Long-term Effects and Safety of DHA Supplementation in Toddlerhood for Children born Preterm

学步期补充 DHA 对早产儿的长期影响和安全性

• 批准号: 10226056
• 负责人: Sarah Keim
• 金额: $ 61.73万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10226056
• 关键词: 1 year old; Accounting; Adverse effects; Age; Alleles; Arachidonic Acids; Attention; Back; Biological; Blood; Brain; Child; Clinical; Cognitive deficits; Consumption; Data; Development; Diet; Dietary Fatty Acid; Early Intervention; Ensure; Equilibrium; Evaluation; Executive Dysfunction; Exhibits; Family; Fatty Acid Desaturases; Fatty Acids; Food; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Goals; Heritability; Impairment; Infant formula; Intervention; Language; Language Development; Language Disorders; Literature; Long-Term Effects; Measures; Methods; Minor; Mission; National Institute of Child Health and Human Development; Neurocognitive Deficit; Neurologic Process; Observational Study; Omega-3 Fatty Acids; Omega-6 Fatty Acids; Outcome; Outcome Assessment; Parents; Participant; Performance; Persons; Placebos; Population; Premature Infant; Problem behavior; Prospective cohort; Public Health; Publishing; Randomized; Recommendation; Reporting; Research; Risk; Role; Safety; Saliva; School-Age Population; Schools; Sex Differences; Specific qualifier value; Structure; Subgroup; Suggestion; Supplementation; Testing; Time; Toddler; Very Long Chain Fatty Acid; Visual; arm; base; blind; cognitive ability; cognitive benefits; cognitive development; cohort; cost; dietary supplements; executive function; fatty acid metabolism; fatty acid supplementation; follow up assessment; genetic variant; high risk; improved; infancy; informant; innovation; insight; intervention program; learned behavior; long chain fatty acid; neurodevelopment; randomized placebo controlled trial; socioeconomics; teacher; treatment effect; virtual

PROJECT SUMMARY/ABSTRACT One in 10 children in the U.S. is born preterm and consequently at high risk for long-term cognitive deficits and poor academic performance. While omega-3 docosahexaenoic fatty acid (DHA) dietary supplements have been touted to promote cognitive development in children born preterm, several recent studies have produced suggestive evidence of long-term adverse effects. The long-term goal is to ensure that interventions to help children born preterm succeed in school are safe and effective. The objective of this application is to determine the long-term effects of DHA supplementation on general cognitive ability, language, and executive function, and to examine genetic explanations for treatment effects, by continuing to follow the children from the fully blind, randomized, placebo-controlled trial called Omega Tots. The central hypothesis is that children born preterm who were randomized to 180 days of DHA at age 1 will exhibit poorer general cognitive ability, greater language deficits, and more impaired executive function at age 9-10 versus children randomized to placebo. The rationale for this project is that a careful examination of the long-term effects of DHA supplementation will offer valuable clarification about the appropriateness of DHA as an intervention to promote neurodevelopment among children born preterm. The central hypothesis will be tested by pursuing 2 specific aims: 1) Determine the long-term effect of DHA supplementation at age 1 year by comparing general cognitive ability, language, and multiple facets of executive function between the DHA and placebo arms at age 9-10. 2) Determine the role of variability in fatty acid metabolism genetics en masse on the effect of DHA supplementation on short and long-term outcomes, and further focus on 2 previously published FADS2 genetic variants. Under Aim 1, the approach will be an innovative prospective cohort of children from Omega Tots who will participate in detailed, in-person assessments at age 9-10 including evaluation by blind assessors and parent and teacher reports of outcomes. For Aim 2, SNP-based heritability methods will examine the role of fatty acid metabolism genes as measured in stored blood or saliva to explain observed treatment effects. The proposed research is innovative, in the applicant's opinion, because it represents a substantive departure from the status quo by conducting robust, multi-informant follow-up assessment of general cognitive development, language and executive function of a large child cohort who participated in a DHA supplementation trial, as well as integrating, for the first time ever, consideration of fatty acid metabolism genetics as possible explanatory factors for short and long-term adverse effects. The expected outcome is the determination of the effects of DHA supplementation at age 1 on cognitive ability, language, and multiple facets of executive function at age 9-10, and new insight into the role of specific genetic contributors as explanatory mechanisms for short and long-term effects. This contribution is expected to be significant because, if DHA supplementation has persistent, adverse effects on the neurodevelopment of US children born preterm, such findings would directly inform clinical recommendations about supplementation.

项目摘要/摘要 美国十分之一的儿童是早产的，因此长期认知缺陷的风险很高 学业表现不佳。欧米茄-3 docosahexaenoic脂肪酸（DHA）饮食补充剂已经是 吹捧以促进早产儿童的认知发展，最近的一些研究已经产生 长期不利影响的暗示证据。长期目标是确保干预措施来帮助 出生的早产儿在学校成功是安全有效的。此应用的目的是确定 补充DHA对一般认知能力，语言和执行功能的长期影响以及 通过继续跟随完全盲人的儿童来检查遗传解释的治疗效果， 随机的，安慰剂对照试验称为欧米茄tots。中心假设是孩子出生的早产 1岁时随机分配到DHA 180天的人将表现出较差的一般认知能力，更高的语言 与随机分配到安慰剂的儿童相比，9-10岁的执行职能障碍和更受损害的执行功能。理由 因为这个项目是对补充DHA的长期影响的仔细检查将提供有价值的 澄清DHA的适当性作为促进儿童神经发育的干预措施 天生的早产。中心假设将通过追求2个具体目标来检验：1）确定长期效果 通过比较一般认知能力，语言和多个方面，在1岁时补充DHA 9-10岁时，DHA和安慰剂臂之间的执行功能。 2）确定变异性在脂肪中的作用 酸代谢遗传学对补充DHA对短期和长期结局的影响， 并进一步关注2个先前发表的FADS2遗传变异。在AIM 1下，该方法将是 来自Omega Tots的创新前瞻性队列，他们将参加详细的，面对面的人 9-10岁的评估包括盲人评估者，父母和教师报告的评估。 对于AIM 2，基于SNP的遗传力方法将检查脂肪酸代谢基因的作用。 存储血液或唾液以解释观察到的治疗效果。拟议的研究是创新的，在 申请人的意见，因为它代表了通过强大的实质性偏离现状 一般认知发展，语言和执行功能的多信息随访评估 参加DHA补充试验的大型儿童队列，并首次融合 考虑脂肪酸代谢遗传学作为短期和长期不良的解释因素 效果。预期的结果是确定1岁时补充DHA对认知的影响 9-10岁的执行功能的能力，语言和多个方面，以及对特定作用的新见解 遗传因素作为短期和长期影响的解释机制。这项贡献有望 要重要，因为如果补充DHA持续存在，对我们神经发育的不利影响 出生早产的孩子，这些发现将直接为补充的临床建议提供信息。