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.

母体物质使用障碍是一个重大的公共卫生问题和神经学问题 产前暴露的后果是对后代长期健康的重大威胁。在全球范围内， 胎儿酒精综合征(Fas)和胎儿酒精光谱障碍(FASD)的患病率在2-7之间 每1000人中分别有20-50人。相比之下，在南非的某些高危社区，流行率 据报道，每1000人中分别高达63人和155人。尽管产前酒精暴露(PAE)是 已知影响中枢神经系统，到目前为止，关于PAE在早期影响的数据很少 童年，在高级大脑网络建立之前，以及其他可能令人困惑的后遗症 自然环境的影响已经开始发挥作用。对于神经发育障碍，研究已经 一贯表明，基于检测和有针对性的干预的早期干预会带来更好的效果 长期结果。我们的目标是通过对大脑和3D进行成像来解决这一精确的知识差距 面对FASD连续体，研究早期生物标记物、轨迹和功能 前瞻性跟踪队列中PAE的相关性从出生到6岁。数据：我们的队列 包括在Drakenstein中登记的具有良好特征的儿童(PAE和健康对照)的子样本 南非开普敦儿童健康研究，新生儿和2-3岁儿童接受扫描 年龄。初步公布的数据显示，PAE和区域灰色和 早在FASD典型诊断年龄之前，新生儿就已经可以辨别出脑白质的变化。一个 额外的6年纵向评估将产生具有3个不同时间点的独特FASD样本 (婴儿、幼儿和儿童)，允许表征大脑和脸部形态和大脑结构 以及在这一先前未被充分研究的早期发育阶段的功能。这项提案涉及 关于脑形态改变的存在、时间和区域特异性的基本差距 与PAE对发育中的脑的影响相关的结构和功能连接 出生到6岁，与面部畸形的关系。研究小组已经成功地 从新生儿和2-3岁的拟议队列中收集数据。扩展的好处 本研究将后续的成像时间点，与更大范围的显影和 神经行为评估，提供了一个前所未有的机会来确定 在这些关键的早年大脑发育轨迹上的PAE，神经和面孔之间的联系 PAE的预测因素和这些发现的长期临床意义。这项研究将在早期阐明 神经发育机制导致随后的行为和神经障碍，这 可能会在大脑可塑性仍然相对不稳定的情况下提供靶向干预的机会。这个项目 也可能导致使用面部和大脑生物标记物进行早期诊断的新策略。