FAS, SIDS and Stillbirths in Cape Town, South Africa

描述（由申请人提供）：婴儿猝死综合征（SIDS）是婴儿死亡的主要原因，在美国的发病率约为0.8/1000活产婴儿，在高危人群中发病率更高，包括美洲原住民和南非的开普有色人种（混合血统）社区。最近的一项研究表明，产前酒精暴露是小岛屿发展中国家的一个重要风险因素，值得进一步调查。据推测，髓质血清素能网络缺陷可能是一些小岛屿发展中国家死亡的部分原因。在过去的5年里，我们一直在与开普敦大学医学院的研究人员合作，对开普有色人种产前酒精暴露的影响进行前瞻性、纵向研究。这项研究证明了我们从这个社区招募母亲的能力；获得关于FAS、产前酒精暴露、母亲酗酒、吸烟和抑郁以及社会环境和医疗风险的有效评估；对开普敦的婴儿进行最先进的神经行为评估。我们发现，在这一人群中，孕妇及其婴儿的酒精滥用和依赖率异常高。在这个大都市区小岛屿发展中国家和FAS的高发病率，容易接近的产妇酗酒人群，以及我们建立的，富有成效的研究合作使开普敦成为一个独特的综合临床站点。拟议的合作协议将扩大我们正在进行的合作，包括病理学和产科的研究人员。目的是：(1)使用现代诊断标准和程序，包括对小岛屿发展中国家受害者和对照组进行神经病理学检查，对开普敦小岛屿发展中国家和死产的发生率进行评估；(2)检验产前酗酒增加SIDS风险的假设，并评估该风险与产前母亲吸烟、早产、婴儿性别和睡姿、季节变化、父母教育程度和母亲抑郁相关的风险；(3)验证饮酒年限、母亲酒精滥用和依赖程度、母亲体重较低和产前吸烟、缺乏ADH2*2等位基因会增加酒精暴露婴儿SIDS发生风险的假设；(4)检查重度酒精暴露的新生儿是否会表现出与小岛屿发展中国家类似的自主神经系统行为的改变，这些行为是由髓质血清素能系统调节的，包括觉醒、心肺反射整合和睡眠/觉醒模式。这项研究有可能提高我们对小岛屿发展中国家所涉及的神经生理机制的理解，并有助于为那些行为表明他们有这种不良后果风险的母亲和婴儿制定干预措施。

DESCRIPTION (provided by applicant):Sudden infant death syndrome (SIDS) is a leading cause of infant mortality with incidence of about 0.8/1000 live births in the U.S. and considerably higher rates in at-risk populations, including Native Americans and the Cape Coloured (mixed ancestry) community in South Africa. A recent study has implicated prenatal alcohol exposure as an important risk factor for SIDS that warrants further investigation. It has been hypothesized that medullary serotonergic network deficits may be responsible, in part, for some SIDS deaths. For the past 5 years, we have been conducting a prospective, longitudinal study on the effects of prenatal alcohol exposure in the Cape Coloured community in collaboration with researchers from the University of Cape Town School of Medicine. This research has demonstrated our ability to recruit mothers from this community; obtain valid assessments of FAS, prenatal alcohol exposure, maternal alcoholism, smoking and depression, and socioenvironmental and medical risk; and perform state-of-the-art infant neurobehavioral assessments with Cape Town infants. We have found an exceptionally high rate of alcohol abuse and dependence among pregnant women in this population and of FAS among their infants. The high incidence of both SIDS and FAS in this large metropolitan area, the readily accessible maternal heavy drinking population, and our established, productive research collaboration make Cape Town uniquely appropriate as a Comprehensive Clinical Site. The proposed cooperative agreement would expand our ongoing collaboration to include researchers in pathology and obstetrics. The aims are (1) to conduct an assessment of the incidence of SIDS and stillbirths in Cape Town, using contemporary diagnostic criteria and procedures, including neuropathological examinations of SIDS victims and controls; (2) to test the hypothesis that prenatal binge drinking increases the risk of SIDS and to evaluate that risk in relation to risks associated with prenatal maternal smoking, preterm birth, infant gender and sleeping position, seasonal variation, parental education, and maternal depression; (3) to test the hypothesis that certain moderator variables-- years of drinking, severity of maternal alcohol abuse and dependence, lower maternal weight and prenatal smoking, and the absence of an ADH2*2 allelo will increase the risk of SIDS in alcohol-exposed infants; and (4) to examine whether heavily alcohol-exposed neonates will exhibit alterations in autonomic nervous system behaviors similar to those described in SIDS victims, which are known to be regulated by the medullary serotonergic system, including arousal, cardiorespiratory reflex integration, and sleep/wake patterns. This research has the potential to improve our understanding of neurophysiological mechanisms involved in SIDS and to contribute to developing interventions for mothers and infants whose behaviors indicate that they are at risk for this adverse outcome.