Chuansha Wu

Maternal urinary bisphenol A levels and infant low birth weight: A nested case–control study of the Health Baby Cohort in China

BACKGROUND Exposure to bisphenol A (BPA), a known endocrine disruptor, has been demonstrated to affect fetal development in animal studies, but findings in human studies have been inconsistent. OBJECTIVES We investigated whether maternal exposure to BPA during pregnancy is associated with an increased risk of infant low birth weight (LBW). METHODS A total 452 mother-infant pairs (113 LBW cases and 339 matched controls) were selected from the participants enrolled in the prospective Health Baby Cohort (HBC) in Wuhan city, China, during 2012-2014. BPA concentrations were measured in maternal urine samples collected at delivery, and the information of birth outcomes was retrieved from the medical records. A conditional logistic regression was used to evaluate the relationship between urinary BPA levels and LBW. RESULTS Mothers with LBW infants had significantly higher urinary BPA levels (median: 4.70μg/L) than the control mothers (median: 2.25μg/L) (p<0.05). Increased risk of LBW was associated with higher maternal urinary levels of BPA [adjusted odds ratio (OR)=3.13 for the medium tertile, 95% confidence interval (CI): 1.21, 8.08; adjusted OR=2.49 for the highest tertile, 95% CI: 0.98, 6.36]. The association was more pronounced among female infants than among male infants, with a statistical evidence of heterogeneity in risk (p=0.03). CONCLUSIONS Prenatal exposure to higher levels of BPA may potentially increase the risk of delivering LBW infants, especially for female infants. This is the first case-control study to examine the association in China.

Novel Chlorinated Polyfluorinated Ether Sulfonates and Legacy Per-/Polyfluoroalkyl Substances: Placental Transfer and Relationship with Serum Albumin and Glomerular Filtration Rate

Per- and polyfluoroalkyl substances (PFASs) may cross the placental barrier and lead to fetal exposure. However, little is known about the factors that influence maternal-fetal transfer of these chemicals. PFAS concentrations were analyzed in 100 paired samples of human maternal sera collected in each trimester and cord sera at delivery; these samples were collected in Wuhan, China, 2014. Linear regression was used to estimate associations of transfer efficiencies with factors. Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs, 6:2 and 8:2) were frequently detected (>99%) in maternal and cord sera. A significant decline in PFAS levels during the three trimesters was observed. A U-shape trend for transfer efficiency with increasing chain length was observed for both carboxylates and sulfonates. Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR). Cord serum albumin was a positive factors for higher transfer efficiency (increased 1.1-4.1% per 1g/L albumin), whereas maternal serum albumin tended to reduce transfer efficiency (decreased 2.4-4.3% per 1g/L albumin). Our results suggest that exposure to Cl-PFAESs may be widespread in China. The transfer efficiencies among different PFASs were structure-dependent. Physiological factors (e.g., GFR and serum albumin) were observed for the first time to play critical roles in PFAS placental transfer.

A case-control study of maternal exposure to chromium and infant low birth weight in China

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.

Prenatal cadmium exposure and preterm low birth weight in China.

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.

Relationship between maternal phthalate exposure and offspring size at birth

Research findings on effects of prenatal phthalate exposure on fetal growth were inconsistent. Increasing evidence from animal studies has indicated a potential sex-specific effect of phthalates on fetal growth, but the current human data was limited. In this study, we aimed to estimate the relationships between maternal phthalate exposure and infant birth size. Six major phthalate metabolite levels of urine samples were measured among pregnant women (n=1002) from the Healthy Baby Cohort (HBC), China. The associations between urinary phthalate metabolites levels and birth size (birth weight, birth length, birth weight z-scores and ponderal index) were estimated using linear regression models. In boys, the ln-transformed di-2-ethylhexyl phthalate (DEHP) metabolite levels were significantly associated with increased birth weight and birth weight z-scores. Additionally, each ln-unit increase in mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) was associated with a 0.25kg/m3 [95% confidence interval (CI): 0.03, 0.47] increase in ponderal index in boys. However, we did not observe any significant association of maternal phthalate metabolite levels with any of the outcomes in girls. Our data suggested potential sex-specific associations of maternal phthalate exposure with increased birth weight and ponderal index, which were merely apparent in boys.

Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort study

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<0·0001) and low birthweight (J-shaped, p=0·0001); the adjusted odds ratios (ORs) for increasing quartiles of urinary vanadium were 1·76 (95% CI 1·05-2·95) for Q2, 3·17 (1·96-5·14) for Q3, and 8·86 (5·66-13·86) for Q4 for preterm delivery, and 2·29 (95% CI 1·08-4·84) for Q2, 3·22 (1·58-6·58) for Q3, and 3·56 (1·79-7·10) for Q4 for low birthweight. Ln-vanadium concentrations were linearly associated with the risk of early-term delivery (linear, p<0·0001) and being small for gestational age (linear, p=0·0027), with adjusted ORs of 1·15 (95% CI 1·10-1·21) for early-term delivery and 1·12 (1·04-1·21) for being small for gestational age per unit increase in Ln-vanadium concentrations. INTERPRETATION Our findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes. FUNDING National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Key Laboratory of Environment and Health.

Critical Windows of Prenatal Exposure to Cadmium and Size at Birth

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.

Relationship between maternal exposure to bisphenol S and pregnancy duration

Bisphenol S (BPS) has been progressively used due to the potential safety problems of bisphenol A (BPA). Thus Human studies are needed to investigate the developmental effects of BPS. In this study, the impact of maternal BPS exposure on birth outcomes was evaluated with linear and logistic regression models. BPS was analyzed in spot urine samples collected from 985 pregnant women at admission to labor. It was found in 93.7% of the urine samples with the specific gravity adjusted geometric mean concentration of 0.17 μg/L. One ln-unit increase in urinary BPS was associated with a 0.72-day increase in pregnancy duration (95% CI: 0.34, 1.09). When stratified by fetal sex, each ln-unit increase in maternal urinary BPS was significantly correlated with increased gestational age [adjusted β = 1.02, 95% confidence intervals (CI): 0.47, 1.57] and increased odds of late term birth [adjusted odds ratio = 1.29, 95% CI: 1.00, 1.67] for girls, but not significantly for boys. Including maternal urinary BPA and BPS in one model did not change the results. Associations of BPS with birth weight or length were not observed. This is the first report about BPS exposure for pregnant women from China. Higher maternal urinary BPS concentrations were associated with increased gestational age, suggesting maternal BPS exposure may interfere with pregnancy duration. The findings require replication but reveal the probable risks posed by the developmental BPS exposure.

The association of repeated measurements of prenatal exposure to triclosan with fetal and early-childhood growth

BACKGROUND Triclosan (TCS) is known to possess endocrine disrupting properties and metabolize rapidly in the human body. Human data concerning repeated measurements of TCS throughout pregnancy in relation to fetal and childhood growth are sparse. OBJECTIVES We investigated the associations between multiple measurements of maternal urinary concentrations of TCS during pregnancy and fetal and early-childhood growth. METHODS The study population included 850 mother-infant pairs who participated in a prenatal cohort established between 2014 and 2015 in Wuhan. Prenatal TCS exposure was measured in a complete series of urine samples collected at the first, second and third trimesters. General linear models and generalized estimating equation models were applied to evaluate the associations of the averaged maternal urinary concentrations of TCS over trimesters and trimester-specific urinary TCS with the z-scores of estimated fetal weight, head circumference, abdominal circumference, and femur length at 16, 24, and 31 gestational weeks, weight and length at birth, and weight and height at 0.5, 1, and 2 years of age. RESULTS In overall infants, we did not observe any significant association of the averaged maternal urinary concentrations of TCS over trimesters with ultrasound parameters and size at birth. However, a positive association of borderline statistical significance was found between averaged prenatal TCS exposure and the third-trimester estimated fetal weight z-score in girls in sex-stratified analyses (β = 0.054, 95% CI: -0.005, 0.113, p = 0.07). Moreover, averaged prenatal TCS exposure was positively associated with 2 year-old weight z-score among total infants (β = 0.046, 95% CI: 0.005, 0.087). After stratifying by sex, the same association was observed in girls with more prominent estimation (β = 0.062, 95% CI: 0.000, 0.124), whereas the association weakened and became not significant in boys (β = 0.033, 95% CI: -0.024, 0.089). TCS exposure at 1st and 2nd-trimester were positively associated with weight z-score at 2 years, in both overall and female infants. CONCLUSIONS Prenatal exposure to triclosan was associated with elevated third-trimester estimated fetal weight and 2 year-old weight z-score in girls, and the early and middle stage of pregnancy may be the windows of vulnerability. Apart from these findings, we did not find strong evidence for prenatal triclosan exposure in relation to fetal and early-childhood growth.

Urinary concentrations of phthalate metabolites associated with changes in clinical hemostatic and hematologic parameters in pregnant women

BACKGROUND Exposure to phthalates, one kind of widely used plasticizers, has been demonstrated to be associated with some clinical hematological changes in circulatory system from animal studies and in vitro experiments, but their relations to hemostatic and hematologic changes in human are unknown. OBJECTIVES We explored the relationships of urinary phthalate metabolites with clinical hemostatic and hematologic parameter changes in pregnant women. METHODS The present study population included 1482 pregnant women drawn from an ongoing prospective birth cohort study in Wuhan, China. Eight urinary phthalate metabolites and eight blood clinical parameters, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), total white blood cell counts (WBC), red blood cell counts (RBC), hemoglobin (Hb), and platelet counts (PLT) were measured in the late third trimester. The associations between phthalate metabolites and blood parameters were analyzed using general linear model. The odds ratios (ORs) for anemia during pregnancy associated with phthalates were also explored by using logistic regression models. RESULTS After adjustment for false discovery rate, a significantly negative association between ln-transformed urinary mono-ethyl phthalate (MEP) concentration and blood Fg, and a positive association between urinary mono-butyl phthalate (MBP) and APTT were found in this study. Higher concentrations of mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) were associated with lower Hb concentrations. In addition, higher levels of MEHP, MEOHP and MECPP were also associated with increased likelihood of anemia. No significant associations were found between phthalates and other hematologic parameters. CONCLUSIONS Higher urinary phthalate metabolites in late third trimester were associated with prolonged blood clotting time, decreased Hb concentrations, and increased likelihood of anemia in pregnant women. Further research is needed to replicate the observed findings and clarify the potential biological mechanism.