This is the first reported case that severe pulmonary valve stenosis with NEC IIIB in an infant who successively underwent exploration of the heart and laparotomy. Several studies have found that NEC can occur pre-or postoperatively with CHD, and the presence of congestive heart failure, systemic to pulmonary arterial shunts, or cyanotic CHD-NEC is associated with higher morbidity and mortality. Moreover, the presence of CHD in neonates with a birth weight > 2500 g is an independent risk factor for NEC[3–6]. However, CHD-NEC reportedly does not significantly increase the risk of in-hospital mortality and only increases the length of hospital stay[7]. Neonates with CHD-NEC tended to have larger birth weights and gestational ages compared to infants with preterm NEC (PT-NEC), and the age of onset was earlier than that of neonates with PT-NEC. The necrotic areas of CHD-NEC have a predilection for the colon and distal ileum, as these areas are prone to disruption of the blood supply to the superior and inferior mesenteric arteries, often referred to as watershed zones[8]. Currently, the pathogenesis of CHD-NEC is still unclear. CHD causes mesenteric hypoperfusion and intestinal hypoxia, which induces endothelial inflammation, increased vascular permeability, cytokine release, epithelial damage, bacterial translocation, mucus degradation, and dysbiosis, which have been reported in association with NEC development[9]. Associated risk factors for CHD-NEC reportedly are prematurity, low birth weight, low cardiac output, trisomy 21 specific congenital heart disease with hypoplastic left heart syndrome, atrioventricular septal defect, truncus arteriosus with aortic pulmonary window, red blood cell transfusion, prostaglandin use, and receiving cardiopulmonary bypass[7, 10, 11]. The occurrence of NEC in this case may be related to the use of prostaglandins, which caused a PDA opening, systemic circulation oligemia, pulmonary circulation congestion, and intestinal ischemic necrosis. To our knowledge, this is the first report of NEC caused by severe pulmonary valve stenosis. Therefore, it is important to understand the dose and duration of prostaglandins when used for cyanotic CHD, which relies on the ductus arteriosus to supply pulmonary circulation while keeping the PDA open. Therefore, the dose and timing of prostaglandin use should be determined, along with hemodynamic assessment, when prostaglandins therapy is necessary for ductal-dependent CHD.
mNGS has a higher detection sensitivity and specificity for pathogens compared to traditional culture. Its detection time is also shorter, which is important for clinical diagnosis and treatment[12–14]. In this case, only NGS of ascitic fluid was used to screen for E. faecalis. After 21 days of infection while on vancomycin, monitored blood concentrations were within the normal range; however, the infant was repeatedly febrile with a progressive increase in CRP levels. We considered the neonate may be infected with vancomycin-resistant Enterococcus (VRE). Vancomycin was replaced with linezolid, and the neonate improved significantly. Known risk factors for VRE colonization include long hospital stays, the need for intensive care, exposure to invasive procedures, critical illness, and receipt of broad-spectrum antibiotics among others[15–17]. This neonate had these risk factors and was, therefore, at a high risk of VRE colonization and infection.
In addition, the neonate developed a right atrial thrombus after undergoing cardiac surgery, which may have been associated with disseminated intravascular coagulation due to central venous catheterization (CVC) puncture and endothelial injury caused by sepsis. Some scholars have suggested that thrombophilia testing is not routinely performed in patients with a first episode of CVC-related venous thromboembolism. In our case, the parents of the neonate had no history of embolism[18]. Enoxaparin was administered as anticoagulant therapy, with close monitoring of coagulation function, thrombin antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), thrombomodulin (TM), and tissue plasminogen activator inhibitor complex (t-PAIC), and adjustment of enoxaparin dose by anti-Xa activity. The 2018 American Society of Hematology guidelines for the management of venous thromboembolism and the 2012 American College of Chest Physicians guidelines for anticoagulant thrombolysis state that for children with right atrial thrombi associated with a central venous access device, eradication of the device is recommended along with anticoagulant therapy. The initial dose of enoxaparin for term infants is recommended at 1.7 mg/kg/time, ih, q12h. Anti-Xa activity should be investigated 4–6 h after the second dose is administered, with a target range of 0.5-1 units/ml[19, 20]. Combination of four makers include TAT, PIC, TM, and t-PAIC for the early prediction of thrombotic disease and for the evaluation of anticoagulant efficacy[21]. TAT reflects the amount of thrombin generated or the extent of coagulation activation, and its elevation suggests a hypercoagulable state with a high risk of thrombosis. PIC reflects the amount of plasmin generated or the degree of fibrinolytic system activation and an elevation suggests hyperfibrinolysis. Our patient did not have a significantly higher thrombin antithrombin complex level, which might be related to early anticoagulation with enoxaparin. Soybean oil, medium-chain triglycerides, olive oil, and fish oil were used for enteral nutrition to avoid the development of intestinal failure-related liver disease because the neonate had a direct bilirubin level was < 2 mg/kg.
CHD, which predisposes patients to NEC, has an earlier age of onset than preterm birth and is associated with a high mortality rate. Utilizing mNGS for the detection of pathogenic organisms and examining TAT, PIC, TM, and t-PAIC levels should be promoted for the care of patients with severe pulmonary valve stenosis with NEC.