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: 10443726
• 负责人: Sarah Keim
• 金额: $ 60.33万
• 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/10443726
• 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; 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 在美国，每10名儿童中就有一名早产，因此患有长期认知缺陷的风险很高 学业成绩不佳。而omega-3二十二碳六烯酸(DHA)膳食补充剂一直是 被吹捧为促进早产儿童的认知发展，最近的几项研究产生了 长期不良影响的提示性证据。长期目标是确保干预措施的帮助 早产的孩子在学校取得成功是安全有效的。此应用程序的目标是确定 补充DHA对一般认知能力、语言和执行功能的长期影响 为了检查治疗效果的遗传解释，通过继续跟踪完全失明的儿童， 名为Omega Tots的随机、安慰剂对照试验。中心假设是早产的孩子 在1岁时被随机分配到180天DHA的人将表现出较差的一般认知能力，较强的语言能力 与随机服用安慰剂的儿童相比，9-10岁的儿童存在缺陷，执行功能受损更多。其基本原理是 对于这个项目来说，仔细检查补充DHA的长期影响将提供有价值的 澄清DHA作为促进儿童神经发育的干预措施的适宜性 早产。中心假设将通过追求两个具体目标来检验：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和安慰剂组之间的执行功能。2)确定变异性在肥胖中的作用 酸代谢遗传学关于补充DHA对短期和长期结果的影响， 并进一步关注已发表的2个FADS2基因变异体。在目标1下，方法将是 来自Omega Tots的创新的潜在儿童队列，他们将参与详细的面对面 在9-10岁时进行评估，包括盲评员的评估和家长和老师对结果的报告。 对于目标2，基于SNP的遗传力方法将检查脂肪酸代谢基因在 储存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，因为它代表着通过进行稳健的、 多信息者对儿童一般认知发展、语言和执行功能的跟踪评估 参加DHA补充试验的大型儿童队列，以及有史以来第一次整合 考虑将脂肪酸代谢遗传学作为短期和长期不良反应的可能解释因素 效果。预期结果是确定在1岁时补充DHA对认知能力的影响 9-10岁时的能力、语言和执行功能的多个方面，以及对特定角色的新见解 基因贡献者作为短期和长期影响的解释机制。这一贡献预计将 重要的是，如果DHA补充剂对美国的神经发育有持续的不利影响 对于早产的儿童，这样的发现将直接为有关补充的临床建议提供信息。