Early Indices of Atypical Neurodevelopment with Fetal Alcohol Exposure

胎儿酒精暴露导致非典型神经发育的早期指标

• 批准号: 8577945
• 负责人: Ludmila Nicole Bakhireva
• 金额: $ 56.82万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8577945
• 关键词: Address; Affect; Age-Months; Alcohols; Applications Grants; Behavior assessment; Behavioral; Biological Markers; Birth; Brain; Brain Injuries; Brain imaging; Characteristics; Child; Clinical; Clinical Research; Cognitive; Cognitive deficits; Control Groups; Coupled; Development; Diagnosis; Diagnostic; Early Diagnosis; Early Intervention; Early identification; Electroencephalography; Ethanol; Face; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Foundations; Frequencies; Future; Goals; Growth; Impairment; Infant; Informal Social Control; Intervention; Lead; Life; Magnetoencephalography; Measures; Mothers; Motor; Newborn Infant; Outcome; Outcome Measure; Performance; Phenotype; Population; Pregnancy; Prevalence; Procedures; Process; Prospective Studies; Questionnaires; Recording of previous events; Regimen; Research; Research Project Grants; Risk; School-Age Population; Sensitivity and Specificity; Sensorimotor functions; Sensory; Short-Term Memory; Staging; Testing; Time; Toddler; Training; Work; alcohol exposure; analytical method; base; behavior measurement; behavior test; cohort; disability; drinking; encephalography; fetal; indexing; innovation; intervention program; neurobehavioral; neurodevelopment; neuroimaging; neurophysiology; novel; pediatrician; prenatal; programs; public health relevance; relating to nervous system; response; screening; social stigma; tool

DESCRIPTION (provided by applicant): It is well-established that children with the facial dysmorphias characteristic of fetal alcohol syndrome (FAS) have cognitive and behavioral deficits. However, many more children with a history of prenatal ethanol exposure (PAE) also have impaired cognitive processing, even in the absence of facial dysmorphia. The prevalence of this broader phenotype, termed fetal alcohol spectrum disorder (FASD), is at least 10 times greater than FAS and represents greater than 1% of the population. In the absence of the characteristic facial dysmorphia, there are currently no reliable bio-behavioral markers to identif young children with FASD, which often delays intervention until behavioral deficits become apparent in school-aged children. The long-term goal of our research program is to address the clinical challenge of developing early and reliable indices of PAE in infants so that interventions can be implemented at earlier stages of development. The objective of this current research project is to establish a birth cohort of 132 children using an innovative approach for the assessment of PAE, through the combined use of a novel panel of maternal and infant ethanol biomarkers and validated maternal questionnaires, and then to measure neurodevelopment using state-of-the-art magneto- and electro- encephalography (MEG/EEG) and behavioral measures at 6 & 20 months of age to identify early indices of functional brain damage in these children. The rationale for the proposed work is that earlier identification and intervention leads to better outcomes; and behavioral measures alone have yet to reliably identify children at- risk for the long-term adverse neurobehavioral consequences associated with PAE. Our prior work suggests that a combination of biomarkers and questionnaires will provide the best sensitivity and specificity for confirming 2nd or 3rd trimester alcohol exposure. Furthermore, based on our prior work in toddlers, we hypothesize that children with PAE will demonstrate delayed or impaired sensorimotor functioning that can be measured with MEG/EEG in infants and these measures will indicate a broader impact of PAE on brain development corresponding to behavioral deficits. To test this hypothesis, we will identify neurophysiological indices of sensorimotor deficits in 6- & 20-month-old infants with PAE using simultaneous MEG/EEG and their correspondence to broader behavioral and cognitive deficits. Finally, we will determine the predictive ability of ethanol biomarkers and the battery of neuroimaging and neurobehavioral measures collected at 6 months of age to identify functional brain and behavioral deficits at 20 months of age. This innovative, prospective study will establish a well-characterized birth cohort using a multi-faceted approach to confirm PAE and will subsequently use a unique multimodal neuroimaging and behavioral testing regimen to identify early indices of atypical brain development in infants. The significance of the proposed research lies in the prospect of establishing a clinical foundation for a significant vertical advancement in overcoming the challenge of earlier diagnosis in children with FASD.

描述（由申请人提供）：众所周知，患有胎儿酒精综合症（FAS）面部畸形特征的儿童存在认知和行为缺陷。然而，更多有产前乙醇暴露（PAE）史的儿童即使没有面部畸形，也有认知处理受损的情况。这种更广泛的表型被称为胎儿酒精谱系障碍 (FASD)，其患病率至少是 FAS 的 10 倍，占人口的比例超过 1%。在不存在特征性面部畸形的情况下，目前没有可靠的生物行为标记来识别患有 FASD 的幼儿，这常常会延迟干预，直到学龄儿童的行为缺陷变得明显。我们研究计划的长期目标是解决开发早期且可靠的婴儿 PAE 指标的临床挑战，以便干预措施 可以在开发的早期阶段实施。当前研究项目的目标是建立一个由 132 名儿童组成的出生队列，采用创新的 PAE 评估方法，通过结合使用一组新型母婴乙醇生物标志物和经过验证的母体问卷，然后使用最先进的脑磁图和脑电图 (MEG/EEG) 以及 6 个月和 20 个月大的行为测量来测量神经发育，以确定早期指标 这些儿童的功能性脑损伤。拟议工作的基本原理是早期识别和干预导致 以获得更好的结果；单独的行为测量尚未可靠地识别存在与 PAE 相关的长期不良神经行为后果风险的儿童。我们之前的工作表明，生物标志物和问卷的结合将为确认妊娠第二或第三个月的酒精暴露提供最佳的敏感性和特异性。此外，根据我们之前对幼儿的研究，我们假设患有 PAE 的儿童会表现出感觉运动功能延迟或受损，这可以通过婴儿的 MEG/EEG 来测量，这些测量结果将表明 PAE 对与行为缺陷相对应的大脑发育有更广泛的影响。为了检验这一假设，我们将使用同步 MEG/EEG 确定 6 个月和 20 个月大 PAE 婴儿的感觉运动缺陷的神经生理学指标及其与更广泛的行为和认知缺陷的对应关系。最后，我们将确定乙醇生物标志物的预测能力以及在 6 个月大时收集的一系列神经影像学和神经行为测量值，以识别 20 个月大时的功能性大脑和行为缺陷。这项创新的前瞻性研究将使用多方面的方法建立一个特征明确的出生队列来确认 PAE，随后将使用独特的多模式神经影像和行为测试方案来识别婴儿非典型大脑发育的早期指标。本研究的意义在于为克服 FASD 儿童早期诊断的挑战而取得显着的纵向进步奠定临床基础。