Iowa CBDRP: Birth Defects Study To Evaluate Pregnancy exposureS

描述(申请人提供)：在美国，重大出生缺陷每年影响数以万计的儿童的发病率和死亡率。据估计，环境暴露(广义)或因果基因变异只能解释发生的所有主要缺陷的大约三分之一。自1996年以来，爱荷华州出生缺陷研究和预防中心(CBDRP)在监测和研究重大出生缺陷方面发挥了领导作用。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一次州内分娩提供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爱荷华州所有99个县的家庭提供服务。这些伙伴关系还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，我们在出生缺陷流行病学方面做出了重大贡献，从方法开发到基因-环境相互作用效应的识别。这项工作为几个主要出生缺陷的病因学提供了关键的见解，并已在影响力较大的期刊上传播。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怀孕早期可改变的母亲暴露可能会增加受某些重大结构性出生缺陷影响的怀孕风险。我们将利用我们成熟和经验丰富的监测和研究基础设施，为屋宇署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、同行评议的期刊上的传播。我们提议的研究活动将使用一种“脚手架”方法来识别风险因素，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口面部裂和颅缝融合的病因学研究，并将其扩展到更多的颅面和肌肉骨骼缺陷。NBDPS和BD-STEPS数据，以及我们的合作者提供的来自独立种群的数据，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方面的初级调查人员。与博士后学生一起，我们将在出生缺陷研究的跨学科团队科学方面培训临床和博士后学者。这项研究将包括方法论、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拟议的研究和培训。所产生的研究成果将用于家庭教育、改善治疗、预防策略的应用和培训活动，这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.