RFA-DD-18-001 Birth Defects Study To Evaluate Pregnancy exposures (BD-STEPS) II Core & Component B Steps -Stillbirth

组分A 在美国，每100个婴儿中就有3个出生时就有结构性缺陷。出生缺陷是美国婴儿死亡的主要原因 和世界各地。患有出生缺陷的儿童通常会经历生活质量下降，并对他们造成严重的社会和心理影响。 经济负担。虽然出生缺陷造成了重大的公共卫生问题，但预防大多数出生缺陷的临床和公共卫生努力 是有限的。大多数非综合征性出生缺陷的病因学缺乏证据是建立预防措施的主要障碍 程序. 1997年，国家出生缺陷预防研究（NBDPS）成立，以调查这些复杂的病因。随着相位 在NBDPS之外，CDC在NBDPS的发现基础上发起了一项新的倡议--评估妊娠暴露的出生缺陷研究 （SD-STEPS）。阿肯色州出生缺陷研究和预防中心，16年来一直是NBDPS的参与者， STEPS I致力于了解出生缺陷的原因，并欢迎有机会继续“为证据基础做出贡献”。 这将有助于制定有效的预防战略。我们有能力在阿肯色州中心的基础上， 确定可能适合早期预防的妊娠早期母体暴露。阿肯色州中心的长期目标是 预防或显著减少出生缺陷的发生。因此，我们建议确定可改变的早期妊娠暴露， 通过参与BO-STEPS II，发现导致出生的基因-环境相互作用， 通过支持从NBDPS和BO-STEPS收集的生物样品的高通量基因组学和表观基因组学分析， 参与者，并通过培训和指导数据分析方面的初级研究人员，帮助培养未来几代出生缺陷研究人员， 手稿准备和其他研究相关活动。通过我们的研究，我们将保持在建立临床和公众 预防出生缺陷的卫生战略。 组件 全球每年有3200万死产。在美国和其他发达国家，死产是一个很大程度上研究不足的围产期结局 尽管这是最常见的不良妊娠结果之一，占所有围产期死亡的一半。2006年，最新 根据美国现有的数据，每1,000名活产婴儿加上胎儿死亡中就有6.05名死产，远远高于许多高收入国家 和美国。2020年胎儿死亡率目标为5.6（每1 000例活产婴儿+胎儿死亡）。死产很难确定 在美国和大多数发达国家和发展中国家。关于死胎流行率的最新国家数据是2006年的， 强调了现有基础设施不足，无法确定和监测这一研究不足的围产期结局。的 疾病控制和预防中心（CDC）通过两项试点研究证明，扩大现有的分娩方法， 死胎监测缺陷登记是监测死胎的可行和具有成本效益的方法。CDC宣布了一项倡议， 评价妊娠暴露的缺陷研究（BO-STEPS）II死胎研究，该研究将重点进行病例对照研究，以阐明 死产的可改变的风险因素，使用出生缺陷研究和预防中心的基础设施， 监视和研究。阿肯色州中心的长期目标是预防或显著减少出生缺陷的发生， 不良妊娠结局。我们建议利用我们在阿肯色州基于人口的死胎主动监测系统， 减少死产发生率的可改变的妊娠暴露。通过我们的研究，我们将在建立 预防出生缺陷和死产的卫生战略。 相关性（参见说明）： 组成部分A：出生缺陷是婴儿死亡的主要原因。在美国，每100个出生的婴儿中就有3个有严重的结构性出生缺陷， 重大公共卫生问题。基于我们之前在NBDPS和BD STEPS I方面的经验，阿肯色州中心将继续确定 孕妇在怀孕早期受到的辐射可以及早预防，从而大大减少出生缺陷的发生。CDC中心的延续 资金将使该中心能够在建立预防出生缺陷的临床和公共卫生战略方面发挥主导作用。 构成部分B：死产占所有围产期死亡的一半，构成严重的公共卫生问题。大多数死产的原因是未知的。基础上 根据我们以前在NBDPS和BO-STEPS I方面的经验，我们将继续确定可能适合早期妊娠的妊娠早期母体暴露。 预防和重点是大大减少死产的发生。CDC中心继续提供资金将使阿肯色州中心能够保持领导作用 制定防止死产的战略。

COMPONENT A Three out of every 100 babies in the US are born with a structural birth defects. Birth defects are a leading cause of infant mortality in the US and worldwide. Children who survive with birth defects often experience a diminished quality of life and impose a substantial social and economic burden. Although birth defects pose a significant public health problem, clinical and public heath efforts to prevent most birth defects are limited. The lack of evidence regarding etiology of most nonsyndromic birth defects represents a major barrier in establishing prevention programs. In 1997, the National Birth Defects Prevention Study (NBDPS) was created to investigate these complex etiologies. With the phasing out of the NBDPS, the CDC initiated a new initiative building on the NBDPS findings -the Birth Defects STudy to Evaluate Pregnancy exposures (SD-STEPS). The Arkansas Center f~r Birth Defects Research and Prevention, a participant in the NBDPS for 16 years and a participant in 8D STEPS I, is dedicated to understani:ling the causes of birth defects and welcomes the opportunity to continue to"contribute to an evidence base that will facilitate development of effective prevention strategies. We are well positioned to build on the foundation of the Arkansas Center by identifying maternal exposures in early pregnancy that may be amenable to early prevention. The long-term goal of the Arkansas Center is to prevent or significantly reduce the occurrence of birth defects. We propose, therefore, to identify modifiable early pregnancy exposures that may decrease the occurrence of selected birth defects by participating in BO-STEPS II, discovering gene-environment interactions that lead to birth defects by supporting high-throughput genomic and epigenomlc analyses of biological samples collected from NBDPS and BO-STEPS participants, and helping develop future generations of birth-defect researchers by training and mentoring junior researchers in data analysis, manuscript preparation, and other study-related activities. Through our studies, we will maintain a leading role in establishing clinical and public health strategies to prevent birth defects. COMPONENTS Each year 32 million stillbirths occur globally. In the US and other developed countries, stillbirth is a largely under-studied perinatal outcome despite being one of the most common adverse pregnancy outcomes, accounting for one-half of all perinatal deaths. In 2006, the most recent data available for the US, stillbirths occurred In 6.05 of every 1,000 live births plus fetal deaths, much higher than many high-income countries and the US. Healthy People 2020 Objective of 5.6 (per 1,000 live births+ fetal deaths) for fetal mortality rates. Stillbirths are poorly ascertained in the US and most developed and developlng countries. The most recent national data available on stillbirth prevalence is from 2006 which underscores the insufficient infrastructure currently in place for ascertainment and monitoring of this understudied perinatal outcome. The Centers for Disease Control and Prevention (CDC) demonstrated through two pilot studies that expanding the current methods of existing birth defects registries for stillbirth surveillance is a viable and cost-effective method for surveillance of stillbirths. CDC announced an initiative, Birth Defects Study to Evaluate Pregnancy exposures (BO-STEPS) II Stillbirth study, which will focus on conducting a case-control study to elucidate modifiable risk factors for stillbirths, using the Centers for Birth Defects Research and Prevention infrastructure as the foundation for surveillance and research. The Arkansas Center's long-term goal is to prevent or significantly reduce the occurrence of birth defects and adverse pregnancy outcomes. We propose to utilize our population-based, active surveillance system of stillbirths in Arkansas to Identify novel modifiable pregnancy exposures that decrease the occurrence of stillbirths. Through our studies, we will maintain a leading role in establishing health strate1;1ies to prevent birth defects and stillbirths. RELEVANCE (See instructions): COMPONENT A: Birth defects are a leadlng cause of infant mortality. Three out of every 100 babies born in the US have a major structural birth defects, posing a significant public health problem. Building on our previous experience with the NBDPS and BD STEPS I, the Arkansas Center is positioned to continue Identifying maternal exposures in early pregnancy that may be amenable to early prevention, greatly reducing the occurrence of birth defects. Continuation of CDC Center funding will enable the Center to maintain a leading role in establishing clinical and public health strategies to prevent birth defects. COMPONENT B: Stillbirths account for half of all perinatal deaths, posing a significant public health problem. The cause of most stillbirths is unknown. Building on our previous experience with the NBDPS and BO-STEPS I, we will continue to identify maternal exposures in early pregnancy that may be amenable to early prevention and focus on greatly reducing the occurrence of stillbirths. Continuation of CDC Center funding will enable the Arkansas Center to maintain a leading role in establishing strategies to prevent stillbirths.