Trial design
congenital bowel obstruction, bradycardia, bleeding, tachycardia, prolapse, congenital anomalies, infections, vomiting, hypoxemia, abdominal distension, hypotension, stoma, sepsis, tachypnea, bilious
ADVERSE REACTIONS, BLEEDING, SKIN EROSION, CONGENITAL MEGACOLON, PROLAPSE, WOUND INFECTION, INFECTIONS, STRICTURE, ADVERSE REACTION, BLIND, SEPSIS, COMPLICATIONS
This study was conducted at the neonatal intensive care unit (NICU) of Seoul National University Children’s Hospital as a single-center, exploratory RCT with parallel enrollment between July 1, 2015 and November 11, 2019. The study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 1407–193-601) and registered with the ClinicalTrials.gov registry (NCT02812095). The study followed the standards established by CONSORT. Written informed consent for the study was obtained from the parents of the preterm infants. Preterm infants born before 35 weeks’ gestation with enterostomy were eligible for enrollment. We excluded patients with congenital anomalies (e.g., congenital bowel obstruction and congenital megacolon), blind pouches, stricture and unstable vital signs. When patients achieved the full feeding levels (volume of enteral feeds > 120 mL/kg/day), those with enterostomy effluent volume ≥ 40 mL/kg/day were categorized as the high-output MFR group, and all infants in that group received MFR. The other patients whose enterostomy effluent was < 40 mL/kg/day were randomly assigned to the control or trial group (defined as normal-output MFR) at a 1:1 ratio, using a computer-generated allocation sequence. Parents and medical staff were not blinded to the group allocation. For all the patient groups, the general management proceeded in the same manner, except MFR. A distal loopogram was constructed before MFR was started, and upon identification of a stricture, the infant was excluded from the study. Even for infants in the control group, they were excluded if the requirement for MFR was identified according to the clinical course.The safety of the study was assessed daily. The patients were monitored for the following adverse reactions: respiratory (hypoxemia, tachypnea), cardiovascular (hypotension, tachycardia, bradycardia); gastrointestinal (bilious gastric remain, abdominal distension, vomiting); skin erosion, stoma problems (prolapse, irritation, bleeding); and infections (culture-proven sepsis, wound infection). If an adverse reaction occurred, the neonatologist in the clinical team appraised the situation and temporarily halted the refeeding as necessary. In case of serious adverse reactions, the intervention was terminated.As this exploratory trial aimed to generate data on MFR for the power calculation of the full-scale RCT, the convenience sample size consisted of all eligible infants in our institution for 4 years. Approximately 5–10 infants required enterostomies per Year, and 20 patients were selected as the adequate number of subjects, assuming a 10% dropout rate.We collected patient demographic and diagnostic characteristics, clinical outcomes, colon diameter on loopogram before reanastomosis, and serum citrulline levels at 4 timepoints: just before refeeding, after 4 weeks, just before reanastomosis, and 12 weeks after reanastomosis. We also collected the biopsy specimens of the distal ileum at the stoma closure and evaluated the infants for any MFR-associated complications.