Safety and feasibility of a novel oesophageal stimulation protocol in modulating aerodigestive mechanisms and outcomes in infants at-risk for gastrostomy: a pilot study.

Background: Safe, independent, and consistent oral feeding is critical before NICU discharge, and delays with eating milestones increases the risk of gastrostomy tube (G-Tube). A novel pathophysiology-guided Vagus-nerve mediated neuro-aero-digestive modulatory stimulation protocol was developed, implemented, and tested to determine safety, feasibility, mechanisms, and clinical outcomes. The working hypothesis was that implementing the bundle of feeding and aerodigestive stimulation therapies (FAST) would modulate reflexes and their functions, improving oral feeding volumes as well as parental stress and efficacy. Methods: This interventional pilot study prospectively examined the impact of the FAST protocol during high resolution manometry (HRM) in nasogastric (NG) fed infants ≥37 weeks postmenstrual age (PMA). Participants were NG tube-fed infants convalescing in the NICU who were under consideration for a G-Tube. These infants were referred to the Innovative Infant Feeding Disorders Program at Nationwide Children's Hospital (Columbus, Ohio, USA) for a diagnostic feeding and G-Tube evaluation study between February 2024 and January 2025. The FAST protocol included weekly aerodigestive stimulation with parental education/biofeedback during HRM and oral nutritive stimulation with every feed. Outcomes were improvement in oral feeding volumes (measured from initial diagnostic manometry to either: 4 weeks of the intervention, full oral feeds [absence of feeding tube], or NICU discharge, whichever is earliest), ideally with avoidance of a G-Tube at discharge, and parent survey metrics (measured prior to the initial diagnostic manometry and again after the last manometry). This trial is registered on ClinicalTrials.gov (NCT06118697). Findings: Eighteen NG-fed infants (mean 30.9 [SD ± 4.9] weeks birth gestation, 43.7 [±2.6] weeks PMA at inception, 48.2 [±4.5] weeks PMA at discharge) completed the protocol with 50% avoiding a G-Tube. Oesophageal stimulation therapy increased 24-h oral intake acutely (p < 0.05). Daily oral volume intake increased from 36% to 67% from initial to final manometry (p < 0.01). Those who reached full oral feeds had a shorter time from enrolment to discharge compared with those who did not achieve the full oral feeds (18 ± 15 vs 44 ± 6 days; p < 0.05). There were no adverse events either during the study procedures or during the FAST protocol period. Parental survey results were limited. Prior to the first HRM, 21 parent surveys were completed. 13 parent surveys were completed after the last HRM. Two (11%) infants had multiple surveys completed. The interpretation of parent survey data was inconclusive given the small sample of analysable responses. Interpretation: The FAST protocol was safe, feasible, applicable at crib-side, and had no associated adverse events. The parent surveys component was inconclusive. Integrated neuro-modulatory and crosstalk mechanisms via Vagus nerve at the pharyngeal, upper oesophageal sphincter, and oesophageal levels may have favoured successful outcomes. The FAST protocol warrants further evaluation. Funding: The National Institutes of Health and the Nationwide Foundation Endowed Chair Fund.