Trajectory of Fetal Alcohol Spectrum Disorders (FASD) Across the Lifespan: Continuing Prevention and Longitudinal Epidemiology

摘要 这是U01-AA015134的竞争续订申请。历史、经验、存在 基础设施，以及我们南非(SA)胎儿酒精谱的经验丰富的员工和合作者 精神障碍(FASD)研究计划为更好地定义以人群为基础的 FASD患儿及其母亲的特点。此外，有机会追求 未来五年对FASD病因学的创新探索是非常好的。我们会 同时追求三个不同但相辅相成的目标。 目标1：在产前诊所筛查育龄妇女饮酒高危人群 以及对产妇风险的持续研究。虽然筛查有多种原因，但在目标1中 目的是选择性(二级)预防FASD。我们将启动一项病例对照疗效研究 (n=400)产前诊所使用单次动机增强疗法(MET)的情况。这些 预防活动是根据以往预防工作中的发现和经验开展的。继续 产前诊所的预防活动还将促进招募新锐学员 AIM 3生物标志物研究。 目标2：继续对FASD早期生命轨迹的纵向研究 两个已建立的队列。我们将继续定期安排，跟踪评估身体状况 197名6-11岁确诊儿童的生长发育和认知/行为轨迹 很多年和他们的母亲。我们还将对第二名产妇/儿童进行类似的发育监测。 在过去两年中招募的队列(n=~230对)。第二批将于2017年10月完成。一个 SMRI测量的嵌套研究也将在队列1的一个子样本中进行。 目标3：收集适当的生物样本以评估酒精的有效性和效用 使用生物标记物和营养和营养遗传学的作用标记物更好地评估 营养和产前饮酒在儿童结局严重程度和病因中的交互作用 FASD的。我们将通过两个生物标志物来评估酒精的使用，乙基葡萄糖醛酸(EtG)和 产前诊所中的磷脂酰乙醇(PEH)和准确评估两者的预防措施 纵向研究和监测预防。自报饮酒量、饮酒频率和饮酒量 妊娠计时(QFT)和审计将作为比较数据。我们还将收集样本和 通过以下组合分析营养成分在影响儿童结局中的作用的数据： 膳食摄入量调查；评估孕妇血浆样本中的多种微量营养素； 影响新陈代谢、吸收和调节的遗传多态(SNP)分析 必需的营养素。

ABSTRACT This is a competitive renewal application for U01-AA015134. The history, experience, existing infrastructure, and experienced staff and collaborators of our South African (SA) fetal alcohol spectrum disorders (FASD) research program present unique opportunities to better define population-based characteristics of children with FASD and their mothers. Furthermore, the opportunity to pursue innovative explorations into etiology of FASD in the coming five years is excellent. We will simultaneously pursue three diverse, but complementary, aims. Aim 1: Screen women of childbearing age drinking in prenatal clinics for high risk drinking and continuing study of maternal risk. While there are multiple reasons for screening, in Aim 1 the purpose is for selective (secondary) prevention of FASD. We will initiate a case control efficacy study (n=400) of the use of one-session motivation enhancement therapy (MET) in prenatal clinics. These prevention activities follow from findings and experience in previous prevention efforts. Continuing prevention activities in antenatal clinics will also facilitate recruitment of participants for cutting-edge biomarker studies in Aim 3. Aim 2: Continue longitudinal studies of the trajectory of FASD in the early years of life in two established cohorts. We will continue regularly-scheduled, follow-up evaluation of the physical growth and cognitive/behavioral trajectory in an established cohort of 197 diagnosed children ages 6-11 years and their mothers. We will also pursue similar developmental monitoring of a second maternal/child cohort (n= ~230 dyads) recruited over the past 2 years. Cohort 2 will be finalized in October, 2017. A nested study of sMRI measurement will also be undertaken in a sub-sample of Cohort 1. Aim 3: Collect appropriate biological samples for assessing the validity and utility of alcohol use biomarkers and markers of the role of nutrition and nutrition genetics to better assess the interactive role of nutrition and prenatal alcohol use in severity of child outcomes and the etiology of FASD. We will assess alcohol use via two biomarkers, ethyl glucuronide (EtG) and phosphatidylethanol (PEth) in antenatal clinics and prevention initiatives for accurate assessment in both longitudinal research and monitoring prevention. Self-reported alcohol use by quantity, frequency, and gestational timing (QFT) and the AUDIT will serve as comparison data. We will also collect samples and data for analyzing the role of nutritional components in affecting child outcomes via a combination of: dietary intake surveys; evaluation of multiple micronutrients in plasma samples from of pregnant women; analysis of genetic polymorphisms (SNPs) influential in metabolism, absorption, and regulation of essential nutrients.