Overview

Necrotising Enterocolitis (NEC) is a life-threatening gastrointestinal disease which almost exclusively affects neonates. NEC has a mortality rate as high as 50 per cent and usually presents in the second or third week of life.¹ Beginning with inflammation of the intestine, NEC progresses following bacterial invasion, causing cellular damage and necrosis of the colon and intestine. The intestine can perforate, causing peritonitis, sepsis, and death.¹ The signs and symptoms of NEC are quite non-specific; however, poor feeding, lethargy, bloody stools, difficulty breathing and vomiting should be considered as early presentation for accurate diagnosis in neonates. Early diagnosis can lead to a better prognosis with reduced morbidity and mortality rates. However, the broad symptom range presents challenges for health professionals when reaching the correct diagnosis. This causes varying clinical assessments with varying requests for laboratory evaluation and imaging tests.¹

What is a typical presentation of NEC?

There are many risk factors and predisposing conditions which can be an indicator of NEC upon clinical assessment. These include:

• Prematurity
• Low birth weight
• Formula feeding
• Oxygen deprivation during birth
• Sepsis at birth
• Swollen abdomen
• Feeding intolerance

What tests are performed to diagnose NEC?

Laboratory evaluation

Early diagnosis and identification of newborns who may develop this condition are limited by the lack of rapid and sensitive tests to detect signs.² Laboratory analysis can be broken down into different test categories. These include tests for non-specific inflammatory markers, metabolic indicators, and haematological and microbiological workups. 

Non-specific inflammatory markers

• Complete Blood Count (CBC): To detect anaemia, leukocytosis, leukopenia, or thrombocytopenia, which may indicate infection or internal bleeding
• C-Reactive Protein (CRP): Elevated levels suggest inflammation throughout the body²

Metabolic indicators

• Electrolytes and Blood Gas: To monitor for metabolic acidosis and electrolyte imbalances. Imbalances include low sodium or high potassium levels, which can lead to dehydration
• Lactate levels: Elevated lactate may indicate reduced blood flow to the bowel and surrounding tissues²

Haematological analysis

• Coagulation Profile: This is performed if disseminated intravascular coagulation (DIC) is suspected, in other words, a cascade of events where excessive blood clots forms throughout the body. This leads to reduced blood flow and uncontrollable tissue bleeding, causing organ damage²

Microbiological analysis

• Blood Cultures: Performed to identify potential bloodstream infections and rule out sepsis, although usually negative
• Stool occult blood test: This tests for blood in stool to aid in identifying gastrointestinal bleeding²

Imaging studies

Abdominal radiography (X-ray)² 

This is the key gold standard diagnostic tool in the diagnosis of NEC. The most important radiographic findings confirming a diagnosis using this method of technology include:

• Pneumatosis intestinalis (hallmark sign): Gas within the walls of the gastrointestinal tract
• Portal venous gas: The presence of air within the veins which carry blood from the digestive tract to the liver
• Pneumoperitoneum: The space lining the abdominal wall contains free air, indicating perforation²

Ultrasound 

This is a great alternative diagnostic method due to its safety and accessibility. Ultrasound can be performed at the bedside, is non-invasive and reduces patient exposure to radiation, enabling frequent checks to be performed. ²Ultrasound can also be important where the X-ray is inconclusive. It is most useful in assessing:

• Bowel wall thickness 
• Bowel wall perfusion
• Volume of intra-abdominal fluid collection
• Rate of peristalsis (involuntary movement of food and fluids through the digestive tract, essential for absorption of nutrients and eliminating waste)²
• Pneumatosis intestinalis and portal venous gas

Serial imaging 

Repeated imaging over time plays an essential role in the diagnosis and management of NEC. These images are compared over time to look for changes in the bowel's condition. Serial imaging is important in monitoring disease progression. It is used to determine the need for, and guidance of, medical or surgical interventions, plus tracking patients' responses to treatment.² If NEC is confirmed or strongly suspected, repeat X-rays occur every 6–12 hours, especially in unstable infants. When infants become stable and symptoms resolve, imaging may be spaced out or stopped.²

What is the best diagnostic approach to NEC? 

Bell’s Staging Criteria was the first classification system published in 1978, created for diagnosing NEC. The system included a set of characteristics combining clinical, radiographic and laboratory findings to classify infants into 1 of 3 stages of NEC. This system separated neonates into cohorts of varying severity of illness to help guide treatment and support the management of NEC.³ In more recent times, these 3 stages have been subdivided into 6 stages with Bells’ staging, remaining the most commonly used criteria for NEC diagnosis.

What is the differential diagnosis of NEC?

The issues associated with diagnosing NEC mean it can be hard to distinguish between it and the many other neonatal or gastrointestinal conditions which can mimic NEC clinically in early stages. These conditions could be considered in a broad differential diagnosis, leading to a delay in actual diagnosis.¹ 

• Congenital abnormalities: Pyloric stenosis (narrowing of the opening between stomach and small intestine), duodenal atresia (part of the small intestine is underdeveloped preventing transport of food and fluids), tracheoesophageal fistula (abnormal connection between the oesophagus and the trachea causing swallowed foods to enter the lungs), gastroschisis (at birth a babys’ intestines protrude outside the abdominal cavity), malrotation (at birth the intestines do not form in the correct position), midgut volvulus (the small intestine twists around its blood supply leading to bowel obstruction and ischemia), intussusception (where one part of the small intestine folds into the section adjacent to it) or testicular torsion (the testicles can rotate around the spermatic cord, bringing blood to the testicle from the abdomen)¹
• Spontaneous intestinal perforation: A life-threatening condition, where a single tear occurs in the intestinal wall⁴
• Infectious causes: Sepsis with ileus, meningitis, pneumonia, urinary tract infection, gastroenteritis¹
• Hirschsprung disease: At birth, nerves are missing from the intestine, causing problems passing stool

Summary 

The use and application of varying tests are essential in reaching a definitive diagnosis of NEC. No single test can lead us to the correct diagnosis, meaning all clinical signs, laboratory test results, and imaging results collectively are significant. The diagnosis and management of necrotising enterocolitis requires an interprofessional team approach. Mortality rates related to the condition are dependent on early recognition and timely intervention. Bells’ staging guidelines have become a very useful and significant tool in the diagnosis and characterisation of NEC, along with assisting clinicians in decisions of medical and surgical management of the condition. Personalised treatment strategies for patients categorised at different stages of the illness would be ideal. However, until diagnostic biomarkers become available for early or predictive intervention, personalised treatment remains an ideal only. Moving forward, more research is required to reach the best potential use for biomarkers as a diagnostic tool in early-stage NEC.² Artificial intelligence (AI) may soon play a role in diagnosing NEC. AI algorithms combined with clinical symptoms and imaging may assist in reaching an early diagnosis of NEC, but this topic is still quite unknown as of now.⁵