Centers for Birth Defects Research and Prevention (CBDRPs)

描述(申请人提供)：在美国出生的婴儿中，每100个婴儿中就有3个受到出生缺陷的影响，它是导致全国和全球婴儿死亡的主要原因，并可能导致存活婴儿的持续发病率。尽管这一公共卫生问题意义重大，但预防大多数出生缺陷的临床和公共卫生努力根本不存在。建立预防计划的一个主要障碍是缺乏关于大多数非综合征性出生缺陷的病因的证据。全国出生缺陷预防研究(NBDPS)于1997年启动，旨在调查30多个主要非综合征性出生缺陷的复杂病因。作为NBDPS的一部分，阿肯色州出生缺陷研究和预防中心致力于了解出生缺陷的原因，并为促进有效预防策略的制定提供证据基础。该中心的长期目标是预防或显著减少出生缺陷的发生。参与NBDPS为阿肯色州中心提供了一个不可替代的信息库，其中包含可能与出生缺陷有关的母亲暴露和生活方式因素，以及大量基于人群的样本中有价值的DNA样本。疾控中心的持续支持将保持阿肯色州在NBDPS方面令人印象深刻的参与，帮助该中心继续产生尖端研究并分享研究成果，并利用CDC的支持在地方层面获得对出生缺陷研究的支持。在即将到来的供资周期中，阿肯色州中心将通过三个具体目标扩大其现有的研究努力，以解决出生缺陷问题：继续参与国家出生缺陷预防研究，并以此扩大阿肯色州中心的流行病学研究能力(目标1)；继续开展地方性合作研究，利用阿肯色州生殖健康监测系统和NBDPS(目标2)的数据调查出生缺陷的复杂病因；并通过增加机构和外部资金的疾控中心支持，继续支持从NBDPS参与者那里收集的生物样本的高通量基因组和表观基因组分析(目标3)。这些目标将通过解决表观遗传机制(改变的基因特异性甲基化)、遗传易感性(单核苷酸多态)、促氧化生活方式因素(吸烟、酒精、肥胖)、母亲营养(如低营养)来实现。 饮食中的叶酸)和母体的天然免疫(免疫反应基因的功能受损)。项目 结果将是对了解出生缺陷的遗传、环境和代谢原因的直接和直接贡献，并为临床和公共卫生一级预防计划奠定必要的基础。国家出生缺陷预防研究、基因组工具的进步和领先的多学科专业知识的融合，有望产生一个可以作为初级预防计划基础的证据基础。

DESCRIPTION (provided by applicant): Birth defects, which affect three of every 100 babies born in the US, are a leading cause of infant mortality both nationally and globally and can cause continuing morbidity for infants who survive. Despite the significance of this public health problem, clinical and public health efforts to prevent most birth defects simply do not exist. A major barrier to establishing prevention programs is the lack of evidence regarding etiology of most nonsyndromic birth defects. The National Birth Defects Prevention Study (NBDPS) was launched in 1997 to investigate the complex etiology of more than 30 major nonsyndromic birth defects. As part of the NBDPS, the Arkansas Center for Birth Defects Research and Prevention is dedicated to understanding the causes of birth defects and contributing to an evidence base that facilitates development of effective prevention strategies. The Center's long-term goal is to prevent or significantly reduce the occurrence of birth defects. Participating in NBDPS has provided the Arkansas Center with an irreplaceable repository of information regarding maternal exposures and lifestyle factors that may be associated with birth defects and valuable DNA samples from a large population-based sample. Continued support from CDC will sustain Arkansas' impressive participation in NBDPS, help the Center continue to generate cutting-edge research and to share research results, and leverage CDC support to gain support for birth defect research at the local level. In the upcoming funding cycle, the Arkansas Center will expand its existing research efforts to address birth defects through three specific aims: continue participation in the National Birth Defects Prevention Study and in so doing expand the epidemiological research capacity of the Arkansas Center (Aim 1); continue to conduct local and collaborative studies that investigate the complex etiology of birth defects by utilizing data from the Arkansas Reproductive Health Monitoring System and NBDPS (Aim 2), and continue to support highthroughput genomic and epigenomic analyses of biological samples collected from NBDPS participants by augmenting CDC support with institutional and extramural funds (Aim 3). These aims will be achieved by addressing epigenetic mechanisms (altered gene-specific methylation), genetic susceptibilities (single nucleotide polymorphisms), pro-oxidant lifestyle factors (smoking, alcohol, obesity), maternal nutrition (e.g., low dietary folate), and maternal innate immunity (impaired function in immune response genes). Project outcomes will be immediate, direct contributions to the understanding of genetic, environmental, and metabolic causes of birth defects and the necessary foundation for clinical and public health primary prevention programs. The convergence of the National Birth Defects Prevention Study, advances in genomic tools, and leading multidisciplinary expertise promises to produce an evidence-base that can be the basis of primary prevention programs.