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

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.