Immediate Post-operative Enterocyte Injury, as Determined by Increased Circulating Intestinal Fatty Acid Binding Protein, Is Associated With Subsequent Development of Necrotizing Enterocolitis After Infant Cardiothoracic Surgery

Abstract

Objectives: 1 Measure serial serum intestinal fatty acid binding protein levels in infants undergoing cardiac surgery with cardiopulmonary bypass to evaluate for evidence of early post-operative enterocyte injury. 2 Determine the association between immediate post-operative circulating intestinal fatty acid binding protein levels and subsequent development of necrotizing enterocolitis. Design: Observational cohort study. Intestinal fatty acid binding protein was measured pre-operatively, at rewarming, and at 6 and 24 h post-operatively. Percent of goal enteral kilocalories on post-operative day 5 and episodes of necrotizing enterocolitis were determined. Multivariable analysis assessed for factors independently associated with clinical feeding outcomes and suspected/definite necrotizing enterocolitis. Setting: Quaternary free-standing children's hospital pediatric cardiac intensive care unit. Patients: 103 infants <120 days of age undergoing cardiothoracic surgery with cardiopulmonary bypass. Interventions: None. Results: Median pre-operative intestinal fatty acid binding protein level was 3.93 ng/ml (range 0.24-51.32). Intestinal fatty acid binding protein levels rose significantly at rewarming (6.35 ng/ml; range 0.54-56.97; p = 0.008), continued to rise slightly by 6 h (6.57 ng/ml; range 0.75-112.04; p = 0.016), then decreased by 24 h (2.79 ng/ml; range 0.03-81.74; p < 0.0001). Sixteen subjects (15.7%) developed modified Bell criteria Stage 1 necrotizing enterocolitis and 9 subjects (8.8%) developed Stage 2 necrotizing Conclusions: Intestinal fatty acid binding protein levels rise following infant cardiopulmonary bypass, indicating early post-operative enterocyte injury. Intestinal fatty acid binding protein was not associated with percent of goal enteral nutrition achieved on post-operative day 5, likely due to protocolized feeding advancement based on clinically observable factors. Higher intestinal fatty acid binding protein at 6 h post-operatively was independently associated with subsequent development of necrotizing enterocolitis and may help identify patients at risk for this important complication.

Clinical Characteristics and Potential Pathogenesis of Cardiac Necrotizing Enterocolitis in Neonates with Congenital Heart Disease: A Narrative Review

“…Normal turnover of small intestinal enterocytes releases low levels of IFABP into the plasma, but much higher plasma levels of IFABP suggest significant disruption of the small intestinal villi [ 39 ]. While also proposed as a biomarker for classical NEC [ 113 , 114 ], circulating IFABP measured 6 h postoperatively has successfully predicted cardiac NEC development in infants undergoing CPB [ 115 ]. However, in a prospective study, Pathan et al found that elevated IFABP, either pre- or postoperatively, poorly predicted clinical outcomes in pediatric CHD cases [ 39 ].…”

Association between glial fibrillary acidic protein, glial-derived neurotrophic factor, and fatty acid-binding protein-2 at birth in the incidence of necrotizing enterocolitis in preterm infants

“…Thus, FABP-2 can be used for early detection ( 34 ). High levels of FABP-2 were found in infants following cardiopulmonary bypass indicating early enterocyte injury that potentially increases the risk of NEC ( 35 ). The FABP-2 assay in this study used umbilical blood immediately after birth, reflecting perinatal conditions.…”

Necrotizing Enterocolitis in Children with Congenital Heart Disease: A Literature Review

“…Fecal calprotectin and intestinal fatty acid binding protein may become useful laboratory biomarkers for NEC [ 59 , 60 ]. Doppler ultrasonography of the mesenteric vessels and abdominal aortic blood flow in diastole may be increasingly used as a predictive strategy, which could increase vigilance among practitioners [ 13 ].…”

“…In an observational cohort study of 120 infants undergoing cardiopulmonary bypass, intestinal fatty acid binding protein was measured at 6 and 24-h post-surgery. Significantly higher levels were noted in patients who subsequently developed NEC [ 60 ].…”