Gastroesophageal reflux disease (GERD) and its troublesome complications constitute serious diagnostic and management challenges to the development of safe feeding and airway protection strategies among infants convalescing in the neonatal intensive care units;thus contributing to prolonged lengths of stay, recurrent hospitalizations, and death. GERD is frequently diagnosed by inadequate criteria, and the relative risks, benefits and indications of GERD therapies are unclear. Significant gaps in knowledge exist in understanding the complex causal or adaptive aerodigestive protective reflex mechanisms implicated in GERD in infants. The long-term goal is to improve digestive health, nutrition, and infant development through the design of simplified personalized treatment paradigms by better understanding the pathophysiology of aerodigestive reflexes. The current objective is to conduct a prospective single center randomized blinded controlled trial comparing the short term effects of our innovative feeding strategy bundle versus standard feeding approach. The central unifying hypothesis is that our innovative feeding strategy bundle will modify the overlapping functions of several aerodigestive reflexes responsible for esophageal clearance and airway protection to improve clinical outcomes in these patients. This hypothesis is formulated based on our prior work during the R01 funding period. The rationale for this proposal is to minimize morbidities from GERD by understanding the integration of afferent-efferent relationships of aerodigestive reflexes in relation to infant feeding approaches. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Comparison of the clinical outcomes of standard feeding approach with the innovative feeding strategy bundle, and 2) Determination of the pathophysiological mechanism of success or failure to either therapy.
Under aim -1, we will test the hypothesis that the innovative feeding strategy bundle is more effective in achieving the oral feeding success and decrease in infant-GER-questionnaire-revised symptom scores.
Under aim -2, we will test the hypothesis and validate results from the preliminary data by utilizing our diagnostic tools to identify difference between the two study arms in regards to aero-digestive reflexes, esophageal clearance mechanisms, enteric neuromotor markers of swallowing, and pH-impedance-symptom indices. The approach is innovative, in that we use state-of-the-art methods including multimodal esophageal sensory provocation methods, videomanometry, pH-Impedance methods, symptom indices, glottal ultrasonography, and innovative feeding strategy. The proposed research is significant, because knowledge gained will provide the scientific and economic rationale for future multicenter effectiveness trials to refine therapies for GERD. New benchmarks to develop preventative and therapeutic strategies for GERD in infants are anticipated, which will positively impact the quality of life for infants and parents.

Public Health Relevance

The proposed research is relevant to public health because the pathophysiology based infant feeding practices will overcome the burden of aerodigestive suffering in infants with gastroesophageal reflux disease. The proposed studies will overcome the critical barrier to progress by providing the scientific and economic rationale for the development of safe feeding paradigms in vulnerable infants, and enhances digestive health in infants, all relevant to the mission of NIH (NIDDK).

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK068158-06A1
Application #
8289148
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Hamilton, Frank A
Project Start
2004-07-01
Project End
2017-03-31
Budget Start
2012-04-15
Budget End
2013-03-31
Support Year
6
Fiscal Year
2012
Total Cost
$466,583
Indirect Cost
$144,357
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Malkar, Manish B; Jadcherla, Sudarshan (2014) Neuromotor mechanisms of pharyngoesophageal motility in dysphagic infants with congenital heart disease. Pediatr Res 76:190-6
Hasenstab, Kathryn A; Jadcherla, Sudarshan R (2014) Respiratory events in infants presenting with apparent life threatening events: is there an explanation from esophageal motility? J Pediatr 165:250-255.e1
Jadcherla, Sudarshan R; Pakiraih, Joanna F; Hasenstab, Kathryn A et al. (2014) Esophageal reflexes modulate frontoparietal response in neonates: Novel application of concurrent NIRS and provocative esophageal manometry. Am J Physiol Gastrointest Liver Physiol 307:G41-9
Jadcherla, Sudarshan R; Chan, Chin Yee; Fernandez, Soledad et al. (2013) Maturation of upstream and downstream esophageal reflexes in human premature neonates: the role of sleep and awake states. Am J Physiol Gastrointest Liver Physiol 305:G649-58
Hill, Crystal D; Jadcherla, Sudarshan R (2013) Esophageal mechanosensitive mechanisms are impaired in neonates with hypoxic-ischemic encephalopathy. J Pediatr 162:976-82
Jadcherla, Sudarshan R; Chan, Chin Yee; Moore, Rebecca et al. (2013) Physiology of esophageal sensorimotor malfunctions in neonatal neurological illness. Am J Physiol Gastrointest Liver Physiol 304:G574-82
Jadcherla, Sudarshan R; Parks, Vanessa N; Peng, Juan et al. (2012) Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals. Am J Physiol Gastrointest Liver Physiol 302:G134-44
Jadcherla, Sudarshan R; Peng, Juan; Moore, Rebecca et al. (2012) Impact of personalized feeding program in 100 NICU infants: pathophysiology-based approach for better outcomes. J Pediatr Gastroenterol Nutr 54:62-70
Jadcherla, Sudarshan R; Peng, Juan; Chan, Chin Yee et al. (2011) Significance of gastroesophageal refluxate in relation to physical, chemical, and spatiotemporal characteristics in symptomatic intensive care unit neonates. Pediatr Res 70:192-8
Pena, Eneysis M; Parks, Vanessa N; Peng, Juan et al. (2010) Lower esophageal sphincter relaxation reflex kinetics: effects of peristaltic reflexes and maturation in human premature neonates. Am J Physiol Gastrointest Liver Physiol 299:G1386-95

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