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: 8867958
• 负责人: Ludmila Nicole Bakhireva
• 金额: $ 56.98万
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8867958
• 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; 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; behavioral outcome; cognitive process; cohort; disability; drinking; encephalography; fetal; indexing; innovation; intervention program; neural correlate; neurobehavioral; neurodevelopment; neuroimaging; neurophysiology; novel; pediatrician; prenatal; programs; public health relevance; 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）：良好的是，胎儿酒精综合征（FAS）具有面部畸形特征的儿童具有认知和行为缺陷。但是，有更多的患有产前乙醇病史（PAE）的儿童也受到了认知处理的损害，即使没有面部畸形。这种更广泛的表型的患病率称为胎儿酒精谱系障碍（FASD），比FAS大10倍，代表大于人口的1％。在没有特征性的面部畸形的情况下，目前尚无可靠的生物行为标记来识别患有FASD的幼儿，这通常会延迟干预，直到行为缺陷在学龄儿童中显而易见。我们的研究计划的长期目标是应对婴儿早期和可靠索引的临床挑战，以便进行干预措施 可以在发展的早期阶段实施。该当前研究项目的目标是通过共同使用新颖的孕产妇和婴儿乙醇生物标志物和经过验证的孕产妇问卷来建立132名儿童的分娩，以评估PAE，然后使用Art-The-Art-Art-Art-Art-Art-Art-Arto-Enceph/ectro-Encephales（Meeg/Eeg）进行衡量的孕产妇问卷，然后测量神经脱发（以及均经）的量表（和eeg）。这些孩子的功能性脑损伤。拟议工作的理由是，早期的识别和干预领导 更好的结果；仅凭行为措施尚未可靠地识别儿童与PAE相关的长期不良神经行为后果的风险。我们先前的工作表明，生物标志物和问卷的结合将为确认第二或第三孕期酒精暴露提供最佳的敏感性和特异性。此外，根据我们先前在幼儿中的工作，我们假设患有PAE的儿童将证明延迟或受损的感觉运动功能，可以用MEG/EEG在婴儿中测量，这些措施将表明PAE对与行为不足有关的大脑发育产生更广泛的影响。为了检验这一假设，我们将使用同时使用MEG/EEG及其对更广泛的行为和认知缺陷的对应关系，以确定6个月和20个月大的儿童中有感觉运动缺陷的神经生理学指标。最后，我们将确定乙醇生物标志物以及在6个月大时收集的神经影像和神经行为措施的预测能力，以鉴定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来确认PAE，并将使用独特的多模式神经影像学和行为测试方案来确定婴儿的早期脑发育指标。拟议的研究的重要性在于为了克服FASD儿童早期诊断的挑战，建立了临床基础的前景。