Role of Human Milk Oligosaccharides on Brain Development in Preterm Infants

母乳低聚糖对早产儿大脑发育的作用

基本信息

批准号：
10580137
负责人：
Paige Kimberly Berger
金额：
$ 24.92万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10580137
关键词：
Adult Affect Anatomy Animals Area Attention Betula Genus Birth Weight Body Composition Brain Brain Injuries Breast Feeding Breastfed infant California Carbohydrates Child Clinical Nutrition Clinical Trials Cognition Cognitive deficits Complex Data Development Diffusion Magnetic Resonance Imaging Exclusive Breastfeeding Exposure to Feasibility Studies Fostering Foundations Funding Future Goals Hispanic Human Milk Impaired cognition Infant Inflammation Lead Learning Skill Life Los Angeles Low Birth Weight Infant MRI Scans Magnetic Resonance Imaging Measures Memory Mentors Mothers Nutritional Nutritional Study Oligosaccharides Outcome Outcome Measure Parents Pediatric Hospitals Phase Play Population Premature Infant Process Research Resources Risk Role Shapes Sialic Acids Signal Transduction Source Structure Techniques Training United States National Institutes of Health Universities Work brain magnetic resonance imaging career cognitive development cognitive enhancement data resource dietary feeding gray matter gut dysbiosis gut inflammation gut microbes gut microbiome high risk infant high risk population myelination neuropsychiatric disorder post-doctoral training prebiotics recruit skills white matter

项目摘要

PROJECT SUMMARY Optimizing early cognitive development is critical, as children with impaired cognition are at greater risk for neuropsychiatric disorders later in life. While it is known that breastfeeding promotes better cognitive development, few studies have identified specific components of breast milk that are involved in this process. One component that may be relevant is a group of non-digestible complex carbohydrates known as human milk oligosaccharides (HMOs). Animal studies reveal that certain HMOs enhance cognitive outcomes of memory, attention, and impulse control, and the relationship may be driven by several mechanisms. First, some HMOs are a source of sialic acid important for brain development. Second, HMOs are a source of prebiotics important for gut microbe development, which is likely to play a role in cognitive development and a focus of the parent R01. Although the first year of life is a critical window for brain development, it is unknown whether HMOs affect structural-functional organization of infant cognition. In this application, Dr. Paige Berger’s goal is to determine associations between HMOs and magnetic resonance imaging (MRI) measures of infant brain development (brain white matter myelination, cortical maturation). During the K99 phase, she will build on an existing NIH sponsored study (R01DK110793) by Dr. Michael Goran. In the parent R01, Hispanic mothers and normal birth weight infants are being followed, with frequent assessment of HMOs up to 24 months. In the proposed project, Dr. Berger will leverage the data and resources on HMOs in a subset of exclusively breastfeeding mother-infant pairs (n=65) at 1 and 6 months. Since brain white matter myelination and cortical maturation were not measured in the parent R01, Dr. Berger will collect these in infants at 1 and 6 months. The K99 hypothesis is that in normal birth weight infants (≥2500 g), brain white matter myelination and cortical maturation will be positively associated with HMOs. Dr. Berger will focus her K99 training on the development of expertise in structural-functional organization of infant cognition, and hone her skills in conducting clinical nutrition research in mother-infant pairs. She will learn the skills and techniques needed to complete the proposed research under her expert team (Drs. Goran, Bradley Peterson, Lars Bode, Leann Birch, Douglas Vanderbilt). Collectively, her expert team has a strong track record of training postdoctoral scholars transitioning to independence. In the R00 phase, Dr. Berger will apply the skills acquired during the mentored phase to initiate a new line of work in low birth weight infants (<2500 g), examining associations between HMOs and cognitive development. The proposed work will provide Dr. Berger with data and support to develop efficient and effective clinical trials, with future implications to validate the roles of HMOs that may have positive effects on cognitive development in a high-risk infant population.

项目概要优化早期认知发展至关重要，因为认知受损的儿童面临更大的风险虽然众所周知，母乳喂养可以促进更好的认知能力。发育过程中，很少有研究确定母乳中参与这一过程的特定成分。可能相关的一个成分是一组不可消化的复杂碳水化合物，称为人类碳水化合物牛奶低聚糖 (HMO) 动物研究表明，某些 HMO 可以增强认知结果。记忆、注意力和冲动控制，并且这种关系可能由多种机制驱动。一些 HMO 是唾液酸的来源，对大脑发育很重要。益生元对肠道微生物的发育很重要，这可能在认知发展和父母关注的焦点 R01 虽然生命的第一年是大脑发育的关键窗口，但目前尚不清楚。 HMO 是否影响婴儿认知的结构功能组织在该应用中，Paige 博士。 Berger 的目标是确定 HMO 与磁共振成像 (MRI) 测量之间的关联婴儿大脑发育（脑白质髓鞘形成、皮质成熟）的 K99 阶段。将以 NIH 资助的现有研究 (R01DK110793) 为基础，该研究由 Michael Goran 博士在母版 R01 中进行。西班牙裔母亲和正常出生体重婴儿正在接受跟踪，频繁评估 HMO 高达在拟议的项目中，Berger 博士将利用 HMO 的一部分数据和资源。 1 个月和 6 个月时纯母乳喂养的母婴对 (n=65)。未在父母 R01 中测量皮质成熟度，Berger 博士将在 1 岁和 6 岁的婴儿中收集这些数据 K99 假设是，在正常出生体重的婴儿（≥2500 克）中，大脑白质髓鞘形成。皮质成熟与 HMO 呈正相关。Berger 博士将把她的 K99 培训重点放在发展婴儿认知结构功能组织方面的专业知识，并磨练她的技能她将学习进行母婴临床营养研究所需的技能和技巧。在她的专家团队（Goran 博士、Bradley Peterson、Lars Bode、Leann 博士）的指导下完成拟议的研究总的来说，她的专家团队在博士后培训方面拥有良好的记录。在R00阶段，伯杰博士将运用在R00阶段获得的技能。指导阶段启动低出生体重婴儿（<2500克）的新工作，检查协会 HMO 和认知发展之间的关系。拟议的工作将为 Berger 博士提供数据和支持。开发高效且有效的临床试验，对未来验证 HMO 的作用可能产生影响对高危婴儿群体的认知发展有积极影响。