Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion

Abstract

The pathogenesis of transfusion-associated necrotizing enterocolitis remains elusive. Splanchnic hypoperfusion associated with packed red blood cell transfusion (PRBCT) and feeding has been implicated, but studies of splanchnic tissue oxygenation with respect to feeding plus PRBCT are lacking. To investigate the oxygen utilization efficiency of preterm gut and brain challenged with bolus feeding during anemia and after transfusion using near-infrared spectroscopy. This prospective cohort study conducted from September 1, 2014, to November 30, 2016, at a tertiary neonatal intensive care unit included 25 hemodynamically stable infants with gestational age less than 32 weeks, birth weight less than 1500 g, and postmenstrual age younger than 37 weeks. Data analysis was performed from August 1, 2017, to October 31, 2018. Infants received PRBCT (15 mL/kg for 4 hours) and at least 120 mL/kg daily of second hourly bolus feedings. Splanchnic fractional tissue oxygen extraction (FTOEs) and cerebral fractional tissue oxygen extraction (FTOEc) measures were made during 75-minute feeding cycles that comprised a 15-minute preprandial feeding phase (FP0) and 4 contiguous 15-minute postprandial feeding phases (FP1, FP2, FP3, and FP4; each 15 minutes long). The intraindividual comparisons of feeding-related changes were evaluated during the pretransfusion epoch (TE0: 4 hours before onset of transfusion) and 3 TEs after transfusion (TE1: first 8 hours after PRBCT completion; TE2: 9-16 hours after PRBCT completion; and TE3: 17-24 hours after PRBCT completion). Of 25 enrolled infants (13 [52%] female; median birth weight, 949 g [interquartile range {IQR}, 780-1100 g]; median gestational age, 26.9 weeks [IQR, 25.9-28.6 weeks]; median enrollment weight, 1670 g [IQR, 1357-1937 g]; and median postmenstrual age, 34 weeks [IQR, 32.9-35 weeks]), 1 infant was excluded because of corrupted near-infrared spectroscopy data. No overall association was found between FTOEs and FPs in a multivariable repeated-measures model that accounted for transfusion epochs (primary analysis approach) (FP0: mean estimate, 11.64; 95% CI, 9.55-13.73; FP1: mean estimate, 12.02; 95% CI, 9.92-14.11; FP2: mean estimate, 12.77; 95% CI, 10.68-14.87; FP3: mean estimate, 12.54; 95% CI, 10.45-14.64; FP4: mean estimate, 12.98; 95% CI, 10.89-15.08; P = .16 for the FP association). However exploratory analyses of postprandial changes in FTOEs undertaken for each transfusion epoch separately found evidence of increased postprandial FTOEs during TE1 (mean [SD] FTOEs, 10.55 [5.5] at FP0 vs 13.21 [5.96] at FP4, P = .046). The primary and exploratory analyses found no association between FTOEc and feeding phases, suggesting that cerebral oxygenation may be protected. The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis. The postprandial changes in FTOEs appear to warrant further investigation in larger randomized studies.