Postnatal Choline Supplementation in Children with Prenatal Alcohol Exposure

产前酒精暴露儿童的产后胆碱补充

基本信息

批准号：
8332275
负责人：
JEFFREY ROBERT WOZNIAK
金额：
$ 21.72万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8332275
关键词：
5 year old Adopted Adoption Adverse effects Affect African American Age Alcohol consumption Alcohols American Animals Area Attenuated Behavior Behavioral Blood Brain Brain Injuries Canned Foods Centers for Disease Control and Prevention (U.S.)Child Child Development Childhood Choline Chronic Clinic Clinical Clinical Trials Cognitive Cognitive deficits Collection Consent Core Facility Counseling Country Coupled Data Development Developmental Disabilities Diagnosis Diagnostic Diet Dose Double-Blind Method Drops Effectiveness Enrollment European Family Female of child bearing age Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fetal Alcohol Syndrome Health Personnel Heavy Drinking Hippocampus (Brain)Hispanics Home environment Human Incidence Individual Infant Institutes International Intervention Learning Life Literature Magnetic Resonance Measures Memory Mental Retardation Methods Minnesota Neurocognitive Neurodevelopmental Disorder Nutrient Outcome Parents Participant Patients Pediatrics Perinatal Phase Pilot Projects Placebo Control Placebos Plastics Population Population Heterogeneity Pre-Clinical Model Pregnancy Preparation Prevention Procedures Process Protocols documentation Psychiatry Psychology Public Health Publishing Randomized Randomized Controlled Trials Rattus Recruitment Activity Research Research Design Research Personnel Research Project Grants Resources Risk Rodent Serum Site Source Supplementation Surveys Thinking Time Translational Research Twin Multiple Birth United States Universities Unplanned pregnancy Visit Woman Work Workplace alcohol abstinence alcohol consumption during pregnancy alcohol exposure base cognitive function design disorder prevention drinking efficacy testing eligible participant executive function follow-up high risk human study improved meetings memory process metropolitan myelination neurobehavioral neuroimaging novel postnatal pre-clinical preclinical study prenatal exposure processing speed programs research study therapy development trend urban Native American willingness

项目摘要

At present, the literature on interventions for individuals with Fetal Alcohol Spectrum Disorders (FASD) is very limited, with only two published randomized controlled trials, yet there are promising new treatment options that have not been applied in humans. Recent pre-clinical studies have dramatically demonstrated that dietary choline supplementation pre-natally and even post-natally, as late as days 21-30 in the rodent (equivalent to human childhood), attenuates the memory and behavioral deficits associated with prenatal alcohol exposure (Thomas et al., 2007; Thomas et al., 2000). We propose a two-year project to evaluate the feasibility and tolerability of post-natal choline supplementation in young children with pre-natal alcohol exposure followed by a three-year double-blind, placebo-controlled pilot study examining the efficacy of choline supplementation in improving the cognitive and behavioral functioning of these children. In the R21 feasibility phase, 20 children between the ages of 12 months and 54 months will be randomized to nine months of choline supplementation or placebo. Follow-up visits at 6 months and 9 months will include parent ratings of behavior, cognitive measures including the Mullen Scales of Early Learning and an elicited imitation (EI) hippocampal paradigm, and electrophysiological measures including a VEP measure of myelination-associated processing speed. Based on data collected in the R21 phase, the study design will be modified and implemented on a larger scale in the R33 phase. During the R33 phase, 40 children will be randomized to choline supplementation or placebo. Follow-up measures will be the same or slightly modified based on the R21 study. Results of the studies will be used to design a larger, full-scale clinical trial to test the efficacy of post-natal choline supplementation in young children with pre-natal alcohol exposure. Given the potential effects on hippocampal development, myelination, and other basic aspects of brain development, this treatment may have significant applicability to a host of other neurodevelopmental disorders.

目前，关于对胎儿酒精谱系障碍 (FASD) 患者进行干预的文献非常多有限，仅发表了两项随机对照试验，但有有希望的新治疗选择尚未应用于人类。最近的临床前研究已经戏剧性地证明，饮食啮齿动物在产前甚至产后最迟第 21-30 天补充胆碱（相当于人类童年），减轻与产前酒精暴露相关的记忆和行为缺陷（托马斯等人，2007 年；托马斯等人，2000 年）。我们提出一个为期两年的项目来评估可行性和产前酒精暴露的幼儿对产后补充胆碱的耐受性通过一项为期三年的双盲、安慰剂对照试点研究来检验补充胆碱的功效改善这些儿童的认知和行为功能。在R21可行性阶段，20 12 个月至 54 个月大的儿童将被随机服用 9 个月的胆碱补充剂或安慰剂。 6 个月和 9 个月的随访将包括家长的评分行为、认知测量，包括马伦早期学习量表和诱发模仿 (EI) 海马范式和电生理测量，包括髓鞘形成相关的 VEP 测量处理速度。根据R21阶段收集的数据，研究设计将被修改并在R33阶段更大规模地实施。在 R33 阶段，40 名儿童将被随机分配到胆碱补充剂或安慰剂。后续措施将根据情况相同或稍作修改 R21研究。研究结果将用于设计更大规模的全面临床试验，以测试其疗效对产前接触酒精的幼儿进行产后胆碱补充。鉴于潜力对海马发育、髓鞘形成和大脑发育的其他基本方面的影响，这治疗可能对许多其他神经发育障碍具有重要的适用性。