In Utero Exposure to Metals and Vitamins B on Placenta and Child Cardiometabolic Outcomes

项目总结/摘要 主要基于动物研究数据的新兴假说表明，肥胖和2型糖尿病 流行病的部分原因可能是在最敏感和最脆弱的时期接触化学品。 发育，主要是在子宫内。我们的首要目标是系统地调查孕产妇的相互作用， 重金属暴露，包括汞（Hg）、铅（Pb）、镉（Cd）、锰（Mn）和硒 (Se)和母体维生素B状态与胎盘病理学和儿童心脏代谢结果的关系 使用生命历程框架。这一提议的动机是，接触这些金属是 在美国普通民众中无处不在。更令人担忧的是，这些金属在超过85%-99%的样品中可检测到。 孕妇的胎盘和胎儿的积累，加上对胎儿的发育构成威胁。 然而，关键的研究差距仍然存在于我们对子宫内暴露于这些物质的影响的理解中。 胎盘上的金属和生命后期的心脏代谢风险。 我们建议进行一项前瞻性的出生队列研究，以检查子宫内 暴露于重金属和B族维生素状态（叶酸、B12和同型半胱氨酸），以及胎盘和儿童 使用生命过程框架的心脏代谢结果。我们将利用 波士顿出生队列（BBC），一个大的，美国城市，主要是低收入的少数民族人口与高利率 母亲和儿童肥胖和高血压，以及普遍暴露于这些金属。我们将分析 英国广播公司约2，000对拥有产后随访数据（分子、流行病学、临床）的母婴 和营养数据库），沿着产前金属暴露，如在母体红细胞中评估的。在 目标1，我们将评估儿童期子宫内金属暴露和心脏代谢结果;目标2，我们 将评估子宫内金属暴露和胎盘病理学发现;在目标3中，我们将探讨 母亲适当的叶酸水平可以减轻金属暴露的不利影响。确保成功 为了实施这个项目，我们组建了一支优秀的研究团队， 在相关多学科领域具有互补专长的研究人员。 该研究通过跨越学科和发展阶段来研究潜在的创新 从产前暴露于金属，到胎盘病理，再到儿童心脏代谢的途径 结果。这项研究将在社会经济处境不利的少数民族妇女中进行， 孩子这项研究的结果与减少美国最脆弱人群的健康差距直接相关。 肥胖和2型糖尿病流行病的代际放大， 这些人口。

Project Summary/Abstract Emerging hypotheses, based primarily on data from animal studies, suggest that obesity and type 2 diabetes epidemics could be due, in part, to chemical exposures during the most sensitive and vulnerable windows of development, mainly in utero. Our overarching aims are to systematically investigate the interplay of maternal heavy metal exposures, including mercury (Hg), lead (Pb), cadmium (Cd), manganese (Mn), and selenium (Se), and maternal vitamin B status in relation to placental pathology and childhood cardiometabolic outcomes using a life course framework. This proposal in motivated by the fact that exposures to these metals are ubiquitous in the general U.S. population. More alarmingly, these metals are detectable in more than 85%-99% of pregnant women, coupled with placental and fetal accumulation, posing a threat to the developing fetus. However, critical research gaps remain on our understanding of the effects of in utero exposure to these metals on the placenta and cardiometabolic risk later in life. We propose to conduct a prospective birth cohort study to examine inter-relationships between in utero exposure to heavy metals and B vitamin status (folate, B12 and homocysteine), and placenta and child cardiometabolic outcomes using a life course framework. We will leverage the exceptional database of the Boston Birth Cohort (BBC), a large, U.S. urban, predominantly low-income minority population with a high rates of maternal and child obesity and hypertension, and prevalent exposure to these metals. We will analyze ~2,000 mother-child pairs of the BBC who have postnatal follow-up data (molecular, epidemiological, clinical and nutritional databases), along with prenatal metal exposures, as assessed in maternal red blood cells. In Aim 1, we will evaluate in utero exposure to metals and cardiometabolic outcomes in childhood; in Aim 2, we will assess in utero exposure to metals and placental pathology findings; and in Aim 3, we will explore if adequate maternal folate status can mitigate the adverse effects of metal exposure. To ensure the successful implementation of this project, we have assembled an outstanding research team comprised of well- established researchers with complementary expertise in relative multi-disciplinary fields. The proposed study is innovative by bridging disciplines and developmental stages to investigate the potential pathways from prenatal exposure to metals, to placental pathology, and to childhood cardiometabolic outcomes. This study will be conducted in a sample of socioeconomically-disadvantaged minority women and children. Findings from this study are directly relevant to reduce health disparities in the most vulnerable U.S. populations, and to break the inter-generational amplification of obesity and type 2 diabetes epidemics within these populations.