Iowa CBDRP: Component A BD-STEPS II Core

爱荷华州 CBDRP：组件 A BD-STEPS II 核心

• 批准号: 10264770
• 负责人: KRISTIN CONWAY
• 金额: $ 90万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10264770
• 关键词: Iowa; CBDRP; Component; BD; STEPS

PROJECT SUMMARY In the US, major birth defects affect a delivery every 4½ minutes and the morbidity and mortality of tens of thousands of children annually. An environmental (i.e. non-inherited) exposure or causal gene variant is estimated to explain about one-third of all defects that occur. Since 1996, the Iowa Center for Birth Defects Research and Prevention (CBDRP) has played a leadership role in surveillance and research of major birth defects. Our partnerships with the Iowa Department of Public Health and Iowa Registry for Congenital and Inherited Disorders provide comprehensive and timely surveillance of deliveries to Iowa residents. With these partnerships, we successfully enrolled mothers in the National Birth Defects Prevention Study (NBDPS) and Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) I. Using exposure data and biologic specimens collected, we made substantial contributions to birth defects epidemiology, ranging from methods development to identifying gene-environment interaction effects. Our work has provided critical insights into birth defect etiology and been disseminated in high-impact journals. We propose to expand the work of the Iowa CBDRP through successful participation in the BD-STEPS II. Our overall goal is to identify modifiable maternal exposures in early pregnancy, which may increase the risk for having a pregnancy affected with a major birth defect. We will expertly conduct comprehensive and timely data collection and reporting for the BD- STEPS II using our highly experienced surveillance and research infrastructures. Our proposed research approach is not only consistent with the BD-STEPS II required activities, but expands and innovates the conceived study design (RFA-DD-18-001). We propose to address critical barriers identified in a recent review of the NBDPS to investigate modifiable risk factors for major birth defects. To accomplish this, we will expand the traditional epidemiology approach (used in the NBDPS and BD-STEPS) by integrating a multiomics systems epidemiology approach. Our systems approach is novel in its application to NBDPS and BD-STEPS data. It will use state of the art genomic analysis to lead to improved characterization of the case phenome and improved delineation of pathways that influence birth defect development via the exposome. The expertise of our key personnel and collaborating investigators, along with access to rich exposure and biologic data from independent populations, provides us with unique resources among all CBDRPs, allowing us to successfully implement our systems approach. Additionally, we will continue our leadership role and expand our training of a future generation of birth defect researchers. Along with continuing to train pre-doctoral and postdoctoral scholars, we will now include bachelor’s scholars. Our key personnel, investigators, and scholars will continue our high productivity in disseminating findings from NBDPS and BD-STEPS through peer-reviewed publications. Research findings generated will provide critical insights into modifiable risk factors for major birth defects and be used for family education, treatment improvements, and application of prevention strategies.

项目摘要 在美国，每4分半钟就有一次重大出生缺陷影响分娩， 每年有数千名儿童。环境（即非遗传性）暴露或致病基因变异是 估计可以解释大约三分之一的缺陷。自1996年以来，爱荷华州出生缺陷中心 研究和预防中心在重大分娩的监测和研究方面发挥了领导作用 缺陷我们与爱荷华州公共卫生部和爱荷华州先天性和 遗传性疾病提供全面和及时的监测交付给爱荷华州居民。与这些 通过建立伙伴关系，我们成功地让母亲参加了国家出生缺陷预防研究（NBDPS）， 出生缺陷研究，以评估妊娠期流产S（BD-STEPS）I。使用暴露数据和生物 标本收集，我们作出了重大贡献，出生缺陷流行病学，从方法 发展到识别基因-环境相互作用效应。我们的工作提供了重要的见解， 出生缺陷病因学，并在高影响力的期刊上传播。我们建议扩大 爱荷华州CBDRP通过成功参与BD-STEPS II。我们的总体目标是确定可修改的 母亲在怀孕早期的暴露，这可能会增加怀孕的风险， 严重的先天缺陷我们会专业地为屋宇署进行全面及适时的数据收集及汇报工作- STEPS II使用我们经验丰富的监控和研究基础设施。我们提出的研究 这种方法不仅与BD-STEPS II所要求的活动相一致，而且扩展和创新了 设想的研究设计（RFA-DD-18-001）。我们建议解决最近一次审查中发现的关键障碍 NBDPS调查重大出生缺陷的可改变风险因素。为了实现这一目标，我们将扩大 传统的流行病学方法（用于NBDPS和BD-STEPS），通过整合多组学 系统流行病学方法。我们的系统方法在NBDPS和BD-STEPS中的应用是新颖的 数据它将使用最先进的基因组分析，以改善对病例表型组的表征， 改善了通过干扰素组影响出生缺陷发展的途径的描述。的专门知识 我们的主要人员和合作研究人员，沿着访问丰富的暴露和生物数据， 独立人群，为我们提供了所有CBDRPs中独特的资源，使我们能够成功地 实施我们的系统方法。此外，我们将继续发挥领导作用，并扩大我们的培训， 下一代的出生缺陷研究者沿着继续培养博士前、博士后 学者，我们现在将包括学士的学者。我们的主要人员，调查人员和学者将继续 我们通过同行评审传播NBDPS和BD-STEPS研究结果的高效率 出版物。所产生的研究结果将为重大分娩的可改变风险因素提供重要见解 缺陷，并用于家庭教育，治疗改进和预防策略的应用。