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.

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.

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

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.

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.

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 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.

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.

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.

Urinary biomarkers of exposure to organophosphate, pyrethroid, neonicotinoid insecticides and oxidative stress: A repeated measurement analysis among pregnant women.

Exposure to insecticides may be associated with increased oxidative stress (OS), but few studies have assessed the associations of OS biomarkers (OSBs) with exposure to multiple insecticides and their mixture, especially in pregnant women who are a vulnerable population. In the present study, 1,094 Chinese pregnant women were recruited and a total of 3,282 urine samples were collected at their three trimesters to measure eight metabolites of organophosphates, three metabolites of pyrethroids, nine typical neonicotinoids/their metabolites, and three OSBs of DNA damage (8-OHdG), RNA damage (8-OHG), and lipid peroxidation (HNE-MA). Among the twenty target insecticide metabolites, sixteen of them were frequently detected; thirteen of them were detected in over 86% of all the urine samples except for imidacloprid (IMI, detection frequency: 72.9%), desnitro-imidacloprid (DN-IMI, 70.0%), and clothianidin (CLO, 79.6%). The reproducibility of their concentrations across the three trimesters was poor to fair (intraclass correlation coefficients <0.50). Multiparity and warm season were related to higher urinary levels of some insecticide metabolites, while higher education level and inadequate weight gain during pregnancy were significantly associated with lower concentrations of certain insecticide metabolites. Linear mixed model analyses suggested that almost all the frequently detected insecticide metabolites [other than 3-phenoxybenzoic acid (3-PBA)] were significantly associated with elevated levels of the three OSBs (8-OHdG, 8-OHG, and HNE-MA), where the percent change (Δ%) ranged 8.10-36.0% for 8-OHdG, 8.49-34.7% for 8-OHG, and 5.92-182% for HNE-MA, respectively, with each interquartile ratio (IQR)-fold increase in the concentrations of the individual exposure biomarkers. Weighted quantile sum models demonstrated that the insecticide metabolite mixture was positively associated with the three OSBs. Overall, urinary desmethyl-clothianidin (DM-CLO) and 3,5,6-trichloro-2-pyridinol (TCPy) were the top insecticide exposure biomarkers contributing to the association with 8-OHdG and 8-OHG levels, while PNP contributed the most to the association with HNE-MA levels. These findings suggested that gestational exposure to organophosphates, pyrethroids, neonicotinoids, their transformation products, and their mixture may increase oxidative damage to lipids, RNA, and DNA during pregnancy.

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.

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.

Altered cord blood mitochondrial DNA content and prenatal exposure to arsenic metabolites in low-arsenic areas.

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 arsenic metabolism in different trimesters was related to cord blood mtDNAcn alteration. 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 using HPLC-ICPMS. We decided on cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each two-fold increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the 3rd trimester were 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 3rd trimester with mtDNAcn. These findings may prove the relationships between arsenic species and mitochondrial dysfunction.

Associations of Trimester-Specific Exposure to Perchlorate, Thiocyanate, and Nitrate with Childhood Neurodevelopment: A Birth Cohort Study in China.

Studies about the impacts of maternal exposure to perchlorate, thiocyanate, and nitrate on offspring neurodevelopment are scarce. Based on a birth cohort in China, 1,028 mothers provided urine samples at three trimesters for determination of the three target analytes, and their offspring neurodevelopment was evaluated at 2 years old. Associations of maternal exposure to the three chemicals with offspring neurodevelopment were estimated using three statistical methods. Trimester-specific analyses using generalized estimating equation models showed that double increment of thiocyanate and nitrate during the first trimester was associated with 1.56 (95% CI: -2.82, -0.30) and 1.22 (-2.40, -0.03) point decreases in the offspring mental development index (MDI), respectively. Weighted quantile sum (WQS) regression analyses showed that the mixture exposure at the first and second trimesters was negatively associated with the offspring MDI (ß = -2.39, 95% CI: -3.85, -0.93; ß = -1.75, 95% CI: -3.04, -0.47, respectively) and thiocyanate contributed the most to the association (65.0 and 91.6%, respectively). Bayesian kernel machine regression analyses suggested an inverted U-shape relationship of maternal urinary thiocyanate with the offspring MDI. These findings suggested that prenatal exposure to the three chemicals (at current levels), especially thiocyanate and nitrate, may impair neurodevelopment. Early pregnancy seems to be the sensitive window.

Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study.

BACKGROUND: Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. OBJECTIVES: We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. METHODS: Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (N=1,041). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. RESULTS: Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): -5.59, -0.74] and 3.06 points (95% CI: -5.45, -0.68) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: -3.89, -0.58) in boys' MDI scores and 1.90 points (95% CI: -3.16, -0.64) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: -5.47, -0.57) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). CONCLUSIONS: Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.

Associations of plasma manganese with adverse pregnancy outcomes: Nested case-control studies in a Chinese birth cohort.

Both insufficient and excessive manganese exposure are associated with adverse pregnancy outcomes. However, no systematic research has established a standardized reference range for manganese levels with the consideration of the associated health risks during pregnancy. To verify the associations of prenatal manganese exposure with adverse outcomes and to identify a proper reference range for manganese based on health risks, we designed three nested case-control studies on three adverse outcomes including hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and low birth weight (LBW) to investigate the associations with manganese levels. Plasma manganese concentrations in early pregnancy were measured. Conditional logistic regression analyses were used to estimate the associations of manganese levels with adverse outcomes. Restricted cubic spline (RCS) models were used to characterize the dose-response relationship of manganese and each outcome. Nonlinear associations were observed for manganese and adverse outcomes. Compared with women in the middle tertile of plasma manganese, we found that those in the highest tertile had a significantly higher risk of HDP (OR = 1.72, 95% CI: 1.02 to 2.89), that women in the lowest tertile had almost a tripled risk of delivering LBW infants (OR = 2.93, 95% CI: 1.67 to 5.17), and that women both in the lowest and the highest tertiles had significantly higher risks of PTB [OR = 1.83 (95% CI: 1.14 to 2.95); OR = 1.70 (95% CI: 1.05 to 2.76)]. U-shaped associations were found between plasma manganese and risk of PTB and infant LBW. Based on the results of RCS models, we identified a proper plasma manganese range of 1.72-3.18 µg/L, with relatively lower risks of adverse pregnancy outcomes. In conclusion, our study found U-shaped associations between manganese exposure and adverse pregnancy outcomes, and provided an optimal range of manganese concentration for pregnant women, based on health risk considerations.

Urinary perchlorate, thiocyanate, and nitrate and their associated risk factors among Chinese pregnant women.

Perchlorate, nitrate, and thiocyanate are well-known inhibitors of iodide uptake and thyroid-disrupting chemicals. Widespread human exposure to them has been identified, whereas studies on their internal exposure levels among Chinese pregnant women are scarce and factors associated with them are not well recognized. The objective of this study is to determine their levels and identify the associated factors among pregnant women (n = 1120), based on a prospective birth cohort in Wuhan, central China, using repeated urine samples of three trimesters. Urinary perchlorate, thiocyanate, and nitrate were 100% detected in the samples, and specific gravity-adjusted median concentrations of them in all the samples were 12.6 ng/mL, 367 ng/mL, and 63.7 µg/mL, respectively. Their concentrations were weakly-to-moderately correlated with each other, with Spearman correlation coefficients ranging from 0.27 to 0.54. Poor reproducibility were observed for the three analytes over the three trimesters, with intraclass correlation coefficient of 0.07, 0.19, 0.04 for perchlorate, thiocyanate, and nitrate, respectively. The women who were overweight or used tap water as drinking water had significantly higher perchlorate concentrations, while those with excessive gestational weight gain had significantly higher thiocyanate concentrations (p < 0.05). The women with a college degree or above had lower nitrate concentrations (p < 0.05). Meanwhile, the median concentration of perchlorate in urine samples collected in spring, thiocyanate in those collected in winter, and nitrate in those collected in autumn, was significantly higher compared to their median concentrations in the samples collected in other three seasons (p < 0.05), respectively. Urinary perchlorate and nitrate concentrations of pregnant women in this study were higher than the concentrations of pregnant women in other countries, while thiocyanate concentrations were lower than that of most other countries. This study suggested potential covariates for future epidemiological analyses.

Prenatal Lead Exposure, Genetic Factors, and Cognitive Developmental Delay.

Importance: Although the effects of lead (Pb) exposure on neurocognition in children have been confirmed, the individual associations of prenatal Pb exposure and its interaction with genetic factors on cognitive developmental delay (CDD) in children remain unclear. Objective: To investigate the association of prenatal Pb exposure and its interaction with genetic factors with CDD risk. Design, Setting, and Participants: Women in Wuhan, China, who had an expected delivery date between March 2014 and December 2017, were recruited for this prospective cohort study. Children were assessed for cognitive development at approximately 2 years of age (March 2016 to December 2019). Maternal venous blood, cord blood, and venous blood from children were collected in a longitudinal follow-up. Data analysis was performed from March 2022 to February 2023. Exposure: Prenatal Pb exposure, and genetic risk for cognitive ability evaluated by polygenic risk score constructed with 58 genetic variations. Main Outcomes and Measures: Cognitive developmental delay of children aged approximately 2 years was assessed using the Chinese revision of the Bayley Scale of Infant Development. A series of multivariable logistic regressions was estimated to determine associations between prenatal Pb exposure and CDD among children with various genetic backgrounds, adjusting for confounding variables. Results: This analysis included 2361 eligible mother-child pairs (1240 boys [52.5%] and 1121 girls [47.5%]; mean [SD] ages of mothers and children, 28.9 [3.6] years and 24.8 [1.0] months, respectively), with 292 children (12.4%) having CDD. Higher maternal Pb levels were significantly associated with increased risk of CDD (highest vs lowest tertile: odds ratio, 1.55; 95% CI, 1.13-2.13), adjusting for demographic confounders. The association of CDD with maternal Pb levels was more evident among children with higher genetic risk (highest vs lowest tertile: odds ratio, 2.59; 95% CI, 1.48-4.55), adjusting for demographic confounders. Conclusions and Relevance: In this cohort study, prenatal Pb exposure was associated with an increased risk of CDD in children, especially in those with a high genetic risk. These findings suggest that prenatal Pb exposure and genetic background may jointly contribute to an increased risk of CDD for children and indicate the possibility for an integrated strategy to assess CDD risk and improve children's cognitive ability.