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

基本信息

批准号：
9788191
负责人：
Kirsty Donald
金额：
$ 49.9万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9788191
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 Diagnostic Dimensions Disease 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 deep neural network design 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

项目摘要

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.

孕产妇物质使用障碍是一个重大的公共卫生问题，神经系统疾病产前暴露的后果是对全球后代长期健康的重大威胁。胎儿酒精综合症 (FAS) 和胎儿酒精谱系障碍 (FASD) 的患病率在 2-7 之间相比之下，在南非的某些高风险社区，患病率分别为每 1000 人 20-50 人。据报道，尽管产前酒精暴露 (PAE) 分别高达每 1000 人 63 例和 155 例。已知 PAE 会影响中枢神经系统，但迄今为止，关于 PAE 对早期疾病影响的数据很少童年时期，在高级大脑网络建立之前以及其他可能令人困惑的后研究表明，出生环境对神经发育障碍产生了影响。一致表明，基于检测和有针对性的干预措施的早期干预可以带来更好的结果我们的目标是通过大脑成像和 3D 技术来解决这一知识差距。面对 FASD 连续体，研究早期生物标志物、轨迹和功能前瞻性跟踪队列中从出生到 6 岁的 PAE 相关性数据：我们的队列。包括在 Drakenstein 中登记的特征明确的儿童子样本（PAE 和健康对照）南非开普敦的儿童健康研究，对新生儿和 2-3 岁时进行了扫描初步公布的数据显示 PAE 与区域灰质和年龄之间存在高度显着的关系。早在 FASD 被诊断出的年龄之前，新生儿就已经可以察觉到白质的变化。 6 年的额外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），可以表征大脑和面部形态以及大脑结构以及在这个先前未被研究的早期发育阶段的功能。关于大脑形态的存在、时间和区域特异性的根本差距结构和功能连接与 PAE 对发育中大脑的影响相关出生至6岁，与面部畸形的关系研究小组已成功。从新生儿和 2-3 岁的拟议队列中收集的数据延长的好处。这项研究到了随后的成像时间点，具有更大范围的发育和神经行为评估，提供了一个前所未有的机会来确定纵向影响 PAE 在这些关键的早年大脑发育轨迹上，神经和面部之间的联系 PAE 的预测因子以及这些发现的长期临床意义将在早期得到阐明。导致随后的行为和神经障碍的神经发育机制，当大脑可塑性仍然相对不稳定时，可能会提供有针对性的干预措施。还可能导致使用面部和大脑生物标志物进行早期诊断的新策略。