Necrotizing enterocolitis (NEC) is the most common GI medical/surgical emergency occurring in neonates. NEC represents a significant clinical problem and affects close to 10% of infants who weigh less than 1500 g, with mortality rates of 50% or more depending on severity. Although it is more common in premature infants, it can also be observed in term and near-term babies. Despite intensive study over the past 30 years, its etiology remains elusive
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, increased gastric residuals, abdominal distension and bloody stools. Symptoms may progress rapidly to abdominal discoloration with intestinal perforation and peritonitis and systemic hypotension requiring intensive medical support
NEC affects the GI tract and, in severe cases, can cause prfund impairment f multiple rgan systems. Initial symptms may be subtle and can include ne r mre f the fllwing: Feeding intlerance Delayed gastric emptying Abdminal distentin, abdminal tenderness, r bth Ileus/decreased bwel sunds Abdminal wall erythema (advanced stages) Hematchezia Systemic signs are nnspecific and can include any cmbinatin f the fllwing: Apnea Lethargy Decreased peripheral perfusin Shck (in advanced stages) Cardivascular cllapse Bleeding diathesis (cnsumptin cagulpathy) Nnspecific labratry abnrmalities can include the fllwing: Hypnatremia Metablic acidsis Thrmbcytpenia Leukpenia r leukcytsis with left shift Neutrpenia Prlnged prthrmbin time (PT) and activated partial thrmbplastin time (aPTT), decreasing fibringen, rising fibrin split prducts (in cases f cnsumptin cagulpathy) Althugh the exact etilgy remains unknwn, research suggests that it is multifactrial; ischemia and/r reperfusin injury, exacerbated by activatin f prinflammatry intracellular cascades, may play a significant rle. Cases that cluster in epidemics suggest an infectius etilgy. Gram-psitive and gram-negative bacteria, fungi, and viruses have all been islated frm affected infants; hwever, many infants have negative culture findings. Furthermre, the same rganisms islated in stl cultures frm affected babies have als been islated frm healthy babies. Extensive experimental wrk in animal mdels suggests that translcatin f intestinal flra acrss an intestinal mucsal barrier rendered vulnerable by the interplay f intestinal ischemia, immunlgic immaturity, and immunlgical dysfunctin may play a rle in the pathgenesis f the disease, spreading it and triggering systemic invlvement. Such a mechanism culd accunt fr the apparent prtectin breast-fed infants have against fulminant NEC. Animal mdel research studies have shed light n the pathgenesis f this disease. Regardless f the triggering mechanisms, the resultant utcme is significant inflammatin f the intestinal tissues, the release f inflammatry mediatrs (eg, leuktrienes, tumr necrsis factr [TNF], platelet-activating factr [PAF]) and intraluminal bile acids, and dwn-regulatin f cellular grwth factrs, all f which lead t variable degrees f intestinal damage. Althugh the pathgenesis f NEC remains uncertain, a large bdy f evidence suggests a multifactrial etilgy, including the presence f abnrmal bacterial flra, intestinal ischemia, reperfusin injury with activatin f prinflammatry cellular cascades, and intestinal mucsal immaturity/dysfunctin. Abnrmal intestinal flra In healthy individuals, the intestinal milieu is characterized by a predminance f bifidbacteria. Such clnizatin is enhanced by the presence f ligfructse, a cmpnent f human milk, in the intestinal lumen. Infants wh receive frmula feedings withut ligfructse as a cnstituent have been nted t have a predminance f clstridial rganisms. Rat pups clnized with Staphylcccus aureus and Escherichia cli demnstrated increased incidence and severity f NEC cmpared with thse whse intestines were ppulated with varius bacterial species.1 Tll-like receptr signaling f intestinal mucsal transmembrane prteins is accmplished by binding f specific bacterial ligands that mediate the inflammatry respnse; the character f the intestinal bacterial milieu is thught t play a rle in the up- r dwn-regulatin f intestinal inflammatin via tll receptr signaling. Many preterm infants receive frequent expsure t brad-spectrum antibacterial agents, further altering the intra-intestinal bacterial envirnment. Experimental and meta-analytical evidence suggests that exgenus administratin f the prbitics bifidbacteria and lactbacilli r prebitics (nndigestible substances that selectively prmte the grwth f beneficial prbiticlike bacteria nrmally present in the gut) may mderate the risk and severity f NEC in preterm infants.2 Intestinal ischemia Epidemilgically, sme have nted that infants expsed t intrauterine envirnments marked by cmprmised placental bld flw (ie, maternal hypertensin, preeclampsia, ccaine expsure) have an increased incidence f NEC. Similarly, infants with pstnatally diminished systemic bld flw, such as is fund in patients with patent ductus arterisus r cngenital heart disease, als have an increased incidence. Animal mdels f induced intestinal ischemia have identified its significant rle in the develpment f NEC. Pathlgically, ischemia induces a lcal inflammatry respnse that results in activatin f a prinflammatry cascade with mediatrs such as PAF, TNF-a, cmplement, prstaglandins, and leuktrienes such as C4 and IL-18. Alteratins in hepatbiliary cell junctin integrity results in leakage f these prinflammatry substances and bile acids int the intestinal lumen, increasing intestinal injury. Cellular prtective mechanisms such as epidermal grwth factr (EGF), transfrming grwth factr β1 (TGF-β1), and erythrpietin are dwn-regulated, further cmprmising the infant's ability t munt a prtective respnse. Subsequent nrepinephrine release and vascnstrictin results in splanchnic ischemia, fllwed by reperfusin injury. Intestinal necrsis results in breach f the mucsal barrier, allwing fr bacterial translcatin and migratin f bacterial endtxin int the damaged tissue. The endtxin then interacts synergistically with PAF and a multitude f ther prinflammatry mlecules t amplify the inflammatry respnse. Activated leukcytes and intestinal epithelial xanthine xidase may then prduce reactive xygen species, leading t further tissue injury and cell death. Experimental administratin f PAF inhibitrs in animal mdels has nt been shwn t mitigate intestinal mucsal injury. Many ther mdulatrs f the inflammatry respnse are being studied bth in viv in animal mdels and in vitr in an attempt t mitigate r prevent the mrbidity and mrtality caused by fulminant NEC. Intestinal mucsal immaturity In the preterm infant, mucsal cellular immaturity and the absence f mature antixidative mechanisms may render the mucsal barrier mre susceptible t injury. Intestinal regulatry T-cell aggregates are a first-line defense t luminal pathgens and may be induced by cllectins f small lymphid aggregates, which are absent r deficient in the premature infant. Experimental and epidemilgic studies have nted that feeding with human milk has a prtective effect; hwever, dnr human milk that has been pasteurized is nt as prtective. Human milk cntains secretry immunglbulin A (IgA), which binds t the intestinal luminal cells and prhibits bacterial transmural translcatin. ther cnstituents f human milk, such as interleukin (IL)-10, EGF, TGF-β1, and erythrpietin may als play a majr rle in mediating the inflammatry respnse. ligfructse encurages replicatin f bifidbacteria and inhibits clnizatin with lactse-fermenting rganisms. Human milk has been fund t cntain PAF acetylhydrlase, which metablizes PAF; preterm human milk has higher PAF acetylhydrlase activity (up t 5 times greater in ne study3) than milk cllected frm wmen wh delivered at term. Frequency
The diagnosis is usually suspected clinically but often requires the aid of diagnostic imaging modalities. Plain radiographs of the abdomen are useful by showing evidence of extraluminal gas i.e. Pneumatosis Intestinalis is pathognomonic (pneumatosis, portal venous gas or pneumoperitoneum) or an abnormal bowel gas pattern, particularly a persistently unaltered gas-filled dilated loop of bowel on serial radiographs (fixed loop). More recently ultrasonography has proven to be useful as it may detect signs and complications of NEC before they are evident on radiographs.
Typical recovery from NEC if medical, non-surgical 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. Longterm complications of medical NEC include bowel obstruction and anemia. Despite a significant mortality risk, long-term prognosis for infants undergoing NEC surgery is improving, with survival rates of 70-80%. "Surgical NEC" survivors are at-risk for complications including short bowel syndrome, and neurodevelopmental disability.
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, parenteral nutrition, and prompt antibiotic therapy. Monitoring is clinical, although serial supine and left lateral decubitus abdominal roentgenograms should be performed every 6 hours. Radiographic signs of worsening NEC include dilated bowel loops, pneumatosis intestinalis, portal venous gas, and pneumoperitoneum. Where the disease is not halted through medical treatment alone, or when the bowel perforates, immediate emergency surgery to resect the dead bowel is required. This may require a colostomy, which may be able to be reversed at a later time. Some children may suffer later as a result of short bowel syndrome if extensive portions of the bowel had to be removed.