Wenyu Liu

Maternal urinary cadmium concentrations in relation to preterm birth in the Healthy Baby Cohort Study in China

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 womans 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=-0.77day; 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.

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.

Prenatal chromium exposure and risk of preterm birth: a cohort study in Hubei, China

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 <0.01]. Logistic regression analyses also indicated that higher maternal chromium [adjusted odds ratio (OR) (95% CI): 1.55(0.99, 2.42) for the medium tertile; 1.89(1.13, 3.18) for the highest tertile; p trend <0.01] was associated with increased risk of preterm birth. The associations appeared to be more pronounced in male infants (adjusted OR (95% CI): 2.54 (1.29, 4.95) for the medium tertile; 2.92 (1.37, 6.19) for the highest tertile; p trend <0.01). Our findings suggest maternal exposure to higher chromium levels during pregnancy may potentially increase the risk of delivering preterm infants, particularly for male infants.

Fetal exposure to lead during pregnancy and the risk of preterm and early-term deliveries

Studies have reported the association between lead exposure during pregnancy and preterm birth. However, findings are still inconsistent. This prospective birth cohort study evaluated the risks of preterm and early-term births and its association with prenatal lead exposure in Hubei, China. A total of 7299 pregnant women were selected from the Healthy Baby Cohort. Maternal urinary lead levels were measured by the Inductively Coupled Plasma Mass Spectrometry. The associations between tertiles of urinary lead levels and the risks of preterm and early-term deliveries were assessed using multiple logistic regression models. The geometric mean of creatinine-adjusted urinary lead concentrations among all participating mothers, preterm birth, and early-term birth were 3.19, 3.68, and 3.17μg/g creatinine, respectively. A significant increase in the risk of preterm births was associated with the highest urinary lead tertile after adjusting for confounders with odds ratio (OR) of 1.96. The association was more pronounced among 25-36 years old mothers with OR of 2.03. Though significant p trends were observed between lead exposure (medium and high tertiles) and the risk of early-term births, their ORs were not significant. Our findings indicate that the risk of preterm birth might increase with higher fetal lead exposure, particularly among women between the age of 25 and 36 years.

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.

Exposure to chromium during pregnancy and longitudinally assessed fetal growth: Findings from a prospective cohort

BACKGROUND Prenatal exposure to chromium may be associated with reduced birth weight; however, critical windows of such exposure for fetal growth are unclear. OBJECTIVE Our study was aimed to assess trimester-specific associations of chromium exposure with fetal growth parameters measured repeatedly by ultrasound and birth size, and to see whether these associations were modified by fetal sex. METHODS We conducted a prospective cohort of 3041 women in Wuhan, China, from 2013 to 2016. Chromium concentrations were measured in maternal urine samples collected in the 1st, 2nd, and 3rd trimesters using an inductively coupled plasma mass spectrometry. We calculated standard deviation scores for ultrasound measured head circumference, abdominal circumference (AC), femur length, and estimated fetal weight (EFW) at 16, 24, and 31 weeks of gestation. Linear regressions with generalized estimating equations were used to estimate the associations of specific gravity-adjusted urinary chromium concentrations in each trimester with fetal growth parameters and birth weight, birth length, and ponderal index. RESULTS Inverse associations of chromium exposure in the 1st trimester with fetal growth parameters at 31 weeks of gestation were observed, resulting in significant reductions in AC of -5.4% (95% confidence interval [CI]: -9.6%, -1.2%) and EFW of -5.6% (95% CI: -9.8%, -1.4%) per unit increase in natural logarithm transformed urinary chromium concentration. Urinary chromium concentration in the 2nd trimester was also associated with reductions in AC of -7.0% (95% CI: -12.5%, -1.4%) and in EFW of -5.0% (95% CI: -10.6%, 0.6%) at 31 weeks, and these inverse associations were evident in boys (reduction in AC of -13.9% [95% CI: -21.1%, -6.7%]; EFW of -9.5% [95% CI: -16.9%, -2.0%]) but not in girls (increase in AC of 2.9% [95% CI: -5.7%, 11.5%]; EFW of 1.5% [95% CI: -6.8%, 9.8%]) (both pineraction < 0.05). Moreover, one-unit increase in urinary chromium concentrations in the 1st and 2nd trimesters were both associated with significant reductions in ponderal index of -0.11 kg/m3 (95% CI: -0.19, -0.03 kg/m3) and -0.15 kg/m3 (95% CI: -0.27, -0.03 kg/m3), respectively. CONCLUSION Our findings suggest that chromium may be a toxic metal for fetal growth. Early and mid-pregnancy seem to be the most vulnerable period for fetal exposure to chromium, but these results need further confirmation.

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.