Study Design and Setting
bilious, comorbidity, NEC, abdominal distention, pneumothorax, Bell stage II, respiratory failure, pain, Comorbidity, regurgitations, vomits, SpONutritional, Respiratory distress syndrome, fecaloid, NRS
PNEUMOTHORAX, RESPIRATORY FAILURE, MINOR, INTRAVENTRICULAR HEMORRHAGE, BRONCHOPULMONARY DYSPLASIA, RESPIRATORY DISTRESS SYNDROME, EVENTS
This randomized clinical trial involved infants who were born between November 1, 2018, and June 30, 2021, at 1 of 13 participating neonatal intensive care units (NICUs) across Italy. The study protocol (All infants with gestational age between 25 and 29 weeks, 7 days of life or less, suitability for enteral feeding (<75 mL/kg/d if already started), and RDS were eligible for the study. Respiratory distress syndrome was defined as respiratory failure requiring respiratory support, and surfactant was administered according to the European Consensus Guidelines on the Management of RDS.The intervention was the randomization of infants to either the NCPAP or HHHFNC arm. Since no conclusive data were available on the efficacy and safety of HHHFNC in extremely preterm infants as a first-intention approach at birth or after extubation, we decided to randomize only infants who proved to be medically stable for at least 48 hours on NRS (stability test). Specifically, these infants maintained transcutaneous peripheral oxygen saturation (SpONutritional data were recorded daily until the full enteral feeding (FEF) was reached. Respiratory data were recorded at each change of respiratory support until its discontinuation. The occurrence of comorbidity was recorded until discharge. Data were collected anonymously by a web-based database.Each participating NICU adopted its own protocols for the clinical management of patients enrolled in the study, although respecting some standard criteria for enteral nutrition and NRS. The advancement of feeding was up to clinicians, but the upper limit was set at 30 mL/kg per day. The interruption of feeding was defined by signs of feeding intolerance from pathological abdominal physical examination (distention, discoloring, visible bowel loops, or pain), pathological gastric residual volume measurement (>100% of previous feed; bilious, hematic, or fecaloid), vomits and/or regurgitations, abnormal feces (mucous or hematic), and associated cardiorespiratory events. These signs were rated according to their severity as minor or major criteria whose combination guided the interruption of feeding (eTables 1, 2, and 3 in Infants were bolus fed by nasogastric or orogastric tube; breastfeeding or bottle feeding was started according to the infant’s capability. The initial suggested setup for NRS was CPAP of between 5 and 7 cm HThe primary outcome was the time to reach FEF, defined as enteral intake of 150 mL/kg per day. Secondary nutritional outcomes were median daily enteral increment, at least 1 episode of feeding interruption, at least 1 episode of feeding interruption lasting more than 24 hours, pathological gastric residual volume, frequent vomits and/or regurgitations (≥3 in a day), abdominal distention score of 2 or higher (eTable 2 in Comorbidity occurred after randomization as NEC (Bell stage II or III), bronchopulmonary dysplasia (oxygen requirement at 36 weeks’ postmenstrual age or 28 days of life), pneumothorax, intraventricular hemorrhage (severe if higher than grade II),