Enteral Nutrition Tolerance And REspiratory Support (ENTARES) Study in preterm infants: study protocol for a randomized controlled trial

Abstract

BackgroundRespiratory 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.MethodsA 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.DiscussionThe 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 registrationClinicalTrials.gov, NCT03548324. Registered on 7 June 2018.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3119-0) contains supplementary material, which is available to authorized users.

Dysbiosis and Prematurity: Is There a Role for Probiotics?

“…Despite some authors highlighting the possible key role of dysbiosis in the pathogenesis of ROP and non-communicable chronic diseases, this evidence remains somewhat speculative, and other factors, such as respiratory support or diet, need to be further investigated [74,75,76].…”

Effect of selective gastric residual monitoring on enteral intake in preterm infants

“…Other studies [ 26 , 27 ] have reported, in contrast, an association between increased GRs and NEC, but they were retrospective and had many confounding factors which limit their value. Thus, GRs alone are an unreliable marker of NEC, while in association with other suspicious clinical signs [ 16 ] they can contribute to a rational management of enteral nutrition and to the planning of any diagnostic tests.…”

“…The latter was determined by abdomen pathological physical examination, regurgitations/vomits, GRs with volume ≥ 100% of previous feed and/or altered (i.e. : hematic, fecaloid), mucous or bloody stools, and onset of apnea/bradycardia [ 16 ]. The severity of these conditions was graded as minor and major criteria of feeding intolerance and were used for deciding the interruption of enteral feeding: the occurrence of one to two minor criteria suggested no change in the volume of feed, while the occurrence of three minor criteria or one major criterion suggested discontinuation of enteral feeding [ 16 ].…”

Implementation of a protocol‐based strategy for weaning nasal high flow therapy in preterm infants

“…Feeding intolerance is a frequent complication in preterm infants receiving noninvasive respiratory support. It is unclear whether nHFT has the same deleterious effect of nCPAP on feeding tolerance in preterm infants 26 . Evidence from one RCT showed that preterm infants treated with nHFT achieved full oral feeding at the same rate as infants treated with nCPAP 27 .…”