Clinical Characteristics of Necrotizing Enterocolitis in Preterm Patients With and Without Persistent Ductus Arteriosus and in Patients With Congenital Heart Disease

Abstract

Background: Diagnosis and management of NEC is based on clinical, radiological, and laboratory findings. Discrimination of pathogens for an improved understanding of NEC in preterm infants and NEC in infants with congenital heart disease has been previously discussed and enables evaluation of further NEC biomarkers. Patients and Methods: Within a study period of 11 years (2008-2019), we identified 107 patients with a diagnosis of NEC at our primary care center. Thirty-six out of 54 patients suffering from NEC in high Bell stages who underwent surgery met inclusion criteria. These patients were classified according to their cardiac status, and analyses of clinical factors influencing NEC were conducted. Additionally, clinical factors associated with a fulminant course of NEC were examined. Univariable and multivariable analyses were performed. Results: The study populations consisted of 12 preterm infants with NEC but without patent ductus arteriosus (PT-NEC), seven preterm infants with NEC and patent ductus arteriosus (PDA-NEC), and 17 infants with NEC and congenital heart disease (CHD-NEC). Blood flow in intestinal vessels was impaired in infants with PDA-NEC and CDH-NEC. Therefore, we used logistic regression to compare PDA-NEC and CDH-NEC infants with PT-NEC infants: positive bacterial culture of intraoperative swabs (p = 0.0199; odds ratio: 21.9) and macroscopic intestinal necrosis (p = 0.0033; odds ratio: 43.5) were observed more frequently in the first group. Furthermore, multiple regression analysis determined the NEC localization (p = 0.0243) as a significant factor correlated with a fulminant course. Compared to a NEC exclusively localized in the colon, there is a 5.8-fold increased risk of a fulminant course when the small intestine is affected and a 42-fold increase of risk when both small intestine and colon were affected. Conclusion: An early diagnosis and timely surgical intervention of NEC, especially in infants with PDA and CDH may be considered to avoid major bowel necrosis (resulting in loss of intestinal tissue) and multiple operations.

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

“…NEC develops in response to an abnormal interaction of exaggerated bacterial signaling in the premature intestine [ 4 ], in which E. coli plays a major role. The results of our study confirm an association of positive intraabdominal swabs and the presence of CHD/PDA, as demonstrated in a recent study [ 11 ] and show a predominance of E. coli and Staphylococcus in intraabdominal swabs. DMBT1 addresses a critical factor in the pathogenesis of NEC.…”

“…The total intestinal DMBT1 expression level was slightly but not significantly higher in infants with PDA/CHD compared to infants without cardiac anomalies. This corresponds to the higher inflammation and supports the results of our own data indicating that infants with PDA/CHD had more frequently macroscopic intestinal necrosis and positive bacterial culture of intraoperative swabs compared to preterm infants without PDA/CHD [ 11 ]. Cellular hypoxia may also lead to higher DMBT1 expression in intestinal epithelium.…”

“…NEC thus remains a multifactorial induced disease. Research of the last decade therefore focused on the separation of pathology of NEC in patient subgroups [ 8 – 11 ]. Various publications were able to confirm differences in incidence, mortality, and clinical factors of patients with CHD with concomitant steal phenomenon.…”

“…A recent publication from Neu proposed to completely separate this intestinal necrosis due to hypoxic mechanisms seen in full-term neonates from the classical NEC of preterm infants [ 12 ] as did the most recent study of Klinke et al [ 13 ]. We were recently able to describe that infants with PDA/CHD had more frequently macroscopic intestinal necrosis and positive bacterial culture of intraoperative swabs compared to preterm infants without PDA/CHD [ 11 ].…”

Neonatal anemia relates to intestinal injury in preterm infants

“…Next, we determined whether Hb level, r s SO 2 , and variability of r s SO 2 were associated with level of I-FABP, and whether Hb level and r s SO 2 measurements were interrelated, on several time points prior to transfusion using Spearman’s Correlation Test, in all infants irrespective of group assignment, and in cases and controls separately. Since was suggested that the blood flow in the intestines may be impaired in infants with a PDA, 34 , 35 we additionally calculated partial correlation coefficients to correct for the potential influence of a PDA. Finally, we performed linear regression analyses to determine the effect size of Hb level, r s SO 2 , and r s SO 2 variability on urinary I-FABP level closest to RBC transfusion.…”