were observed in the BKMR models. PFDA, PFOS, PFNA and PFHpS were identified as important contributors. In the sex-stratified analysis of BKMR models, the associations between PFAS mixtures and adipokines were more pronounced in males. CONCLUSIONS: PFAS levels were significantly associated with adipokines in cord serum, suggesting that intrauterine mixture of PFAS exposure may be related to decreased fetal leptin level but increased fetal adiponectin level and the associations may be sex-specific.