Non-invasive Biomarkers of Symptom Severity and Treatment Response in Pediatric Feeding Disorders

项目摘要 小儿喂养障碍是非常常见的，影响5-20%的儿童，他们造成 显著的患者发病率，降低儿童和父母的生活质量，增加医疗保健 利用率和成本。这些患者中的许多人需要放置饲管，但即使这样也不能确保 成功的喂养和成长。多达50%的胃造口管儿童患有喂养不耐受， 定义为呕吐或不能耐受足够的饲料量以维持生长。尽管高 由于这一问题的普遍性和对健康的巨大影响，没有前瞻性研究可以帮助管理部门了解情况。 此外，导致喂养不耐受的胃肠道机制在很大程度上仍然未知， 阻碍了我们有效地针对患者病理生理学进行治疗的能力。 喂养不耐受的两种机制是（1）胃排空延迟和（2）胃排空障碍 胃调节我们已经证明，49%的喂养不耐受的儿童， 排空;然而，没有研究将胃排空延迟与喂养不耐受症状或 评估了胃生理学的其他异常如调节受损的作用。目标1， 在这项建议中，我们将使用横断面研究设计来充分表征（使用超声检查和 胃排空和调节模式在有和没有胃造口术的患者中的比较 喂养不耐受在目标2中，我们将使用前瞻性队列设计来评估胃生理学的变化 红霉素（可改善胃排空）治疗后出现进食不耐受症状 或赛庚啶（改善胃适应性）。 医学博士苏珊娜·赫希是哈佛医学院（HMS）的讲师，也是 波士顿儿童医院（BCH）的呼吸消化中心。她已经获得了大量的临床研究 在她的医疗培训经验，并已证明致力于学术生涯的病人- 导向研究。她的职业目标是从根本上推进对胃功能障碍的科学认识 并利用这种机制知识来推动循证护理和燃料 治疗创新。该职业发展奖提供的指导和培训对于以下方面至关重要： 博士赫希的学术发展。她的主要导师，雷切尔罗森博士，是一个专家，在儿科运动 她的共同导师Odd Helge Gilja博士是胃肠道超声检查专家-两者都是 杰出的研究人员，长期致力于指导。赫希博士精心制作了一个 职业发展计划，有机会获得胃超声检查和临床研究方面的技能 方法.她将攻读公共卫生硕士学位，包括重复测量课程，纵向 数据分析和临床试验设计。她的研究活动将在无与伦比的学术 她说，她在波黑和平委员会和皇家海军的环境中，坚定地致力于她成功地过渡到独立。

PROJECT SUMMARY Pediatric feeding disorders are extremely common, affecting 5-20% of children, and they cause significant patient morbidity, decreased quality of life for children and parents, and increased healthcare utilization and cost. Many of these patients require feeding tube placement, but even this does not ensure successful feeding and growth. Up to 50% of children with gastrostomy tubes suffer from feeding intolerance, defined as vomiting or inability to tolerate adequate feed volumes to sustain growth. Despite the high prevalence and large health impact of this problem, no prospective studies exist to help inform management. Furthermore, the gastrointestinal mechanisms underlying feeding intolerance remain largely unknown, hindering our ability to effectively target treatments toward patient pathophysiology. Two proposed mechanisms of feeding intolerance are (1) delayed gastric emptying and (2) impaired gastric accommodation. We have shown that 49% of children with feeding intolerance have delayed gastric emptying; however, no studies have correlated delayed gastric emptying with feeding intolerance symptoms or assessed the role of other abnormalities of gastric physiology such as impaired accommodation. In Aim 1 of this proposal, we will use a cross-sectional study design to fully characterize (using both ultrasonography and scintigraphy) gastric emptying and accommodation patterns in gastrostomy-fed patients with and without feeding intolerance. In Aim 2, we will use a prospective cohort design to assess changes in gastric physiology and feeding intolerance symptoms after initiating therapy with erythromycin (which improves gastric emptying) or cyproheptadine (which improves gastric accommodation). Dr. Suzanna Hirsch, MD is an Instructor at Harvard Medical School (HMS) and a subspecialist within the Aerodigestive Center at Boston Children’s Hospital (BCH). She has gained substantial clinical research experience during her medical training and has demonstrated commitment to an academic career in patient- oriented research. Her career goal is to fundamentally advance scientific understanding of gastric dysfunction in pediatric feeding disorders and to use this mechanistic knowledge to drive evidence-based care and fuel treatment innovation. The mentorship and training afforded by this career development award will be critical for Dr. Hirsch’s academic development. Her primary mentor, Dr. Rachel Rosen, is an expert in pediatric motility disorders, and her co-mentor, Dr. Odd Helge Gilja, is an expert in gastrointestinal ultrasonography – both are exceptional researchers with longstanding commitments to mentorship. Dr. Hirsch has carefully crafted a career development plan with opportunities to gain skills in gastric ultrasonography and clinical research methods. She will pursue a Master’s in Public Health including coursework in repeated measures, longitudinal data analyses, and clinical trial design. Her research activities will be conducted in the unparalleled academic environments of BCH and HMS, which are firmly committed to her successful transition to independence.