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A stepwise approach is currently considered the best choice to manage gastroesophageal reflux (GER) in preterm infants. This study aimed to evaluate the effect of different tube feeding techniques on GER frequency and features in symptomatic tube-fed preterm neonates. Tube-fed infants < 34 weeks' gestation were eligible for this prospective, bicentric, cross-over study if, due to GER symptoms, they underwent a diagnostic 24-h combined pH and multiple intraluminal impedance (pH-MII) monitoring. During the monitoring period, each infant received the same feeding cycle, repeated twice: continuous tube feeding, bolus feeding followed by tube feeding permanence and by tube feeding removal. The impact of these three feeding modalities on pH-MII GER features was assessed. Thirty-one infants were enrolled. Despite a low number of reflux episodes, a significant decrease in total GERs (P < 0.001), in GERs detected by pH monitoring (P < 0.001), and in both acid and non-acid GERs detected by MII (P < 0.001 and P = 0.009, respectively) was observed in association with continuous feeding compared to bolus feeds, followed or not by tube feeding removal. Compared to continuous feeding, both bolus feeding modalities were associated with a significantly higher number of proximal GERs (P < 0.001). No difference in any pH-MII parameter was observed in relation to tube feeding persistence after bolus feeding administration., Conclusions: Continuous feeding and boluses may have a different impact on pH-MII GER features in symptomatic tube-fed preterm infants, whereas the permanence of the feeding tube across LES did not seem to worsen GER indexes., What Is Known: • Due to the functional and anatomical immaturity of the gastrointestinal tract, gastroesophageal reflux (GER) is common in preterm infants. • A stepwise therapeutical approach which firstly undertakes conservative strategies is the most advisable choice to avoid potentially harmful pharmacological overtreatments in the preterm population., What Is New: • Continuous feeding and boluses may have a different impact on GER features assessed by pH-MII monitoring in tube-fed preterm infants. • The permanence of the feeding tube during or after the feeding period did not seem to worsen GER occurrence. • By reducing GER features, especially acid GER, continuous feeding may potentially contribute to limit the need for antiacid medications in this population., (© 2024. The Author(s).)

Background: Respiratory distress syndrome (RDS) and feeding intolerance are common conditions in preterm infants and among the major causes of neonatal mortality and morbidity. For many years, preterm infants with RDS have been treated with mechanical ventilation, increasing risks of acute lung injury and bronchopulmonary dysplasia. In recent years non-invasive ventilation techniques have been developed. Showing similar efficacy and risk of bronchopulmonary dysplasia, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) have become the most widespread techniques in neonatal intensive care units. However, their impact on nutrition, particularly on feeding tolerance and risk of complications, is still unknown in preterm infants. The aim of the study is to evaluate the impact of NCPAP vs HHHFNC on enteral feeding and to identify the most suitable technique for preterm infants with RDS., Methods: A multicenter randomized single-blind controlled trial was designed. All preterm infants with a gestational age of 25-29 weeks treated with NCPAP or HHHFNC for RDS and demonstrating stability for at least 48 h along with the compliance with inclusion criteria (age less than 7 days, need for non-invasive respiratory support, suitability to start enteral feeding) will be enrolled in the study and randomized to the NCPAP or HHHFNC arm. All patients will be monitored until discharge, and data will be analyzed according to an intention-to-treat model. The primary outcome is the time to reach full enteral feeding, while parameters of respiratory support, feeding tolerance, and overall health status will be evaluated as secondary outcomes. The sample size was calculated at 141 patients per arm., Discussion: The identification of the most suitable technique (NCPAP vs HHHFNC) for preterm infants with feeding intolerance could reduce gastrointestinal complications, improve growth, and reduce hospital length of stay, thus improving clinical outcomes and reducing health costs. The evaluation of the timing of oral feeding could be useful in understanding the influence that these techniques could have on the development of sucking-swallow coordination. Moreover, the evaluation of the response to NCPAP and HHHFNC could clarify their efficacy as a treatment for RDS in extremely preterm infants., Trial Registration: ClinicalTrials.gov, NCT03548324 . Registered on 7 June 2018.