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Necrotizing enterocolitis (NEC) is an intestinal disease that affects premature or very low birth weight infants. Symptoms may include poor feeding,
bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, pressu ...
, decreased activity,
blood in the stool Blood in stool looks different depending on how early it enters the digestive tract—and thus how much digestive action it has been exposed to—and how much there is. The term can refer either to melena, with a black appearance, typically or ...
,
vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
of
bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
, multi-organ failure, and potentially
death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...
. 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. Other risk factors potentially implicated include
congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly, congenital cardiovascular malformation, and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital he ...
, birth asphyxia, exchange transfusion, and prelabor rupture of membranes. The underlying mechanism is believed to involve a combination of poor blood flow and
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
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 revea ...
. Maternal factors such as chorioamnionitis, cocaine abuse, intrauterine growth restriction, intrahepatic cholestasis during pregnancy, increased
body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...
, lack of prenatal steroids, mode of delivery, placental abruption,
pre-eclampsia Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of hypertension, high blood pressure and often a significant amount of proteinuria, protein in the urine or by the new onset of high blood pressure a ...
, and
smoking Smoking is a practice in which a substance is combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...
have not been consistently implicated with the development of NEC. Prevention includes the use of
breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by the mammary glands in the breasts of women. Breast milk is the primary source of nutrition for newborn infants, comprising fats, proteins, carbohydrates, and a var ...
and
probiotics Probiotics are live microorganisms that provide health benefits when consumed, generally by improving or restoring the microbiota in the Gut microbiota, gut. Probiotics are considered GRAS, generally safe to consume, but may cause bacteria– ...
. Treatment includes bowel rest, orogastric tube,
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 nutr ...
, 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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
. 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. 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 An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensive care medicine. An inten ...
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, 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. Peo ...
, and bloody stools. Symptoms may progress rapidly to abdominal discoloration with intestinal perforation and
peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and covering of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One pa ...
and systemic
hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
requiring intensive medical support.


Cause

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


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 medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of pr ...
for patent ductus arteriosus closure


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


Diagnosis

Diagnosis is usually suspected clinically, but often requires the aid of diagnostic imaging, most commonly
radiography Radiography is an imaging technology, 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 ("diagnostic" radiog ...
, which can show the intestines and may show areas with dead tissue or a bowel perforation. Specific radiographic signs of NEC are associated with specific Bell's stages of the disease: * Bell's stage 1 (suspected disease): ** Mild systemic disease (
apnea Apnea (also spelled apnoea in British English) is the temporary 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 ...
, 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 hig ...
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 kidn ...
, too few platelets in the bloodstream) * Bell's stage 3 (advanced disease): ** Severe systemic illness ( low blood pressure) ** Additional intestinal signs (striking abdominal distention, peritonitis) ** Severe radiologic signs ( pneumoperitoneum) ** 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 Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems ...
)
Ultrasonography Medical ultrasound includes diagnostic techniques (mainly imaging) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, joints, ...
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, Esophagus, stomach and intestines of affected infant showing intestinal necrosis, pneumatosis intestinalis, and intestinal perforation (arrow) (autopsy specimen) Image:Neonatal necrotizing enterocolitis, gross pathology 20G0023 lores.jpg, Close-up of intestine showing necrosis and pneumatosis (autopsy specimen) 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 the largest professional association of pediatricians in the United States. It is headquartered in Itasca, Illinois, and maintains an office in Washington, D.C. The AAP has published hundreds of poli ...
recommended feeding preterm infants human milk, 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, pasteurizes, and dispenses by prescription human milk donated by nursing mothers who are not biologically related to the recipient infant. The optim ...
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 (updated in 2023) found low- to moderate-quality evidence that supplementation of probiotics enterally "prevents severe NEC, as well as all-cause mortality in preterm infants" but cautioned that the evidence was not sufficient to inform policy and practice and that further high-quality trials are needed. 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), or intravenous feeding, 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 entities or standard ph ...
, 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 tract is the largest of the body's systems, after the cardiovascular system. T ...
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, 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 i ...
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 In anatomy, a fistula (: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") is an abnormal connection (i.e. tube) joining two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other h ...
or connection to the distal bowel may be helpful, as this allows for refeeding of ostomy 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. 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 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 i ...
and neurodevelopmental disability.


Society and advocacy

Th
NEC Society
is a 501(c)(3), non-profit organization dedicated to building a world without necrotizing enterocolitis (NEC) through research, advocacy, and education. The NEC Society was launched in January 2014 by Jennifer Canvasser after her son, Micah, died from complications of NEC just before his first birthday. The NEC Society is a patient-led organization that collaborates with expert clinicians and researchers to better understand, prevent, and treat this devastating neonatal intestinal disease. Today, patient-families and experts from around the world work together to improve outcomes for the most vulnerable infants at risk of NEC. Their work and numerous initiatives combine the patient-family perspective with solutions based on the best available scientific evidence.


NEC Symposium

The NEC Society hosts an in-person, biennial Symposium where clinicians, scientists and patient-families come together to listen, learn and collaborate. It is held as an
All-In Meeting
, where all stakeholders are fully integrated and empowered. Patient-families are central to the planning, preparation, and execution of the meeting. Each session is dedicated to a baby affected by NEC. Patient-families take part in each session as faculty and also present posters.


References


External links

{{Digestive system diseases Neonatology Gastrointestinal tract disorders Wikipedia medicine articles ready to translate