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: 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
• 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

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.

产妇药物使用障碍是一个重大的公共卫生问题和神经学问题