Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects premature or very low birth weight infants.Gephart S.M., Quinn M. A call to action to fight for equity and end necrotizing enterocolitis disparities. ''Adv. Neonatal Care.'' 2021;21(5):333-335. doi:10.1097/ANC.0000000000000940 Symptoms may include poor feeding, bloating, decreased activity, blood in the stool,

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...

, bowel death, multiorgan failure, and even death. The exact cause is unclear. However, several risk factors have been identified. Consistently described risk factors include formula feeding, intestinal dysbiosis, low birth weight, and prematurity. Maternal factors such as chorioamnionitis, cocaine abuse, ''in utero'' growth restriction, intrahepatic cholestasis during pregnancy, increased body mass index, lack of prenatal steroids, mode of delivery, placental abruption, preeclampsia, and smoking have not been consistently implicated with the development of NEC. Other risk factors potentially implicated include

congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...

birth asphyxia Perinatal asphyxia (also known as neonatal asphyxia or birth asphyxia) is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. ...

, exchange transfusion, and

prelabor rupture of membranes Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labor. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complicati ...

. The underlying mechanism is believed to involve a combination of poor blood flow and

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

of the intestines. Diagnosis is based on symptoms and confirmed with

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...

. Prevention includes the use of

breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...

and

probiotics Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria-host i ...

. Treatment includes

bowel rest Nothing by mouth is a medical instruction meaning to withhold food and fluids. It is also known as nil per os (npo or NPO), a Latin phrase that translates to English as "nothing through the mouth". Variants include nil by mouth (NBM), nihil/non/nu ...

orogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the oesophagus, and down into the stomach. Orogastric intubation is a similar process involving the inserti ...

intravenous fluids Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

, and intravenous

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...

. Surgery is required in those who have free air in the abdomen. A number of other supportive measures may also be required. Complications may include short-gut syndrome, intestinal strictures, or

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, c ...

. About 7% of those who are born prematurely develop NEC; however the odds of an infant developing this illness is directly related to the intensive care unit they are placed in. Onset is typically in the first four weeks of life. Among those affected, about 25% die. The sexes are affected with equal frequency. The condition was first described between 1888 and 1891.

Signs and symptoms

The condition is typically seen in premature infants, and the timing of its onset is generally inversely proportional to the gestational age of the baby at birth (i.e., the earlier a baby is born, the later signs of NEC are typically seen). Initial symptoms include feeding intolerance and

failure to thrive Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...

, increased gastric residuals,

abdominal distension Abdominal distension occurs when substances, such as air (gas) or fluid, accumulate in the abdomen causing its expansion. It is typically a symptom of an underlying disease or dysfunction in the body, rather than an illness in its own right. Pe ...

, and bloody stools. Symptoms may progress rapidly to abdominal discoloration with

intestinal perforation Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe ab ...

and

peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part or ...

and systemic

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

requiring intensive medical support.

Cause

The exact cause is unclear. Several risk factors have been implicated:

Maternal factors

* Acid-suppressing medications * Chorioamnionitis * Cocaine abuse * ''In utero'' growth restriction * Increased body mass index * Intrahepatic cholestasis during pregnancy * Lack of prenatal steroids * Mode of delivery * Placental abruption * Pre-eclampsia * Smoking

Main risk factors

* Low birth weight * Prematurity * Formula feeding (bovine based) * Intestinal dysbiosis

Other risk factors

* Acute hypoxia * Antibiotic exposure * Blood transfusions * Cardiac anomalies * Neonatal anemia * Poor intestinal perfusion * Prolonged use of

indomethacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription drug, prescription medication to reduce fever, pain, joint stiffness, stiffness, and swelling (medical), swelling from infl ...

for patent ductus arteriosus closure

Diagnosis

Diagnosis is usually suspected clinically, but often requires the aid of diagnostic imaging, most commonly

radiography Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeut ...

, which can show the intestines and may show areas with death tissue or a bowel perforation. Specific radiographic signs of NEC are associated with specific Bell's stages of the disease:Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006 Oct 7;368(9543):1271–83. * Bell's stage 1 (suspected disease): ** Mild systemic disease (

apnea Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ...

, lethargy, slowed heart rate, temperature instability) ** Mild intestinal signs (abdominal distention, increased gastric residuals, bloody stools) ** Nonspecific or normal radiological signs * Bell's stage 2 (definite disease): ** Mild to moderate systemic signs ** Additional intestinal signs (absent bowel sounds, abdominal tenderness) ** Specific radiologic signs (

pneumatosis intestinalis Pneumatosis intestinalis (also called intestinal pneumatosis, pneumatosis cystoides intestinalis, pneumatosis coli, or intramural bowel gas) is pneumatosis of an intestine, that is, gas cysts in the bowel wall. As a radiological sign it is highly ...

or portal venous gas) ** Laboratory changes (

metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...

, too few platelets in the bloodstream) * Bell's stage 3 (advanced disease): ** Severe systemic illness (

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

) ** Additional intestinal signs (striking abdominal distention, peritonitis) ** Severe radiologic signs (

pneumoperitoneum Pneumoperitoneum is pneumatosis (abnormal presence of air or other gas) in the peritoneal cavity, a potential space within the abdominal cavity. The most common cause is a perforated abdominal organ, generally from a perforated peptic ulcer, althou ...

) ** Additional laboratory changes (metabolic and respiratory acidosis,

disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts o ...

)

Ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

has proven to be useful, as it may detect signs and complications of NEC before they are evident on radiographs, specifically in cases that involve a paucity of bowel gas, a gasless abdomen, or a sentinel loop.Muchantef K, Epelman M, Darge K, Kirpalani H, Laje P, Anupindi SA. Sonographic and radiographic imaging features of the neonate with necrotizing enterocolitis: correlating findings with outcomes. Pediatr Radiol. 2013 Jun 15. Diagnosis is ultimately made in 5–10% of very-low-birth-weight infants (<1,500g). Image:Neonatal necrotizing enterocolitis, gross pathology 20G0022 lores.jpg, Alimentary tract of infant showing intestinal necrosis, pneumatosis intestinalis, and perforation site (arrow) (autopsy) Image:Neonatal necrotizing enterocolitis, gross pathology 20G0023 lores.jpg, Close-up of intestine of infant showing necrosis and pneumatosis intestinalis (autopsy) Diagnosis of NEC is more challenging in premature infants, due to inexplicit symptoms and radiographic signs. The most preterm infant is at highest risk of developing NEC.

Prevention

Prevention includes the use of breast milk and probiotics. A 2012 policy by the

American Academy of Pediatrics The American Academy of Pediatrics (AAP) is an American professional association of pediatricians, headquartered in Itasca, Illinois. It maintains its Department of Federal Affairs office in Washington, D.C. Background The Academy was founded ...

recommended feeding preterm infants

human milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates (lactos ...

, finding "significant short- and long-term beneficial effects," including reducing the rate of NEC by a factor of one-half to three-quarters. Small amounts of oral feeds of human milk starting as soon as possible, while the infant is being primarily fed intravenously, primes the immature gut to mature and become ready to receive greater intake by mouth. Human milk from a

milk bank A human milk bank, breast milk bank or lactarium is a service that collects, screens, processes, and dispenses by prescription human milk donated by nursing mothers who are not biologically related to the recipient infant. The optimum nutrition ...

or donor can be used if mother's milk is unavailable. The gut mucosal cells do not get enough nourishment from arterial blood supply to stay healthy, especially in very premature infants, where the blood supply is limited due to immature development of the capillaries, so nutrients from the lumen of the gut are needed. Towards understanding intervention with human milk, experts have noted cow's and human milk differ in their immunoglobular and glycan compositions. Due to their relative ease of production, human milk oligosaccharides (HMO) are a subject of particular interest in supplementation and intervention. A Cochrane review in 2020 found low- to moderate-quality evidence that supplementation of probiotics enterally "prevents severe NEC, as well as all-cause mortality in preterm infants" and that further high-quality trials are needed to inform policy and practice. Advancing enteral feed volumes at lower rates does not appear to reduce the risk of NEC or death in very preterm infants and seems to increase the risk of invasive infection. Not beginning feeding an infant by mouth for more than 4 days does not appear to have protective benefits.

Treatment

If a baby is diagnosed with NEC, treatment should begin immediately. Treatment consists primarily of supportive care, including providing bowel rest by stopping enteral feeds, gastric decompression with intermittent suction, fluid repletion to correct electrolyte abnormalities and third-space losses, support for blood pressure,

parenteral nutrition Parenteral nutrition (PN) is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding companies. The person receives a nutritional mix ...

, and prompt antibiotic therapy. Monitoring is clinical, although serial supine and left lateral decubitus abdominal X-rays should be performed every six hours. As an infant recovers from NEC, feeds are gradually introduced. "Trophic feeds" or low-volume feeds (<20 ml/kg/day) are usually initiated first. How and what to feed are determined by the extent of

bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

involved, the need for surgical intervention, and the infant's clinical appearance. Where the disease is not halted through medical treatment alone, or when the bowel perforates, immediate emergency surgery to resect the dead bowel is generally required, although abdominal drains may be placed in very unstable infants as a temporizing measure. Surgery may require a

colostomy A colostomy is an opening ( stoma) in the large intestine (colon), or the surgical procedure that creates one. The opening is formed by drawing the healthy end of the colon through an incision in the anterior abdominal wall and suturing it int ...

, which may be able to be reversed at a later time. Some children may develop

short bowel syndrome Short bowel syndrome (SBS, or simply short gut) is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may in ...

if extensive portions of the bowel must be removed. In the case of an infant whose bowel is left in discontinuity, the surgical creation of a mucous

fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...

or connection to the distal bowel may be helpful, as this allows for refeeding of

ostomy In anatomy, a stoma (plural stomata or stomas) is any opening in the body. For example, a mouth, a nose, and an anus are natural stomata. Any hollow organ can be manipulated into an artificial stoma as necessary. This includes the esophagus, stoma ...

output to the distal bowel. This refeeding process is believed to improve bowel adaptation and aid in advancement of feeds.

Prognosis

Typical recovery from NEC if medical, nonsurgical treatment succeeds, includes 10–14 days or more without oral intake, and then demonstrated ability to resume feedings and gain weight. Recovery from NEC alone may be compromised by co-morbid conditions that frequently accompany prematurity. Long-term complications of medical NEC include bowel obstruction and anemia. In the United States, NEC caused 355 deaths per 100,000 live births in 2013, down from 484 per 100,000 live births in 2009. Rates of death were almost three times higher for the black population than for the white population. When NEC is diagnosed and treated immediately, the prognosis for babies is generally very good. Most babies recover fully without any additional health problems. Overall, about 70-80% of infants who develop NEC survive.Schanler, R.J. (2017). "Management of necrotizing enterocolitis in newborns". ''UpToDate''. Medical management of NEC shows an increased chance of survival compared to surgical management. Despite a significant mortality risk, long-term prognosis for infants undergoing NEC surgery is improving, with survival rates of 70–80%. However, "Surgical NEC" survivors are still at risk for possible long-term complications, such as narrowing of the intestines or short bowel syndrome and neurodevelopmental disability.

References

External links

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