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

PASS 队列中的大脑和认知发展：产前酒精暴露的影响

• 批准号: 10172802
• 负责人: ELIZABETH R SOWELL
• 金额: $ 52.62万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172802
• 关键词: 3-Dimensional; Address; Affect; Age; Alcohol consumption; Alcohols; Amygdaloid structure; Animal Experimentation; Animal Model; Area; Attenuated; Authoritarianism; Behavior; Behavioral; Birth; Brain; Brain imaging; Brain region; Cerebellar vermis structure; Child; Child Rearing; Childhood; Cognition; Cognitive; Cohort Studies; Communities; Corpus Callosum; Data; Development; Diffusion; Discipline of obstetrics; Dose; Dysmorphology; Early Intervention; Enrollment; Environment; Environmental Risk Factor; Evaluation; Exhibits; Face; Family; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; First Pregnancy Trimester; Frequencies; Functional Magnetic Resonance Imaging; Hippocampus (Brain); Human; Image; Impaired cognition; Income; Individual; Infant; Intellectual functioning disability; Knowledge; Lateral; Life; Life Experience; Light; Literature; Magnetic Resonance Imaging; Maternal Age; Measures; Mediating; Medical; Mental Health; Morphology; Mothers; Parents; Participant; Pattern; Perinatal; Positioning Attribute; Pregnancy; Prevalence; Problem behavior; Prospective Studies; Prospective cohort study; Reporting; Research; Resources; Rest; Risk; Risk Factors; Sampling; Sampling Biases; Societies; South Africa; South African; Stress; Structure; Sudden infant death syndrome; Surface; Thick; Three-dimensional analysis; Time; United States National Institutes of Health; aged; base; behavior measurement; brain volume; cingulate cortex; cognitive development; cognitive function; cognitive testing; cohort; cost; drinking; drinking behavior; early childhood; early life adversity; early pregnancy; experience; externalizing behavior; girls; in utero; insight; low socioeconomic status; maternal alcohol use; maternal risk; multimodality; neuroimaging; nutrition; parity; perinatal period; postnatal; pregnant; prenatal; prospective; protective factors; public health relevance; recruit; resilience; social; social stigma; stillbirth; substance use; white matter

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).

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，但仍然是已知的三大原因之一 智力残疾。 BCF关联对PAE效应的巨大差异可能部分是从 孕产妇消耗模式的可变性，包括数量，频率和时机（QFT）和早期 身世。在 怀孕使得难以准确了解哪种PAE模式最有害 发展。大多数FASD的儿童比非暴露儿童经历的早期逆境更大，但是 现有关于PAE如何影响大脑发育的研究无法解散早期的影响 生活逆境。据信早期干预是衰减PAE效应的关键，可能部分取决于 了解QFT和早期生活经验的影响。在此提案中，我们旨在更好地了解 PAE的QFT以及早期生活经验会影响大脑和认知发展。大多数前瞻性研究 Pae招募了偏向中等重型的PAE的样品，限制了我们对整个的理解 PAE模式的范围，包括最小的暴露。在这里，我们利用一个独特的潜在社区 样本的大约6,000名南非儿童的母亲报告了饮酒行为 怀孕是产前酒精，SIDS和死产（通过）网络的一部分。因此，我们处于特殊 了解PAE的QFT如何独立或交互影响：1）大脑之间的关联 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/产妇因素。 400名通过参与者（300个PAE/100个非暴露对照； 50％女孩）老年 8 - 10年入学时，将经历多模式神经影像学评估a）大脑结构MRI测量 体积，厚度和表面积； b）基础白质微观结构的扩散成像（即 结构连通性）； c）静止状态功能MRI（即功能连接）。认知度量 将使用NIH工具箱认知电池，并将衡量孕妇的早期生活经验（即年龄， 营养，平价，心理健康，共同实用的使用，育儿风格，亲子亲密关系）和环境 （即SES的多种测量，获取资源，压力）风险因素，围产期和期间测量 童年。来自3D面部成像的定量测量将与神经影像和 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 通过时间等。 频率，然后是PAE的时机。例如，我们希望看到非常低的儿童中的PAE效应 整个怀孕的暴露在更外侧的大脑区域（后来在子宫内发育），而狂风般的高 怀孕初期的暴露会显示出更多的中线脑异常（在子宫内发展）。