Tracking and Prediction of Early Brain-Face Biomarkers of Prenatal Alcohol Exposure from Neonates to Children

新生儿产前酒精暴露的早期脑面生物标志物的跟踪和预测

• 批准号: 10442572
• 负责人: Kirsty Donald
• 金额: $ 50.12万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2024-04-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442572
• 关键词: 2 year old; 3 year old; 3-Dimensional; 6 year old; Address; Adolescent; Affect; Age; Alcohols; Amygdaloid structure; Behavior; Behavioral; Biological Markers; Birth; Brain; Brain imaging; Cellular Phone; Child; Child Health; Childhood; Classification; Cognitive; Communities; Computing Methodologies; Data; Detection; Development; Diagnosis; Dimensions; Dysmorphology; Early Diagnosis; Early Intervention; Emotional; Enrollment; Face; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Fetal alcohol effects; Foundations; Funding; Gestational Age; Goals; Health; Hippocampus (Brain); Human; Image; Individual; Infant; Intervention; Knowledge; Lead; Learning; Life; Link; Liquid substance; Longevity; Longitudinal cohort; Machine Learning; Magnetic Resonance Imaging; Maps; Measures; Methodology; Modeling; Morphology; Neonatal; Neuraxis; Neurodevelopmental Disorder; Neurologic; Newborn Infant; Outcome; Patients; Phenotype; Play; Population; Pregnancy; Prevalence; Principal Component Analysis; Public Health; Publishing; Reporting; Research; Rest; Sampling; Scanning; Severities; Shapes; Societies; South Africa; Specificity; Structure; Substance Use Disorder; Symptoms; Techniques; Thalamic structure; Time; Toddler; United States National Institutes of Health; alcohol exposure; antenatal; base; brain abnormalities; brain behavior; brain morphology; clinically significant; cohort; connectome; cost; data fusion; deep neural network; design; diagnostic strategy; disease diagnostic; early childhood; early detection biomarkers; efficacy testing; fetal diagnosis; gray matter; high dimensionality; high risk; imaging modality; improved; innovation; insight; maternal alcohol use; maternal cigarette smoking; maternal depression; multimodality; neonatal brain; neonate; neurobehavioral; neurodevelopment; neuroimaging; novel; offspring; prenatal exposure; prospective; relating to nervous system; shape analysis; statistics; white matter; white matter change

Maternal substance use disorders are a substantial public health concern and the neurological consequences of prenatal exposure are a major threat to the long-term health of offspring. Globally, prevalence of Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Spectrum Disorders (FASD) is between 2-7 and 20-50 per 1000, respectively. By contrast, in certain high-risk communities in South Africa, prevalence is reported to be as high as 63 and 155 per 1000, respectively. Though prenatal alcohol exposure (PAE) is known to affect the central nervous system, to date, little data exists in respect of the impact of PAE in early childhood, before both higher-level brain networks are established and other potentially confounding post- natal environmental influences have come into play. For neurodevelopmental disorders, studies have consistently shown that early intervention, based on detection and targeted interventions, leads to better long-term outcomes. We aim to address this precise gap in knowledge by imaging the brain and 3D face across the FASD continuum to investigate early biomarkers, trajectories and functional correlates of PAE in a cohort followed prospectively from birth to age 6 years. Data: Our cohort includes a well characterized subsample of children (PAE and healthy controls) enrolled in the Drakenstein Child Health Study in Cape Town, South Africa, who have been scanned as neonates and at 2-3 years of age. Preliminary published data shows highly significant relationships between PAE and regional gray and white matter changes, already discernible in newborns, well before the age FASD is typically diagnosed. An additional longitudinal assessment at 6-years will yield a unique FASD sample with 3 distinct time points (infants, toddlers and children), allowing characterization of brain and face morphology and brain structure and function in this previously understudied early developmental period. This proposal addresses fundamental gaps concerning the presence, timing and regional specificity of altered brain morphology and structural and functional connectivity in association with the effects of PAE on the developing brain from birth to 6 years, and the relationships with facial dysmorphology. The research team has successfully gathered data from the proposed cohort as neonates and at 2–3 years of age. The benefits of extending this research to a subsequent imaging time-point, with a larger range of developmental and neurobehavioral assessments, provides an unprecedented opportunity to determine longitudinal effects of PAE on the trajectory of the developing brain in these critical early years, the links between neural and face predictors of PAE and the long-term clinical significance of these findings. This research will illuminate early neurodevelopmental mechanisms leading to subsequent behavioral and neurological disturbances, which may allow opportunities for targeting interventions when brain plasticity is still relatively fluid. This project might also lead to new strategies for early diagnosis using both face and brain biomarkers.

孕产妇使用障碍是一个实质性的公共卫生问题和神经系统 产前暴露的后果是对后代长期健康的主要威胁。在全球 胎儿酒精综合征（FAS）和胎儿酒精谱系（FASD）的患病率在2-7之间 和每1000分的20-50。相比之下，在南非的某些高风险社区中 据报道，每1000次分别高达63和155。尽管产前酒精暴露（PAE）是 已知会影响中枢神经系统，迄今为止，对PAE在早期的影响方面几乎没有数据 童年，在建立高级大脑网络之前，并在其他潜在的混淆之前 出生的环境影响已经发挥作用。对于神经发育障碍，研究 始终表明，基于检测和针对性干预措施的早期干预会导致更好 长期结局。我们的目标是通过成像大脑和3D来解决知识中的精确差距 FASD的面孔继续研究早期的生物标志物，轨迹和功能 从出生到6岁的人群中，PAE的相关性。数据：我们的队列 包括在德拉肯斯坦（Drakenstein 南非开普敦的儿童健康研究，他们被扫描为新生儿，并在2-3岁时 年龄。初步发布的数据显示PAE与区域灰色和区域灰色之间的关系非常重要 白质变化，在新生儿中已经可以辨别的，就在通常被诊断出FASD之前。一个 在6年内进行的额外纵向评估将产生独特的FASD样本，具有3个不同的时间点 （婴儿，幼儿和儿童），允许大脑表征和面部形态和大脑结构 并在以前理解的早期发育时期的功能。该提案解决了 关于改变脑形态的存在，时机和区域特异性的基本差距 结构和功能连通性与PAE对发育中的大脑的影响相关 出生到6年，以及与面部畸形学的关系。研究团队已成功 从拟议的队列和2-3岁时收集了来自拟议的队列的数据。扩展的好处 这项研究对随后的成像时间点，具有更大范围的发展和 神经行为评估，提供了一个前所未有的机会来确定 在这些关键的早期，神经和面部之间的联系 PAE的预测因素和这些发现的长期临床意义。这项研究将早日照亮 神经发育机制导致随后的行为和神经系统疾病，这 当大脑可塑性仍然相对流动时，可能会有机会进行靶向干预措施。这个项目 也可能导致使用面部和脑生物标志物的早期诊断策略。