Jie Hu1, Yang Peng2, Tongzhang Zheng3, Bin Zhang4, Wenyu Liu2, Chuansha Wu2, Minmin Jiang2, Joseph M Braun3, Simin Liu5, Stephen L Buka3, Aifen Zhou4, John Pierce Wise6, Yiming Zhang4, Yangqian Jiang2, Chen Hu2, Xiaomei Chen2, Zheng Huang2, Dan Zheng2, Kunchong Shi3, Xichi Zhang7, Ashley Truong3, Zhengmin Qian8, Wei Xia2, Yuanyuan Li2, Shunqing Xu9. 1. Key Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA; Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 2. Key Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 3. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA. 4. Wuhan Women and Children Medical Care Center, Wuhan, Hubei, China. 5. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA; Division of Endocrinology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA. 6. Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY, USA. 7. The George Washington University, Washington, DC, USA. 8. Department of Epidemiology, College for Public Health and Social Justice, Saint Louis University, St Louis, MO, USA. 9. Key Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: xust@hust.edu.cn.
Abstract
BACKGROUND: Identification of windows of heightened vulnerability to environmental factors has substantial public health implications. Prenatal exposure to vanadium has been linked to adverse birth outcomes; however, critical windows for such exposure during fetal growth remain unknown. We aimed to assess trimester-specific associations of vanadium exposure with ultrasound measures of fetal growth and birth size in a Chinese longitudinal cohort. METHODS: The present study was embedded in our ongoing prospective prenatal cohort study at the Wuhan Women and Children Medical Care Center (Wuhan, Hubei, China). Pregnant women were eligible for inclusion if they provided signed informed consent and were less than 16 weeks pregnant with a single gestation, and agreed to take in-person interviews, undergo ultrasound examinations, and provide blood and urine samples. We collected urine samples and measured urinary vanadium concentrations using inductively coupled plasma mass spectrometry. We calculated SD scores for ultrasound-measured biparietal diameter, head circumference, occipitofrontal diameter, abdominal circumference, femur length, and estimated fetal weight at 16, 24, and 31 weeks of gestation. We applied linear regressions with generalised estimating equations to estimate associations of urinary vanadium concentrations in each trimester with ultrasound-measured fetal growth parameters or neonatal size at birth. FINDINGS: As of Oct 12, 2016, we recruited 3075 women who were non-smokers and non-drinkers during pregnancy, provided up to three urine samples during the first, second, and third trimesters, and gave birth to live singletons without birth defects. We excluded women who did not provide information on ultrasound measurements (n=20) or who only had one ultrasound measurement of fetal crown-rump length at the first trimester (n=14). We excluded another 16 women because they had missing values for confounding variables, leaving 3025 women retained in the study. Every doubling of urinary vanadium concentration in the first trimester was associated with a significant increase in femur length (adjusted percentage change 6·4%, 95% CI 0·7 to 12·1) at 16 weeks of gestation and reductions in biparietal diameter (-4·2%, -8·2 to -0·1), head circumference (-6·0%, -10·1 to -1·9), occipitofrontal diameter (-5·7%, -9·9 to -1·5), and abdominal circumference (-5·3%, -9·4 to -1·2) at 31 weeks of gestation. Every doubling of urinary vanadium concentration in the second trimester was significantly associated with reductions in SD scores for head circumference (-7·2%, -14·1 to -0·3) and abdominal circumference (-6·9%, -13·8 to -0·1) at 31 weeks of gestation. The highest quartile of urinary vanadium concentration (>1·18 μg/L) in the first trimester, when compared with the lowest quartile (≤0·60 μg/L), was associated with a mean decrease in birthweight of 12·6 g (95% CI 2·5-22·8; ptrend=0·0055) and a mean decrease in ponderal index of 0·07 kg/m3 (0·01-0·12; ptrend=0·0053). Moreover, newborns with restricted birth size had higher vanadium exposure in the first and third trimesters. INTERPRETATION: Vanadium might be toxic to humans and impair fetal growth. The first, early second, and late third trimesters could be critical windows for heightened vulnerability to vanadium for fetal growth. Our findings require further investigation in other populations. FUNDING: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Huazhong University of Science and Technology.
BACKGROUND: Identification of windows of heightened vulnerability to environmental factors has substantial public health implications. Prenatal exposure to vanadium has been linked to adverse birth outcomes; however, critical windows for such exposure during fetal growth remain unknown. We aimed to assess trimester-specific associations of vanadium exposure with ultrasound measures of fetal growth and birth size in a Chinese longitudinal cohort. METHODS: The present study was embedded in our ongoing prospective prenatal cohort study at the Wuhan Women and Children Medical Care Center (Wuhan, Hubei, China). Pregnant women were eligible for inclusion if they provided signed informed consent and were less than 16 weeks pregnant with a single gestation, and agreed to take in-person interviews, undergo ultrasound examinations, and provide blood and urine samples. We collected urine samples and measured urinary vanadium concentrations using inductively coupled plasma mass spectrometry. We calculated SD scores for ultrasound-measured biparietal diameter, head circumference, occipitofrontal diameter, abdominal circumference, femur length, and estimated fetal weight at 16, 24, and 31 weeks of gestation. We applied linear regressions with generalised estimating equations to estimate associations of urinary vanadium concentrations in each trimester with ultrasound-measured fetal growth parameters or neonatal size at birth. FINDINGS: As of Oct 12, 2016, we recruited 3075 women who were non-smokers and non-drinkers during pregnancy, provided up to three urine samples during the first, second, and third trimesters, and gave birth to live singletons without birth defects. We excluded women who did not provide information on ultrasound measurements (n=20) or who only had one ultrasound measurement of fetal crown-rump length at the first trimester (n=14). We excluded another 16 women because they had missing values for confounding variables, leaving 3025 women retained in the study. Every doubling of urinary vanadium concentration in the first trimester was associated with a significant increase in femur length (adjusted percentage change 6·4%, 95% CI 0·7 to 12·1) at 16 weeks of gestation and reductions in biparietal diameter (-4·2%, -8·2 to -0·1), head circumference (-6·0%, -10·1 to -1·9), occipitofrontal diameter (-5·7%, -9·9 to -1·5), and abdominal circumference (-5·3%, -9·4 to -1·2) at 31 weeks of gestation. Every doubling of urinary vanadium concentration in the second trimester was significantly associated with reductions in SD scores for head circumference (-7·2%, -14·1 to -0·3) and abdominal circumference (-6·9%, -13·8 to -0·1) at 31 weeks of gestation. The highest quartile of urinary vanadium concentration (>1·18 μg/L) in the first trimester, when compared with the lowest quartile (≤0·60 μg/L), was associated with a mean decrease in birthweight of 12·6 g (95% CI 2·5-22·8; ptrend=0·0055) and a mean decrease in ponderal index of 0·07 kg/m3 (0·01-0·12; ptrend=0·0053). Moreover, newborns with restricted birth size had higher vanadium exposure in the first and third trimesters. INTERPRETATION:Vanadium might be toxic to humans and impair fetal growth. The first, early second, and late third trimesters could be critical windows for heightened vulnerability to vanadium for fetal growth. Our findings require further investigation in other populations. FUNDING: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Huazhong University of Science and Technology.
Authors: Mary Kate M Lane; Mahlet Garedew; Emma C Deary; Cherish N Coleman; Melissa M Ahrens-Víquez; Hanno C Erythropel; Julie B Zimmerman; Paul T Anastas Journal: Chem Res Toxicol Date: 2022-02-07 Impact factor: 3.739