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

子宫内接触金属和维生素 B 对胎盘和儿童心脏代谢结果的影响

• 批准号: 9978051
• 负责人: Guoying Wang
• 金额: $ 8.19万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978051
• 关键词: Adverse effects; Affect; Air; Antiinflammatory Effect; Antioxidants; Biogenesis; Biological Markers; Birth; Blood Pressure; Blood Vessels; Boston; C-reactive protein; Cadmium; Cardiovascular Diseases; Cell physiology; Chemical Exposure; Chemicals; Child; Childhood; Clinical; Cohort Studies; Coupled; Data; Databases; Development; Diabetes Mellitus; Discipline; Elderly; Ensure; Epidemic; Epidemiology; Erythrocytes; Exposure to; Fertilizers; Fetal Development; Fetal Growth; Fetus; Folic Acid; Food; Food Supplements; Fortified Food; Health; Heavy Metals; High Prevalence; Histologic; Homocysteine; Hypertension; Inflammation; Insulin; Knowledge; Lead; Lead levels; Leptin; Life; Life Cycle Stages; Light; Lipids; Low income; Malignant Neoplasms; Manganese; Maternal Exposure; Mediating; Mercury; Metal exposure; Metals; Minority; Molecular; Mothers; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Obesity; Outcome; Overweight; Pathology; Pathway interactions; Perception; Placenta; Placentation; Play; Population; Pregnant Women; Proxy; Public Health; Publications; Reproductive Health; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Selenium; Soil; Third Pregnancy Trimester; Time; Trace Elements; Vascular Endothelium; Vitamin B 12; Vitamin B Complex; Water; Weight; Woman; adiponectin; age group; animal data; anti-cancer; base; blood lead; cardiometabolic risk; cardiometabolism; cohort; commercial application; effective intervention; environmental chemical exposure; fetal; follow-up; health disparity; improved; in utero; innovation; intergenerational; maternal obesity; methyl group; multidisciplinary; novel; nutrition; obesity in children; obesity prevention; obesogenic; persistent organic pollutants; postnatal; prenatal; prenatal exposure; prospective; protective effect; protective factors; socioeconomic disadvantage; toxic metal

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.

项目摘要/摘要 主要基于动物研究数据的新兴假设表明肥胖症和2型糖尿病 流行病可能部分归因于最敏感和脆弱的窗户中的化学暴露 开发，主要在子宫内。我们的总体目的是系统地研究孕产妇的相互作用 重金属暴露，包括汞（HG），铅（PB），镉（CD），锰（MN）和硒 （SE）和与胎盘病理学和儿童心脏代谢结果有关的母体维生素B状态 使用人生课程框架。这一提议是由这些金属暴露的事实是 在美国普通人群中无处不在。更令人震惊的是，这些金属可在超过85％-99％中检测到 孕妇，再加上胎盘和胎儿的积累，对发育中的胎儿构成威胁。 但是，关键的研究差距仍然是我们对子宫对这些影响的影响的理解 胎盘上的金属和心脏代谢的风险以后生命。 我们建议进行一项前瞻性出生队列研究，以检查子宫中的相互关系 暴露于重金属和B维生素状态（叶酸，B12和同型半胱氨酸）以及胎盘和儿童 使用生活课程框架的心脏代谢结果。我们将利用 波士顿出生队列（BBC），这是一个大型的城市，主要是低收入少数族裔人口 孕产妇和儿童肥胖和高血压，并普遍接触这些金属。我们将分析 BBC的2,000对具有产后随访数据的母子对（分子，流行病学，临床 和营养数据库），以及产前金属暴露，如母体红细胞所评估。在 AIM 1，我们将在子宫内评估儿童时期的金属和心脏代谢结果；在AIM 2中，我们 将在子宫内评估金属和胎盘病理学发现；在AIM 3中，我们将探索是否 足够的母体叶酸状况可以减轻金属暴露的不利影响。确保成功 实施该项目，我们组建了一个由良好的研究团队组成的杰出研究团队 在相对多学科领域具有互补专业知识的成熟研究人员。 拟议的研究是通过弥合学科和发展阶段来研究潜力的创新性的 从产前暴露于金属，胎盘病理学和儿童心脏代谢的途径 结果。这项研究将在社会经济占据占领的少数妇女和 孩子们。这项研究的发现与减少美国最脆弱的健康差异直接相关 种群，并打破肥胖和2型糖尿病的代代相传的扩增 这些人群。