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Last updated:
May 14, 2015
Years published: 2015
NORD gratefully acknowledges Arvin Bundhoo, MD and Adam Matson, MD, MS, Division of Neonatology, Connecticut Children’s Medical Center, Hartford, CT; Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, for preparing this report.
Necrotizing enterocolitis, abbreviated NEC, is a devastating disease that affects a newborn’s intestines. It typically occurs in premature infants, born less than 37 weeks, and is characterized by severe inflammation of a baby’s small or large intestines, which may progress to tissue death (necrosis). NEC occurs in about 1 case per 1000 live births [1]. NEC can occur in full term babies but it is much more common in very premature infants, especially very low birth weight babies — incidence ranges from 3% in infants with birth weight of 1251 to 1500 grams (2 pounds 12.13 ounces to 3 pounds 4.91 ounces) to 11% for infants born weighing less than 750 grams (1 pounds 10.46 ounces) [2]. NEC typically occurs when a newborn is several weeks old and on enteral feeds. Initially babies present with vomiting, large distended belly, bloody stools, long pauses in their breathing, and decreased activity. This can further progress to bowel necrosis and perforation. Medical treatment involves discontinuation of enteral feeds (the delivery of nutritionally complete feeds directly into the stomach), initiation of broad-spectrum antibiotics and supportive care [3]. Surgical intervention is indicated when there is evidence of bowel perforation and necrotic bowel. This serious gastrointestinal disease is associated with significant morbidity (complications associated with the disease) and mortality. Despite treatment, about 15% of babies who develop NEC die and some babies that survive suffer from numerous complications such as short bowel syndrome, poor growth, and long-term neurodevelopmental impairments [4]. The exact mechanism of this disease, while not fully understood, is believed to be multifactorial and related to a premature intestine, abnormal gut microbial colonization, and intestinal inflammation.
NEC remains a leading cause of morbidity and mortality in the neonatal intensive care unit despite significant advances in the care being provided to premature infants [5;6]. It remains primarily a disease of prematurity. Term infants with risk factors such as congenital heart disease, sepsis, or hypotension (low blood pressure) can also develop NEC [7]. Bell’s classification was introduced in 1978 and is still widely used to clinically stage NEC based on disease severity: stage I being suspected NEC, stage II being confirmed NEC, and stage III being confirmed NEC with intestinal perforation and/or multi-system involvement [8]. More recently, the terminology of acquired neonatal intestinal diseases (ANIDs) was introduced by Gordon et al. to further classify NEC into subgroups based on associated clinical factors: these include NEC in term infants, NEC associated with red blood cell transfusions, NEC associated with cow’s milk intolerance, NEC associated with contagion and/or lymphocytosis, NEC associated with extreme prematurity, and NEC-like diseases [9].
Onset of NEC is typically during the first several weeks after birth when feeds have been started, and the age of onset inversely related to gestational age at birth. Early in the disease process, neonates can exhibit signs of feeding intolerance with vomiting, increased gastric aspirates, bile-tinged (green) gastric aspirates, or decreased bowel sounds with abdominal distention and tenderness. Gross or occult blood can be present in stools indicating mucosal injury. Many of these signs are non-specific and can occur with other disorders. Progression of NEC results in systemic signs such as lethargy, long pauses in breathing called apnea, temperature instability, and poor perfusion (pumping of fluid through an organ or tissue.) Ultimately this can lead to respiratory failure and cardiovascular collapse requiring mechanical ventilation and vasopressors. A palpable mass and erythema (abnormal redness of the skin due to capillary congestion, as in inflammation) of the abdominal wall is indicative of a more advanced disease process.
After many years of research and clinical observation, the etiology and pathogenesis of NEC remain elusive. Some key risk factors have been consistently identified as important prerequisites for initiation of intestinal injury leading to NEC. These include prematurity, formula feeding, abnormal microbial intestinal colonization, and ischemia (when blood vessels to the intestines become narrowed or blocked, reducing blood flow.) [3;10;11].
Prematurity remains the main important risk factor associated with NEC. The immaturity of intestinal epithelial cell barrier and immune system appear to contribute to the pathogenesis. Before birth, the fetus has a sterile intestinal environment and becomes colonized rapidly with bacteria after birth. Inappropriate colonization with predominance of gram negative bacteria can lead to disruption of normal intestinal epithelium, bacterial translocation, and trigger an excessive inflammatory response [10;12-14]. The hallmark histologic findings seen in NEC are inflammation and coagulation necrosis [11] (a pattern of tissue death.) Ischemia is another important pathophysiologic factor in the development of NEC. Decreased oxygen supply to intestinal cells can lead to cellular injury and necrosis.
NEC affects 5 to 10% of premature infants born weighing less than 1500 g. Among the risk factors defined for NEC, prematurity and birth weight remain inversely related to risk for NEC. Term infants who develop NEC usually have specific risk factors such as congenital heart disease, sepsis, and low blood pressure.
NEC is diagnosed clinically and radiographically. Once clinical suspicion arises, an abdominal X-ray is performed as an initial evaluation. This is repeated serially depending on acuity and clinical course to assess disease progression. Characteristic findings on NEC process on abdominal radiographs include pneumatosis intestinalis (air in the intestinal wall), abnormal persistent dilated loops, thickened bowel wall, pneumoperitoneum and portal vein gas. Pneumoperitoneum defined as abdominal free air is a surgical emergency indicating bowel perforation and usually requires intervention. Abdominal ultrasonography can also be used to evaluate for free fluid in the abdominal cavity or abscess formation. Addition laboratory studies to evaluate severity of NEC include a blood culture, coagulation studies and complete blood count with manual differential to assess for leukocytosis with bandemia, neutropenia, anemia and thrombocytopenia. Blood gases are checked serially to assess severity of acidosis and need for respiratory support or to assist with fluid management.
Treatment of NEC depends on the clinical staging. In cases of suspected NEC, stage I, initial treatment consists of bowel rest with discontinuation of enteral feeds, nasogastric decompression, cultures of blood, and initiation of broad-spectrum antibiotics. While infant remains NPO, “nothing by mouth”, intravenous parenteral nutrition is initiated. Close observation with serial examinations and radiographs is essential. Surgical consultation is obtained once NEC is confirmed, stage II or III. Supportive care includes respiratory support, inotropic (cardiac function) support, fluid resuscitation and correction of acid-base imbalance. Patients with NEC can develop disseminated intravascular coagulation (DIC) (a condition that prevents blood from clotting normally) from consumption of clotting factors and require blood product transfusions. The principal indication for surgical intervention in NEC is a perforated or necrotic intestine. Other indications include clinical deterioration and severe abdominal distention causing abdominal compartment syndrome (organ dysfunction or failure due to a severe increase in the pressure within the abdomen.) Two surgical approaches are usually done depending on clinical presentation, laparotomy with resection (removal) of necrotic bowel or primary peritoneal drainage (the procedure of inserting a Penrose drain into the space within the abdomen that contains the intestines, the stomach, and the liver).
Prevention of NEC has the greatest potential to reduce adverse outcomes related with NEC. Currently, breast milk has been clearly shown to be protective against NEC compared with formula feeding [15;16]. Establishment of a standardized feeding protocol with objective criteria for withholding feeds has also been shown to reduce the risk of NEC [17]. Probiotics have the potential to prevent NEC by restoring gut microbial flora but it still requires further investigation as to optimum dosage and duration of treatment [18].
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NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/
