Brain and Cognitive Development in the PASS Cohort: The Impact of Prenatal Alcohol Exposure

项目摘要/摘要 产前酒精暴露(PAE)会对大脑、认知和面部形态产生巨大影响 (Bcf)。胎儿酒精谱系障碍(FASD)是可以预防的，但仍是已知的三大致病原因之一 智力残疾。PAE对BCF关联的影响的巨大变异性可能部分原因是 母亲饮酒模式的变异性，包括数量、频率和时机(QFT)和早期 生活经历。对母亲饮酒模式的耻辱和回顾评估 怀孕使人们很难准确地了解PAE的哪些模式对 发展。大多数患有FASD的儿童比未接触FASD的儿童经历更大的早期生活逆境，但 关于PAE如何影响大脑发育的现有研究还无法理清早期PAE的影响 生活中的逆境。早期干预被认为是减弱PAE影响的关键，而且可能部分取决于 了解QFT和早期生活体验的影响。在这项提案中，我们的目标是更好地了解 PAE的QFT加上早期生活经历会影响大脑和认知发展。大多数前瞻性研究 PAE招募了偏向中重度PAE的样本，限制了我们对整个 PAE模式的范围，包括最低限度的暴露。在这里，我们利用了一个独特的潜在社区 大约6,000名南非儿童的样本，这些儿童的母亲报告了他们在 怀孕是产前酒精、小岛屿发展中国家和死产网络的一部分。因此，我们正处于一个例外的时期 能够独立或交互地理解PAE的QFT如何影响大脑之间的关联：1)大脑 和认知；2)大脑和早期生活环境；以及3)大脑和面部形态作为 环境/母体因素。400名PASS参与者(300名PAE/100名非暴露对照组；50%为女孩) 注册时8-10年，将接受多模式神经成像以评估A)脑结构MRI测量 体积、厚度和表面积；B)底层白质微结构的扩散成像(即， 结构连通性)；以及C)静止状态功能MRI(即，功能连通性)。认知测量方法 将使用NIH工具箱认知电池，早期生活体验将针对母亲(即，年龄， 营养、产次、心理健康、共用物质使用、父母教养方式、亲子亲密度)和环境 (例如，多项社会经济状况、资源获取、压力)风险因素，在围产期和期间进行测量 童年。3D面部成像的定量测量将与神经成像并行使用，并 认知评估。利用整个PAE范围，我们期望独立和交互(例如，数量 按时间等)QFT对BCF关联的影响最大的是数量驱动，其次是 频率，然后是PAE的定时。例如，我们预计在患有非常低的PAE的儿童中会看到PAE效应 在怀孕期间暴露在更多的侧脑区(在宫内发育较晚)，而狂欢般的高 在怀孕早期暴露会显示更多的中线脑部异常(在子宫中更早出现)。

Project Summary/Abstract Prenatal alcohol exposure (PAE) can produce dramatic effects on brain, cognition, and facial morphology (BCF). Fetal alcohol spectrum disorder (FASD) is preventable, yet remains among the top 3 known causes of intellectual disability. The large variability in PAE-effects on BCF associations likely results, in part, from variability in maternal alcohol consumption patterns including quantity, frequency and timing (QFT) and early life experience. Both stigma and retrospective assessment of maternal alcohol consumption patterns during pregnancy have made it difficult to accurately understand what patterns of PAE are most harmful to development. Most children with FASD experience greater early life adversity than non-exposed children, but existing research on how PAE impacts brain development has not been able to disentangle the impact of early life adversity. Early intervention is believed to be key in attenuating PAE-effects, and may depend, in part, on understanding the impact of QFT and early life experience. In this proposal, we aim to better understand how QFT of PAE plus early life experience impact brain and cognitive development. Most prospective studies of PAE have recruited samples biased towards moderate-heavy PAE, limiting our understanding of the entire range of PAE patterns including minimal exposure. Here we capitalize on a unique prospective, community sample of approximately 6,000 South African children whose mothers reported on drinking behavior during pregnancy as part of the Prenatal Alcohol, SIDS and Stillbirth (PASS) Network. Thus, we are in an exceptional position to understand how QFT of PAE independently, or interactively, impacts associations between: 1) brain and cognition; 2) brain and early life environment; and 3) brain and facial morphology as function of environmental/maternal factors. 400 PASS participants (300 PAE/100 non-exposed Controls; 50% girls) aged 8-10 years at enrollment, will undergo multi-modal neuroimaging to assess A) structural MRI measures of brain volume, thickness and surface area; B) diffusion imaging of underlying white matter microstructure (i.e., structural connectivity); and C) resting state functional MRI (i.e., functional connectivity). Measures of cognition will utilize the NIH Toolbox Cognition Battery, and early life experience will be measured for maternal (i.e., age, nutrition, parity, mental health, co-substance use, parenting style, parent-child closeness) and environmental (i.e., multiple measures of SES, access to resources, stress) risk factors, measured both perinatally and during childhood. Quantitative measures from 3D facial imaging will be utilized in parallel with neuroimaging and cognitive assessments. Utilizing the entire range of PAE, we expect independent and interactive (e.g., quantity by timing, etc.) effects of QFT on BCF associations, with the largest effects driven by quantity, followed by frequency, and then timing of PAE. For example, we expect to see PAE-effects among children with very low exposure throughout pregnancy in more lateral brain regions (develop later in utero), whereas binge-like high exposure in early pregnancy will show more midline brain anomalies (develop earlier in utero).