The age of onset of NEC varies inversely with birth weight and gestation; NEC in VLBW neonates occurs later than in older and larger infants.[1,2] For infants <30 weeks gestation, the mean age at diagnosis is approximately 20 days. Those ≥34 weeks have an onset of approximately 5 days. See Sidebar 1 for a discussion of NEC in full-term neonates.
Symptoms of NEC may be sudden and profound or insidious and subtle. An insidious onset is more common in growing preterm neonates. The clinical presentation and diagnosis of NEC are based on well-defined staging criteria.[8,9,10] Stage I is nonspecific and mirrors other processes such as feeding intolerance, infection, or GI bleeding. Gross blood in the stool is a common finding associated with NEC, with an incidence of 25% to 63%.
No single laboratory feature is diagnostic of NEC. Neutropenia, caused by sequestration of neutrophils in the peritoneal fluid, is more common than an elevated white blood cell count. The worst prognosis is associated with infants who have the lowest neutrophil counts, progressively lower absolute neutrophil counts, and persistent thrombocytopenia.
Abdominal distension and feeding intolerance are initial clinical indicators of NEC. Abdominal distension progresses as gas builds up in the bowel. Continued abdominal distension further compromises GI blood flow (Fig 1).
Example of neonatal abdominal distension. Note abdominal wall erythema, seen here in a neonate with NEC. Photograph courtesy of Francois I. Luks, MD, Division of Pediatric Surgery, Hasbro Children's Hospital and Brown University School of Medicine, Providence, RI. Reprinted with permission (https://bms.brown.edu/pedisurg/).
Identifying pathologic abdominal distension in tiny preterm neonates is challenging because of their size, inherently weak abdominal musculature, the presence of medical equipment, and coexisting disease states and therapies. Despite the imperative for developmentally sensitive care, there is no replacement for serial physical assessment by the bedside care provider. Clinicians must consider numerous causes of abdominal distension unrelated to NEC; inadvertant distension from nasal continuous positive airway pressure is a frequent culprit.
A common practice in the NICU is to measure gastric residual (GR) before nasogastric (NG) feedings. This is a theoretic, albeit indirect, measure of feeding intolerance. Although incorporated in GI signs of stage I NEC, there is little published evidence to support the predictive value of GR. No uniform or concise definition of normal GR has been evaluated and tested. Further, the relationship between GR and feeding intolerance in tiny preterm neonates has not been established.
On a practical level, NG tubes that are placed too high (in the lower esophagus or upper segment of the stomach) may fail to measure existing residual accurately. Conversely, tubes placed too deeply may be in the jejunum. Both the diameter of the syringe used to aspirate GI contents and the nature and size of the NG tube may have an impact on the volume aspirated. The negative pressure generated during aspiration may move the lumen of the tube against the stomach wall, precluding the return of gastric contents.
A recent randomized, controlled multicenter trial assessed GR in 99 infants with birth weights <1,000 g (mean gestation, 26 weeks; mean birth weight, 820 g) who were receiving breastmilk or formula. Bolus gavage feedings of 12 mL/kg were initiated at 48 hours of age. Infants were fed every 2 hours and, if tolerated, the volume was advanced by 12 mL/kg every 24 hours. GR was assessed before each feeding. Study protocol dictated that a GR of 2 mL was acceptable for neonates ≤750 g, and 3 mL was accepted for neonates weighing 751 to 1,000 g. Five infants developed NEC with clinical diagnosis of absent bowel sounds, abdominial tenderness, and pneumatosis intestinalis. The mean GR in these 5 neonates was 1.2 mL and did not predict NEC. GR volume or color did not have a significant effect on feeding volumes in the study. In the absence of other clinical manifestations, green GR at <2 to 3 mL was not a significant finding for feeding intolerance and NEC in this population. The authors state that in an ongoing trial in neonates with birth weights up to 1,500 g, the authors accepted GR up to 5 mL/kg. It is important to note that bilious GR may be indicative of other forms of GI obstruction, such as duodenal atresia or malrotation, requiring further urgent evaluation.
Although neonatal stool patterns are not formally included in the clinical staging of NEC, they are often the focus of clinical discussions. A retrospective chart review compared stool patterns in infants with and without at least stage II NEC (n = 68; mean gestational age, 29 weeks). Those infants who developed NEC passed their first stool approximately 14 hours after the first feeding as compared with non-NEC controls, who first passed stool 13 hours before the first feeding (P = 0.008). Further research evaluating stool patterns is needed. Documentation of stool patterns may be helpful in identifying infants at risk for NEC.
A useful clinical marker might facilitate the early differentiation of neonates who are at low risk for NEC (eg, stage I), avoiding the prolonged cessation of enteral feedings and the use of unneeded laboratory tests, radiographs, and antimicrobial agents. Various investigations have evaluated the use of a number of potential clinical markers, including the following[3,4,18,19]:
GI tonometry (measurement of intramucosal pH by equilibration with a fluid-filled balloon)
Urinary D-lactate levels
Exhaled breath hydrogen
Endotoxin elevations in stool
Plasma intestinal fatty acid binding protein
Although investigations continue, widespread clinical application of these markers is limited.
Glutamine and arginine, amino acids known to be essential fuel for GI muscle cells, have been found to be decreased for at least 10 days before clinical recognition of NEC. It is unclear if this is a marker of disease or a contributing factor in pathogenesis. Low arginine levels may result in insufficient nitric oxide, a compound synthesized through the arginine pathways, which is needed for bowel vasodilatation and repair. In adult populations with multisystem failure, dietary augmentation with increased arginine has proven beneficial. Further research is needed to determine if neonatal parallels exist.
Adv Neonatal Care. 2003;3(3) © 2003 W.B. Saunders
Cite this: Part 1. Current Controversies in the Understanding of Necrotizing Enterocolitis - Medscape - Jun 01, 2003.