Search

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

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

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

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

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

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

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

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

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

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

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

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

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

Background: Phthalates are a family of endocrine disruptors with short elimination half-lives in the human body. To date, few epidemiological studies have examined repeated measures of maternal urinary phthalates and the combined effects of prenatal exposure to multiple phthalates on children's neurocognitive development. Objectives: We aimed to investigate the association between children's neurocognitive development at 2 years of age and prenatal phthalate exposure, as assessed by repeated measurements during pregnancy, and to further examine the effects of co-exposure to multiple phthalates using cumulative risk assessment. Method: Within a prenatal cohort in Wuhan, China, we measured five high-molecular-weight (HMW) phthalates and three low-molecular-weight (LMW) phthalate metabolites' concentrations in three urine samples collected in the 1st, 2nd, and 3rd trimester of pregnancy from each mother. We assessed neurocognitive development by Bayley Scales of Infant and Toddler Development (BSID) at 2 years of age (n = 476) to obtain the children's mental development index (MDI) and psychomotor development index (PDI). Results: Higher exposure levels to LMW phthalates compared to HMW phthalates were observed in our population. Ln-transformed averaged concentration of mono-n-butyl phthalate (MnBP), a metabolite of the LMW phthalate di-n-butyl phthalate (DnBP) during pregnancy, was associated with decreased PDI scores in all children (β = −1.90, 95% CI: −3.43, −0.37). Similarly, the averaged sum concentration of ∑dibutyl phthalate (∑DBP) was associated with decreased PDI scores in all children (β = −1.89, 95% CI: −3.63, −0.15). A negative trend of association between exposure to HMW phthalates and PDI scores was observed in girls, while a positive association was found in boys. In cumulative risk assessment analyses, we consistently observed that the hazard quotient of DnBP (the parent compound of MnBP) was inversely associated with PDI scores in all children, whereas the hazard quotient of di-2-ethylhexyl phthalate (DEHP), an HMW phthalate, was positively associated with PDI scores in boys only. Conclusions: This study is the first to use repeated measurement of maternal urinary phthalates in all three trimesters to assess prenatal exposure in relation to children's neurodevelopment. Our study suggested a negative association between prenatal exposure to MnBP and children's psychomotor development, and potentially sex-specific associations between HMW phthalates and neurocognitive development among boys and girls. These findings warrant further confirmation. Keywords: Phthalate metabolites, Child neurodevelopment, Prenatal exposure, Trimester-specific, Cumulative risk assessment

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