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

描述（由申请人提供）：PASS网络中发育生物学和病理学中心（DBPC）的使命是对酒精相关损伤的生物学方面进行人类研究，因为它们与死产、婴儿猝死综合征（SIDS）和胎儿酒精谱系障碍（FASD）有关。DPBC的四个具体目标是：胎盘-确定母体酒精暴露的作用，可能被其他环境因素改变，在胎盘功能障碍和病理学;脑干-确定产前酒精的作用，可能被其他环境因素改变，在SIDS和死胎的神经递质脑干病理学;大脑皮层--为了确定产前酒精暴露的影响，因为其他环境因素可能会改变这种影响，对大脑皮层神经递质和突触发育的影响在胎儿和婴儿的神经网络中调节认知功能遗传学-确定拷贝数变异在改变与产前酒精暴露相关的SIDS、死产和FASD风险中的作用。除了人体组织中的酒精相关研究外，DBPC的使命还包括：1）监督研究中胎盘、脑和DNA研究以及所有未来组织相关研究的集中组织库; 2）出于所有研究目的，与病理学小组委员会一起确定胎儿和婴儿死亡的原因。根据RFA的要求，我们在此介绍：1）我们在标本管理、病理学方案培训和咨询以及病例审查和分类过程（DBPC基础设施）方面的进展; 2）我们在胎盘、发育脑和遗传分析（特定目标）方面的进展和计划。这项研究意义重大，因为它有可能回答重要的临床问题，产前酒精暴露对SIDS婴儿脑干中的脑干稳态（多巴胺能）系统有毒吗？基因拷贝数变异是否改变了产前酒精中毒的影响？这些和其他关键问题的答案将有助于塑造未来的方向，在降低风险的信息和预测SIDS，死产的原因，和认知评估的婴儿暴露于产前酒精。这项拟议的研究也是创新的，因为它直接将人类胎盘和发育中的大脑中的病理信息与在一个大型的、特征良好的队列中前瞻性收集的产前暴露的深入信息联系起来。这项研究的潜在影响是帮助建立产前酒精毒性的生物学基础，直接在人类胎盘和发育中的大脑作为改善干预策略的基础。

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.