Necrotizing enterocolitis is an inflammatory intestinal disorder primarily seen in premature infants, characterized by variable damage to the intestinal tract, ranging from mucosal injury to full-thickness necrosis and perforation. (Zani and Pierro, 2015).
The incidence of NEC in VLBW infants, stable over the years, is between 5–7%; a slight increase over the period 2000–2009 was reported in the intensive care unit neonatal (NICU) of the Vermont Oxford Network (VON) (Esposito et al., 2017).
Mortality from NEC varies depending from the degree of bowel involvement and comorbidities, up to 50% in those forms which require surgical treatment (Eaton et al., 2017).
Although the majority of cases of NEC occur among premature infants, a small subset of babies born at term or shortly before (that is, ≥35 weeks of gestation) develop NEC-like gastrointestinal signs and symptoms, frequently in association with other conditions (Christensen et al., 2013).
Despite the complex and multifactorial nature of the pathogenesis of NEC, three major risk factors have been implicated in its development: prematurity, bacterial colonization of the gut and formula-feeding (Hackam et al., 2013).
The cornerstone of effective NEC treatment relies on accurately diagnosing the disease, which can usually be established on the basis of readily available clinical, radiographic and laboratory data.The typical neonate with NEC is a premature infant who is thriving, yet suddenly presents with feeding intolerance, abdominal distension, bloody stools and signs of sepsis (that is, changes in heart rate, respiratory rate, temperature and blood pressure). (Sharma and Hudak, 2013)
Signs of sepsis can be associated with high gastric residuals (defined as the volume that remains in the stomach before the next enteral feeding35) of ≥2 ml/kg or >50% of the previous feeding volume, which could indicate the presence of feeding intolerance (Li , 2014 ).
Radiographic features are the mainstay of definitive diagnosis of NEC. The pathognomonic signs for NEC are pneumatosis intestinalis (Fig. 1) and portal venous gas (Fig. 2b). Sonographic detection of portal air can also help in early diagnosis. Serial radiographs are clinically invaluable in following the progression of disease, particularly in the first 2 d after the onset of NEC (Kasivajjula and Maheshwari, 2014).
Diagnostic and prognostic validity of ultrasound findings in the diagnosis of NEC depicted by ultrasound and is considered in most studies. The leadoff studies done in this field suggested that PVG may be detected earlier by ultrasound than by AR (Bömelburg and von., 1992).
This may be the reason why PVG detected by ultrasound is not necessarily accompanied by such a poor prognosis as formerly presumed based on AR findings (Epelman et al, 2007). Nevertheless, recent larger studies showed that PVG detected by ultrasound in NEC of all stages has a sensitivity of only 16–45% (Dilli et al, 2011).
In NEC confirmed by intraoperative findings as gold standard, the sensitivity is remarkably higher and reaches 82% (Bohnhorst et al, 2011).
In any case, PVG in ultrasound does not differentiate between NEC stages (Dördelmann et al, 2009).
The specificity of PVG in ultrasound reaches 90–98%, since apart from suspected or confirmed NEC there is only one other neonatal disease which is associated with PVG in ultrasound, called ‘benign pneumatosis coli’ (Dilli et al, 2011).
Sensitivity and specificity of PVG in AR have not yet been calculated, but detection rates of PVG by AR vary from 2.6% to 58%, thus suggesting low sensitivity. (Dilli et al, 2011) PI is detected by ultrasound in 13–100% of infants with NEC of all stages, the corresponding value for AR ranges from 20% to 95%. (Dilli et al, 2011) Recently, PI was detected by AR impressively more often than by ultrasound in cases of advanced NEC (74% vs 13%) (Dilli et al, 2011) Our own study on patients with surgically confirmed NEC revealed a sensitivity of 75% and a specificity of 91% for detection of PI and/or PVG in AR in diagnosing NEC (Bohnhorst et al, 2011).
Abdominal ultrasonography (AUS) provides a more detailed understanding of the state of the bowel in patients with NEC and may thus make management decisions easier and potentially change outcome (Epleman et al, 2007).
In case of clinical suspicion for NEC, abdominal plain film is the primary modality for diagnosis, which may confirm the diagnosis in definite and advanced stages. Early in the disease process radiological findings include distension of bowel loops and loss of the mosaic pattern of the loops of bowel is often seen. Later on, pneumatosis intestinalis occurs with an incidence over 19%. The pattern varies from localized cystic collection of air to diffuse linear collections that outline an area of the bowel wall. Intramural gas is a non-specific radiological sign that may precede clinical signs (Franco and Ramji, 2008).
In addition, organ-specific biomarkers, such as those that would indicate enterocyte injury or intestinal barrier impairment, include intestinal fatty acid-binding protein, liver fatty acid-binding protein, faecal calprotectin, trefoil factor 3 and claudin-3 (Ng, 2014 ).
Treatment for NEC includes bowel decompression and rest, fluid resuscitation, antibiotic therapy, and supportive care. (Henen and Duchon, 2018).
Pneumoperitoneum is an indication for urgent surgical intervention in infants with NEC. Treatment options include either primary peritoneal drain and/or exploratory laparotomy. Studies have failed to show consistent benefits of one approach. (Heida et al., 2015).
The outcome of children with NEC is characterized by high overall morbidity ranging from 20–50%, as patients experience recurrence, intestinal strictures, short bowel syndrome, growth delay and neurodevelopmental impairment (Papillon et al., 2013).
Infants with NEC have longer hospitalization stays, increased risk of death before discharge and accrue higher financial costs compared with premature infants without NEC (Stey, 2015).
In the long term, patients who survive NEC are frequently affected by neurodevelopmental impairment, demonstrated by their impaired performance in cognitive and developmental assessments such as the Bayley Scales of Infant Development, the Griffiths Quotient and the Stanford–Binet test (Henry, 2008), underscoring the far-reaching sequelae of this disease (Niño et al., 2016).
Emerging consensus is that the use of probiotics in NEC could be effective in reducing the incidence of the disease without increasing rates of sepsis or other adverse events.Mechanistic insights supporting the use of probiotics are scarce but are starting to emerge. Administration of the probiotic bacteria Lactobacillus rhamnosus was shown to increase enterocyte proliferation and differentiation of Paneth cells in enteroids grown in a 3D bioscaffold (Shaffiey et al., 2016).
Early surgical intervention is life saving for those infants. In conclusion, our results suggest AUS to be superior to abdominal plain radiography in demonstrating portal venous gas, free or focal fluid collection, bowel wall thinning and free air. Earlier detection of bowel wall thinning and PVG allow early surgical intervention prior to development of perforation and so decrease the morbidity and mortality rates. Moreover, early surgical management if echogenic focal fluid collection is observed by AUS in a clinically deteriorated NEC case may be lifesaving being an early sign of intestinal perforation. Therefore, addition of AUS to plain radiography is valuable in managing patients with necrotizing enterocolitis. (Shebrya et al., 2012).
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