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
Shubert, T R; Sitaram, S; Jadcherla, S R (2016) Effects of pacifier and taste on swallowing, esophageal motility, transit, and respiratory rhythm in human neonates. Neurogastroenterol Motil 28:532-42
Sankaran, Janani; Qureshi, Aslam H; Woodley, Frederick et al. (2016) Effect of Severity of Esophageal Acidification on Sleep vs Wake Periods in Infants Presenting with Brief Resolved Unexplained Events. J Pediatr 179:42-48.e1
Jadcherla, Sudarshan (2016) Dysphagia in the high-risk infant: potential factors and mechanisms. Am J Clin Nutr 103:622S-8S
McGrattan, Katlyn E; Sivalingam, Maneesha; Hasenstab, Kathryn A et al. (2016) The physiologic coupling of sucking and swallowing coordination provides a unique process for neonatal survival. Acta Paediatr 105:790-7
Slaughter, Jonathan L; Stenger, Michael R; Reagan, Patricia B et al. (2016) Neonatal Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Treatment at United States Children's Hospitals. J Pediatr 174:63-70.e3
Jadcherla, Sudarshan R; Shubert, Theresa R; Malkar, Manish B et al. (2015) Gestational and postnatal modulation of esophageal sphincter reflexes in human premature neonates. Pediatr Res 78:540-6
Jadcherla, Sudarshan R; Shubert, Theresa R; Gulati, Ish K et al. (2015) Upper and lower esophageal sphincter kinetics are modified during maturation: effect of pharyngeal stimulus in premature infants. Pediatr Res 77:99-106
Jadcherla, Sudarshan R; Hasenstab, Kathryn A; Shaker, Reza et al. (2015) Mechanisms of cough provocation and cough resolution in neonates with bronchopulmonary dysplasia. Pediatr Res 78:462-9
Gulati, Ish K; Shubert, Theresa R; Sitaram, Swetha et al. (2015) Effects of birth asphyxia on the modulation of pharyngeal provocation-induced adaptive reflexes. Am J Physiol Gastrointest Liver Physiol 309:G662-9
Qureshi, Aslam; Malkar, Manish; Splaingard, Mark et al. (2015) The Role of Sleep in the Modulation of Gastroesophageal Reflux and Symptoms in NICU Neonates. Pediatr Neurol 53:226-32

Showing the most recent 10 out of 39 publications