DMBT1 expression and neutrophil-to-lymphocyte ratio during necrotizing enterocolitis are influenced by impaired perfusion due to cardiac anomalies

Abstract

Background Deleted in malignant brain tumors 1 (DMBT1) is involved in innate immunity and epithelial differentiation. It has been proven to play a role in various states of inflammation or hypoxia of fetal gastrointestinal and pulmonary diseases. Discrimination of pathogenesis in necrotizing enterocolitis (NEC) based on cardiac status improves the understanding of NEC in different patient subgroups. We aimed at examining DMBT1 expressions regarding their association with cardiac status leading to impaired intestinal perfusion, intraoperative bacteria proof, and a fulminant course of NEC. Methods Twenty-eight patients with NEC were treated surgically between 2010 and 2019 at our institution. DMBT1 expression was examined in intestinal sections using immunohistochemistry to detect DMBT1 protein. Associations of clinical parameters and DMBT1 expression were analyzed. Results We examined DMBT1 levels in 10 patients without cardiac defects and 18 patients with persisting ductus arteriosus (PDA) and congenital heart defects (CHD). Compared to patients without cardiac malformations, DMBT1 levels tended to score higher in patients with PDA/CHD (p = 0.2113) and were negatively correlated with C-reactive protein in these infants (p = 0.0172; r = − 0.5533). The number of DMBT1-expressing macrophages was elevated in the PDA/CHD-subgroup (p = 0.0399). Ratios of neutrophils and monocytes to lymphocytes were significantly higher in infants with PDA/CHD (p = 0.0319 and 0.0493). DMBT1 expression was significantly associated with positive bacterial culture of intraoperative swabs (p = 0.0252) and DMBT1 expression of the serosa was associated with a fulminant course of NEC (p = 0.0239). Conclusions This study demonstrates that DMBT1 expression may be influenced by cardiac anomalies with an impaired intestinal perfusion in the neonatal intestine. NEC in PDA/CHD infants is associated with more DMBT1-positive macrophages and a significantly elevated neutrophil-to-lymphocyte ratio.

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

“…Infants with cardiac NEC are typically of higher birth weight and gestational age [ 15 ] than preterm infants with classical NEC. While some groups have argued that cardiac NEC more often involves the colon [ 16 , 17 , 18 ], the ileum, as with classical NEC, also appears to be a significant site of injury in cardiac NEC [ 19 , 20 , 21 ]. The postnatal age at which term CHD infants acquire NEC is often earlier than preterm infants with classical NEC [ 16 ], and preterm infants with DD cardiac NEC are often diagnosed at a later postnatal age than term infants with the same CHD diagnosis [ 22 ].…”

The beneficial role of simple inflammatory blood indices in pediatric cardiology

“…Infants diagnosed with necrotizing enterocolitis with patent ductus arteriosus (PDA) and congenital heart defects had significantly higher NLR and MLR than children without cardiac abnormalities. 33 Higher NLR and MLR resulted in very intense local inflammation involving infiltration of the intestines by neutrophils and circulating monocytes. The monocytes differentiated into macrophages in situ in infants with impaired intestinal perfusion and systemic circulation caused by cardiac anomalies.…”

“…Arterial hypertension is an increasing problem in children due to obesity, sedentary lifestyle and excessive [21], [27], [29], [30], [31], [32], [33], [41], [44], [45], [46], [55], [56], [57], [59], [60], [62], [63], [71] Platelet count Kawasaki disease -coronary artery aneurysms acute rheumatic carditis arterial hypertension [20], [30], [41] PLR Fontan patients neonatal sepsis ECMO use IVIG resistance in Kawasaki disease arterial hypertension [21], [41] MLR necrotizing enterocolitis in PDA children severity of valvular involvement in acute rheumatic carditis [33], [35] ECMO -extracorporeal membrane oxygenation; ICU -intensive care unit; IVIG -intravenous immunoglobulin; MLR -monocyte-to-lymphocyte ratio; NLR -neutrophil-to-lymphocyte ratio; PDA -patent ductus arteriosus; PLE -protein-losing enteropathy; PLR -platelet-to-lymphocyte ratio.…”