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

项目摘要/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，但早产儿仍在经历 新生儿重症监护病房出院后神经发育障碍发生率高(50%-60%) (NICU)。这些损害给儿童和家庭带来负担，并为早期干预招致巨大的社会成本。 和特殊教育服务。神经发育障碍的一个重要因素是 宫外生长受限，这很常见(50%)，反映了NICU期间的营养不良 住院治疗。大脑的正常发育取决于特定敏感期关键营养物质的供应情况 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“脑生长突发期”。NICU减少营养不良的营养策略 在这个大脑发育的关键时期，可能会导致更好的长期神经发育 结果。美国儿科学会建议所有早产儿都要强化母乳饮食， 而在美国各地的NICU中，母乳的使用量正在上升。然而，因为母乳在其 要持续满足母乳喂养婴儿的营养需求是一项挑战。 强化母乳喂养与配方奶喂养的早产儿体重增加和头部生长缓慢的证据 这表明，目前的母乳强化战略不足以完全支持它们的生长。的目的是 这项研究是为了研究一种新的、个性化的母乳强化方法，利用技术 从乳品行业分析母乳成分的角度进行关爱和针对性的强化，以确保 蛋白质和能量的摄入量始终符合推荐标准。我们提议研究这一新的 通过在以下人群中进行个别靶向与标准防御工事的随机对照试验来采取这种方法 接受母乳喂养的早产儿(母乳加上必要时的供体乳，不含配方奶)。结果将会 包括身体生长和身体成分(脂肪和脱脂质量)、用于评估大脑大小定量核磁共振 和微结构，以及在一系列领域(认知、执行功能、 注意，行为)在2岁的校正年龄。我们的首要目标是改善长期健康和 通过务实、循证的营养创新对极早产儿的发育结果 在NICU住院期间的护理。目前这项研究的影响将是确定 个别针对性的母乳强化不仅对身体生长，而且对结构和功能 发育中的大脑。这些答案是为更大规模的临床试验提供信息以及将 这和其他有希望的营养策略进入临床实践。这项工作有可能使 美国每年有6.3万名早产儿出生，全世界还有更多的早产儿。

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.