Aerodigestive Pathophysiology-Driven Mechanisms of Infant Feeding Difficulties

项目摘要：对婴儿吞咽障碍(DD)缺乏明确的认识，即损害- 进食、吞咽功能障碍和空气消化症状是导致患病率上升和 脱水、营养不良、高管喂率、神经发育缺陷和慢性疾病的后果 去医院看病。这些问题在新生儿重症监护病房(NICU)毕业生中很常见，尤其是 在那些早产或在围产期神经病理后存活的人中。每种神经病变的估计成本- 幸存的人从35万美元到50万美元不等，早产导致令人震惊的、被低估的健康 护理负担超过260亿美元。这项建议解决了这一知识赤字问题，并为早期 和安全喂养干预方案，通过解决诊断和康复-Chal-Chal- 长时间缓解婴儿进食担忧，这对改善空气消化健康和神经发育至关重要， 这是我们的长期目标。中心假设是咽部、上段食道的特征 括约肌和食道运动反射，以及它们的毗邻和跨系统关系将在 控制和研究婴儿。我们的基本原理是，识别这些感觉-运动生物标记物将澄清特定的 神经病理婴儿的病理生理变化导致DD，因此可诱导自我调节 可以开发功能和恢复策略。为了实现这一点，新颖、高保真、视频集成、 在婴儿床侧将采用高分辨率阻抗测压方法，同时监测生理 无神经病变的DD患儿(对照组)和DD合并神经病变的患儿的安全参数 RO病理学(研究婴儿)。我们的两个具体目标是1)识别与咽炎相关的诊断生物标记物- 对照中区分基线吞咽机制和主动吞咽机制的食道动力和呼吸道安全性 对比研究婴儿，2)测试有针对性的语言营养刺激恢复的安全性和有效性 管饲对照和研究婴儿在成熟期的咽部-食道运动和呼吸道安全功能。 应用强大的最先进技术，使用视频集成的高分辨率阻抗矩阵- 在婴儿床边，通过检查定向挑衅的影响，将获得新的机械学见解 关于全柱食道运动，以及呼吸道-消化的相互作用。完成建议的目标将包括： Vance数据分析算法和馈送协议，以促进跨学科培训、生物反馈和 家长教育；以及2)设计决策过程，以改进个性化营养疗法。这 该提案通过检查独特的机制和定义 预防和纠正疗法的基础对解决这一具有挑战性的公共卫生负担至关重要， 这造成了巨大的社会经济负担，住院时间延长，神经发育迟缓， 或者死亡。这将通过改善婴儿喂养、吞咽、呼吸道和消化困难以及 促进营养、生长和长期神经发展，所有这些都在NIDDK的使命范围内。

PROJECT SUMMARY: The lack of a clear understanding of Disorders of Deglutition (DD) in infants, i.e., impair- ments in eating, dysfunctional swallowing, and aerodigestive symptoms contributes to the rising prevalence and consequences of dehydration, malnutrition, high tube-feeding rates, neurodevelopmental deficits, and chronic hospital visits. These problems are common in the neonatal intensive care units (NICUs) graduates, particularly among those born prematurely or surviving after perinatal neuropathology. The estimated cost per neuropathol- ogy survivor varies from 350K to 500K US$, and prematurity contributes to a staggering, underestimated health care burden of over ~26 billion US$. This proposal addresses this knowledge deficit and sets the stage for early and safe-feeding intervention protocols in infants with DD by addressing both diagnostic- and rehabilitative-chal- lenges to alleviate infant eating concerns that are vital to improving aerodigestive health and neurodevelopment, which is our long-term goal. The central hypothesis is that characteristics of pharyngeal-, upper esophageal sphincter-, and esophageal-motility reflexes, and their contiguous and cross-systems relationships will differ in control and study infants. Our rationale is that identifying these sensory-motor biomarkers will clarify the specific pathophysiological changes contributing to DD in infants with neuropathology, so that inducible self-regulatory functions and recovery strategies can be developed. To accomplish this, novel, high-fidelity, video-integrated, high-resolution impedance manometry methods will be employed at the crib-side while monitoring physiological safety parameters in infants with DD but without neuropathology (control infants) and infants with DD and neu- ropathology (study infants). Our two specific aims are 1) to identify diagnostic biomarkers related to pharyngo- esophageal motility and airway safety which distinguish baseline and active swallowing mechanisms in control vs. study infants, and 2) to test the safety and effectiveness of targeted lingual nutritive stimulation in restoring pharyngo-esophageal motility and airway safety functions in tube-fed control and study infants during maturation. Applying robust state-of-the-art technological advances using video-integrated, high-resolution impedance ma- nometry at the crib-side, new mechanistic insights will be gained by examining the effects of targeted provocation on full column esophageal motility, and airway-digestive interactions. Completion of the proposed aims will 1) ad- vance data analysis algorithms and feeding protocols to facilitate transdisciplinary training, bio-feedback, and parent education; and 2) design a decision-making process to improve personalized nutritive therapies. This proposal addresses a critical need in neonatal gastroenterology by examining unique mechanisms and defining the basis for preventative and corrective therapies critical to addressing this challenging public health burden, which contributes to significant socio-economic burden, prolonged hospital stays, neurodevelopmental delays, or death. This will be accomplished by improving infant feeding, swallowing, airway, and digestive difficulties and advancing nutrition, growth, and long-term neurodevelopment, all within NIDDK's mission.