Hongxiu Liu

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.

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.

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.

Association between prenatal nickel exposure and preterm low birth weight: possible effect of selenium

There is a proposed link between prenatal nickel (Ni) exposure and preterm low birth weight (PLBW); however, this association remains unclear. Selenium (Se) may modify this relationship by protecting against Ni toxicity. Concentrations of Ni and Se were measured in urine samples collected from 408 pregnant women (102 PLBW cases and 306 matched controls) in China. Conditional logistic regression was utilized to explore the association between Ni levels and PLBW, as well as the effect modification by Se on this association. A significant association was observed between higher maternal urinary Ni levels and risk of PLBW [adjusted odds ratio (OR) = 2.80 (95% confidence interval (CI): 1.44, 5.44) for the highest tertile], and this association was more apparent among female infants than that among male infants. Further analyses showed that mothers with high urinary Ni and low urinary Se levels had a significantly increased risk for PLBW [adjusted OR = 2.87 (95% CI: 1.09, 7.56)] compared with the mothers with low urinary Ni and high urinary Se levels. Our study indicates that prenatal exposure to Ni was a risk factor for PLBW. Se might provide protection against the toxicity of Ni.

Associations between repeated measures of maternal urinary phthalate metabolites during pregnancy and cord blood glucocorticoids

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.

Maternal exposure to nickel in relation to preterm delivery

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.

Cadmium body burden and pregnancy-induced hypertension

Previous studies provided a strong evidence of the association between environmental exposure to cadmium (Cd) and hypertension in the general population. However, the role of Cd in pregnancy-induced hypertension (PIH) remains unclear. A total of 5429 pregnant women was selected from a birth cohort in Wuhan, China to investigate the association between Cd exposure and risk of PIH. Among them, 199 (3.7%) women were diagnosed with PIH. The Cd concentrations in maternal urine collected at delivery were measured by inductively coupled plasma mass spectrometry. Multivariable logistic regression was performed on Cd concentrations as a continuous variable (natural logarithm transformed) or as a categorical variable (tertiles). For about 3-fold increase in urinary Cd concentrations, there was 75% increase in the odds of PIH after adjusting for potential confounders (odds ratio (OR) =1.75; 95% confidence interval (CI): 1.45, 2.11). Women in the highest tertile of urinary Cd had 2.2-fold increased OR of PIH, compared with women in the lowest tertile (2.24; 95% CI: 1.47, 3.41). Furthermore, we found a significant interaction between Cd exposure and maternal socioeconomic status on PIH (P for interaction=0.04). Our findings indicate that higher Cd exposure might increase the risk of PIH, and the association might be modified by socioeconomic status.