Independent feeding and breathing skills are the two important functions for survival in human infants. Feeding difficulties coupled with airway-related complications in infants contribute significantly to infant mortality and morbidity. Lack of a proper understanding of the physiology and pathophysiology of reflexes protective against aspiration during health or disease in developing infants is a fundamental problem that challenges management strategies. Our long-term goal is to develop evidence-based safe feeding strategies in infants at-risk. The current objective is to define the normal development as a basis for understanding abnormality of the sensory-motor neural and muscular control of foregut motility and aerodigestive tract defense mechanisms in human infants. There is a critical need for safety-ensured mechanistic studies that will provide a solid foundation for the management of feeding and airway safety in (1) healthy premature infants and in conditions such as (2) GERD and (3) neurological disease.
In aim 1, peristaltic reflexes induced by esophageal stimulation in preterm healthy infants in sleep and awake states are investigated.
In aim 2, the relationship of GERD on reflux clearance- and glottal closure- reflexes and comparison with healthy controls are investigated.
In aim 3, the effects of neurological malfunction on aerodigestive protective mechanisms and comparison with healthy controls are investigated. Using safety packed, cutting-edge techniques and micromanometry system and novel pharyngo-esophageal manometry catheters, synchronized and integrated respiratory measurements, we will evaluate the sensory and motor elements of the peristaltic reflexes in premature infants, GERD, and neurological illness. In addition, we will evaluate airway protective reflexes with concurrent ultrasound. ANOVA, multiple logistic regression and student's t- test will be used. The new information will create a context for understanding sensory-motor-pathways involved with peristaltic reflexes and airway safety;thus providing a basis for future clinical care or trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK068158-03S1
Application #
7772021
Study Section
Special Emphasis Panel (ZRG1-DIG-C (02))
Program Officer
Hamilton, Frank A
Project Start
2006-05-01
Project End
2011-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
3
Fiscal Year
2009
Total Cost
$1,420
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Collins, Carissa R; Hasenstab, Kathryn A; Nawaz, Saira et al. (2018) Mechanisms of Aerodigestive Symptoms in Infants with Varying Acid Reflux Index Determined by Esophageal Manometry. J Pediatr :
Jadcherla, Sudarshan R; Prabhakar, Varsha; Hasenstab, Kathryn A et al. (2018) Defining pharyngeal contractile integral during high-resolution manometry in neonates: a neuromotor marker of pharyngeal vigor. Pediatr Res 84:341-347
Lang, Ivan M; Medda, Bidyut K; Shaker, Reza et al. (2018) The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS? Pediatr Res 83:731-738
Hart, Brandon J; Viswanathan, Sreekanth; Jadcherla, Sudarshan R (2018) Persistent feeding difficulties among infants with fetal opioid exposure: mechanisms and clinical reasoning. J Matern Fetal Neonatal Med :1-7
Hasenstab, Kathryn A; Sitaram, Swetha; Lang, Ivan M et al. (2018) Maturation Modulates Pharyngeal-Stimulus Provoked Pharyngeal and Respiratory Rhythms in Human Infants. Dysphagia 33:63-75
Jensen, P S; Gulati, I K; Shubert, T R et al. (2017) Pharyngeal stimulus-induced reflexes are impaired in infants with perinatal asphyxia: Does maturation modify? Neurogastroenterol Motil 29:
El-Mahdy, Mohamed A; Mansoor, Fatma A; Jadcherla, Sudarshan R (2017) Pharmacological management of gastroesophageal reflux disease in infants: current opinions. Curr Opin Pharmacol 37:112-117
Jadcherla, Sudarshan R; Khot, Tanvi; Moore, Rebecca et al. (2017) Feeding Methods at Discharge Predict Long-Term Feeding and Neurodevelopmental Outcomes in Preterm Infants Referred for Gastrostomy Evaluation. J Pediatr 181:125-130.e1
Kashou, Nasser H; Dar, Irfaan A; El-Mahdy, Mohamed A et al. (2017) Brain Lesions among Orally Fed and Gastrostomy-Fed Dysphagic Preterm Infants: Can Routine Qualitative or Volumetric Quantitative Magnetic Resonance Imaging Predict Feeding Outcomes? Front Pediatr 5:73
Sivalingam, Maneesha; Sitaram, Swetha; Hasenstab, Kathryn A et al. (2017) Effects of Esophageal Acidification on Troublesome Symptoms: An Approach to Characterize True Acid GERD in Dysphagic Neonates. Dysphagia 32:509-519

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