FAS, SIDS and Stillbirths in Cape Town, South Africa

描述(申请人提供)：婴儿猝死综合症(SID)是导致婴儿死亡的主要原因，在美国，活产婴儿的发病率约为千分之0.8，高危人群的发病率相当高，包括美洲原住民和南非的开普省有色人种(混血)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危险因素，值得进一步研究。有人推测，延髓5-羟色胺能网络缺陷可能是导致一些小岛屿发展中国家死亡的部分原因。在过去的5年里，我们与开普敦大学医学院的研究人员合作，对开普敦有色人种社区产前酒精暴露的影响进行了一项前瞻性的纵向研究。这项研究证明了我们有能力从这个社区招募母亲；获得对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；并对开普敦婴儿进行最先进的婴儿神经行为评估。我们发现，在这一人群中，孕妇滥用酒精和依赖酒精的比例非常高，她们的婴儿中有非常高的Fas。在这个大都市地区，小岛屿发展中国家和小儿麻痹症的高发病率，容易接近的孕妇酗酒人口，以及我们成熟的、富有成效的研究合作，使开普敦成为唯一合适的综合临床地点。拟议的合作协议将扩大我们正在进行的合作，将病理学和产科的研究人员包括在内。目的是(1)利用现代诊断标准和程序，包括对小岛屿发展中国家患者和对照组的神经病理学检查，对开普敦的小岛屿发展中国家和死产的发病率进行评估；(2)检验产前酗酒会增加小岛屿发展中国家风险的假设，并评估风险与产前母亲吸烟、早产、婴儿性别和睡姿、季节变化、父母教育和母亲抑郁有关的风险；(3)检验假设某些调节变量--饮酒年限、母亲酗酒和依赖的严重程度、孕妇体重较低和产前吸烟，以及缺乏ADH2*2等位基因--会增加酒精暴露婴儿患SID的风险；及(4)研究重度酒精暴露的新生儿是否会出现类似于SIDS患者的自主神经系统行为的变化，这些行为已知受延髓5-羟色胺系统调节，包括唤醒、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面临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.