Maternal Exposure to Low Level Mercury, Metabolome, and Child Cardiometabolic Risk in Multi-Ethnic Prospective Birth Cohorts

多种族预期出生队列中母亲接触低水平汞、代谢组和儿童心脏代谢风险

• 批准号: 10321291
• 负责人: XIAOBIN WANG
• 金额: $ 23.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-21 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321291
• 关键词: 21 year old; Adult; Adverse effects; Affect; Alcohol consumption; Animals; Anti-Inflammatory Agents; Antioxidants; Biological Markers; Birth; Blood Pressure; Body mass index; Boston; Cardiometabolic Disease; Cardiovascular Diseases; Chemical Exposure; Child; China; Clinical; Collaborations; DNA Methylation; Data; Development; Diabetes Mellitus; Dietary intake; Disease; Dose; Endothelium; Environmental Exposure; Environmental Health; Environmental Pollutants; Epidemic; Ethnic Origin; Exposure to; Fatty Acids; Fetal Development; Fetus; Fishes; Folic Acid; Food; Future; Growth; Health; Homocysteine; Human; Hypertension; Indoor Air Pollution; Inflammatory; Insulin; Intervention; Investigation; Iron; Laboratories; Lead; Life; Lipids; Maternal Exposure; Measures; Mediating; Mercury; Meta-Analysis; Metabolic; Metals; Methods; Micronutrients; Modeling; Modification; Neurotoxins; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nucleic Acids; Nutrient; Obesity; Outcome; Overweight; Passive Smoking; Pathway interactions; Placenta; Population; Pregnancy; Pregnancy Trimesters; Primary Prevention; Procedures; Property; Public Health; Publishing; Quality Control; Race; Research; Research Design; Resources; Risk; Risk Assessment; Role; Scientist; Seafood; Selenium; Side; Socioeconomic Status; Statistical Methods; Testing; Third Pregnancy Trimester; Time; Toxic Environmental Substances; Umbilical Cord Blood; Uterus; Vitamin B Complex; age group; base; bioaccumulation; biological specimen archives; blood pressure elevation; cardiometabolic risk; cardiometabolism; cell growth; cohort; data archive; early onset; early pregnancy; fetal; global health; improved; in utero; insight; intergenerational; metabolome; metabolomics; multi-ethnic; novel; nutrition; offspring; overweight child; prenatal; prenatal exposure; prospective; quality assurance; repaired; response

Abstract This US-China collaborative study will leverage extensive data and archived biospecimens from two well- established prospective birth cohorts: one in Boston, US; and the other in Shanghai, China, to examine the temporal and dose-response relationships between maternal exposure to Hg at critical developmental windows (preconception and specific trimesters) and child cardio-metabolic outcomes from birth to age 21 years. This proposal has a strong scientific premise. Hg is a persistent and widespread environmental pollutant worldwide and a known neurotoxicant at high doses, and its role in cardio-metabolic health is beginning to be recognized. Studies in adults have suggested that low dose Hg exposure was associated with cardiovascular diseases, diabetes, and obesity. A critical unanswered question is whether maternal prenatal low dose Hg exposure can have a long-lasting impact on the developing fetus. This proposal presents a prime opportunity for a US-China collaboration on environmental health since US and China are among the top emitters of Hg in the world. This proposal focuses on the effect of in-utero Hg exposure on child’s long-term cardio-metabolic health, which is novel, important, and critically needed, given Hg’s ability to cross the placenta and the well- documented fetal bioaccumulation of Hg. Our preliminary data showed a very high correlation of maternal-cord blood Hg and a dose-response relationship between maternal Hg levels and child BMI and blood pressure. These findings raise the hypothesis that maternal low dose prenatal exposure to Hg affects fetal future cardio- metabolic health and warrant further investigation. This proposal uses vigorous scientific methods. Both the US and China lack clear and effective strategies to reduce the adverse health effects of low dose Hg exposure. We plan to evaluate to what extent maternal micronutrient status (e.g., folate) counteracts the adverse effects of Hg exposure on child cardio-metabolic outcomes based on our preliminary data. Furthermore, motivated by our preliminary data that maternal Hg exposure can alter both maternal and fetal circulating metabolomic profile, we will explore maternal and fetal metabolome to gain novel insight to mechanistic pathways. This proposal provides an exceptional platform for US-China scientists to leverage resources and expertise on both sides. The two cohorts can serve as a discovery and replication cohort for each other as well as meta-analysis, using a similar study design and outcome and covariate definitions; and same laboratory and quality assurance and control (QA/QC) procedures and statistical methods. By doing so, it greatly enhances our ability to test the study hypotheses and make the study findings far more generalizable and impactful. This proposal has significant clinical and public health implications. It represents a significant step forward in elucidating the roles of prenatal exposure to low dose Hg and micronutrients in child long-term cardio-metabolic outcomes, as well as the potential mechanisms. If successful, it can serve as a model to rigorously investigate other early life environmental exposures.

抽象的 这项美国 - 中国合作研究将利用两个良好的数据和存档的生物测量。 既定的前瞻性出生队列：美国波士顿；另一个在中国上海，检查 关键发育窗口处的母乳暴露于HG之间的临时和剂量反应关系 （先入为主和特定的三个月）以及从出生到21岁的儿童心脏代谢结果。这 提案有很强的科学前提。汞是一种持久而广泛的环境污染物 全球及其高剂量的已知神经毒性，其在心脏代谢健康中的作用开始是 认可。成年人的研究表明，低剂量HG暴露与心血管有关 疾病，糖尿病和肥胖症。一个关键的未解决的问题是产妇产前低剂量HG是否 暴露会对发育中的胎儿产生持久影响。该提议提出了一个主要的机会 自美国和中国是HG的最高发射器之一以来 世界。该提案重点介绍了In-Utero HG暴露对儿童长期心脏代谢的影响 鉴于HG的跨越和良好的能力，健康是新颖，重要且急需的 据记录的HG胎儿生物积累。我们的初步数据显示出母亲的相关性很高 血液HG和Mater HG水平与儿童BMI和血压之间的剂量反应关系。 这些发现提出了这样的假设，即材料低剂量产前暴露于HG会影响胎儿未来的心脏 代谢健康和保证进一步调查。该建议使用有力的科学方法。两个都 美国和中国缺乏减少低剂量HG的不良健康影响的明确有效的策略 接触。我们计划评估材料的微量营养素状态（例如叶酸）在何种程度上抵消 汞暴露对儿童心脏代谢结果的不利影响基于我们的初步数据。 此外，通过我们的初步数据成熟，材料hg暴露会改变母乳和胎儿 循环代谢组谱，我们将探索母校和胎儿代谢组，以获得新颖的见解 机械途径。该提案为美国 - 中国科学家提供了一个非凡的平台 双方的资源和专业知识。这两个队列可以作为发现和复制队列 彼此以及荟萃分析，使用类似的研究设计和结果和协变量定义；和 相同的实验室和质量保证和控制（QA/QC）程序和统计方法。这样， 它极大地增强了我们检验研究假设的能力，并使研究结果更加普遍 和有影响力。该提案具有重大的临床和公共卫生影响。它代表 在阐明产前暴露于低剂量Hg和微量营养素的儿童中的作用方面的重要一步 长期心脏代谢结果以及潜在机制。如果成功，它可以用作 严格研究其他早期生活环境暴露的模型。