Aerodigestive Pathophysiology-Driven Mechanisms of Infant Feeding Difficulties

项目总结：缺乏对婴儿吞咽障碍（DD）的明确理解，即，损害─ 进食障碍、吞咽功能障碍和呼吸消化道症状导致患病率上升， 脱水、营养不良、高管饲率、神经发育缺陷和慢性 医院探访这些问题在新生儿重症监护病房（NICU）毕业生中很常见， 早产或在围产期神经病理学后存活的患者中。每名神经病患者的估计费用- OGY幸存者从35万到50万美元不等，早产导致了惊人的，被低估的健康状况 护理负担超过260亿美元。该提案解决了这一知识不足问题，并为早期 和安全喂养干预方案，通过解决诊断和康复挑战， 致力于减轻对改善呼吸消化健康和神经发育至关重要的婴儿饮食问题， 这是我们的长期目标。中心假设是咽部、上食管的特征 括约肌和尿道运动反射，以及它们的连续和跨系统关系将在以下方面有所不同： 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志物将澄清特定的 导致神经病理学婴儿DD的病理生理变化，因此诱导性自我调节 可以制定功能和恢复策略。为了实现这一点，新颖，高保真，视频集成， 高分辨率阻抗测压法将在床侧使用，同时监测生理 患有DD但无神经病理学的婴儿（对照婴儿）和患有DD和neu的婴儿中的安全性参数。 病理学（研究婴儿）。我们的两个具体目标是：1）鉴定与咽部相关的诊断生物标志物- 食管动力和气道安全性，区分对照组的基线和主动吞咽机制 vs.研究婴儿，和2）测试有针对性的舌营养刺激在恢复中的安全性和有效性 管饲对照组和研究组婴儿在成熟期的咽-食管动力和气道安全功能。 应用强大的最先进的技术进步，使用视频集成，高分辨率阻抗MA， 在床边的nometry，新的机制的见解将获得通过检查有针对性的挑衅的影响， 全列食管运动和气道消化相互作用。完成拟议目标将：1）和- 万斯数据分析算法和喂养协议，以促进跨学科的培训，生物反馈， 家长教育; 2）设计决策过程，以改善个性化的营养治疗。这 一项提案通过检查独特的机制和定义新生儿胃肠病学的关键需求， 预防和矫正疗法的基础对于解决这一具有挑战性的公共卫生负担至关重要， 这会造成严重的社会经济负担、延长住院时间、神经发育迟缓， 或者死亡这将通过改善婴儿喂养、吞咽、气道和消化困难来实现， 促进营养、生长和长期神经发育，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.