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

项目总结/摘要 产前酒精暴露（PAE）可对大脑，认知和面部形态产生显着影响 （BCF）。胎儿酒精谱系障碍（FASD）是可以预防的，但仍然是三大已知原因之一， 智力残疾。PAE对BCF相关性的影响存在很大的变异性，部分原因可能是 母亲饮酒模式的变异性，包括数量、频率和时间（QFT），以及早期 生活经验母亲饮酒模式的耻辱感和回顾性评估 怀孕使人们很难准确地理解什么样的PAE模式对女性最有害。 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， 关于PAE如何影响大脑发育的现有研究还无法解开早期脑损伤的影响。 生活逆境早期干预被认为是减轻PAE效应的关键，并且可能部分取决于 理解QFT和早期生活经验的影响。在这份提案中，我们的目标是更好地了解如何 PAE的QFT加上早期生活经验影响大脑和认知发育。大多数前瞻性研究 PAE招募的样本偏向于中重度PAE，限制了我们对整个PAE的理解。 PAE模式的范围，包括最小暴露。在这里，我们利用一个独特的前景，社区 大约6，000名南非儿童的母亲报告了他们的饮酒行为， 作为产前酒精、小岛屿发展中国家和死产网络的一部分。因此，我们处于一个特殊的 了解PAE的QFT如何独立地或交互地影响以下之间的关联：1）大脑 和认知; 2）大脑和早期生活环境; 3）大脑和面部形态作为功能， 环境/母体因素。400名PASS受试者（300名PAE/100名未暴露对照; 50%为女孩），年龄 8-10在入组时，将接受多模态神经成像，以评估A）大脑的结构MRI测量 体积、厚度和表面积; B）下面的白色物质微结构的扩散成像（即， 结构连接性）;和C）静息状态功能MRI（即，功能连接性）。认知指标 将利用NIH认知测验，并测量母亲的早期生活经验（即，年龄， 营养、平等、心理健康、辅助物质使用、养育方式、亲子亲密度）和环境 (i.e.,多种措施的SES，获得资源，压力）的风险因素，测量围产期和期间 童年.来自3D面部成像的定量测量将与神经成像并行使用， 认知评估利用PAE的整个范围，我们期望独立和互动（例如，数量 时间等）。QFT对BCF关联的影响，数量驱动的影响最大，其次是 频率，然后是PAE的时间。例如，我们预计在极低血糖的儿童中会看到PAE效应。 在整个怀孕期间，更多的侧脑区域（在子宫内发育较晚）暴露，而暴食样高 怀孕早期的暴露将显示更多的中线脑异常（在子宫内发育更早）。

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).