Targeting human milk fortification to improve preterm infant growth and brain development

针对母乳强化以改善早产儿生长和大脑发育

• 批准号: 10247537
• 负责人: Mandy Brown Belfort
• 金额: $ 74.54万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247537
• 关键词: Academy; Adverse effects; Age; American; Attention; Behavior; Biological Markers; Birth; Body Composition; Brain; Cerebellum; Child; Clinical; Clinical Trials; Cognition; Data; Development; Diet; Dietary Intervention; Diffusion; Early Intervention; Energy Intake; Ensure; Family; Fatty acid glycerol esters; Goals; Growth; Growth and Development function; Head; Health; Health Benefit; Hospitalization; Human Milk; Impairment; Individual; Industry; Infant; Infant formula; Informal Social Control; Intake; Internal Capsule; Intervention; Limb structure; Macronutrients Nutrition; Magnetic Resonance Imaging; Malnutrition; Measures; Milk; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care; Neonatal Intensive Care Units; Neurodevelopmental Impairment; Nutrient; Nutritional; Nutritional Requirements; Nutritional Support; Nutritional status; Observational Study; Outcome; Outcome Measure; Participant; Pediatrics; Pilot Projects; Population; Pregnancy; Premature Infant; Proteins; Randomized Controlled Trials; Recommendation; Research; Serum; Services; Structure; Techniques; Technology; Testing; Thinness; Third Pregnancy Trimester; Translations; Variant; Weight; Weight Gain; Work; base; brain size; clinical care; clinical practice; cognitive function; critical period; design; donor milk; evidence base; executive function; experience; fortification; group intervention; improved; innovation; intervention effect; meetings; myelination; neurodevelopment; neuroimaging; novel; novel strategies; nutrition; nutritional approach; pasteurization; personalized approach; point of care; protein intake; randomized trial; societal costs; standard of care; sustained attention; white matter

Project Summary / Abstract Despite marked improvement in survival in the past 3 decades, very preterm infants continue to experience high rates (50-60%) of neurodevelopmental impairment after discharge from the neonatal intensive care unit (NICU). These impairments burden children and families and incur large societal costs for early intervention and special educational services. An important contributing factor to neurodevelopmental impairment is extrauterine growth restriction, which is common (50%) and reflects undernutrition during the NICU hospitalization. Normal brain development depends on the availability of key nutrients during specific sensitive or critical periods, and preterm infants are entirely dependent on the nutrition they receive in the NICU during the “brain growth spurt” of the third trimester. Nutritional strategies in the NICU that reduce undernutrition during this critical period for brain development are likely to result in better long-term neurodevelopmental outcomes. The American Academy of Pediatrics recommends a fortified human milk diet for all preterm infants, and human milk use is rising in NICUs across the U.S. However, because human milk is highly variable in its macronutrient content, consistently meeting nutrient requirements for human milk-fed infants is a challenge. Evidence of slower weight gain and head growth in fortified human milk- vs. formula-fed very preterm infants suggests that current human milk fortification strategies are inadequate to fully support their growth. The aim of this study is to investigate a new, individualized approach to human milk fortification, leveraging technology from the dairy industry to analyze human milk composition at the point of care and target fortification to ensure that protein and energy intakes consistently meet recommendations. We are proposing to study this new approach by conducting a randomized, controlled trial of individually targeted vs. standard fortification among preterm infants receiving human milk (maternal milk plus donor milk if needed, no formula). Outcomes will include physical growth and body composition (fat and fat-free mass), quantitative MRI to assess brain size and microstructure, and neurodevelopment assessed across a range of domains (cognition, executive function, attention, behavior) at 2 years’ corrected age. Our overarching goal is to improve long-term health and developmental outcomes of very preterm infants through pragmatic, evidence-based innovations in nutritional care during the NICU hospitalization. The impact of the current study will be to determine the benefits of individually targeted human milk fortification not just to physical growth, but also to the structure and function of the developing brain. These answers are needed to inform larger-scale clinical trials and for the translation of this and other promising nutritional strategies into clinical practice. This work has the potential to benefit over 63,000 very preterm infants born each year in the U.S. and many more worldwide.

项目概要/摘要 尽管过去 3 年来生存率显着提高，但极早产儿仍继续经历 从新生儿重症监护病房出院后神经发育障碍的发生率很高（50-60%） （新生儿重症监护病房）。这些损伤给儿童和家庭带来负担，并为早期干预带来巨大的社会成本。 和特殊教育服务是神经发育障碍的一个重要因素。 宫外生长受限，这种情况很常见（50%），反映了 NICU 期间的营养不良 住院期间正常的大脑发育取决于关键营养素的可用性。 或关键时期，早产儿完全依赖于他们在 NICU 期间接受的营养 新生儿重症监护病房 (NICU) 中减少营养不良的营养策略。 在大脑发育的关键时期可能会导致更好的长期神经发育 美国儿科学会建议所有早产儿采用强化母乳饮食， 美国新生儿重症监护病房 (NICU) 中母乳的使用量正在上升。然而，由于母乳的成分差异很大 常量营养素含量，持续满足母乳喂养婴儿的营养需求是一项挑战。 与配方奶喂养的极早产儿相比，强化母乳的体重增加和头部生长较慢的证据 表明当前的母乳强化策略不足以完全支持它们的生长。 这项研究旨在利用技术研究一种新的、个性化的母乳强化方法 来自乳制品行业，在护理和目标强化时分析母乳成分，以确保 我们建议研究这一新的蛋白质和能量摄入量。 通过对个体目标强化与标准强化进行随机对照试验来进行方法 接受母乳的早产儿（母乳加上捐赠乳（如果需要），没有配方奶）。 包括身体生长和身体成分（脂肪和去脂质量）、定量 MRI 来评估大脑大小 以及微观结构和神经发育的跨领域评估（认知、执行功能、 注意力、行为）在 2 岁校正年龄时我们的首要目标是改善长期健康和 通过务实、循证的营养创新，改善极早产儿的发育结果 NICU 住院期间的护理 当前研究的影响将是确定 NICU 住院期间的益处。 单独针对性的母乳强化不仅有利于身体生长，而且有利于婴儿的结构和功能 发育中的大脑需要这些答案来为更大规模的临床试验和翻译提供信息。 这项工作和其他有前景的营养策略有可能在临床实践中受益。 美国每年有 63,000 名极早产儿出生，全球范围内还有更多。