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: 7942035
• 负责人: JEFFREY ROBERT WOZNIAK
• 金额: $ 20.18万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942035
• 关键词: 5 year old; Adherence; 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; 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; 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; public health relevance; research study; therapy development; trend; urban Native American; willingness

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Alcohol consumption during pregnancy is known to contribute to permanent brain damage in the child, yet there are no established treatments. Recently, animal studies have demonstrated that postnatal supplementation with choline, an essential nutrient found in many foods, can attenuate the cognitive and behavioral deficits typically seen in alcohol-exposed animals. A human study of choline supplementation in children has not yet been done. The proposed study will evaluate if choline supplementation during a specific developmental window when the child's brain remains somewhat plastic is able to attenuate the deficits in thinking, memory, processing speed, and behavior that are common in children with Fetal Alcohol Spectrum Disorders (FASD). We expect that this study will provide important information about the practicality of choline supplementation in children 1-5 years of age and will provide initial estimates of its effectiveness.

描述(申请人提供)：目前，关于胎儿酒精谱系障碍(FASD)个体干预的文献非常有限，只有两个已发表的随机对照试验，但有希望的新治疗方案尚未在人类身上应用。最近的临床前研究戏剧性地表明，在啮齿类动物出生前甚至出生后补充胆碱，直到第21-30天(相当于人类童年)，可以减轻与产前酒精暴露相关的记忆和行为缺陷(Thomas等人，2007年；Thomas等人，2000年)。我们提出了一个为期两年的项目，以评估出生前酒精暴露的幼儿产后补充胆碱的可行性和耐受性，然后进行为期三年的双盲、安慰剂对照的初步研究，以检验补充胆碱在改善这些儿童认知和行为功能方面的效果。在R21可行性阶段，20名年龄在12个月到54个月之间的儿童将随机接受9个月的胆碱补充或安慰剂治疗。在6个月和9个月的随访将包括父母的行为评级，认知测量包括早期学习的马伦量表和诱发模仿(EI)海马体范式，以及电生理测量包括髓鞘相关处理速度的VEP测量。根据在R21阶段收集的数据，研究设计将在R33阶段进行更大规模的修改和实施。在R33阶段，40名儿童将被随机给予胆碱补充剂或安慰剂。后续措施将在R21研究的基础上保持不变或略有修改。研究结果将被用于设计一项更大规模的临床试验，以测试产后补充胆碱对产前酒精暴露的幼儿的疗效。考虑到对海马体发育、髓鞘形成和大脑发育的其他基本方面的潜在影响，这种治疗方法可能对许多其他神经发育障碍具有重要的适用性。 公共卫生相关性：众所周知，怀孕期间饮酒会导致儿童永久性脑损伤，但目前还没有既定的治疗方法。最近，动物研究表明，出生后补充胆碱可以减轻酒精暴露动物通常出现的认知和行为缺陷。胆碱是许多食物中的一种基本营养物质。对儿童补充胆碱的人体研究尚未完成。拟议的研究将评估在儿童大脑保持某种可塑性的特定发育窗口期间补充胆碱是否能够缓解患有胎儿酒精谱系障碍(FASD)的儿童在思维、记忆、处理速度和行为方面的常见缺陷。我们希望这项研究将提供有关1-5岁儿童胆碱补充的实用性的重要信息，并将提供其有效性的初步估计。

项目成果

Overweight and obesity among children and adolescents with fetal alcohol spectrum disorders.

• DOI: 10.1111/acer.12516
• 发表时间: 2014-09
• 期刊: Alcoholism, clinical and experimental research
• 作者: Fuglestad AJ;Boys CJ;Chang PN;Miller BS;Eckerle JK;Deling L;Fink BA;Hoecker HL;Hickey MK;Jimenez-Vega JM;Wozniak JR
• 通讯作者: Wozniak JR

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability.

• DOI: 10.1016/j.nutres.2013.08.005
• 发表时间: 2013-11
• 期刊: Nutrition research (New York, N.Y.)
• 作者: Wozniak JR;Fuglestad AJ;Eckerle JK;Kroupina MG;Miller NC;Boys CJ;Brearley AM;Fink BA;Hoecker HL;Zeisel SH;Georgieff MK
• 通讯作者: Georgieff MK

Inadequate intake of nutrients essential for neurodevelopment in children with fetal alcohol spectrum disorders (FASD).

• DOI: 10.1016/j.ntt.2013.06.005
• 发表时间: 2013-09
• 期刊: NEUROTOXICOLOGY AND TERATOLOGY
• 影响因子: 2.9
• 作者: Fuglestad, Anita J.;Fink, Birgit A.;Eckerle, Judith K.;Boys, Christopher J.;Hoecker, Heather L.;Kroupina, Maria G.;Zeisel, Steven H.;Georgieff, Michael K.;Wozniak, Jeffrey R.
• 通讯作者: Wozniak, Jeffrey R.