Prenatal DHA & Neurofunctional Development

产前 DHA

• 批准号: 9124472
• 负责人: KATHLEEN M GUSTAFSON
• 金额: $ 63.49万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-08 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9124472
• 关键词: Accounting; Age; Age-Months; Attention; Autonomic nervous system; Behavior; Birth; Blood specimen; Brain; Cardiac; Cardiac Electrophysiologic Techniques; Child; Complex; Data; Development; Diet; Dietary Fatty Acid; Dietary History; Disease; Docosahexaenoic Acids; Dose; Double-Blind Method; Electroencephalography; Ensure; Equilibrium; Essential Fatty Acids; Failure; Fatty Acids; Fetal Heart Rate; Fetus; Future; Gestational Age; Goals; Health; Incidence; Infant; Lead; Learning; Life; Link; Magnetoencephalography; Maintenance; Measures; Methods; Mission; Mothers; Motor; National Institute of Child Health and Human Development; Nervous system structure; Neurosciences; Nutritional status; Oils; Phase; Phase III Clinical Trials; Placebos; Population; Postpartum Period; Pregnancy; Pregnancy Trimesters; Pregnant Women; Proxy; Public Health; Randomized; Randomized Clinical Trials; Recommendation; Reporting; Research; Sampling; Staging; Supplementation; System; Testing; Time; Vision; Woman; aging brain; auditory stimulus; base; behavior measurement; cognitive function; fetal; habituation; heart rate variability; in utero; indexing; infancy; innovation; insight; international health organization; nervous system development; neurodevelopment; novel; offspring; postnatal; prenatal; prenatal exposure; programs; public health priorities; public health relevance; sustained attention; visual stimulus

 DESCRIPTION (provided by applicant): Docosahexaenoic acid (DHA) is essential for neurodevelopment. If maternal DHA reserves are adequate during pregnancy, at parturition RBC-DHA of the mother would be ≥ the infant, i.e., DHA equilibrium. Previously, we randomized pregnant women to placebo oil or DHA (600 mg/day). We discovered that the majority of subjects did not achieve DHA equilibrium (5% placebo, 35% DHA), indicating DHA insufficiency, which has been reported to limit infant neurodevelopment. To test whether DHA insufficiency limited fetal neurodevelopment in our sample, we applied an innovative analysis method to estimate fetal brain maturation. Results confirmed that maternal DHA insufficiency significantly constrained fetal autonomic brain age scores (fABAS). Our hypothesis is that many pregnant women fail to get adequate DHA in their diet and that DHA insufficiency constrains fetal and infant neurodevelopment. The long-term goal is to provide the neuroscience to inform public health recommendations related to the use and dose of prenatal DHA supplementation, the influence of dietary fatty acids and the effect on offspring neurodevelopment. This is aligned with the strategic and scientific vision of NICHD and the mission of national and international health organizations that recognize that prenatal exposures set the stage for future health and disease. We propose a randomized Phase III clinical trial of 200 or 800 mg/day DHA during the last two trimesters of pregnancy to achieve these aims: Aim 1) Increase the incidence of DHA equilibrium with 800 mg/day maternal DHA supplementation. Hypothesis: The dosing strategy will result in significant group differences with a higher incidence of DHA equilibrium in the grou receiving 800 mg/day DHA supplementation. Aim 2) Establish whether failure to achieve DHA equilibrium constrains fetal neurodevelopment. Hypothesis: DHA insufficiency will constrain fetal neurodevelopment as evidenced by lower fetal cardiac and brain autonomic indices (HRV, fABAS) at 32 and 36 weeks GA. Aim 3) Determine if fetal neurodevelopmental scores predict infant neurodevelopment. Hypothesis: DHA insufficiency associated with lower fetal HRV and fABAS scores will have a programming effect evidenced by 1) lower band-limited EEG power at 1 month of age to infrequent auditory stimuli, 2) decreased habituation to familiar visual stimuli at 6 and 12 months, evidenced by a larger ERP negative central (NC) component and 3) reduced maintenance of sustained attention and longer overall ocular latency between 4-6 months. Relevance to Public Health: Currently, there are no FDA recommendations for DHA supplementation during pregnancy. If the aims of this proposal are achieved, it could lead to informed recommendations with respect to the appropriate use and effective dose of supplemental DHA and dietary recommendations during pregnancy, especially in populations where the nutritional status of the diet is suboptimal.

 描述(申请人提供)：二十二碳六烯酸(DHA)是神经发育所必需的。如果母亲在怀孕期间有足够的DHA储备，在分娩时，母亲的红细胞-DHA将是≥的婴儿，即DHA平衡。此前，我们随机给孕妇服用安慰剂油或DHA(600毫克/天)。我们发现大多数受试者没有达到DHA平衡(5%的安慰剂，35%的DHA)，这表明DHA不足，据报道，这限制了婴儿的神经发育。在我们的样本中，为了测试DHA不足是否限制了胎儿神经发育，我们应用了一种创新的分析方法来估计胎儿大脑的成熟度。结果证实，母亲DHA不足显著限制了胎儿自主神经脑龄评分(FABAS)。我们的假设是，许多孕妇在饮食中没有获得足够的DHA，DHA不足会限制胎儿和婴儿的神经发育。其长期目标是提供神经科学，为与产前DHA补充剂的使用和剂量、饮食脂肪酸的影响以及对后代神经发育的影响有关的公共卫生建议提供信息。这与NICHD的战略和科学愿景以及国家和国际卫生组织的使命相一致，这些组织认识到产前暴露为未来的健康和疾病奠定了基础。我们建议在妊娠的最后两个三个月内每天补充200或800 mg的DHA，以达到这些目的：目的1)补充800 mg/d的DHA以增加DHA平衡的发生率。假设：剂量策略将导致显著的组差异，接受800 mg/天DHA补充组的DHA平衡发生率较高。目的2)确定不能达到DHA平衡是否会限制胎儿神经发育。假设：DHA不足将限制胎儿神经发育，表现为胎龄32周和36周时胎儿心脏和脑自主神经指数(HRV，Fabas)较低。目的3)探讨胎儿神经发育评分对婴儿神经发育的预测作用。假设：DHA不足与较低的胎儿HRV和Fabas评分相关，将产生编程效应，表现为1)1个月龄时对罕见听觉刺激的带限脑电功率较低，2)6个月和12个月时对熟悉的视觉刺激的习惯性降低，表现为较大的事件相关电位负中枢(NC)成分，以及3)持续注意力的维持减少和4-6个月之间整体眼睛潜伏期的延长。与公共卫生相关：目前，FDA没有关于怀孕期间补充DHA的建议。如果这项建议的目标得以实现，它将产生关于适当使用和有效剂量补充DHA的知情建议和孕期饮食建议，特别是在饮食营养状况不佳的人群中。