Iowa CBDRP: Birth Defects Study To Evaluate Pregnancy exposureS

描述（由申请人提供）：在美国，重大出生缺陷每年影响到成千上万儿童的发病率和死亡率。据估计，环境暴露（广义定义）或致病基因变异只能解释所有主要缺陷的三分之一。自1996年以来，爱荷华州出生缺陷研究和预防中心（CBDRP）在重大出生缺陷的监测和研究中发挥了领导作用。我们与爱荷华州先天性和遗传性疾病登记处的合作伙伴关系为每个州内分娩提供了及时和全面的积极监测。我们与爱荷华州公共卫生部的合作伙伴关系为所有99个爱荷华州县的家庭提供了外展服务。这些合作伙伴关系也使我们能够成功地将母亲纳入国家出生缺陷预防研究（NBDPS）和相关研究，以收集环境暴露和生物数据。利用这些数据，我们对出生缺陷流行病学做出了重大贡献，从方法开发到基因-环境相互作用效应的鉴定。这项工作为几种主要出生缺陷的病因学提供了重要的见解，并在高影响力的期刊上传播。我们建议通过成功参与评估妊娠暴露的出生缺陷研究（BD-STEPS）来扩大爱荷华州CBDRP的工作。我们的总体目标是确定可改变的母亲暴露在怀孕早期，可能会增加风险，有一个怀孕的影响，某些重大的，结构性的出生缺陷。我们将利用我们成熟和经验丰富的监测和研究基础设施，为BD-STEPS进行全面和及时的数据收集和报告。我们还将向国家和国际科学家扩展跨学科合作，以增加NBDPS和BD-STEPS研究结果在高影响力同行评审期刊上的传播。我们建议的研究活动将使用“支架”方法进行风险因素识别，通过同时检查环境暴露和基因变异，从“发现”到“确认”再到“相互作用”。“特别是，我们将继续我们的高影响力的病因学研究的口面裂和颅缝早闭，并扩大到其他颅面和肌肉骨骼缺陷。NBDPS和BD-STEPS数据，沿着我们合作者提供的独立人群数据，将为环境暴露、基因和基因-环境相互作用效应的分析提供丰富的资源。此外，我们将继续发挥领导作用，并扩大我们的培训计划，以培养出生缺陷研究的初级研究人员。沿着博士前学生，我们将培养临床和研究博士后学者在跨学科团队科学的出生缺陷研究。这项研究将包括方法学，病因学和翻译研究。凭借我们的科学专业知识和经验丰富的基础设施，我们有能力成功完成我们提出的研究和培训。所产生的研究结果将用于家庭教育，改善治疗，预防策略的应用和培训活动将有助于下一代出生缺陷研究人员。

DESCRIPTION (provided by applicant): In the U.S., major birth defects impact the morbidity and mortality of tens of thousands of children annually. An environmental exposure (broadly defined) or causal gene variant is estimated to explain only about one-third of all major 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 partnership with the Iowa Registry for Congenital and Inherited Disorders provides timely and comprehensive active surveillance of each in-state delivery. Our partnership with the Iowa Department of Public Health provides outreach to families in all 99 Iowa counties. These partnerships have also allowed us to successfully enroll mothers in the National Birth Defects Prevention Study (NBDPS) and related studies to collect environmental exposure and biological data. Using these data, we have made substantial contributions to birth defects epidemiology, ranging from methods development to identification of gene-environmental interaction effects. This work has provided critical insights into the etiology of several major birth defects and has been disseminated in high-impact journals. We propose to expand the work of the Iowa CBDRP through successful participation in the Birth Defects Study To Evaluate Pregnancy Exposures (BD-STEPS). Our overall goal is to identify modifiable maternal exposures in early pregnancy that may increase the risk for having a pregnancy affected by certain major, structural birth defects. We will conduct comprehensive and timely data collection and reporting for the BD-STEPS using our established and experienced surveillance and research infrastructure. We will also extend interdisciplinary collaborations to national and international scientists to increase dissemination of NBDPS and BD-STEPS findings in high-impact, peer-reviewed journals. Our proposed research activities will use a "scaffold" approach for risk factor identification, by simultaneously examining environmental exposures and gene variants from "discovery" to "confirmation" to "interaction." In particular, we will continue our high-impact etiological studie of orofacial clefts and craniosynostosis, and expand them to additional craniofacial and musculoskeletal defects. NBDPS and BD-STEPS data, along with those from independent populations provided by our collaborators, will offer rich resources for analyses of environmental exposures, genes, and gene-environmental interaction effects. Additionally, we will continue our leadership role and expand our training program to develop junior investigators in birth defects research. Along with pre-doctoral students, we will train clinical and research post- doctoral scholars in interdisciplinary team science for birth defects research. This research will encompass methodological, etiological, and translational studies. With our scientific expertise and highly experienced infrastructure, we are well-positioned to successfully complete our proposed research and training. Research findings generated will be used for family education, improvements in treatment, and application of prevention strategies and training activities will contribute to the next generation of birth defect researchers.