Aerodigestive Pathophysiology-Driven Mechanisms of Infant Feeding Difficulties

婴儿喂养困难的呼吸消化病理生理学驱动机制

• 批准号: 10430145
• 负责人: Sudarshan R Jadcherla
• 金额: $ 51.1万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10430145
• 关键词: Acute; Address; Age; Algorithmic Analysis; Algorithms; Apple; Behavioral; Biofeedback; Biological Markers; Caring; Cessation of life; Characteristics; Chronic; Clinical; Coupled; Data; Data Analyses; Decision Making; Deglutition; Deglutition Disorders; Dehydration; Development; Diagnosis; Diagnostic; Digestive System Disorders; Distal; Eating; Economic Burden; Education; Effectiveness; Enteral Feeding; Esophagus; Esophagus motility; Feeding Methods; Feeds; Functional disorder; Funding; Gastroenterology; Goals; Growth; Health; Health Care Costs; Healthcare; Hospitals; Impairment; Infant; Intervention; Juice; Knowledge; Length of Stay; Liquid substance; Malnutrition; Manometry; Mathematics; Medical Research; Methods; Milk; Mission; Monitor; Motor; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Neonatal Intensive Care Units; Neurodevelopmental Deficit; Nutrition Disorders; Oral; Outcome; Parents; Pathologic; Perinatal; Physiologic Monitoring; Physiological; Pregnancy; Prevalence; Process; Productivity; Protocols documentation; Provider; Public Health; Quality of life; Recovery; Reflex action; Rehabilitation therapy; Reproducibility; Research; Resolution; Risk; Safety; Saline; Sensory; Side; Sterility; Stimulus; Sucrose; Survivors; Symptoms; System; Taste Perception; Techniques; Testing; Time; Training; Translational Research; Translations; Tube; Upper Esophageal Sphincter; Variant; Visit; Water; base; behavioral response; care burden; cell motility; clinical care; clinical decision-making; cost estimate; data acquisition; design; diagnostic algorithm; diagnostic biomarker; electric impedance; expectation; feeding; improved; insight; neurodevelopment; neuropathology; novel; novel diagnostics; novel therapeutics; nutrition; personalized diagnostics; premature; response; safety testing; socioeconomics

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.

项目摘要：缺乏对婴儿脱发（DD）的清晰了解，即损害 饮食，功能失调的吞咽和机能症状的食物导致患病率上升和 脱水，营养不良，高管喂养率，神经发育缺陷和慢性的后果 医院探访。这些问题在新生儿重症监护病房（NICUS）毕业生中很常见，特别是 在围产期神经病理学后出生或生存的人中。估计每神经病的成本 OGY幸存者从350K到500k US不等，早产贡献了惊人的，低估的健康 超过260亿美元的护理负担。该建议解决了这种知识赤字，并为早期设定了舞台 通过解决诊断和康复 - 卫生疗法，以及DD婴儿的豁免干预方案 减轻婴儿饮食问题的关注，这些问题对于改善机动性健康和神经发育至关重要， 这是我们的长期目标。中心假设是咽部食管的特征 括约肌和食管动力反射，它们的连续和跨系统关系在 控制和研究婴儿。我们的理由是，识别这些感觉运动生物标志物将阐明特定 神经病理学的婴儿有助于DD的病理生理变化，因此可诱导的自我调节 可以制定功能和恢复策略。为了实现这一点，新颖，高保真，视频融合， 高分辨率阻抗测压方法将在婴儿床侧使用，同时监测生理 患有DD的婴儿的安全参数，但没有神经病理学（对照婴儿）和患有DD和NEU-的婴儿 疾病学（研究婴儿）。我们的两个具体目标是1）确定与pharyngo-的诊断生物标志物 食管运动和气道安全，区分基线和主动吞咽机制 vs.研究婴儿，以及2）测试靶向舌营养刺激在恢复中的安全性和有效性 pharyngo-posophegeal运动和气道安全性在成熟过程中的管子喂养和研究婴儿中的功能。 使用视频集成的高分辨率阻抗MA-应用强大的最新技术进步 在婴儿床侧的名义，通过检查目标挑衅的影响将获得新的机械见解 在全柱食管运动和气道消化互动上。拟议目标的完成1） 万斯数据分析算法和喂养方案，以促进跨学科培训，生物反馈和 父母教育； 2）设计一个决策过程，以改善个性化的营养疗法。这 提案通过检查独特的机制并定义，解决了新生儿胃肠病学的关键需求 预防和纠正疗法的基础，对于解决这一挑战的公共卫生负担至关重要， 这会导致重大社会经济负担，长期住院，神经发育延迟， 或死亡。这将通过改善婴儿喂养，吞咽，气道和消化困难以及 在NIDDK的任务中推进营养，成长和长期神经发育。