This study is a prospective cohort study of ELBW infants conducted from January 2020 to August 2021. The measurement time for each observation was 7 days after birth. Approval was obtained from the Ethics Committee of the Fujita Health University Hospital (HM19-477). The procedures used in this study adhered to the tenets of the Declaration of Helsinki.
The inclusion criteria were admission to neonatal intensive care unit (NICU) with a birth weight less than 1,000 g and use of only donor milk for enteral feeding . During the study period, the donor milk dose was 0.5 ml at the start and 3 ml at the upper limit. The exclusion criterion was serious complications such as unstable circulatory status, complex cardiac malformations, and severe neonatal asphyxia. At the time of inclusion, we recorded the main clinical characteristics of the infants; appropriate for gestational age (AGA), small for gestational age (SGA), birth weight, gestational age, Apgar score at five minutes, time of initiation of oral feeding, SMA blood flow velocity, PV blood flow velocity, diastolic blood pressure, systolic blood pressure, patent ductus arteriosus (PDA) closure number, and the onset data of FIP. The diagnostic criteria for FIP were surgical or pathological findings, and the procedures were ileostomy or drainage.
Sixteen ELBW infants were admitted to the NICU. Of the 16 infants, 15 (male-to-female ratio [M:F] = 6:9) met the eligibility criteria, and one infant was excluded due to complex cardiac malformations. All infants were on pressure-raising drugs (dopamine and dopamine), and steroids were administered to them to prevent chronic lung injury. Indomethacin was administered at low dose to prevent cerebral hemorrhage, regardless of the status of the ductus arteriosus (i.e., open or closed). Of the 15 included ELBW infants, six patients (M:F = 1:5) had the non-surgery group (Group I). Four patients (M:F = 3:1) who developed FIP and underwent surgery had the surgery group (Group II). Five patients (M:F = 2:3) had been administered TJ-100 (Group III), and there were no surgical cases in Group 3. No infections were seen during the observation period.
The ultrasonic pulse Doppler method was used in this study. Ultrasonic waves were generated using the PHILIPS iE33 imaging system, and the linear S12 ultrasound probe was used. The examination was performed by a neonatologist. The infants were placed in supine position, and measurements were taken at about the same time. If an infant was on enteral feeding, examination was performed before light enteral feeding. Warm gel was used to reduce movement, minimize discomfort, and maintain respiration rate and heart rate, thereby avoiding blood circulation changes. To measure SMA blood flow velocity, the Doppler window was positioned such that the SMA is centered, and peak systolic velocity, which was measured at least three times, was used to determine absolute indexes. To measure PV blood flow velocity, the hilar region and the portal trunk were identified.
TJ-100 was randomly administered. A dose of 0.2 g/kg of TJ-100 was administered through the anus using a tube twice a day. The administration of TJ-100 was started within 12 hours after the start of oral administration.
Longitudinal evaluation of SMA blood flow and PV blood flow, which were measured using the ultrasound pulsed Doppler method, was performed to investigate their relationship with surgery. The relationship between SMA blood flow and PV blood flow following TJ-100 administration was also evaluated.
Steel-Dwass test was used to multiple compare continuous variables between groups. All measurement values were presented as average ± standard deviation. Regression analysis was also performed to compare variables. The Mahalanobis squared distance was used to detect outliers. P values ≤ 0.05 were considered statistically significant. Statistical tests were carried out using JMP12.2 (SAS Institute Inc, Cary, NC, USA).