Neonatal necrotizing enterocolitis (NEC) is one of the most severe acquired intestinal diseases in neonates and is a common complication in preterm infants, especially in very-low and extremely-low birth-weight infants, occurring in approximately 10% at term (1, 2). Among these, NEC induced by congenital heart disease (CHD) accounts for approximately 20% of cases of term infants with NEC (3, 4). We present the case of a full-term infant with severe pulmonary valve stenosis whose intensive care course was complicated by the development of NEC.

An 11-day-old female neonate was diagnosed with severe pulmonary valve stenosis during the fetal period. She was born at 40 1/7 weeks' gestation with a birth weight of 3,450 g and was admitted to another hospital upon birth for prostaglandin E1 (alprostadil) treatment to maintain patency of the ductus arteriosus (PDA). After 1–2 days, she developed dyspnea, abdominal distension, and oliguria, and was then transferred to a different hospital. The preoperative cardiac ultrasound revealed severe pulmonary valve stenosis (Figure 1A). Subsequently, due to the large PDA, surgical repair of the pulmonary valve stenosis, arterial catheter ligation, and tricuspid valvuloplasty were performed under cardiopulmonary bypass. During the surgery, the partial valve was resected, and the pulmonary artery incision was closed with an autologous pericardial patch to augment the pulmonary artery sinus. Postoperative cardiac ultrasonography revealed an approximately 12 mm × 9 mm right atrial thrombus (Figure 1B), for which low-molecular-weight heparin was administered for anticoagulation. “The preoperative cardiac ultrasound was normal and is shown in Figure 1A”. The cardiac ultrasound shows severe pulmonary valve was stenosis rather than normal. The infant received two central catheters that were placed in the right femoral vein and left femoral artery, respectively. However, 6 days after cardiac surgery, her abdominal symptoms worsened. Abdominal paracentesis revealed ascitic fluid with bile, and an abdominal X-ray suggested a gastrointestinal perforation (Figure 2). An abdominal drainage tube was inserted. After 48 h of worsening symptoms, she was transferred to our hospital.

Medications were administered, and the infant was intubated and mechanically ventilated. The medications included vancomycin, meropenem, and low-molecular-weight heparin. Abdominal distention persisted after the abdominal drainage. Thus, 3 days after admission, she underwent an exploratory laparotomy, intestinal resection, and ileostomy. Ink green ascites, which contained feces and purulent debris, were found internally. There was a necrotic perforation of the ileum approximately 5 cm from the ileocecal site (Figure 3), and a 5-cm fistula was created after resection of the necrotic ileum. She was diagnosed with necrotizing enterocolitis IIIB.

Enterococcus faecium was detected in the ascitic fluid using metagenomic next-generation sequencing (mNGS). However, the blood and ascitic fluid cultures were negative. She developed a fever, and her C-reactive protein (CRP) level was markedly elevated to 231 mg/L on the 10th day of hospitalization. The possibility of vancomycin-resistant E. faecium was considered, and linezolid (10 mg/kg/time, Q8 h) was administered. Her temperature returned to normal, and the CRP level gradually decreased to a normal level (Figure 4). Antibiotics were discontinued after 3 weeks.

The patient was monitored for disseminated intravascular coagulation, thrombus formation, and anti-Xa activity. The patient exhibited marked elevations in the thrombin-antithrombin complex (TAT) (9 ng/mL, normal range <4.0 ng/mL) and α2-plasmininhibitor-plasmin complex (PIC) (2.1 µg/mL, normal range <0.8 µg/mL). Fresh frozen plasma was repeatedly infused. Low-molecular-weight heparin was administered with close monitoring of coagulation function and adjustment of the dose according to anti-Xa activity. The initial recommended dose of low-molecular-weight heparin for term infants is 1.7 mg/kg/time, ih, q12h (5). Anti-Xa activity was measured 4–6 h after the second dose was administered, with a target range of 0.5–1 units/mL. Repeat heart ultrasonography showed no right atrial thrombus after 35 days of anticoagulant therapy.

As for nutritional management, the infant was continuously maintained nil per os from the initial onset of abdominal distension after birth until the 7th day after the laparotomy, and received total parenteral nutrition for 23 days. The total parenteral nutrition incorporated a compounded intravenous lipid preparation comprising soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) for the maintenance of vital functions and growth. SMOF was used for enteral nutrition to avoid the development of intestinal failure-related liver disease because the direct bilirubin level of the neonate was <2 mg/dL. The decision to resume enteral feeding after withholding feeds was mainly based on an assessment of the infant's clinical status, which included improved respiratory support, hemodynamic stability, absence of significant abdominal distention or vomiting, and radiography showing no notable bowel dilation or pneumatosis. The early initiation of trophic feeding could prevent gastrointestinal atrophy, facilitate intestinal maturation, and help preserve gut barrier function, thereby reducing the risk of allergic enterocolitis. An extensively hydrolyzed formula was administered due to the lack of breast milk, first via a nasogastric tube and then transitioning to oral intake. The patient underwent fistula surgery 2 months later. After 2 years of follow-up, the patient exhibited normal growth and development.

CHD, which predisposes patients to NEC, has an earlier age of onset than preterm birth and is associated with high mortality. Prolonged high-dose alprostadil treatment should be administered cautiously in neonates with ductal-dependent CHD; otherwise, closely monitoring gastrointestinal signs and symptoms is required. For critically ill neonates, it is recommended to utilize mNGS for pathogen identification and to facilitate clinical diagnosis and treatment. Moreover, monitoring coagulation function via four thrombotic biomarkers, namely, TAT, PIC, TM, and tPAIC, is recommended in critically ill neonates.