Postnatal Choline Supplementation in Children with Prenatal Alcohol Exposure

产前酒精暴露儿童的产后胆碱补充

• 批准号: 8530112
• 负责人: JEFFREY ROBERT WOZNIAK
• 金额: $ 20.17万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8530112
• 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

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，关于胎儿酒精谱系障碍（FASD）个体干预的文献非常少。 有限，只有两个已发表的随机对照试验，但有希望的新的治疗选择 还没有应用于人类。最近的临床前研究已经戏剧性地证明， 出生前甚至出生后补充胆碱，在啮齿动物中迟至第21-30天（相当于 人类童年），减弱与产前酒精暴露相关的记忆和行为缺陷 （托马斯等人，2007;托马斯等人，2000）。我们提出了一个为期两年的项目，以评估可行性， 出生前暴露于酒精的幼儿出生后补充胆碱的耐受性 通过一项为期三年的双盲、安慰剂对照的试点研究， 改善这些儿童的认知和行为功能。在R21可行性阶段，20 年龄在12个月到54个月之间的儿童将随机接受9个月的胆碱治疗， 补充剂或安慰剂。6个月和9个月时的随访访视将包括父母对以下方面的评级： 行为、认知测量，包括早期学习的马伦量表和诱发性模仿（EI） 海马范例和电生理学测量，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，将修改研究设计， 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至 胆碱补充剂或安慰剂。后续措施将保持不变或根据 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 出生前接触酒精的幼儿出生后补充胆碱。考虑到潜在的 对海马发育、髓鞘形成和大脑发育的其他基本方面的影响， 治疗对许多其它神经发育障碍具有显著的适用性。