Prenatal Alcohol in Sudden Infant Death Syndrome and Stillbirth (PASS) Network

婴儿猝死综合症和死产中的产前酒精 (PASS) 网络

• 批准号: 8535560
• 负责人: Hannah Chase Kinney
• 金额: $ 71.81万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-26 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8535560
• 关键词: Abbreviations; Affect; Alcohols; Anxiety; Autopsy; Biological; Biological Neural Networks; Brain; Brain Stem; Cerebral cortex; Child; Classification; Clinical; Cognitive; Communities; Complex; Consultations; DNA; Data Analyses; Data Coordinating Center; Development; Developmental Biology; Electroencephalography; Enrollment; Environmental Risk Factor; Ethanol toxicity; Etiology; Face; Failure; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Death; Fetal Development; Fetal Growth; Fetal Ultrasonography; Fetus; Forensic Medicine; Functional disorder; Future; Genetic; Goals; Growth; Hearing; Human; Infant; Infant Development; Injury; Intervention; Investigation; Knowledge; Life; Link; Maternal Age; Measures; Mediating; Medical; Mental Depression; Mission; Neurotransmitters; Outcome; Participant; Pathologic; Pathology; Pattern; Performance; Perfusion; Perinatal; Phase; Physiological; Placenta; Pregnancy; Principal Investigator; Process; Protocols documentation; Public Health; Reporting; Request for Applications; Research; Research Infrastructure; Risk; Risk Reduction; Role; Shapes; Site; Specimen; Stress; Structure; Sudden infant death syndrome; Supervision; Synapses; System; Time; Tissue Banking; Tissue Banks; Tissues; Training; Ultrasonography; Variant; adverse outcome; alcohol exposure; alcohol research; base; cognitive function; cohort; critical period; fetal; fetal tobacco exposure; follow-up; genetic analysis; high risk; human tissue; improved; in vivo; indexing; infant death; innovation; interest; neurobehavioral; nutrition; prenatal; prenatal exposure; prevent; programs; resilience; response; stillbirth; tobacco exposure

DESCRIPTION (provided by applicant): The mission of the Developmental Biology and Pathology Center (DBPC) in the PASS Network is to conduct human research into the biological aspects of alcohol-related injury as they relate to stillbirth, sudden infant death syndrome (SIDS), and fetal alcohol spectrum disorders (FASD). The four Specific Aims of the DPBC are: Placenta-To determine the role of maternal alcohol exposure, as potentially modified by other environmental factors, in placental dysfunction and pathology; Brainstem-To determine the role of prenatal alcohol, as potentially modified by other environmental factors, in neurotransmitter brainstem pathology in SIDS and stillbirth; Cerebral Cortex-^To determine the effects of prenatal alcohol exposure, as potentially modified by other environmental factors, on the neurotransmitter and synaptic development of the cerebral cortex In the fetus and infant in neural networks that mediate cognitive functions known to be abnormal In FASD; and Genetics-^To determine the role of copy number variants in modifying the risk for SIDS, stillbirth, and FASD associated with prenatal alcohol exposure. In addition to alcohol-related research in human tissues, the DBPC's mission includes: 1) the supervision of a centralized tissue bank for placental, brain, and DNA research in the study, as well as for all future tissue-related studies 2) the determination of the cause of the fetal and infant deaths with the Pathology Subcommittee for all study purposes. As requested in the RFA, we present here: 1) our progress in specimen management, training and consultation in pathology protocols, and process of case review and classification (DBPC infrastructure); and 2) our progress and plans for the placental, developmental brain, and genetic analyses (Specific Aims). The proposed study is significant because it has the potential to answer important clinical questions, is prenatal alcohol exposure toxic to the brainstem homeostatic (serotonergic) systems in the brainstem of SIDS infants? Do genetic copy number variants modify the effects of prenatal alcohol toxicity? The answers to these and other key questions will help shape future directions in risk reduction messages and predictors for SIDS, stillbirth causation, and cognitive assessment of infants exposed to prenatal alcohol. The proposed study is also innovative because it directly links pathological information in the human placenta and developing brain with in-depth information on prenatal exposure collected prospectively in a large, well-characterized cohort. The potential impact of this study is to help establish the biologic underpinnings of prenatal alcohol toxicity directly in the human placenta and developing brain as the basis for improved intervention strategies.

描述（由申请人提供）：通过网络中发育生物学和病理学中心（DBPC）的使命是对与酒精相关损伤的生物学损伤的生物学方面进行研究，因为它们与死产，猝死综合症（SIDS）和胎儿酒精疾病（FASD）有关。 DPBC的四个特定目的是：胎盘确定孕产妇酒精暴露的作用，可能会因其他环境因素，胎盘功能障碍和病理学而改变；脑干 - 确定在SID和死产中神经递质脑干病理学中可能通过其他环境因素修饰的产前酒精的作用。脑皮质 - 确定其他环境因素可能改变了产前酒精暴露的影响，对胎儿和婴儿在FASD中介导已知认知功能的神经网络中大脑皮层的神经递质和突触发育。和遗传学 - 确定拷贝数变体在修改与产前酒精暴露相关的SID，死产和FASD的风险中的作用。除了在人体组织中与酒精相关的研究外，DBPC的任务还包括：1）研究中集中式组织库进行胎盘，大脑和DNA研究的监督，以及所有未来与组织相关的研究的监督2）确定所有研究目的的病理学小组的胎儿和婴儿死亡原因。按照RFA的要求，我们在此处提出：1）我们在病理方案的标本管理，培训和咨询方面的进展以及病例审查和分类的过程（DBPC基础架构）； 2）我们对胎盘，发育大脑和遗传分析的进步和计划（具体目的）。拟议的研究之所以重要，是因为它有可能回答重要的临床问题，在SIDS婴儿脑干中，产前酒精暴露会使脑干稳态（血清素能）系统有毒吗？遗传拷贝数变体是否会改变产前酒精毒性的影响？这些和其他关键问题的答案将有助于塑造降低风险的消息和小岛屿发展中国家的预测因素，死亡因果关系以及暴露于产前酒精的婴儿的认知评估的方向。拟议的研究也具有创新性，因为它直接将人胎盘中的病理信息与大脑之间的病理信息联系起来，并深入介绍了有关在大型，良好的特征良好的队列中预期收集的产前暴露的信息。这项研究的潜在影响是帮助建立直接在人胎盘中的产前酒精毒性的生物基础，并发展大脑作为改善干预策略的基础。