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Chromium exposure from increasing industrial releases has become a threat for pregnant women due to the potential health effects on vulnerable embryos. Previous studies have suggested that maternal chromium exposure is associated with adverse birth outcomes, but no epidemiological research has been conducted to examine the relationship between chromium exposure and premature rupture of membranes (PROM). This study aimed at investigating the association of maternal urinary chromium exposure levels with PROM and was performed with 5408 pregnant women recruited from 2012 to 2014 in the city of Wuhan, China. Maternal urinary chromium collected before labor was adjusted with creatinine, and its association with PROM was evaluated using logistic regression. Each one unit increase in the natural logarithm transformed maternal urinary chromium concentration (μg/g creatinine), an odds ratio (OR) of 1.47 [95% confidence interval (CI): 1.36, 1.58] for PROM was observed. Compared to the lowest tertile of maternal urinary chromium, PROM was positively correlated with increased urinary levels of chromium (adjusted OR = 1.42; 95% CI: 1.09, 1.84 for the medium tertile; adjusted OR = 2.77; 95% CI: 2.18, 3.52 for the highest tertile). Additionally, the association of chromium with PROM appeared to be more significant among male infants (adjusted OR = 3.52; 95% CI: 2.51, 4.94 for the highest tertile) than female infants (adjusted OR = 2.16; 95% CI: 1.52, 3.06 for the highest tertile) ( p for interaction = 0.05). Our large birth cohort showed an association between maternal urinary chromium levels and PROM, and the association may differ by infant gender. Further studies from different populations are needed to confirm the observed association.

Background: Health effects of exposure to particulate matter (PM) on male reproductive health remain unclear. Only a limited number of studies have investigated the effects of PM2.5 or PM10 exposure on semen quality, and the results were largely inconsistent. Objectives: To quantitatively assess the exposure-response association between PM exposure and semen quality in Chinese men who were exposed to a wide concentration range of PM. Methods: We investigated 1759 men from Wuhan, China, who were partners of women undergoing assisted reproductive technology procedures, and had semen examined at least once between 2013 and 2015. Individual PM2.5 and PM10 exposures during 0–90, 0–9, 10–14 and 70–90 days before each semen examination (corresponding to the entire and three key periods of sperm development, respectively) were retrospectively estimated by inverse distance weighting interpolation. Linear mixed models were used to assess exposure-response relations of PM exposure with sperm concentration, count and motility. Results: PM2.5 exposure during 0–90 lag days ranged from 27.3 to 172.4 μg/m3. It was linearly and inversely associated with sperm concentration (β: −0.20; 95% CI: −0.34, −0.07) and count (−0.22; −0.35, −0.08). For the three key exposure periods, only PM2.5 exposure during the 70–90 lag days was significantly associated with sperm concentration (−0.12; −0.22, −0.03) and count (−0.12; −0.21, −0.02). Sensitivity analyses for a subgroup (n = 1146) excluding subjects with abnormal sperm concentration, count or motility yielded similar results. Compared with PM2.5, we found generally similar associations for PM10 exposure in relation to sperm concentration and count, except that the associations appeared to be nonlinear with inverted J-shaped relationships. Neither PM2.5 nor PM10 exposure was significantly associated with sperm motility (all p > 0.05). Conclusions: Our results suggest that ambient PM exposure during sperm development adversely affects semen quality, in particular sperm concentration and count. Keywords: Air pollution, Particulate matter, Semen quality, Sperm concentration, Exposure-response relation

Background: Prenatal cadmium (Cd) exposure has been associated with adverse birth outcomes, but the findings of previous studies are inconsistent. The aim of this study was to evaluate the association between prenatal Cd exposure and birth outcomes. Methods: This study was conducted in 5364 pregnant women with a live singleton birth, who were recruited between September 2012 and October 2014 in the Healthy Baby Cohort (HBC) in Wuhan, China. Gestational age (in days) was estimated using both the woman's last menstrual period (LMP) and ultrasound data. All the birth outcomes including birth weight and birth length were measured in the hospital within one hour after birth through standardized procedures. Cd was measured in maternal urine collected before delivery with inductively coupled plasma mass spectrometry. Results: The geometric mean of Cd concentration in maternal urine was 0.55 (range 0.01–2.85) μg/g creatinine. We found each ln-unit increase in Cd concentration (μg/g creatinine) in maternal urine was associated with decreased gestational age [adjusted β = −0.77 day; 95% confidence interval (CI): −1.15, −0.39 for all infants; −0.77; 95% CI: −1.29, −0.25 for boys; and −0.80; 95% CI: −1.35, −0.25 for girls]. Increased likelihood of preterm birth (PTB) was associated with ln-unit increase in urinary Cd (μg/g creatinine) [adjusted odds ratio (OR) = 1.78; 95% CI: 1.45, 2.19 for all infants; 1.97; 95% CI: 1.46, 2.65 for boys; and 1.67; 95% CI: 1.24, 2.25 for girls]. Maternal urinary Cd was not significantly associated with low birth weight (LBW) and small for gestational age (SGA). Conclusions: Maternal exposure to Cd during pregnancy was associated with decreased gestational age and increased likelihood of PTB. Keywords: Cadmium, Birth outcomes, Preterm birth, Low birth weight, Urine

Developmental exposure to bisphenol A (BPA) has been linked to impaired glucose homeostasis and pancreatic function in adulthood, which has been hypothesized to result from the disruption of pancreatic β-cell development at early life. Here we evaluated whether maternal BPA exposure disrupts β-cell development and glucose tolerance and the role of epigenetic modifications of key regulator in this process. We found that maternal exposure to BPA (10 μg kg−1 d−1) reduced the pancreatic β-cell mass and the expression of pancreatic and duodenal homeobox 1 (Pdx1) at birth, as well as the expression of Pdx1 at gestational day (GD) 15.5. In parallel with the decreased expression of Pdx1, histones H3 and H4 deacetylation, along with demethylation of histone 3 lysine 4 (H3K4) and methylation of histone 3 lysine 9 (H3K9), were found at the promoter of Pdx1, while no significant changes in DNA methylation status were detected at this region. Moreover, these alterations were observed in adult life along with impaired glucose tolerance. We conclude that maternal exposure to BPA reduces pancreatic β-cell mass at birth by reducing PDX1+ progenitors during fetal development through altering the histone modifications of Pdx1, which can be propagated to later life and increase the susceptibility to glucose intolerance.

Background: Several studies have reported that cadmium (Cd) is associated with type 2 diabetes. However, little is known about Cd exposure and the risk of gestational diabetes mellitus (GDM). Objective: We examined the association between Cd body burden in early pregnancy and the risk of GDM. Methods: We conducted a prospective study of 2,026 pregnant women from a single tertiary medical center between 2013 and 2016 in Wuhan, China. Cd body burden was reflected by Cd concentrations in urine samples collected between gestational weeks 8 and 14. GDM was diagnosed according to International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations. Results: The geometric mean of Cd concentrations in maternal urine of all pregnant women was 0.59μg/L. A total of 198 (9.8%) women were diagnosed with GDM. After adjustment for potential confounders, the risk ratios (RRs) of GDM were 1.04 (95% CI: 0.74, 1.44) for the middle tertile of Cd levels and 1.36 (95%: CI: 0.98, 1.90) for the top tertile compared with the bottom tertile. In addition, we found a significant interaction between fetal sex and maternal Cd levels on the risk of GDM (p for interaction=0.03). Among women carrying male fetuses, the RR of GDM was 1.86 (95% CI: 1.14, 2.93) for the top tertile of Cd levels compared with the bottom tertile. Conclusions: To our knowledge, this is the first report of an association between urinary Cd levels in early pregnancy and GDM. Our findings suggest that Cd body burden increases the risk of GDM and that the association may be modified by fetal sex. https://doi.org/10.1289/EHP2716

Pregnant women are a unique group undergoing profound structural modifications in uterus, breast, adipose tissue and extracellular fluids. Amino acid metabolic stress is a unique physical process that occurs during pregnancy. Metals constitute a fundamental part of the maternal body and have a universal effect on amino acid metabolism. However, the exact interaction between metals and amino acid metabolism during pregnancy is unknown. The aim of the present study was to determine the correlations of metals with amino acid metabolic intermediates in the urine of 232 healthy pregnant women in their first, second and third trimesters during normal pregnancy. Sixteen metals in the urine of 232 healthy pregnant women in their first, second and third trimesters were quantified using inductively coupled plasma mass spectrometry (ICP-MS). An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-QTOFMS)-based metabolomics approach was conducted to detect intermediate products involved in amino acid metabolism during the entire pregnancy period. A panel regression model was established to investigate the relationship between urine metals and amino acid metabolism. Seven metals-cadmium, cobalt, copper, cesium, manganese, thallium and vanadium-showed significant association with amino acid metabolic intermediates, including 2-oxoarginine, 3-indoleacetonitrile, indole, indole-5,6-quinone, N2-succinyl-l-glutamic acid 5-semialdehyde, N-methyltryptamine and N-succinyl-l,l-2,6-diaminopimelate, in the healthy pregnant women. These findings indicated that exposure to cadmium, cobalt, copper, cesium, manganese, thallium and vanadium significantly affected the metabolic status of tryptophan, arginine, proline, tyrosine and lysine metabolism in the maternal body during normal pregnancy.

Background Thallium (Tl) is a highly toxic heavy metal widely present in the environment. Case reports have suggested that maternal exposure to high levels of Tl during pregnancy is associated with low birth weight (LBW), but epidemiological data are limited. Objectives This study was designed to evaluate whether prenatal Tl exposure is associated with an increased risk of LBW. Methods This case–control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted in Hubei Province, China, in 2012–2014. Tl concentrations were measured in maternal urine collected at delivery, and associations with LBW were evaluated using conditional logistic regression. Results Higher maternal urinary Tl levels were significantly associated with increased risk of LBW [crude odds ratio (OR) = 1.52; 95% CI: 1.00, 2.30 for the highest vs. lowest tertile], and the association was similarly elevated after adjustment for potential confounders (adjusted OR = 1.90; 95% CI: 1.01, 3.58 for the highest vs. lowest tertile). Stratified analyses showed slightly higher risk estimates for LBW associated with higher Tl levels for mothers < 28 years old and for mothers with lower household income; however, there was no statistical evidence of heterogeneity in risk according to maternal age (p for heterogeneity = 0.18) or household income (p for heterogeneity = 0.28). Conclusion To our knowledge, ours is the first case–control study to investigate the association between prenatal Tl exposure and LBW. The results suggest that prenatal exposure to high levels of Tl may be associated with an increased risk of LBW. Citation Xia W, Du X, Zheng T, Zhang B, Li Y, Bassig BA, Zhou A, Wang Y, Xiong C, Li Z, Yao Y, Hu J, Zhou Y, Liu J, Xue W, Ma Y, Pan X, Peng Y, Xu S. 2016. A case–control study of prenatal thallium exposure and low birth weight in China. Environ Health Perspect 124:164–169; http://dx.doi.org/10.1289/ehp.1409202

Prior studies have suggested the reproductive effects of nickel; however, few epidemiological studies have investigated the associations of maternal exposure to nickel with preterm delivery. To investigate prenatal exposure to nickel as a risk factor for preterm delivery (37 weeks) in a large birth cohort. A total of 7291 pregnant women participated in the study were recruited between September 2012 and October 2014 in the longitudinal Healthy Baby Cohort (HBC) in Wuhan, China. Inductively Coupled Plasma Mass Spectrometry was employed to examine levels of nickel in urine from pregnant women collected before labor. The median urinary creatinine-corrected nickel was 5.05 creatinine μg/g with an inter-quartile range of 2.65-9.51 creatinine μg/g. We adjusted for potential confounders and found that each doubling in concentration of maternal urinary nickel was associated with an increase of 16% in adjusted odds ratios (ORs) for preterm delivery (95% CI: 1.08, 1.24). The associations were consistent for both spontaneous and iatrogenic preterm delivery. Our findings suggest that higher maternal urinary nickel concentrations were associated with an increased risk of preterm delivery.

Thallium (Tl) is a well-recognized hazardous toxic heavy metal that has been reported to have embryotoxicity and fetotoxicity. However, little is known about its association with preterm birth (PTB) in humans. We aimed to evaluate the predictors of Tl exposure and assessed its relation with PTB. The study population included 7173 mother-infant pairs from a birth cohort in Wuhan, China. Predictors of Tl concentrations were explored using linear regression analyses, and associations of Tl exposure with risk of PTB or gestational age at birth were estimated using logistic regression or generalized linear models. The geometric mean and median values of urinary Tl concentrations were 0.28 μg/L (0.55 μg/g creatinine) and 0.29 μg/L (0.53 μg/g creatinine). We found that maternal urinary Tl concentrations varied by gestational weight gain, educational attainment, multivitamin and iron supplementations. Women with Tl concentrations higher than 0.80 μg/g creatinine were at higher risk of giving birth prematurely versus those with Tl concentrations lower than 0.36 μg/g creatinine [adjusted odds ratio (95% confidence interval (CI)): 1.55 (1.05, 2.27)], and the association was more pronounced in PTB with premature rupture of membranes (PROM) rather than in PTB without PROM. About 3-fold increase in creatinine-corrected Tl concentrations were associated with 0.99-day decrease in gestational length (95% CI: −1.36, −0.63). This is the first report on the associations between maternal Tl exposure and the risk of PTB.

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

Few studies have investigated the association of environmental chromium exposure and preterm birth in general population. This study was designed to investigate whether maternal chromium exposure during pregnancy is associated with reduced gestational age or risk of preterm birth using the data from Healthy Baby Cohort study conducted in Hubei, China between 2012 and 2014 (n = 7290). Chromium concentrations in maternal urine samples collected at delivery were measured with inductively coupled plasma mass spectrometry. Tertiles of chromium concentrations was negatively associated with gestational age in multivariable linear regression analyses [β (95% CI): low = reference; middle = −0.67 days (−1.14, −0.20); high = −2.30 days (−2.93, −1.67); p trend p trend p trend

Prenatal cadmium (Cd) exposure has been associated with adverse birth outcomes, but the findings of previous studies are inconsistent. We measured Cd concentrations in urine samples at or near 13, 24, and 35 gestational weeks from 282 women in Wuhan, China. We used generalized estimating equation models to assess the associations between maternal creatinine adjusted urinary Cd concentrations at each trimester and birth size. A significant inverse association was observed between higher maternal Cd levels measured during the 1st trimester and birth size in girls. For each log unit increase in Cd (µg/g creatinine) levels from the 1st trimester, there was a decrease in birth weight by 116.99 g (95% confidence interval (CI): −208.87, −25.11 g). The Cd levels from the 1st and 2nd trimesters were also borderline significantly associated with ponderal index in girls. Joint estimation of trimester-specific effects suggested that associations with Cd levels for ponderal index (pint = 0.02) were significantly different across trimesters, and differences for effects across trimesters for birth weight were marginally significant (pint = 0.08) in girls. No significant associations were observed between Cd levels from any trimester and birth size in boys. Maternal Cd exposure during earlier periods of pregnancy may have a larger impact on delayed fetal growth.

Early studies have investigated the effect of prenatal cadmium (Cd) exposure on birth outcomes, such as preterm birth and low birth weight, although the results of these studies are inconsistent. The aim of the present study was to investigate the association between prenatal exposure to Cd and the risk of preterm low birth weight (PLBW). A total of 408 mother-infant pairs (102 PLBW cases and 306 pair matched controls) were selected from the participants enrolled in the Healthy Baby Cohort (HBC) study between 2012 and 2014 in Hubei province, China. Concentrations of Cd in maternal urine collected before delivery were measured by inductively coupled plasma mass spectrometry and adjusted by creatinine. A significant association was observed between higher maternal urinary Cd levels and risk of PLBW (adjusted odds ratio (OR)=1.75 for the medium tertile, 95% confidence interval (CI): 0.88, 3.47; adjusted OR=2.51 for the highest tertile, 95% CI: 1.24, 5.07; P trend=0.03). The association was more pronounced among female infants than male infants. Our study suggested that prenatal exposure to Cd at the current level encountered in China may potentially increase the risk of delivering PLBW infants, particularly for female infants.

Background Manganese (Mn) is an essential element for humans, but exposure to high levels has been associated with adverse developmental outcomes. Early epidemiological studies evaluating the effect of Mn on fetal growth are inconsistent. Methods We investigated the association between maternal urinary Mn during pregnancy and the risk of low birth weight (LBW). Mn concentrations in maternal urine samples collected before delivery were measured in 816 subjects (204 LBW cases and 612 matched controls) recruited between 2012 and 2014 in Hubei Province, China. Results The median Mn concentration in maternal urine was 0.69 μg/g creatinine. Compared to the medium tertile of Mn levels, an increased risk of LBW was observed for the lowest tertile (≤0.30 μg/g creatinine) [adjusted odds ratio (OR) = 1.28; 95 % confidence interval (CI) = 0.67, 2.45], and a significantly increased risk of LBW was observed for the highest tertile (≥1.16 μg/g creatinine) [adjusted OR = 2.04; 95 % CI = 1.12, 3.72]. A curvilinear relationship between maternal urinary Mn and risk of LBW was observed, showing that the concentration at 0.43 μg/g creatinine was the point of inflection. Similar associations were observed among the mothers with female infants and among the younger mothers

Study question Is prenatal vanadium exposure associated with adverse birth outcomes? Summary answer The odds of low birthweight (LBW) are increased 2.23-fold in mothers with a urinary vanadium of ≥2.91 μg/g creatinine compared with that in mothers with a urinary vanadium of ≤1.42 μg/g creatinine. What is known already Human exposure to vanadium occurs through intake of food, water and polluted air. Vanadium has been suggested to have fetotoxicity and developmental toxicity in animal studies, and epidemiological studies have reported an association between a decrease in birthweight and vanadium exposure estimated from particulate matter. Study design, size, duration A nested case-control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted with data from the prospective Healthy Baby Cohort between 2012 and 2014 in the province of Hubei, China. Participants/materials, setting, methods Vanadium concentrations in 816 maternal urine samples collected before delivery [the median gestational age was 39 weeks (range 27-42 weeks)] were measured by inductively coupled plasma mass spectrometry. Information on the infants' birth outcomes was obtained from medical records. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Main results and the role of chance The median urinary vanadium concentration of the cases was much higher than that of the controls (3.04 μg/g creatinine versus 1.93 μg/g creatinine). The results revealed a significant positive trend between the odds of LBW and level of maternal urinary vanadium [relative to the lowest tertile; adjusted OR = 1.69 (95% CI: 0.92, 3.10) for the medium tertile; adjusted OR = 2.23 (95% CI: 1.23, 4.05) for the highest tertile; P-trend = 0.02]. Additionally, the association was not modified by maternal age (P for heterogeneity = 0.70) or infant gender (P for heterogeneity = 0.21). Limitations, reasons for caution The maternal urine sample was collected before labor, and the maternal urinary vanadium levels measured at one point in time may not accurately reflect the vanadium burden during the entire pregnancy. Wider implications of the findings The results of this study can enrich the biological monitoring data on urinary vanadium in pregnant women; and may be evidence that vanadium may affect fetal development. Study funding/competing interests This work was supported by the National Natural Science Foundation of China (21437002, 81372959 and 81402649), the R&D Special Fund for Public Welfare Industry (Environment) (201309048) and the Fundamental Research Funds for the Central Universities, HUST (2016YXZD043). The authors have no conflicts of interest to declare.

Exposure to chromium is increasing due to environmental pollution from industrial processes. Several epidemiological studies have investigated chromium exposure and reproductive outcomes, but few studies have investigated the association of chromium exposure and low birth weight (LBW). This study was designed to investigate whether maternal exposure to chromium during pregnancy is associated with an increased risk of LBW. Chromium concentrations in maternal urine samples collected at delivery were measured in 204 LBW cases and 612 matched controls recruited between 2012 and 2014 in Hubei Province, China. Risk of LBW was associated with higher levels of chromium in maternal urine [adjusted odds ratio (OR) = 1.77 for the medium tertile, 95% confidence interval (CI): 0.95, 3.29; adjusted OR = 2.48 for the highest tertile, 95% CI: 1.33, 4.61; P trend = 0.01]. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile, 95% CI: 1.50, 8.97) than among male infants (adjusted OR = 1.22 for the highest tertile, 95% CI = 0.48, 3.11) (p heterogeneity = 0.06). Our findings suggest that maternal exposure to higher levels of chromium during pregnancy may potentially increase the risk of delivering LBW infants, particularly for female infants.

We investigated the association between prenatal exposure to lead (Pb) and the risk of preterm low birth weight (PLBW). Pb concentrations in maternal urine collected at birth from 408 subjects (102 cases and 306 matched controls) were analyzed and adjusted by creatinine. The median Pb concentration in the PLBW cases (10.60 μg Pb/g creatinine) was higher than that of the controls (7.28 μg Pb/g creatinine). An adjusted odds ratio (OR) of 2.96 (95% CI = 1.49-5.87) for PLBW was observed when the highest tertile was compared to the lowest tertile of Pb levels. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile; 95% CI = 1.35-9.93) than male infants (adjusted OR = 1.91 for the highest tertile; 95% CI = 0.74-4.95). Our study suggests that prenatal exposure to levels of Pb encountered today in China is associated with an elevated risk of PLBW.