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

摘要 这项中美合作研究将利用来自两个井的大量数据和存档生物标本， 建立了前瞻性出生队列：一个在美国波士顿，另一个在中国上海，以检查 关键发育期母体汞暴露的时间和剂量-反应关系 （孕前和特定孕期）和儿童从出生到21岁的心脏代谢结果。这 这个建议有很强的科学性。汞是一种持久和广泛的环境污染物 它是一种已知的高剂量神经毒物，它在心脏代谢健康中的作用开始被人们所关注。 认可.对成年人的研究表明，低剂量汞暴露与心血管疾病有关。 疾病、糖尿病和肥胖症。一个尚未回答的关键问题是，孕妇产前低剂量汞 暴露在空气中会对发育中的胎儿产生长期影响。这项提议提供了一个绝佳的机会 由于美国和中国都是2008年最大的汞排放国， 世界该建议关注宫内汞暴露对儿童长期心脏代谢的影响， 健康，这是新的，重要的，迫切需要的，鉴于汞的能力，通过胎盘和井- 有文件证明胎儿体内存在汞的生物累积。我们的初步数据显示母带-脐带 血汞以及母亲汞水平与儿童体重指数和血压之间的剂量反应关系。 这些发现提出了一个假设，即母亲产前低剂量接触汞会影响胎儿未来的心脏功能。 代谢健康，需要进一步调查。这一建议采用了有力的科学方法。两 美国和中国缺乏明确有效的战略来减少低剂量汞对健康的不利影响 exposure.我们计划评估产妇微量营养素状况（例如，叶酸）抵消 根据我们的初步数据，汞暴露对儿童心脏代谢结果的不利影响。 此外，根据我们的初步数据，母体汞暴露可以改变母体和胎儿， 循环代谢组学概况，我们将探讨母体和胎儿代谢组学，以获得新的见解， 机械路径。该提案为美中科学家提供了一个特殊的平台， 双方的资源和专业知识。这两个组群可以作为发现和复制组群， 使用相似的研究设计、结局和协变量定义进行相互分析以及荟萃分析;以及 相同的实验室和质量保证和控制（QA/QC）程序和统计方法。通过这样做， 它极大地增强了我们检验研究假设的能力，并使研究结果更具普遍性 影响力很大这项建议具有重大的临床和公共卫生意义。它代表了一 在阐明产前接触低剂量汞和微量营养素对儿童健康的作用方面迈出了重要一步。 长期的心脏代谢结果，以及潜在的机制。如果成功，它可以作为一个 模型，以严格调查其他早期生活环境暴露。

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.