Centers for Birth Defects Research and Prevention (CBDRPs)

描述（由申请人提供）：出生缺陷影响美国每100个婴儿中有3个，是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病因的证据。国家出生缺陷预防研究（NBDPS）于1997年启动，旨在调查30多种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，并为制定有效的预防策略提供证据基础。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为阿肯色中心提供了一个不可替代的信息库，其中包括可能与出生缺陷相关的母亲暴露和生活方式因素，以及来自大量人口样本的有价值的DNA样本。疾病预防控制中心的持续支持将使阿肯色州继续参与NBDPS，帮助该中心继续开展前沿研究并分享研究成果，并利用疾病预防控制中心的支持在地方一级获得对出生缺陷研究的支持。在即将到来的资金周期中，阿肯萨斯中心将通过三个具体目标扩大其现有的研究工作，以解决出生缺陷问题：继续参与国家出生缺陷预防研究，并以此扩大阿肯萨斯中心的流行病学研究能力（目标1）；继续开展本地和合作研究，利用阿肯色州生殖健康监测系统和NBDPS的数据调查出生缺陷的复杂病因（目标2），并继续支持从NBDPS参与者收集的生物样本的高通量基因组和表观基因组分析，通过增加CDC的机构和校外资金支持（目标3）。这些目标将通过解决表观遗传机制（基因特异性甲基化改变）、遗传易感性（单核苷酸多态性）、促进氧化的生活方式因素（吸烟、酒精、肥胖）、孕产妇营养（如低叶酸水平）来实现

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.