Efficacy of PIMUN by Reducing Intermittent Hypoxia Events

Preterm infants frequently experience intermittent hypoxia (IH) events despite current treatments, leading to potential neurodevelopmental and systemic sequelae. Many of these episodes are related to an ineffective respiratory drive, a central component of apnea of prematurity (AOP). Previous research has shown that dorsal and extremity stimulation can elicit spontaneous respiratory effort in preterm infants. Several clinical studies have demonstrated that mechanized stimulation can reduce the number of apneas and the total time of oxygen saturation below 90%, a key indicator of IH severity.

Building on prior work, the investigators developed and optimized a stimulation protocol that reliably triggers effective breathing. This protocol was incorporated into a novel medical device called PIMUN. PIMUN consists of a soft cotton garment with an integrated inflatable dorsal chamber. The system includes hardware that captures and releases ambient air to generate pulsatile dorsal stimulation according to a proprietary software algorithm. The device operates using electro-mechanical energy and has been designed to ensure safety and comfort during neonatal use.

This pilot, randomized, crossover experimental study aims to evaluate whether pulsatile dorsal kinesthetic stimulation delivered by PIMUN can reduce the total duration of intermittent hypoxia (defined as oxygen saturation \<90%) in preterm infants. Secondary analyses include evaluation of deeper desaturation thresholds (\<85% and \<80%), heart rate parameters, frequency and type of apneas, resuscitation needs, supplemental oxygen requirements, oxidative stress markers, sleep architecture, and regional brain oxygen saturation. Risk monitoring will include assessment of thermoregulation, skin integrity, comfort (NIPS scale), and device performance and safety alarms.

Eligible participants will be preterm infants under 34 weeks of gestation, within the first month of life, and not requiring mechanical ventilation. Each subject will undergo two intervention periods (with and without PIMUN) in randomized order, separated by a washout period. Continuous monitoring using cardiorespiratory and sleep recording systems will allow precise measurement of oxygen saturation, apnea characteristics, heart rate, and sleep stages. Blood and urine samples will be analyzed for oxidative stress markers.

The investigators hypothesize that PIMUN stimulation will decrease total time spent under hypoxic thresholds and reduce the duration and frequency of apneic events without compromising safety, thermoregulation, or sleep quality. This study is expected to generate proof-of-concept data supporting the efficacy and safety of pulsatile dorsal stimulation as an adjunctive approach to managing apnea of prematurity.

• Total Time of Oxygen Saturation <85% and <80% [Time frame: 48-hour data baseline versus 48- hour data with PIMUN]
• Neonatal infant pain scale (NIPS) [Time frame: 48-hour data baseline versus 48- hour data with PIMUN]
• Total Time of Heart Rate <100 bpm [Time frame: 48-hour data baseline versus 48- hour data with PIMUN]
• Number of Apnea Events (Central, Mixed, or Obstructive) [Time frame: 48-hour data baseline versus 48- hour data with PIMUN]
• Duration of Desaturation Episodes [Time frame: 48-hour data baseline versus 48- hour data with PIMUN]
• REM and Non-REM Sleep Duration [Time frame: baseline versus during the use of PIMUN]
• Need for Resuscitation or Respiratory Support [Time frame: 48-hour data baseline versus 48- hour data with PIMUN]
• Oxidative Stress Marker Levels [Time frame: baseline versus after 48- hour using PIMUN]