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

摘要 这是U 01-AA 015134的竞争性续展申请。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工作人员和合作者 疾病（FASD）研究计划提供了独特的机会，以更好地定义基于人群的 FASD儿童及其母亲的特征。此外，有机会追求 在未来五年内对FASD病因学进行创新性探索是非常好的。我们将 同时追求三个不同但互补的目标。 目标1：筛查产前诊所饮酒的育龄妇女是否存在高危饮酒 并继续研究产妇风险。虽然筛查有多种原因，但目标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）的使用一个会话的动机增强疗法（MET）在产前诊所。这些 预防活动是根据以往预防工作的调查结果和经验开展的。继续 产前诊所的预防活动也将有助于招募参与者， 目标3中的生物标志物研究。 目标2：继续对FASD在生命早期的轨迹进行纵向研究， 两个已建立的队列。我们将继续定期进行身体评估， 197名6-11岁确诊儿童的生长和认知/行为轨迹 岁月和母亲我们还将对第二名孕产妇/孩子进行类似的发育监测 队列（n=约230对）在过去2年中招募。队列2将于2017年10月完成。一 还将在队列1的子样本中进行sMRI测量的巢式研究。 目的3：收集适当的生物样本，以评估酒精的有效性和效用 使用生物标志物和营养和营养遗传学作用的标志物，以更好地评估 营养和产前饮酒在儿童预后严重程度和病因学中的相互作用 的FASD。我们将通过两种生物标志物评估酒精使用情况，乙基葡萄糖醛酸苷（EtG）和 磷脂酰乙醇（PEth）在产前诊所和预防倡议，以准确评估 纵向研究和监测预防。自我报告的酒精使用量，频率和 妊娠时间（QFT）和AUDIT将作为比较数据。我们还将收集样本， 通过以下组合分析营养成分在影响儿童结果中的作用的数据： 膳食摄入量调查;评价孕妇血浆样本中的多种微量营养素; 分析影响代谢、吸收和调节的遗传多态性（SNP）， 必需营养素

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.