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

描述(由申请人提供)：本申请是对一封邀请函(LOI-HD-05-111)的回应，该邀请函要求开展与社区相关的研究，以调查产前酒精暴露在小岛屿发展中国家、死产和Fas风险中的作用，并确定这些不同结果如何相互关联。拟议的研究将由研究人员产前酒精、小岛屿发展中国家和死胎(PASS)研究网络与NICHD和NIAAA合作进行。这项研究涉及以下各方的合作：1)两个综合性临床网站，服务于产前酒精暴露、小岛屿发展中国家和死产的高危人群，即南非开普敦北部平原和开普敦有色人种的美洲印第安人；2)一个中央发育生物学和病理学中心(DBPC)；3)一个中央数据协调和分析中心(DCAC)；4)一个中央生理学评估中心(PAC)；以及5)NICHD和NIAAA的项目科学家和官员。这一特殊应用适用于泰格伯格综合临床站点(CCS)。这项实验设计包括一项对7000例妊娠的前瞻性研究，以及两项基于身体解剖的回顾性研究 关于小岛屿发展中国家和死产的研究。 安全通道研究的长期目标是降低胎儿和婴儿死亡率，并改善产前孕妇饮酒高危社区的儿童健康。该网络的具体目标如下：1)确定产前酒精暴露与婴儿呼吸窘迫综合征和死产风险之间的联系；2)确定产前酒精暴露的时间、模式和数量以及其他环境因素在人类早期生命的发病率和死亡率风险中的作用；3)确定特定基因在改变与产前酒精暴露有关的早期生命的发病率和死亡率风险中的作用；4)确定怀孕期间酒精暴露的作用，以及酒精暴露与环境和遗传修饰因素之间的相互作用，以改变胎儿和婴儿的自主活动和婴儿的神经行为结果；5)确定受特定环境和遗传因素影响的母亲酒精暴露在胎盘功能受损中的作用，从而增加胎儿和/或婴儿发病率和死亡率的风险；以及6.确定胎儿和/或婴儿大脑中关键神经递质系统的异常，以传递猝死的风险，并确定产前暴露在特定环境和遗传因素影响下在其发病机制中的作用。CCS的任务是确保正确识别怀孕期间使用酒精的围产期风险，及早发现这些风险，并进行与酒精导致的人脑和胎盘损伤有关的基础研究。这项多学科的国际研究将确定胎儿在怀孕期间接触酒精是否会导致婴儿猝死、死产和其他并发症。从这项研究中获得的知识将有助于医护人员为孕妇提供更好的护理。

DESCRIPTION (provided by applicant): This application is in response to a Letter of Invitation (LOI-HD-05-111) to conduct community-linked studies to investigate the role of prenatal alcohol exposure in the risk for SIDS, stillbirth and FAS, and to determine how these different outcomes are inter-related. The proposed research will be conducted by the investigators the Prenatal Alcohol, SIDS, and Stillbirth (PASS) Research Network in a cooperative agreement with NICHD and NIAAA. This research involves the collaboration of: 1) two comprehensive clinical sites serving populations that are high risk for prenatal alcohol exposure, SIDS, and stillbirth, i.e. the American Indians in the Northern Plains and the Cape Coloured in Cape Town, South Africa; 2) a central Developmental Biology and Pathology Center (DBPC); 3) a central Data Coordinating and Analysis Center (DCAC); 4) a central Physiology Assessment Center (PAC); and 5) program scientists and officers at the NICHD and NIAAA. This particular application pertains to the Tygerberg Comprehensive Clinical Site (CCS). The experimental design involves a prospective study of 7,000 pregnancies, and two retrospective, autopsybased studies of SIDS and stillbirth. The long-term goals of the SAFE PASSAGE STUDY are to decrease fetal and infant mortality and improve child health in communities at high risk for prenatal maternal alcohol consumption. The Specific Aims of the Network are as follows: 1) to determine the association between prenatal alcohol exposure and the risk for SIDS and stillbirth; 2) to determine the role of the timing, pattern, and amount of prenatal alcohol exposure and other environmental factors in the risk for morbidity and mortality in early human life; 3) to determine the role of specific genes in modifying the risk for morbidity and mortality in early life that is associated with prenatal alcohol exposure; 4) to determine the role of alcohol exposure during pregnancy, and interactions among alcohol exposure and environmental and genetic modifiers, in altering profiles of autonomic activity of the fetus and infant, and neurobehavioral outcomes in the infant; 5) to determine the role of maternal alcohol exposure, as influenced by specific environmental and genetic factors, in the impairment of placental function, and thereby the increased risk for fetal and/or infant morbidity and mortality; and 6. To determine abnormalities in key neurotransmitter systems in the brains of fetuses and/or infants that convey risk for sudden death, and to determine the role of prenatal alcohol exposure, as influenced by specific environmental and genetic factors, in their pathogenesis. The mission of the CCS is to ensure the proper identification of the perinatal risks of the use of alcohol during pregnancy, early detection of these risks and to perform basic research related to alcohol-induced injury in the human brain and placenta. This multidiscipline international study will determine whether the exposure of the fetus to alcohol during pregnancy leads to SIDS stillbirths and other complications. Knowledge gained from the study will help health care workers to provide better care for pregnant women.