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

RFA-DD-18-001 评估妊娠暴露的出生缺陷研究 (BD-STEPS) II 核心

• 批准号: 10421038
• 负责人: Wendy N Nembhard
• 金额: $ 95万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10421038
• 关键词: RFA; DD; 18; 001; Birth

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.

A组份 在美国，每 100 个婴儿中就有 3 个出生时患有结构性先天缺陷。出生缺陷是美国婴儿死亡的主要原因 以及全世界。患有先天缺陷的儿童往往会经历生活质量下降，并遭受严重的社会和社会影响。 经济负担。尽管出生缺陷构成了重大的公共卫生问题，但临床和公共卫生部门正在努力预防大多数出生缺陷 是有限的。缺乏大多数非综合征性出生缺陷病因的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，旨在调查这些复杂的病因。随着分相 在 NBDPS 之外，CDC 发起了一项以 NBDPS 调查结果为基础的新举措 - 评估妊娠暴露的出生缺陷研究 （SD-步骤）。阿肯色州出生缺陷研究和预防中心，NBDPS 参与者 16 年，8D 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中心的基础上继续发展 确定孕早期可能适合早期预防的母亲暴露情况。阿肯色中心的长期目标是 预防或显着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，这些暴露可能 通过参与 BO-STEPS II 发现导致出生的基因与环境相互作用，减少特定出生缺陷的发生 通过支持对从 NBDPS 和 BO-STEPS 收集的生物样本进行高通量基因组和表观基因组分析来发现缺陷 参与者，并通过培训和指导数据分析方面的初级研究人员来帮助培养下一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，我们将在建立临床和公共 预防出生缺陷的健康策略。 成分 全球每年发生 3200 万死产。在美国和其他发达国家，死产是一种基本上未被充分研究的围产期结局 尽管它是最常见的不良妊娠结局之一，占所有围产期死亡的一半。最近的一次是在 2006 年 美国现有数据显示，每 1,000 名活产婴儿中就有 6.05 名死产，加上胎儿死亡，远高于许多高收入国家 和美国。健康人群 2020 胎儿死亡率目标为 5.6（每 1,000 个活产儿+胎儿死亡）。死产的确定性较差 在美国以及大多数发达国家和发展中国家。关于死产发生率的最新国家数据来自 2006 年，其中 强调目前用于确定和监测这一未充分研究的围产期结局的基础设施不足。这 疾病控制与预防中心 (CDC) 通过两项试点研究证明，扩大现有的分娩方法 用于死产监测的缺陷登记是一种可行且具有成本效益的死产监测方法。疾病预防控制中心宣布了一项倡议，“出生” 评估妊娠暴露的缺陷研究 (BO-STEPS) II 死产研究，重点是进行病例对照研究以阐明 死产的可改变风险因素，利用出生缺陷研究和预防基础设施中心作为基础 监视和研究。阿肯色中心的长期目标是预防或显着减少出生缺陷的发生和 不良妊娠结局。我们建议利用阿肯色州基于人口的主动死产监测系统来识别新的死产情况 可改变的妊娠暴露可减少死产的发生。通过我们的研究，我们将在建立 健康战略1;1旨在预防出生缺陷和死产。 相关性（参见说明）： 成分 A：出生缺陷是婴儿死亡的主要原因。在美国出生的每 100 名婴儿中就有 3 名患有严重的结构性出生缺陷，构成了 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，阿肯色中心致力于继续识别 母亲在怀孕早期接触的物质可能适合早期预防，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制定预防出生缺陷的临床和公共卫生战略方面保持主导作用。 成分 B：死产占所有围产期死亡的一半，构成了重大的公共卫生问题。大多数死产的原因尚不清楚。建立在 根据我们之前在 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母亲暴露情况 预防为主，大大减少死产的发生。疾病预防控制中心的持续资助将使阿肯色中心保持领先地位 制定预防死产的策略。

项目成果

Prevalence of structural birth defects among infants with Down syndrome, 2013-2017: A US population-based study.

• DOI: 10.1002/bdr2.1854
• 发表时间: 2021-01-15
• 期刊: Birth defects research
• 影响因子: 2.1
• 作者: Heinke D;Isenburg JL;Stallings EB;Short TD;Le M;Fisher S;Shan X;Kirby RS;Nguyen HH;Nestoridi E;Nembhard WN;Romitti PA;Salemi JL;Lupo PJ;National Birth Defects Prevention Network
• 通讯作者: National Birth Defects Prevention Network

Maternal occupational exposure to polycyclic aromatic hydrocarbons and the risk of isolated congenital heart defects among offspring.

• DOI: 10.1016/j.envres.2020.109550
• 发表时间: 2020-07
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Patel J;Nembhard WN;Politis MD;Rocheleau CM;Langlois PH;Shaw GM;Romitti PA;Gilboa SM;Desrosiers TA;Insaf T;Lupo PJ;National Birth Defects Prevention Study
• 通讯作者: National Birth Defects Prevention Study

Regionalization of Congenital Heart Surgery: Can We Make it Reality?

先天性心脏病手术的区域化：我们能实现吗？

• DOI: 10.1016/j.athoracsur.2020.10.070
• 发表时间: 2021
• 期刊: The Annals of thoracic surgery
• 作者: Bolin,ElijahH;Nembhard,WendyN;Collins2nd,RThomas
• 通讯作者: Collins2nd,RThomas

Prevalence and mortality in children with congenital diaphragmatic hernia: a multicountry study.

• DOI: 10.1016/j.annepidem.2020.11.007
• 发表时间: 2021-04
• 期刊: Annals of epidemiology
• 影响因子: 5.6
• 作者: Politis MD;Bermejo-Sánchez E;Canfield MA;Contiero P;Cragan JD;Dastgiri S;de Walle HEK;Feldkamp ML;Nance A;Groisman B;Gatt M;Benavides-Lara A;Hurtado-Villa P;Kallén K;Landau D;Lelong N;Lopez-Camelo J;Martinez L;Morgan M;Mutchinick OM;Pierini A;Rissmann A;Šípek A;Szabova E;Wertelecki W;Zarante I;Bakker MK;Kancherla V;Mastroiacovo P;Nembhard WN;International Clearinghouse for Birth Defects Surveillance and Research
• 通讯作者: International Clearinghouse for Birth Defects Surveillance and Research

Cancer Risk by Attained Age among Children with Birth Defects in Arkansas.

阿肯色州出生缺陷的儿童达到的癌症风险。

• DOI: 10.1016/j.canep.2020.101796
• 发表时间: 2020-10
• 期刊: Cancer epidemiology
• 影响因子: 2.6
• 作者: Patel J;Schraw JM;Lupo PJ;Mian A;Nembhard WN
• 通讯作者: Nembhard WN