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: 10005401
• 负责人: Mandy Brown Belfort
• 金额: $ 76.03万
• 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/10005401
• 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.

项目总结/摘要 尽管在过去的30年里，早产儿的存活率有了显著的提高，但早产儿仍然会经历 从新生儿重症监护室出院后神经发育障碍的发生率较高（50-60%） （新生儿重症监护病房）。这些缺陷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 特殊教育服务。神经发育障碍的一个重要因素是 子宫外生长受限，这是常见的（50%），反映了NICU期间的营养不良 住院正常的大脑发育取决于特定敏感期内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。 妊娠晚期的“大脑快速生长期”NICU中减少营养不良的营养策略 在这个大脑发育的关键时期， 结果。美国儿科学会建议所有早产儿食用强化母乳， 母乳的使用在美国的NICU中正在上升。然而，由于母乳在其 然而，要想持续满足母乳喂养的婴儿的营养需求，就必须确保大量营养素含量。 强化母乳喂养的极早产儿与配方奶粉喂养的极早产儿相比，体重增加和头部生长较慢的证据 目前的母乳强化策略不足以完全支持其生长。的目的 本研究旨在研究一种新的、个性化的母乳强化方法， 从乳制品行业分析母乳成分的护理点和目标强化，以确保 蛋白质和能量摄入量始终符合建议。我们建议研究这一新的 方法，在受试者中进行个体靶向与标准强化的随机对照试验， 接受母乳喂养的早产儿（如果需要，母乳加母乳，不含配方奶粉）。成果将 包括身体生长和身体组成（脂肪和无脂肪质量）、定量MRI以评估大脑大小 和微观结构，以及在一系列领域（认知，执行功能， 注意力、行为）。我们的首要目标是改善长期健康， 通过实用的、循证的营养创新， NICU住院期间的护理。目前研究的影响将是确定 个别针对性的人乳强化不仅对身体生长，而且对结构和功能， 大脑发育。这些答案是需要通知大规模的临床试验和翻译 这和其他有前景的营养策略应用于临床实践。这项工作有可能受益于 美国每年有63，000名极早产儿出生，世界各地还有更多。