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.