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.

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.

Associations of cord serum polybrominated diphenyl ether (PBDE) mixture with birth outcomes and mediating role of thyroid function: Evidence from the Sheyang Mini Birth Cohort Study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), a series of worldwide applied flame retardants, may influence fetal growth and interfere with thyroid function. The study intended to explore the relationship between in-utero exposure to PBDE mixture and newborn anthropometric indexes and to further examine the potential mediating role of thyroid function. METHODS: Demographics and laboratory measures of 924 mother-infant pairs were obtained from the database of the Sheyang Mini Birth Cohort Study. We applied gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay to measure nine PBDE congeners and seven thyroid function parameters in umbilical cord serum samples, respectively. We fitted generalized linear models and Bayesian kernel machine regression (BKMR) to evaluate associations of lipid-adjusted cord serum PBDEs, as individuals and as a mixture, with newborn anthropometric and cord serum thyroid function parameters. We applied causal mediation analysis to test our hypothesis that thyroid function parameters act as a mediator between PBDEs and birth outcomes. RESULTS: The molarity of cord serum ∑9PBDE had a median value of 31.23 nmol/g lipid (IQR 19.14 nmol/g lipid, 54.77 nmol/g lipid). BDE-209 was the most dominant congener. Birth length was positively associated with both single exposure to BDE-28 and cumulative exposure to PBDEs. Correspondingly, ponderal index (PI) was negatively associated with BDE-28 and the total effects of PBDE mixture. Free triiodothyronine had a negative trend with BDE-209 and PBDE mixture. In the sex-stratified analysis, BDE-153 concentrations were positively correlated with PI among males (ß = 0.03; 95%CI: 0.01, 0.05; P = 0.01) but not among females. Cord serum thyrotropin mediated 14.92% of the estimated effect of BDE-153 on PI. CONCLUSIONS: In-utero mixture exposure to PBDEs was associated with birth outcomes and thyroid function. Thyroid function might act as a mediator in the process in which PBDEs impact the growth of the fetus.

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.

Effectss of persistent obesity on lung function in school age children / 中国学校卫生

Objective@#To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children.@*Methods@#A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations.@*Results@#The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05).@*Conclusion@#Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

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.

Mediating effect of endocrine hormones on association between per- and polyfluoroalkyl substances exposure and birth size: Findings from sheyang mini birth cohort study.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to affect fetus growth, but current results were inconsistent and their mechanism remained unclear. OBJECTIVES: We aimed to evaluate the associations of prenatal exposure to single and/or multiple PFAS with birth size and to elucidate whether thyroid hormones and reproductive hormones mediate these associations. METHODS: A total of 1087 mother-newborn pairs from Sheyang Mini Birth Cohort Study were included in the present cross-sectional analysis. 12 PFAS, 5 thyroid hormones and 2 reproductive hormones were measured in cord serum. Multiple linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations of PFAS with either birth size or endocrine hormones. One-at-a-time pairwise mediating effect analysis was applied to estimate the mediating effect of single hormone in the association between individual chemical and birth size. High-dimensional mediation approach including elastic net regularization and Bayesian shrinkage estimation were further performed to reduce exposure dimension and figure out the global mediation effects of joint endocrine hormones. RESULTS: Perfluorononanoic acid (PFNA) exposure was positively associated to weight for length z score [WLZ, per log10-unit: regression coefficient (ß) = 0.26, 95% confidence intervals (CI): 0.04, 0.47] and ponderal index (PI, ß = 0.56, 95% CI: 0.09, 1.02), and PFAS mixture results fit by BKMR model showed consistent consequences. High-dimensional mediating analyses revealed that thyroid stimulating hormone (TSH) explained 6.7% of the positive association between PFAS mixtures exposure and PI [Total effect (TE) = 1.499 (0.565, 2.405); Indirect effect (IE) = 0.105 (0.015, 0.231)]. Besides, 7.3% of the PI variance was indirectly explained by 7 endocrine hormones jointly [TE = 0.810 (0.802, 0.819); IE = 0.040 (0.038, 0.041)]. CONCLUSIONS: Prenatal PFAS mixtures exposure, especially PFNA, was positively associated to birth size. Such associations were partly mediated by cord serum TSH.

Prenatal perfluoroalkyl substances exposure and neurodevelopment in toddlers: Findings from SMBCS.

BACKGROUND: Prenatal perfluoroalkyl substances (PFAS) exposure has been reported to affect offspring neurodevelopment, while epidemiological evidences were limited and inconsistent. OBJECTIVES: We aimed to evaluate the associations between cord serum PFAS concentrations and neurodevelopment in toddlers from 1 to 3 years of age. METHODS: A total of 716 children from Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. 12 PFAS concentrations were quantified in cord serum. Neurodevelopment was assessed using the Developmental Screen Test for Children Aged 0-6 Years at 1 year and the Gesell Developmental Schedules (GDS) at 2 and 3 years, respectively. Development quotient (DQ) z-score was standardized from DQ to eliminate the difference caused by two methods. We used generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) to explore the associations of single or mixture PFAS exposure with neurodevelopment measurements at each time point. Associations between PFAS exposure and longitudinal changes in DQ z-score were investigated through generalized estimating equation (GEE) and trajectory analysis. RESULTS: In general, prenatal PFAS concentrations showed negative associations with neurodevelopment measurements at specific age. When accounting for longitudinal changes from 1 to 3 years of age, PFOA was negatively associated with DQ z-score (ß = -0.212, 95% CI: -0.422, -0.003), the association was only found significant in boys after stratified by gender (ß = -0.327, 95% CI: -0.616, -0.038). Meanwhile, increased PFBS (OR = 2.159, 95% CI: 1.177, 3.959) and PFHpA (OR = 1.700, 95% CI: 1.016, 2.846) exposure was associated with elevated odds for the low-score trajectory group. The results of mixture of PFAS further confirmed above findings. CONCLUSIONS: Our findings suggested that prenatal PFAS exposure may be associated with adverse neurodevelopment effects in the first 3 years of life. Further studies are warranted to confirm our findings.

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.

Multiple mediation effects on association between prenatal triclosan exposure and birth outcomes.

BACKGROUND: Triclosan is a broad-spectrum antimicrobial, and was thought to affect intrauterine development, but the mechanism remains unclear. OBJECTIVE: To explore the association between prenatal triclosan exposure and birth outcomes. METHODS: Based on 726 mother-child pairs from the Sheyang Mini Birth Cohort Study (SMBCS), we used the available (published) data of triclosan in maternal urines, the hormones including thyroid-related hormones, gonadal hormones in cord blood, and adipokines, trimethylamine-N-oxide (TMAO) and its precursors in cord blood to explore possible health effects of triclosan on birth outcomes through assessing different hormones and parameters, using Bayesian mediation analysis. RESULTS: Maternal triclosan exposure was associated with ponderal index (ß = 0.317) and head circumference (ß = -0.172) in generalized linear models. In Bayesian mediation analysis of PI model, estradiol (ß = 0.806) and trimethylamine (TMA, ß = 0.164) showed positive mediation effects, while total thyroxine (TT4, ß = -0.302), leptin (ß = -2.023) and TMAO (ß = -0.110) showed negative mediation effects. As for model of head circumference, positive mediation effects were observed in free thyroxine (FT4, ß = 0.493), TMA (ß = 0.178), and TMAO (ß = 0.683), negative mediation effects were observed in TT4 (ß = -0.231), testosterone (ß = -0.331), estradiol (ß = -1.153), leptin (ß = -2.361), choline (ß = -0.169), betaine (ß = -0.104), acetyl-L-carnitine (ß = -0.773). CONCLUSION: The results indicated triclosan can affect intrauterine growth by interfering thyroid-related hormones, gonadal hormones, adipokines, TMAO and its precursors.

Urinary para-nitrophenol levels of pregnant women and cognitive and motor function of their children aged 2 years: Evidence from the SMBCS (China).

BACKGROUND: Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general population even after global restriction for years. And the concern whether there is an association of PNP level with child development of the nervous system is increasing. The current study aimed to evaluate the maternal urinary PNP concentrations during late pregnancy and the associations of PNP levels with cognitive and motor function of their children at the age of 2 years. METHODS: 323 mother-child pairs from the Sheyang Mini Birth Cohort Study were included in the current study. Gas chromatography-tandem mass spectrometry was used to measure concentrations of PNP, the specific metabolite of EP and MP, in maternal urine samples during pregnancy. Developmental quotients (DQs) scores measured with Gesell Developmental Scales were employed to evaluate cognitive and motor function of children aged 2 years. Generalized linear models were performed to analyze the associations of PNP concentrations in pregnant women's urine samples with cognitive and motor function of their children. RESULTS: Maternal PNP was detected in all urine samples with a median of 4.11 µg/L and a range from 0.57 µg/L to 109.13 µg/L, respectively. Maternal urinary PNP concentrations showed a negative trend with DQ of motor area [regression coefficient (ß) = - 1.35; 95 % confidence interval (95 %CI): - 2.37, - 0.33; P < 0.01], and the children whose mothers were in the fourth quartile exposure group performed significantly worse compared to the reference group (ß = - 1.11; 95 %CI: - 1.80, - 0.42; P < 0.01). As for average DQ score, children with their mothers' urinary PNP concentrations in the third quartile group had higher scores than those in the first quartile group (ß = 0.39; 95 %CI: 0.03, 0.75; P = 0.04). In sex-stratified analyses, a negative trend between maternal urinary PNP concentrations and DQ scores in motor area of children was only observed in boys (ß = - 1.62; 95 %CI: - 2.80, - 0.43; P < 0.01). Boys in the third quartile group had higher DQ average scores than those in the lowest quartile as reference (ß = 0.53; 95 %CI: 0.02, 1.04; P = 0.04). CONCLUSIONS: The mothers from SMBCS may be widely exposed to EP and/or MP, which were associated with the cognitive and motor function of their children aged 2 years in a sex-specific manner. Our results might provide epidemiology evidence on the potential effects of prenatal exposure to EP and/or MP on children's cognitive and motor function.

Associations of Diet with Urinary Trimethylamine-N-Oxide (TMAO) and Its Precursors among Free-Living 10-Year-Old Children: Data from SMBCS.

Trimethylamine-N-oxide (TMAO), a diet-derived cometabolite linked to cardiometabolic disease, has been associated with elevated dietary status, particularly in people with kidney failure and adults with dietary modulations. However, the influence of the current diet on TMAO levels in free-living children has not been adequately described. This study was to explore associations of food compositions and dietary diversity with urinary TMAO and its precursor concentrations. Urinary TMAO and its precursor concentrations of 474 healthy children from the Sheyang Mini Birth Cohort were quantified by ultra-performance liquid chromatography−Q Exactive high-resolution mass spectrometer (UPLC-Q Exactive HRMS). Individual food compositions from 24 h dietary recall data were classified into 20 groups and diversity scores were calculated according to the guidelines of the Food and Agriculture Organization of the United Nations (FAO). Associations of urinary TMAO and its precursors with food compositions and dietary diversity scores were assessed by generalized linear regression models. In models adjusted for potential confounders, urinary TMAO was significantly associated with intakes of fish (ß, regression coefficient = 0.155, p < 0.05) and vegetables (ß = 0.120, p < 0.05). Eggs intake showed positive associations with TMAO's precursors (trimethylamine: ß = 0.179, p < 0.05; choline: ß = 0.181, p < 0.05). No association between meat intake and TMAO was observed, whereas meat and poultry intakes were related to the levels of acetyl-L-carnitine and L-carnitine (ß: 0.134 to 0.293, p < 0.05). The indicators of dietary diversity were positively correlated to TMAO concentration (ß: 0.027 to 0.091, p < 0.05). In this free-living children-based study, dietary factors were related to urinary TMAO and its precursors, especially fish, meat, and eggs. As such, dietary diversity was positively related to the level of TMAO.

Prenatal exposure to parabens in association with cord serum adipokine levels and offspring size at birth.

BACKGROUND: Paraben exposure is linked to the release of adipokine such as leptin and adiponectin, and both paraben and adipokine may affect fetal growth. The present study aimed to explore the associations among maternal paraben exposure, adipokine level and offspring size. METHODS: 942 mother-newborn pairs from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. Data of birth weight, length, head circumference and ponderal index (PI) were obtained from medical records. Maternal urinary parabens were determined by gas chromatography tandem mass spectrometry. Cord serum leptin and adiponectin were measured using ELISA assay. Generalized linear regression was applied to explore the associations among parabens, adipokines and offspring size. RESULTS: The median levels of leptin and adiponectin were 13.13 µg/L and 161.82 µg/mL. Benzylparaben level was positively associated with leptin (regression coefficient (ß) = 0.06, 95% confidence interval (CI): 0.03-0.09; p < 0.01). Leptin level was positively associated with neonatal weight (ß = 84.11, 95% CI: 63.22-105.01; p < 0.01), length (ß = 0.25, 95% CI: 0.14-0.37; p < 0.01), head circumference (ß = 0.15, 95% CI: 0.07-0.22; p < 0.01) and PI (ß = 0.23, 95% CI: 0.08-0.39; p < 0.01). Adiponectin was positively associated with neonatal weight (ß = 75.94, 95% CI: 29.65-122.23; p < 0.01) and PI (ß = 0.43, 95% CI: 0.09-0.77; p = 0.01). Urinary propylparaben concentration (ß = -0.10, 95% CI: -0.17 to -0.02; p = 0.01) was negatively associated with head circumference. Sex-stratified analyses indicated the negative association of propylparaben and head circumference was only remained in male neonates. CONCLUSIONS: Prenatal paraben exposure might affect cord serum leptin levels. Both paraben and adipokine levels may affect fetal growth, and sex-specific differences may exist.

Carbamate pesticides exposure and delayed physical development at the age of seven: Evidence from the SMBCS study.

BACKGROUND: Carbamate pesticides are widely used in agriculture and cause widespread human exposure. The health effect of carbamates on physical development remains unclear. The current study aimed to explore the carbamate's health effect on physical development. METHODS: Prenatal, 3-year-old, 7-year-old urinary carbofuranphenol concentration was measured by gas chromatography tandem mass spectrometry and adjusted by creatinine. Anthropometric indices were measured by standard method and z-score standardized. Generalized linear models (GLM) were using to assess associations between exposure measurements and anthropometric indices. The generalized estimate equation (GEE) was applied to analyze the association between multiperiod exposure and anthropometric indices, and time-interaction terms were used to exam health effect consistency of exposure in each period. Gender-stratified analysis were conducted according to results of gender-interaction terms to identify gender-specific effects. RESULTS: The gender-interaction term of prenatal exposure with height z-score was significant (ß = -0.057; 95% CI: -0.113, -0.001; p = 0.045). The 3-year-old carbofuranphenol level showed negative associations with weight z-score (ß = -0.019; 95% CI: -0.038, -0.000; p = 0.040), height z-score (ß = -0.015; 95% CI: -0.028, -0.001; p = 0.026), chest circumference (ß = -0.086; 95% CI: -0.171, -0.001; p = 0.046), and waist circumference (ß = -0.128; 95% CI: -0.230, -0.026; p = 0.014). No statistically significant trend was found for prenatal and 7-year-old carbofuranphenol levels. In GEEs, carbofuranphenol level was negatively associated with weight z-score (ß = -0.103; 95% CI: -0.195, -0.011; p = 0.027), height z-score (ß = -0.087; 95% CI: -0.152, -0.022; p = 0.008), and chest circumference (ß = -0.472; 95% CI: -0.918, -0.026; p = 0.037). Boy's height z-score was inversely associated with carbamate exposure (ß = -0.140; 95% CI: -0.227, -0.053; p = 0.001). CONCLUSIONS: Prenatal and postnatal carbamate exposure may affect physical developmental process.

Cord Blood Manganese Concentrations in Relation to Birth Outcomes and Childhood Physical Growth: A Prospective Birth Cohort Study.

Gestational exposure to manganese (Mn), an essential trace element, is associated with fetal and childhood physical growth. However, it is unclear which period of growth is more significantly affected by prenatal Mn exposure. The current study was conducted to assess the associations of umbilical cord-blood Mn levels with birth outcomes and childhood continuous physical development. The umbilical cord-blood Mn concentrations of 1179 mother-infant pairs in the Sheyang mini birth cohort were measured by graphite furnace atomic absorption spectrometry (GFAAS). The association of cord-blood Mn concentrations with birth outcomes, and the BMI z-score at 1, 2, 3, 6, 7 and 8 years old, were estimated separately using generalized linear models. The relationship between prenatal Mn exposure and BMI z-score trajectory was assessed with generalized estimating equation models. The median of cord-blood Mn concentration was 29.25 µg/L. Significantly positive associations were observed between Mn exposure and ponderal index (ß, regression coefficient = 0.065, 95% CI, confidence interval: 0.021, 0.109; p = 0.004). Mn exposure was negatively associated with the BMI z-score of children aged 1, 2, and 3 years (ß = -0.383 to -0.249, p < 0.05), while no significant relationships were found between Mn exposure and the BMI z-score of children at the age of 6, 7, and 8 years. Prenatal Mn exposure was related to the childhood BMI z-score trajectory (ß = -0.218, 95% CI: -0.416, -0.021; p = 0.030). These results indicated that prenatal Mn exposure was positively related to the ponderal index (PI), and negatively related to physical growth in childhood, which seemed most significant at an early stage.

Umbilical cord serum perfluoroalkyl substance mixtures in relation to thyroid function of newborns: Findings from Sheyang Mini Birth Cohort Study.

BACKGROUND: The epidemiological evidence on the associations between prenatal exposure to perfluoroalkyl substances (PFAS) and thyroid hormones in newborns was inconclusive. OBJECTIVES: We aimed to estimate associations of fetal exposure to PFAS individually and in mixtures with thyroid function of newborns. METHODS: A total of 490 mother-newborn pairs were included from Sheyang Mini Birth Cohort Study (SMBCS), a prospective cohort that recruited between June 2009 and January 2010. 12 PFAS and 7 thyroid function indicators were quantified in umbilical cord serum. We examined associations of prenatal exposure to individual and a mixture of PFAS with thyroid function indicators using multivariable linear regression and weighted quantile sum (WQS) regression models with adjustment for potential confounders, respectively. RESULTS: Higher cord serum concentrations of PFAS mixtures were related to increases in TT4 and FT4 levels, and reductions in TSH concentrations of newborns. Combining single-chemical models with multiple-chemical models, PFOS, PFNA and PFUnDA were associated with increased TT4 levels with contributing to the mixture effects of 46.4%, 22.8%, and 16.7%, respectively. PFOS exposure was in positive association with cord serum FT4 concentrations and contributed 28.9% to the joint effects of mixtures. PFNA and PFHpA were the most important contributors to the decreases of TSH levels of newborns with 46.3% and 45.0% among the mixtures, respectively. CONCLUSIONS: The current findings indicated the thyroid disruption of individual PFAS and their mixtures in cord serum. Additional studies are warranted to explore the underlying biological mechanisms, particularly for PFAS mixtures.

Prenatal exposure to multiple phenolic compounds, fetal reproductive hormones, and the second to fourth digit ratio of children aged 10 years in a prospective birth cohort.

Select phenols are known to possess hormone-disrupting properties, but no previous study has addressed the potential effects of prenatal exposure to phenol mixtures on fetal reproductive hormones and children's second to fourth digit (2D: 4D) ratio, a marker for in utero testosterone (T) exposure. We aimed to explore interrelations of prenatal phenol exposures individually and in mixtures, cord serum reproductive hormones, and 2D: 4D ratio of children aged 10 years. Urinary 11 phenol concentrations were determined from 392 pregnant women participating in a longitudinal birth cohort. We estimated associations of prenatal phenol exposures individually and in mixtures with cord reproductive hormones and children's 2D:4D ratio using three statistical approaches, including generalized linear models (GLMs), elastic net regression (ENR) models and Bayesian kernel machine regression (BKMR) models. In female newborns, the three models showed that maternal triclosan (TCS) concentrations were significantly negatively associated with cord serum T levels [regression coefficient (ß) = -0.076, 95% confidence interval (CI): 0.138, -0.013; p = 0.018]. Additionally, maternal urinary bisphenol A (BPA) levels were related to decreases in 2D:4D ratio of the left hand in girls by GLMs (ß = -0.003, 95% CI: 0.007, -0.001; p = 0.024) and ENR models, but not BKMR models. We provided evidence that prenatal TCS exposure predicted lower cord serum T levels, and maternal BPA exposure was related to decreased 2D:4D ratio of the left hand in females.

Dietary diversity and determinants among left behind children in rural area / 中国学校卫生

Objective@#To evaluate the status of dietary diversity and determinants among school age left behind children.@*Methods@#A total of 501 children aged 9-10 years in Sheyang Mini Cohort Study were enrolled from Sheyang City in Jiangsu Province during 2019. A questionnaires survey was administrated to collect left behind and socioeconomic information. Twenty four hour dietary recall survey was conducted, dietary diversity score (DDS 10 and DDS) and food variety score (FVS) were computed according to Food and Agriculture Organization (FAO). Weight and height of children were measured and sex and age standardized body mass index was used to define obesity. Multivariable regression models were preformed to explore the determinants of dietary diversity in school age left behind children.@*Results@#The proportion of left behind children was 40.9%. The mean value and standard deviation of three kinds of dietary diversity score (DDS 10 , DDS, FVS) in left behind children were (5.69±1.31)(6.55±1.44) and (13.48± 4.23 ), respectively. All of these were lower than that in non left behind children (DDS 10 :5.99±1.29; DDS:6.79±1.40; FVS:14.15±4.22). Significant difference in DDS 10 between left behind and non left behind children was observed ( P =0.01). The results of multivariable regression demonstrated that gender, passive smoking, family education level and family economic status were related to dietary diversity scores ( P <0.05).@*Conclusion@#Dietary diversity in school age left behind children was not optimistic and gender, passive smoking, parental education level, family economic status and left behind situation play a critical role in dietary diversity among these children.

Early-life carbamate exposure and intelligence quotient of seven-year-old children.

BACKGROUND: Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention. METHODS: Three hundred and three children at age of seven were included in the current study. Urinary carbofuranphenol concentrations were measured using gas chromatography-tandem mass spectrometry. Verbal, performance and full-scale intelligence quotients (IQV, IQP, and IQFS) were assessed using Wechsler Intelligence Scale for Children-Chinese Revised. Generalized linear models were used to explore the associations between carbofuranphenol levels and IQs. Generalized estimating equations were used to explore long-term health effect and sensitive time window. RESULTS: Carbofuranphenol was detected in 96.6% of the seven-year-old urinary samples, the geometric mean, median, and inter quartile range of the carbofuranphenol concentrations were 0.67 µg/L, 0.30 µg/L, and 0.09-3.72 µg/L, respectively, which were similar with the level of three-year-old children from the SMBCS cohort. Seven-year-old carbofuranphenol level was negatively associated with IQP [ß = -0.044; 95% confidence interval (CI): -0.087, -0.001; p = 0.045]. Three-year-old carbofuranphenol level was negatively associated with IQP (ß = -0.100; 95% CI: -0.186, -0.014; p = 0.022) and IQFS (ß = -0.087; 95% CI: -0.173, -0.001; p = 0.047). Carbamate exposure of maternal and children at both three and seven years old had negative associations with IQP (ß = -0.089; 95% CI: -0.171, -0.007; p = 0.034), and IQFS (ß = -0.064; 95% CI: -0.127, -0.000; p = 0.049) of children at age of seven. CONCLUSION: Results of the present study verify that children in an agricultural region of China were widely exposed to carbamate pesticides. Carbamate exposure in utero and at three and seven years may adversely impact children's neurodevelopment.

Umbilical cord serum PBDE concentrations and child adiposity measures at 7 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment. Toxicological studies suggested PBDEs may interfere with adipogenic pathways. However, few human evidence addressed PBDE exposures in utero related to childhood adiposity. OBJECTIVE: We assessed associations between PBDEs concentrations in cord serum and childhood adiposity measures at 7 years. METHODS: Among 318 mother-child pairs from Sheyang Mini Birth Cohort Study (SMBCS) in China, nine PBDE congener concentrations were quantified in umbilical cord serum using gas chromatography-negative chemical ionization mass spectrometry (GC-NCI-MS). Anthropometric indicators of children aged 7 years were measured, including weight, height and waist circumference. Age and sex-specific body mass index (BMI) z scores were calculated based on World Health Organization (WHO)'s child growth standards. Multivariate linear and logistic regression models adjusted for putative confounders were performed to examine associations between PBDE congeners and adiposity parameters. RESULTS: BDE-209 was the most abundant congener of PBDEs with a median value of 19.5 ng/g lipid. The geometric mean values of nine PBDE congeners ranged from below limit of detection (LOD) to 18.1 ng/g lipid, and the detection rates were 46.5%~96.5%. Cord serum BDE-153 and BDE-154 concentrations were associated with lower childhood BMI z score (regression coefficient, ß=-0.15, 95% confidence interval: -0.29, -0.02; p=0.02; ß=-0.23, 95%CI: -0.43, -0.03; p=0.03, respectively) and lower waist circumference (ß=-0.75 cm, 95%CI: -1.43, -0.06; p=0.03; ß=-1.22 cm, 95%CI: -2.23, -0.21; p=0.02, respectively), after controlling for potential confounders. Moreover, prenatal BDE-154 exposure was related to a decreased obesity risk of children aged 7 years (odds ratio, OR=0.46, 95%CI: 0.22, 0.94; p=0.03). These effects were only observed among boys in sex-straitified analyses. CONCLUSIONS: Cord serum BDE-153 and BDE-154 concentrations were related to reduced adiposity measures at 7 years of age. Further evidence regarding the impacts of prenatal PBDE exposures on childhood development is warranted.