Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study.

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 < 0.05). CONCLUSION: Our results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.

Synergy between nanoplastics and benzo[a]pyrene promotes senescence by aggravating ferroptosis and impairing mitochondria integrity in Caenorhabditis elegans.

Micro-nano plastics have been reported as important carriers of polycyclic aromatic hydrocarbons (PAHs) for long-distance migration in the environment. However, the combined toxicity from long-term chronic exposure beyond the vehicle-release mechanism remains elusive. In this study, we investigated the synergistic action of Benzo[a]pyrene (BaP) and Polystyrene nanoparticles (PS) in Caenorhabditis elegans (C. elegans) as a combined exposure model with environmental concentrations. We found that the combined exposure to BaP and PS, as opposed to single exposures at low concentrations, significantly shortened the lifespan of C. elegans, leading to the occurrence of multiple senescence phenotypes. Multi-omics data indicated that the combined exposure to BaP and PS is associated with the disruption of glutathione homeostasis. Consequently, the accumulated reactive oxygen species (ROS) cannot be effectively cleared, which is highly correlated with mitochondrial dysfunction. Moreover, the increase in ROS promoted lipid peroxidation in C. elegans and downregulated Ferritin-1 (Ftn-1), resulting in ferroptosis and ultimately accelerating the aging process of C. elegans. Collectively, our study provides a new perspective to explain the long-term compound toxicity caused by BaP and PS at real-world exposure concentrations.

Intrauterine chromium exposure and cognitive developmental delay: The modifying effect of genetic predisposition.

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children's cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child's cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one's adverse genetic background jointly contribute to an increased risk of CDD in children.

Low-grade systemic inflammation links heavy metal exposures to mortality: A multi-metal inflammatory index approach.

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (ß = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Prenatal arsenic metabolite exposure is associated with increased newborn mitochondrial DNA copy number: evidence from a birth cohort study.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether maternal urinary arsenic metabolite levels in different trimesters were related to neonatal cord blood mtDNAcn. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters. We determined cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each one-unit increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the third trimester was related to 8.43% (95% CI 1.13%, 16.26%) and 12.15% (95% CI 4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the third trimester with mtDNAcn (DMA percent changes (%Δ) = 25.60 (95% CI 6.73, 47.82), for the highest vs the lowest tertile (P = 0.02); TAs %Δ = 40.31 (95% CI 19.25, 65.10), for the highest vs the lowest tertile (P = 0.0002)). These findings may prove the relationships between prenatal arsenic species levels and neonatal mitochondrial dysfunction.

Associations of multiple hydroxy-polycyclic aromatic hydrocarbons with serum levels of lipids in the workers from coking and non-ferrous smelting industries.

Epidemiological evidence indicates that exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with certain metabolic diseases. However, the relationship between PAHs and serum lipid profiles in exposed subjects remain unknown. Herein, the associations of multiple (8) urinary hydroxylated PAHs (OH-PAHs) in workers of coking (n = 655) and non-ferrous smelting (n = 614) industries with serum lipid levels (marking lipid metabolism) were examined. Multivariable linear regression, Bayesian kernel machine regression, and quantile g-computation were used. Most urinary OH-PAHs were significantly higher (p < 0.001) in coking workers than in non-ferrous smelting workers. In workers of both industries, OH-PAH exposure was associated with elevated levels of serum total cholesterol, total triglyceride, and low-density lipoprotein, as well as reduced high-density lipoprotein levels. Specifically, urinary 4-hydroxyphenanthrene was significantly positively associated with serum total cholesterol, total triglyceride, and low-density lipoprotein levels in non-ferrous smelting workers; however, the completely opposite association of 4-hydroxyphenanthrene with these lipid levels was observed in coking workers. The results of this pioneering examination suggest that exposure to OH-PAHs may contribute to dyslipidemia in coking and non-ferrous smelting workers, and distinct patterns of change were observed. Further prospective studies involving larger sample sizes are needed to further validate the findings.

Metabolic signatures of prenatal exposure to 'Cocktails' of benzotriazoles and benzothiazoles and its health implications.

Prenatal exposure to benzotriazoles and benzothiazoles (collectively as BTs) was associated with pregnancy complications. Identifying the metabolites associated with prenatal BTs exposure may help elucidate the mechanism and characterize the exposure risk. In this prospective study of 158 pregnant women from Wuhan, China, urinary BTs were repeatedly measured across three trimesters to provide an accurate estimation of exposure during pregnancy. We conducted high-throughput targeted metabolomics with great coverage and high accuracy to characterize the urinary metabolic profile in late pregnancy. We first identified the perturbed metabolites of cocktail BTs exposure and then pinned down to the pairwise associations between individual BTs and the identified metabolites. A total of 44 metabolites were identified as perturbed biomarkers of cocktail BTs exposure based on the variable influence on projection (VIP > 1.2) score. Further pairwise associations analysis showed positive association of BTs with oxidative stress related biomarkers and negative association of BTs with neuronal function metabolites. The shared metabolic signatures among BTs in the co-occurrence network of pairwise association analysis may partially be attributed to the correlation among cocktail BTs exposure. The findings provide the potential mechanisms of BTs-associated pregnancy complications and offer insight into the health implications for prenatal BTs exposure. Furthermore, the framework we employed, which integrates both cocktail exposure and individual exposure, may illuminate future epidemiological research that seeks to incorporate exposure to mixtures and omics scale data.

First-trimester fetal size, accelerated growth in utero, and child neurodevelopment in a cohort study.

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 < 0.01) at age 2 years, respectively. No significant association was observed between fetal growth rate and PDI. For children with restricted first-trimester fetal size (the lowest tertile of first-trimester CRL), those with "intrauterine accelerated growth" pattern (higher growth rates) had significantly higher MDI (adjusted beta estimate = 6.14, (95% CI: 3.80, 8.49), P < 0.001) but indistinguishable PDI compared to those with "intrauterine faltering growth" pattern (lower growth rates). Main limitations of this study included potential misclassification of gestational age due to recall bias of the last menstrual period and residual confounding. CONCLUSIONS: The current study suggests that restricted first-trimester fetal size is associated with mental and psychomotor developmental delay in childhood. However, in children with restricted first-trimester fetal size, intrauterine accelerated growth was associated with improved mental development but had little effect on psychomotor development. Additional studies are needed to validate the results in diverse populations.

Associations of pentachlorophenol exposure during pregnancy with maternal and infant reproductive hormones based on a birth cohort.

Pentachlorophenol (PCP), a typical environmental endocrine disruptor and a new persistent organic pollutant, has been extensively used as a pesticide worldwide. Although its use has been restricted for decades, PCP remains prevalent in both the environment and human bodies. Despite the known endocrine-disrupting and exogenous hormonal effects of PCP, few epidemiological studies examined such impact, especially among sensitive populations and during critical periods. Based on a prospective birth cohort in Wuhan, China, we collected maternal (first trimester; 13.0 ± 1.02 gestational weeks) and infant urine samples (1.16 ± 0.22 months postpartum) from 720 mother-infant pairs. We aimed to examine the association of PCP exposure during early pregnancy with maternal and infant urinary sex steroid hormones, including estrogens (estrone, E1; estradiol, E2; estriol, E3), progestogens (progesterone, P4; pregnenolone, P5; 17α-OH-Progesterone, 17OHP4; 17α-OH-Pregnenolone, 17OHP5), and androgens (testosterone, Testo; dihydrotestosterone, DHT; dehydroepiandrosterone, DHEA; androstenedione, A4). Additionally, gonadotropins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were measured in infant urine. Detection frequencies of all the sex steroid hormones in the maternal urine samples (>99 %) were higher than those in the infants' [most ≥80 %, except for E1 (3.36 %) and E2 (21.4 %)]. Maternal urinary PCP concentration was found to be significantly related with increased maternal sex steroid hormone concentrations; each interquartile increase in PCP concentration was positively related with percent change of the hormones (%Δ) ranging from 26.6 % to 48.5 %. On the other hand, maternal PCP exposure was associated with significantly increased P4 in male infants [%Δ (95 % confidence interval): 10.5 (0.56, 21.4)] but slightly decreased P4 in female infants [-11.9 (-21.8, 0.68)]. In addition, maternal PCP exposure was significantly associated with decreased FSH [%Δ (95 % CI): -9.90 (-17.0, -2.18)] and LH [-8.44 (-16.0, -0.19)] in the female infants, but not in the male infants. Sensitivity analyses, excluding infertility related treatment, pregnancy complications, preterm birth, or low birth weight, showed generally consistent results. Our findings implied that maternal/prenatal PCP exposure might disrupt the homeostasis of maternal and infant reproductive hormones. However, further studies are needed to confirm the findings.

Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Occurrence of pentachlorophenol in surface water from the upper to lower reaches of the Yangtze River and treated water in Wuhan, China.

Pentachlorophenol (PCP), a persistent organic pollutant, has been banned in many countries, but it is still used in China as a wood preservative, molluscicide, or reagent for fish-pond cleaning, which may pose risks to the ecosystem and humans. However, data on the occurrence of PCP in the environment are scarce in the recent decade. The Yangtze River was regarded as a priority area of PCP pollution according to previous documents. This study aimed to examine the spatial distribution of PCP in the Yangtze River water, the differences in dry and wet seasons, the ecological risk for aquatic organisms, and its removal efficiency in tap water treatment plants. The river water samples (n = 144) were collected from the upper, middle, and lower reaches across ten provinces (or municipalities) in December 2020 and June 2021, respectively. PCP was detected in 88.9% of all the samples, ranging from

SARS-CoV-2 infection in animals: Patterns, transmission routes, and drivers.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is more widespread in animals than previously thought, and it may be able to infect a wider range of domestic and wild species. To effectively control the spread of the virus and protect animal health, it is crucial to understand the cross-species transmission mechanisms and risk factors of SARS-CoV-2. This article collects published literature on SARS-CoV-2 in animals and examines the distribution, transmission routes, biophysical, and anthropogenic drivers of infected animals. The reported cases of infection in animals are mainly concentrated in South America, North America, and Europe, and species affected include lions, white-tailed deer, pangolins, minks, and cats. Biophysical factors influencing infection of animals with SARS-CoV-2 include environmental determinants, high-risk landscapes, air quality, and susceptibility of different animal species, while anthropogenic factors comprise human behavior, intensive livestock farming, animal markets, and land management. Due to current research gaps and surveillance capacity shortcomings, future mitigation strategies need to be designed from a One Health perspective, with research focused on key regions with significant data gaps in Asia and Africa to understand the drivers, pathways, and spatiotemporal dynamics of interspecies transmission.

Associations of intrauterine exposure to manganese with fetal and early-childhood growth: a prospective prenatal cohort study.

Prenatal manganese (Mn) exposure may be related to poor birth outcomes; however, there are few relevant epidemiological reports on the effects of intrauterine Mn levels on intrauterine fetal and early childhood growth. From 2013 to 2016, 2082 pairs of mothers and infants were recruited in Wuhan, China, who provided an entire set of urine samples during their first, second, and third trimesters. Fetal head circumference (HC), abdominal circumference (AC), femoral length (FL), and estimated fetal weight (EFW) were obtained by ultrasound at the 16, 24, and 31 weeks of pregnancy. When the children were born, 6 months old, 12 months old, and 24 months old, their weight, height, weight-for-height, and BMI were measured. We used generalized linear models, generalized estimated equations, and restricted cubic spline curves (RCS) to investigate the linear and nonlinear relationships between antenatal Mn levels and fetal and early childhood growth. In all fetuses, Mn exposure during the 1st and 2nd gestation was associated with decreased fetal AC, FL, and EFW at 24 weeks (e.g., for each doubling of urinary Mn concentrations during the 1st and 2nd gestation, the SD score of EFW at 24 weeks decreased by - 4.16% (95% CI, - 6.22%, - 2.10%) and - 3.78% (95% CI, - 5.86%, - 1.70%)). Mn concentrations in the highest tertile group of the 1st and 2nd gestation were related to decreased fetus growth parameters compared to the lowest tertile group. For each doubling of the average Mn concentrations during pregnancy, the z-scores of weight, weight-for-height, and BMI at 12 months decreased, with percentage changes of - 2.93% (95% CI, - 5.08%, - 0.79%), - 3.25% (95% CI, - 5.56%, - 0.94%), and - 3.09% (95% CI, - 5.44%, - 0.73%). In the RCS model, we found a reverse U-shaped association between 1st trimester Mn concentration and fetal FL at 16 weeks and HC at 31 weeks in male fetuses and a non-linear association between mean Mn concentration during pregnancy and girls' weight-for-height and BMI at 6 months. Intrauterine exposure to Mn may be related to restricted growth in the fetus and early childhood, especially in fetuses at 24 weeks of gestation and children at 12 months of age. Also, meaningful curvilinear relationships were found in the sex stratification.

Prenatal exposure to organophosphate esters and growth trajectory in early childhood.

Maternal exposure to organophosphate esters (OPEs) has been linked to an increased risk of adverse birth outcomes. However, the impact of OPEs on childhood growth remains uncertain. This study assessed the associations between prenatal concentrations of OPE metabolites and the growth trajectory in early childhood. 212 singleton pregnant women were included in this study, and they were recruited between August 2014 and August 2016 in Wuhan, China. We measured the urinary concentrations of OPE metabolites during the 1st, 2nd, and 3rd trimesters. Standard deviation scores for weight and length were calculated for children at birth, 1, 6, 12, and 24 months. Trajectories of weight-for-age z-score (WAZ) and weight-for-length z-score (WLZ) were classified into four groups using group-based trajectory modeling. Trajectories of length-for-age z-score (LAZ) were classified into three groups with the same model. Then, we calculated odds ratios (ORs) and 95 % confidence interval (95%CI) using multinomial logistic regression to estimate increases in odds of different growth trajectories per doubling in OPE concentrations compared with moderate-stable trajectory. For average concentrations of OPE metabolites and growth trajectory, our results indicated that higher bis(2-butoxyethyl) phosphate, total aromatic OPE metabolites, and total OPE metabolites during pregnancy were associated with a higher likelihood of children falling into the low-stable and low-rising WAZ trajectory. Furthermore, compared to the moderate-stable LAZ trajectory, increased concentrations of 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate were linked to an elevated risk of a low-stable LAZ trajectory. Additionally, the 1st and 2nd trimesters may represent critical windows of heightened vulnerability to the effects of OPE metabolites on childhood growth. In conclusion, our study proves that prenatal exposure to OPE metabolites is inversely related to childhood growth. It is essential to conduct further research involving larger populations and to consider other compounds with known developmental toxicity to obtain more reliable and comprehensive results.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [ß = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 µg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 µg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

Associations of maternal urinary rare earth elements individually and in mixtures with neonatal size at birth.

Prenatal rare earth elements (REEs) exposure is linked to unfavorable health consequences. Epidemiologic research on repeated measurements of REEs during gestation correlated with fetal growth is exiguous. Until now, few studies have characterized exposure characteristics of REEs in pregnant women. We aimed to ascertain the characteristics and predictors of REEs exposure over three trimesters among pregnant women and examine the possible effects of prenatal REEs exposure on size at birth. Urinary REEs concentrations exhibited considerable within-subject variation with intraclass correlation coefficients ranging from 0.16 to 0.58. Maternal age, household income, gestational weight gain, passive smoking during pregnancy, parity, and neonatal gender were associated with maternal urinary REEs concentrations. Elevated maternal urinary holmium and thulium concentrations in the 3rd trimester were significantly related to reductions in birth weight. Weighted quantile sum (WQS) regression model identified that urinary REEs mixture in the 3rd trimester were negatively related to birth weight (WQSREEs ß = -26.22; 95% confidence interval [CI]: -47.62, -4.82), with holmium (40%) and thulium (24%) receiving the highest weights. Male infants received the most weight (>50%) related to decreased birth weight. This study revealed a significant association between individual and mixture REE exposure in late pregnancy with a reduction in birth weight.

Association between prenatal exposure to rare earth elements and the neurodevelopment of children at 24-months of age: A prospective cohort study.

The increasing consumption of rare earth elements (REEs) has resulted in a considerable risk of environmental exposure. However, the adverse effects of prenatal REEs exposure on children's neurodevelopment are not yet fully recognized. Therefore, we investigated the individual and joint effects of prenatal exposure to 13 REEs on children's neurocognitive development based on 809 mother-child pairs from a large birth cohort in Wuhan, China. Maternal urinary concentrations of 13 REEs were repeatedly measured by inductively coupled plasma mass spectrometry. Children's neurodevelopment [e.g., mental and psychomotor development index (MDI/PDI)] at 24-months was assessed using Bayley Scales of Infant Development of Chinese Revision. GEE and BKMR models were applied to estimate the individual and joint effects of prenatal REE exposure on child neurodevelopment level. After controlling for typical confounders, we observed that exposure to 9 REEs during the first trimester were significantly associated with decreased MDI scores [ßs and 95% confidence intervals (CIs) ranging from -2.24 (-3.86 âˆ¼ -0.63) to -1.44 (-2.26∼ -0.26)], and 7 REEs during third trimester were significantly associated decreased PDI scores [ß and 95% CIs ranging from -1.95 (-3.19 âˆ¼ -0.71) to -1.25 (-2.34 âˆ¼ -0.16)]. Higher quantiles of REE mixture in first and third trimester were associated with decreased MDI and PDI score. Thulium, erbium in the first trimester and cerium, lanthanum in the third trimester accounted most importance to joint effects on MDI and PDI, respectively. In conclusion, prenatal exposure to higher concentrations of REEs during the first and third trimester were negative associated with children's neurodevelopment.

Associations of maternal exposure to 2,4-dichlorophenoxyacetic acid during early pregnancy with steroid hormones among one-month-old infants.

BACKGROUND: Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D), a widely used hormonal herbicide, may disrupt steroid hormone homeostasis. However, evidence from population-based studies is limited, especially for one-month-old infants whose steroid hormones are in a state of adjustment to extrauterine life and can be important indicators of endocrine development. This study aimed to explore the associations between maternal 2,4-D exposure during early pregnancy and infant steroid hormone levels. METHODS: The 885 mother-infant pairs were from a birth cohort in Wuhan, China. Maternal exposure to 2,4-D was determined in urine samples from early pregnancy, and nine steroid hormones were determined in infant urine. The associations of maternal 2,4-D exposure with infant steroid hormones and their product-to-precursor ratios were estimated based on generalized linear models, and bioinformatic analysis was conducted with public databases to explore the potential mechanisms involved. RESULTS: The detection frequency of 2,4-D was 99.32 %, and the detection frequency of steroid hormones ranged from 98.42 % to 100.00 %. After adjusting for covariates, an interquartile range increase in 2,4-D concentrations was associated with a 7.84 % decrease in 11-deoxycortisol (95 % confidence interval, CI: -14.12 %, -1.10 %), an 8.09 % decrease in corticosterone (95 % CI: -14.56 %, -1.14 %), an 8.67 % decrease in cortisol (95 % CI: -14.43 %, -2.52 %), a 13.00 % decrease in cortisone (95 % CI: -20.64 %, -4.62 %), and an 11.17 % decrease in aldosterone (95 % CI: -19.62 %, -1.83 %). Maternal 2,4-D was also associated with lower infant cortisol/17α-OH-progesterone, cortisol/pregnenolone, and aldosterone/pregnenolone ratios. In bioinformatic analysis, pathways/biological processes related to steroid hormone synthesis and secretion were enriched from target genes of 2,4-D exposure. CONCLUSIONS: Maternal urinary 2,4-D during early pregnancy was associated with lower infant urinary 11-deoxycortisol, corticosterone, cortisol, cortisone, and aldosterone, reflecting that 2,4-D exposure may interfere with infant steroid hormone homeostasis. Further efforts are still needed to study the relevant health effects of exposure to 2,4-D, particularly for vulnerable populations.