• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Necrotizing Enterocolitis
 

Necrotizing Enterocolitis

on

  • 9,342 views

 

Statistics

Views

Total Views
9,342
Views on SlideShare
9,325
Embed Views
17

Actions

Likes
3
Downloads
362
Comments
1

1 Embed 17

http://www.slideshare.net 17

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel

11 of 1 previous next

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
  • I found this very exciting and will be very beneficial in the manage and prevention of NEC in NICU
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Necrotizing Enterocolitis Necrotizing Enterocolitis Presentation Transcript

    • NECROTIZING ENTEROCOLITIS By AYMAN ABOU MEHREM, MD, CABP Assistant Consultant Department of pediatrics King Abdulaziz Hospital, Al-Ahsa November 25, 2007
    • Necrotizing Enterocolitis Definitions Epidemiology Risk Factors Pathogenesis Pathophysiology Clinical Presentation Diagnosis Management Prognosis Prevention
    • Definitions Necrotizing Enterocolitis: an acquired neonatal acute intestinal necrosis of unknown etiology NEC is neither a uniform nor a well-defined disease entity.1 1 Gordon PV et al, Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's criteria?, J Perinatol. 2007 Nov;27(11):661-71.
    • Definitions Isolated spontaneous intestinal perforation (SIP): ill-defined clinical syndrome of undetermined cause resembling NEC with less systemic involvement and a less severe clinical course. It may present a variant of classical NEC. The National Institute of Child Health and Human Development Neonatal Network (NICHD): intestinal perforation without evidence of pneumatosis since 2002.1 1 Gordon PV et al, Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's criteria?, J Perinatol. 2007 Nov;27(11):661-71.
    • Definitions Acquired neonatal intestinal diseases (ANIDs)1 Wider umbrella includes different pathologies affecting gastrointestinal tract in preterm and term infants. Some which do lead to the common final pathology of NEC and some which do not. Includes: NEC SIP Viral enteritis of infancy Cow’s milk protein allergy 1 Gordon PV et al, Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's criteria?, J Perinatol. 2007 Nov;27(11):661-71.
    • Epidemiology Incidence: 0.3-2.4 / 1000 live births 2-5 % of all NICU admissions 5-10 % of VLBW infants Over 90 % of cases occur in preterm babies About 10 % occur in term newborns: essentially limited to those that have some underlying illness or condition requiring NICU admission.2 2 Lambert DK et al. Necrotizing enterocolitis in term neonates: data from a multihospital health-care system . J Perinatol. 2007 Jul;27(7):437-43 .
    • Epidemiology Sporadic or epidemic clusters Sex, race, geography, climate, season: No role Holman et al.3: o Male VLBW infants are at greater risk of death. o Black infants: increased risk of NEC, and its associated mortality 3 HolmanRC et al. The epidemiology of necrotizing enterocolitis infant mortality in the United States. Am J Public Health 1997; 87: 2026–31.
    • Risk Factors: Prematurity Prematurity is the single greatest risk factor The risk is inversely related to birth weight and gestational age.4 4 LinPW, Stoll BJ. Necrotizing enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83. 5 Czyrko C et al. Maternal cocaine abuse and necrotizing enterocolitis: outcome and survival. J Pediatr Surg. 1991 Apr;26(4):414-8; discussion 419-21.
    • Risk Factors: Genetics Familial: Fried and Vure (1974) reported a consanguineous Jewish Ashkenazi family in which three of four children died within a few weeks after birth from severe enterocolitis.5 Mégarbané and Sayad (2007) reported a Lebanese consanguineous family where three term sibs presented with severe early and lethal enterocolitis, all with delayed meconium passage.6 5 FriedK, Vure E. A lethal autosomal recessive entero-colitis of early infancy. Clin Genet 1974 (6), 195-196. 6 Mégarbané A, Sayad R. Early lethal autosomal recessive enterocolitis: report of a second family. Clin Genet. 2007 Jan;71(1):89-90.
    • Risk Factors: Genetics Twins: Bhandari et al, in a multicenter retrospective study of 450 twin pairs born at < or =32 weeks of gestation, showed that intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are familial in origin.7 7 Bhandari et al. Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics. 2006 Jun;117(6):1901-6.
    • Risk Factors: Gene Polymorphism Vascular endothelial growth factor: Bányász et al suggest that VEGF G+405C polymorphism might be associated with a higher risk of preterm birth and that VEGF C- 2578A polymorphism may participate in the development of perinatal complications such as NEC and ARF.8 Carbamoyl phosphate synthetase: Moonen et al suggested that the CPS1 T1405N polymorphism may be associated with the risk of NEC in preterm infants.9 8 Bányász et al. Genetic polymorphisms for vascular endothelial growth factor in perinatal complications. Eur Cytokine Netw. 2006 Dec;17(4):266-70. 9 Moonen RM et al. Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis. Pediatr Res. 2007 Aug;62(2):188-90.
    • Risk Factors: G-6-PD Deficiency Schutzman and Porat, in a retrospective study10, found: G6PD deficiency was significantly higher (27.8%) in infants with NEC compared with the 5.3% prevalence among NICU admissions (odds ratio = 6.9; 95% confidence interval = 2 to 23.5). G6PD deficiency also was found to be a marker for more severe NEC. G6PD deficiency should be considered a risk factor for NEC. 10 Schutzman DL, Porat R. Glucose-6-phosphate dehydrogenase deficiency: another risk factor for necrotizing enterocolitis?. J Pediatr. 2007 Oct;151(4):435-7.
    • Risk Factors: Cocaine Maternal cocaine abuse increases the risk by 2.5 folds (95% CI = 1.17 to 5.32, P = 0.02) 11 11 CzyrkoC et al. Maternal cocaine abuse and necrotizing enterocolitis: outcome and survival. J Pediatr Surg. 1991 Apr;26(4):414-8; discussion 419-21.
    • Risk Factors: Indomethacin Indomethacin for Tocolysis: Metaanalysis 2007 Recent exposure (within 48 hours of delivery) to antenatal indomethacin was associated with necrotizing enterocolitis (OR, 2.2; 95% CI; 1.1-4.2). 12 Some limitations. 12 AminSB et al. Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes. Am J Obstet Gynecol. 2007 Nov;197(5):486.e1-10.
    • Risk Factors: Indomethacin Indomethacin in Early Life: Associated with SIP 13 Prolonged versus Short Course of Indomethacin for the treatment of PDA in preterm infants: Systematic Review 14 o The reduction of transient renal impairment does not outweigh the increased risk of NEC associated with the prolonged course. o Based on these results, a prolonged course of indomethacin cannot be recommended for the routine treatment of PDA in preterm infants. 13 Schmidt B et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344: 1966–1972. 14 Herrera C et al. Prolonged versus short course of indomethacin for the treatment of patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD003480.
    • Risk Factors: Dexamethasone Paquette et al showed that the combined use of indomethacin and dexamethasone increases the risk of SIP in VLBW neonates. 15 15 Paquette et al. Concurrent use of indomethacin and dexamethasone increases the risk of spontaneous intestinal perforation in very low birth weight neonates. J Perinatol. 2006 Aug;26(8):486-92.
    • Risk Factors: H2-Blockers Guillet et al, in large case control study using NICHD Neonatal Research Network, showed that “Antecedent H2-blocker use was associated with an increased incidence of NEC. (OR 1.71, 95% CI 1.34-2.19, P < .0001) 16 16 Guillet R et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006 Feb;117(2):e137-42.
    • Risk Factors: Co-amoxiclav Kenyon et al. in a Systematic Review: Co-amoxiclav should be avoided in women at risk of preterm delivery because of the increased risk of neonatal necrotising enterocolitis. 17 (RR 4.60, 95% CI 1.98 to 10.72) 17 KenyonS et al. Antibiotics for preterm rupture of membranes . Cochrane Database Syst Rev. 2003;(2):CD001058 .
    • Risk Factors: Acyclovir Montjaux-Régis et al, case report: 18 Term baby, developed NEC after receiving prophylactic acyclovir. Mother had herpes genitalis and pROM at 32 wks of GA, treated with acyclovir until vaginal delivery. Acyclovir treatment in utero and after birth is discussed as a possible cause of necrotizing enterocolitis in the infant. 18 Montjaux-RégisN et al. Necrotizing enterocolitis in a full-term infant. Is acyclovir involved?. Arch Pediatr. 2007 Oct 10.
    • Risk Factors: Kayexalate Rugolotto et al., case report: 19 Necrotizing enterocolitis in a 850 gram infant receiving sorbitol-free sodium polystyrene sulfonate Their case report shows that Kayexalate per se, and not necessarily suspended in sorbitol, can lead to gastrointestinal tract complications and NEC in preterm infants. 19 RugolottoS et al. Necrotizing enterocolitis in a 850 gram infant receiving sorbitol-free sodium polystyrene sulfonate (Kayexalate): clinical and histopathologic findings. J Perinatol. 2007 Apr;27(4):247-9.
    • Risk Factors: UAC Rand et al. suggested that UAC cause a decrease in mesenteric blood flow. Therefore, their use in hemodynamically unstable neonates or in those with gastrointestinal disease should be very carefully considered. 20 High vs. low UAC: necrotising enterocolitis are not more frequent with high compared to low catheters. 21 Havranek et al.: Preprandial SMA BFV and postprandial SMA BFV responses to minimal enteral feedings were not affected by the presence of a UAC. 22 20 Rand T et al. Effects of umbilical arterial catheterization on mesenteric hemodynamics. Pediatr Radiol. 1996 Jul;26(7):435-8. 21 Barrington KJ. Umbilical artery catheters in the newborn: effects of position of the catheter tip. Cochrane Database Syst Rev. 2000;(2):CD000505. 22 Havranek T et al. Umbilical artery catheters do not affect intestinal blood flow responses to minimal enteral feedings. J Perinatol. 2007 Jun;27(6):375-9.
    • Risk Factors: UVC Butler-O'Hara et al. compared long-term (up to 28 days) and short-term (7-10 days) use of umbilical venous catheters in premature infants with birth weights of less than 1251 grams. 23 There were no differences in time to full feedings or to regain birth weight or in the incidence of necrotizing enterocolitis or death. 23 Butler-O'HaraM et al. A randomized trial comparing long-term and short-term use of umbilical venous catheters in premature infants with birth weights of less than 1251 grams. Pediatrics. 2006 Jul;118(1):e25-35.
    • Risk Factors: PDA Patole et al., in prospective observational study, reported that: 24 No association between significant PDA and NEC. The age at starting feed and full enteral feed was significantly delayed in infants with significant PDA. 24 Patole SK et al. Does patent ductus arteriosus affect feed tolerance in preterm neonates?. Arch Dis Child Fetal Neonatal Ed. 2007 Jan;92(1):F53-5.
    • Risk Factors: in Term Babies Limited to those that have some underlying illness or condition requiring NICU admission.2 Congenital Heart Disease Intrauterine growth restriction Polycythemia Hypoxic-ischemic events 2 Lambert DK et al. Necrotizing enterocolitis in term neonates: data from a multihospital health-care system. J Perinatol. 2007 Jul;27(7):437-43.
    • Risk Factors: Exchange Transfusion Dempsey and Barrington in a Systematic Review 25 showed: There is no evidence of long term benefit from partial exchange in polycythaemic infants. The incidence of gastrointestinal injury is increased. NEC (RR 8.68; 95% CI 1.06 to 71.1) 25 Dempsey EM, Barrington K. Short and long term outcomes following partial exchange transfusion in the polycythaemic newborn: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2006 Jan;91(1):F2-6.
    • Pathogenesis
    • Pathophysiology Hypoxic-Ischemic insult Enteral Feeding Microbiologic Flora Cytokines and Inflammatory Mediators
    • Hypoxic-ischemic insult Hypoxia-Reoxygenation. Ischemia-Reperfusion. Intramural microcirculation. Balance between Endothelin-1 and Nitric Oxide.26 26 NowickiPT. Ischemia and necrotizing enterocolitis, Where, when, and how. Seminars in Pediatric Surgery (2005) 14, 152-158.
    • Enteral Feeding Formula vs. Donor Breast Milk: 27, 28 Formula is associated with higher risk of NEC 27 Quigley M et al. Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971. 28 Boyd CA et al. Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F169-75.
    • Enteral Feeding Disadvantages of Formula: Higher osmolality ± Lack of immunoprotective factors Lack of growth factors Altering intestinal flora
    • Microbiologic Flora and Infection Several organisms have been accused, but non has been proven to be causative: Enterobacteriaceae Enterobacter sakazakii Coagulase-negative staphylococci: SIP Closrtidium perfringens Candida species: SIP Cytomegalovirus Torovirus HIV Mucormycosis
    • Cytokines and Inflammatory Mediators Platelet Activating Factor (PAF) Tumor Necrosis Factor (TNF) High-mobility group box 1 protein (HMGB 1) Interferon-gamma (INF-gamma) Interleukins (ILs) Matrix metalloproteinases (MMPs)
    • Inflammatory cascade. The inflammatory cascade results in the secretion of multiple proinflammatory and counterregulatory cytokines that eventually lead to the generation of toxic metabolites and destruction of the intestinal mucosa. 29 Markel TA et al. Cytokines in necrotizing enterocolitis. Shock. 2006 Apr;25(4):329-37.
    • Pathophysiology, in summary Ischemic or toxic mucosal Enteral feeding damage Loss of mucosal integrity Bacterial proliferation Invasion of mucosa and submucosa Intramural gas Transmural necrosis Perforation Peritonitis
    • Pathology Closeup of intestine of infant showing necrosis and pneumatosis intestinalis. Autopsy
    • Pathology Postmortem photograph of bowel involved with severe NEC. The arrows indicate areas of the bowel wall where there has been so much necrosis and sloughing of the mucosa, submucosa, and muscularis that only the serosa is intact. 30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285–305.
    • Pathology NEC induced by an intravenous injection of PAF in a rat model
    • Pathology Microscopic images of (A) normal bowel and (B) characteristic findings of NEC, which illustrates hemorrhagic necrosis, beginning in the mucosa and extending to the muscular bowel wall, where the potential for perforation exists. NEC frequently involves the terminal ileum. Reprinted with permission from WebPath, courtesy of Edward C. Klatt, MD, Florida State University College of Medicine, Tallahassee, FL (http://medlib.med.utah.edu/WebPath).
    • Pathology Parietal ileal pneumatosis in neonatal necrotizing enterocolitis
    • Clinical Presentation Onset varies with gestational age VLBW 14 – 20 days Term first week Course of the disease Fulminant presentation Slow, paroxysmal presentation
    • Clinical Presentation Systemic signs: Respiratory distress, apnea, bradycardia Lethargy, irritability Temp. instability Poor feeding Hypotension Acidosis Oligurea Bleeding diathesis
    • Clinical Presentation Abdominal (enteric) signs: Distension Tenderness Gastric aspirate, vomiting Ileus Abdominal wall erythema, induration Ascites Abdominal mass Bloody stool
    • Clinical Presentation
    • Diagnosis A high index of suspicion is required Sometimes cannot be differentiated from sepsis
    • Diagnosis, Laboratory studies No lab test is specific for NEC The most common triad (!): Thrombocytopenia Persistent metabolic acidosis Severe refractory hyponatremia ↑ WBC, ↓ WBC, ↓ PMN Hyperkalemia Stool: reducing substances, occult blood
    • Diagnosis, Radiologic studies Abdominal X-ray: Abnormal gas pattern, ileus Bowel wall edema Pneumatosis intestinalis Fixed position loop Intrahepatic portal venous gas ( in the absence of UVC) Pneumoperitonium, left lateral decubitus or cross- table lateral views
    • Diagnosis, Radiologic studies Supine radiograph of the abdomen of a normal neonate shows a normal bowel gas pattern. Gas is distributed throughout the small and large bowel, and it is difficult to differentiate the small bowel from the large bowel. Each loop causes impressions on adjacent loops, giving each loop a multifaceted appearance; the overall pattern resembles that of a mosaic. The loops are generally not rounded or elongated. 30Epelman M et al. Necrotizing enterocolitis, review of state-of-the- art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285–305.
    • Diagnosis, Radiologic studies Pneumatosis intestinalis. Very obvious case. Tremendous amount of air in bowel walls Reference: Radiology Cases In Neonatology Copyright 1996, Loren Yamamoto
    • Diagnosis, Radiologic studies Pneumatosis intestinalis. Note the air visible in the bowel wall. The air dissects the bowel wall giving it a double lined appearance (ie., railroad tracks without the ties) Reference: Radiology Cases In Neonatology Copyright 1996, Loren Yamamoto
    • Diagnosis, Radiologic studies Pneumatosis intestinalis
    • Diagnosis, Radiologic studies Supine AXR, The bowel is mildly dilated with gas, mainly on the left side. The bubbly pattern of gas seen mainly in the right lower quadrant represents intramural gas. 30Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285–305.
    • Diagnosis, Radiologic studies Free intraperitoneal gas is present anteriorly (arrows) 30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285–305.
    • Diagnosis, Radiologic studies NEC with perforation
    • Diagnosis, Radiologic studies Left lateral decubitus radiograph shows free air Ref: Necrotizing Enterocolitis, emidicine.com, Beverly P Wood, MD, MS, PhD
    • Diagnosis, Radiologic studies Abdominal ultrasound: Thick-walled loops of bowel with hypomotility. Intraperitoneal fluid is often present. Intramural gas can be identified in early-stage NEC 31 In the presence of pneumatosis intestinalis, gas is identified in the portal venous circulation within the liver. Color Doppler US is more accurate than abdominal radiography in depicting bowel necrosis in NEC. 32 31 Kim WY et al. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis. Pediatr Radiol. 2005 Nov;35(11):1056-61. 32 Faingold R et al. Necrotizing Enterocolitis: Assessment of Bowel Viability with Color Doppler US, Radiology 2005;235:587-594.
    • Diagnosis, Radiologic studies Sonogram of a bowel loop shows differentiation of intraluminal gas from intramural gas. The intraluminal gas (L) is surrounded by a thickened bowel wall. Within the bowel wall are multiple hyperechoic foci (arrows), which represent intramural gas. 30Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285–305.
    • Diagnosis, Radiologic studies Sonogram shows a bowel loop with a large amount of intramural gas (arrows) in the more dependent and vertically oriented parts of the loop. This gives the bowel wall a typical granular appearance and causes a posterior artifact. 30Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285–305.
    • Diagnosis, Radiologic studies Abdominal Doppler ultrasound: Murdoch et al., in a prospective cohort study, concluded that neonates with high resistance patterns of blood flow velocity in the superior mesenteric artery on the first day of life are at increased risk of developing necrotizing enterocolitis. 33 33 Murdoch EM et al. Doppler flow velocimetry in the superior mesenteric artery on the first day of life in preterm infants and the risk of neonatal necrotizing enterocolitis. Pediatrics. 2006 Nov;118(5):1999-2003.
    • Modified Bell’s Staging Criteria Stage I : Suspected NEC Clinical signs and symptoms No diagnostic radiograph
    • Modified Bell’s Staging Criteria Stage II : Definite (confirmed) NEC A: Mild NEC • Sign & symptoms, absent B/S, gross blood in stool • AXR: ileus, focal areas of pneumatosis intestinalis B: Moderate NEC • Systemically ill • AXR: extensive pneumatosis intestinalis, early ascites, possible intrahepatic portal venous gas
    • Modified Bell’s Staging Criteria Stage III: Advanced NEC A: Severe NEC without perforation • Critically ill • Abdominal wall induration, extensive erythema • AXR: prominent ascites, paucity of bowel gas, persistent fixed loop B: Severe NEC with perforation
    • Differential Diagnosis Systemic infection: sepsis, pneumonia Surgical abdominal catastrophes Infectious enterocolitis Allergic collitis Feeding intolerance
    • Management The main principle of management of confirmed NEC is to treat it as an acute abdomen with impending or septic peritonitis Isolation: cohort isolation in case of epidemic clusters
    • Management, Medical Basic NEC protocol: for all stages NPO NGT with low pressure suction Close monitoring of vital signs & abdominal girth Remove UAC and UVC Septic workup: blood, urine, and stool cultures LP and CSF culture: controversial Antibiotics: ampicillin + gentemicin or cefotaxime add metronidazole or clindamycin if peritonitis or perforation is suspected
    • Management, Medical Basic NEC protocol …..continued Monitor for GI bleeding Fluid balance: maintain urine output 1-3 ml/kg/hr Lab.: CBC, PLT, electrolytes q 8-12 hrs PT, PTT, LFT’s as indicated CRP 34 Radiology: serial AXR q 6-8 hrs in the first 2-3 days Family support 34 Pourcyrous M et al. C-reactive protein in the diagnosis, management, and prognosis of neonatal necrotizing enterocolitis. Pediatrics. 2005 Nov;116(5):1064-9.
    • Management, Medical Stage I Basic NEC protocol If all cultures are negative, the infant improved clinically, and AXR is normal, antibiotics can be stopped after 2-3 days and feeding can be resumed.
    • Management, Medical Stage II Basic NEC protocol NPO for 14 days TPN, 90-110 kcal/kg/day Antibiotics for 14 days Respiratory support ± Inotropic support Surgical consultation
    • Management, Medical Stage III As stage II Inotropic support Treat anemia, thrombocytopenia, coagulopathy Surgical intervention
    • Management, Surgical Early Surgical Consultation Indications for surgery: Perforation: 20-30 % of cases 12-48 hrs after onset Full-thickness necrosis Deterioration despite aggressive medical treatment
    • Management, Surgical Surgical Approach: Exploratory laparotomy Peritoneal drainage
    • Management, Surgical Exploratory laparotomy: The most commonly used approach. Intestinal resection with enterostomy. Primary anastomosis. 35, 36 35 Hall NJ et al. Resection and primary anastomosis is a valid surgical option for infants with necrotizing enterocolitis who weigh less than 1000 g. Arch Surg. 2005 Dec;140(12):1149-51. 36 Singh m et al. Surgery for intestinal perforation in preterm neonates: anastomosis vs stoma. J Pediatr Surg. 2006 Apr;41(4):725-9.
    • Management, Surgical Peritoneal drainage: More conservative approach, Started in 1977 Insertion of a peritoneal draine local anaesthesia Initially, used for very sick premature babies, with weight ≤ 1000 g Now, it is used more commonly with larger and more stable babies It is used as a definite treatment in some centers
    • Management, Surgical Algorithm for the treatment of necrotizing enterocolitis 37 Xavier Demestre et al Peritoneal drainage as primary management in necrotizing enterocolitis: A prospective study, J Pediatr Surg. 2002 Nov • Volume 37 • Number 11 • p1534 to p1539.
    • Management, Surgical Laparoscopy: Clarck and Mackinaly reported the use of laparoscopy on day 30 of life in the treatment of a VLBW infant (900 g) with perforated NEC.38 Tan et al.: 4 babies (500-1000 g) Needlescopic diagnosis is feasible and appears to be safe, even in critically ill micropremmies less than 1000 g. The technique can provide useful information for surgical decision-making and allows for precise placement of a microlaparotomy incision over the site of perforation, thus minimizing the trauma from open surgery in this special group of patients. 39 38 Clark C, Mackinlay GA. Laparoscopy as an adjunct to peritoneal drainage in perforated necrotizing enterocolitis. J Laparoendosc Adv Surg Tech A. 2006 Aug;16(4):411-3. 39 Tan HL et al. The role of diagnostic laparoscopy in micropremmies with suspected necrotizing enterocolitis. Surg Endosc. 2007 Mar;21(3):485-7.
    • Prognosis and Outcome NEC with perforation: mortality 20-40 % Recurrent NEC : rare complication, 4% Subacute or intermittent symptoms of bowel obstruction: strictures, 10-35 % Short-gut syndrome: FTT, high mortality. The type of operation (peritoneal drain vs. laparotomy) performed for perforated NEC does not influence survival or other clinically important early outcomes in preterm infants. 40 40 Moss RL et al. Laparotomy versus Peritoneal Drainage for Necrotizing Enterocolitis and Perforation. N Engl J Med. 2006 May 25;354(21):2225-34.
    • Neurodevelopmental Outcome Soraisham et al.: Preterm infants who develop NEC are at a significantly higher risk for developing neurodevelopmental disability. 41 41 SoraishamAS et al. Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight < or =1250 g?. J Paediatr Child Health. 2006 Sep;42(9):499-504.
    • Neurodevelopmental Outcome Rees et al. Systematic Review (UK): NEC is associated with significantly worse neurodevelopmental outcome than prematurity alone. Presence of advanced NEC and need for surgery increase the risk of neurological impairment. 42 Schulzke et al. Systematic Review (Australia): Survivors of stage II or higher NEC are at risk for long- term neurodevelopmental impairment, especially if they require surgery for the illness. 43 42 Rees CM et al. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8. 43 Schulzke SM et al. Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing enterocolitis: a systematic review of observational studies. Arch Pediatr Adolesc Med. 2007 Jun;161(6):583-90.
    • Neurodevelopmental Outcome Adesanya et al. Retrospective Study: Intestinal perforation caused by NEC, as compared to SIP, is associated with worse neurodevelopmental outcome at 1 year. 44 Blakely et al. Retrospective Study: the risk-adjusted odds ratio favoring laparotomy for death or impairment, indicate the need for a large, multicenter clinical trial to assess the effect of the initial surgical therapy on outcome at > or =18 months. 45 44 Adesanya OA et al. Intestinal perforation in very low birth weight infants: growth and neurodevelopment at 1 year of age. J Perinatol. 2005 Sep;25(9):583-9. 45 Blakely ML et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age. 2006 Apr;117(4):e680-7.
    • Prevention Breast milk Antenatal Steroid therapy Oral immunoglobulins Oral antibiotics Probiotics (Lactobacillus, Bifidobacterium) Feeding strategies Oral PAF antagonists Glutamine Arginine Polyunsaturated fatty acids (PUFA) Lactoferin Pentoxifylline
    • Prevention: Breast Milk Formula vs. Donor Breast Milk: 27, 28 Breast milk is associated with lower risk of NEC slower growth in the early postnatal period 27 Quigley M et al. Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971. 28 Boyd CA et al. Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F169-75.
    • Prevention: Antenatal Steroids Antenatal corticosteroids for women at risk of preterm birth: Systematic Review 46 Decreased risk of NEC RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants 46 Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004454.
    • Prevention: Oral Immunoglobulin The evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomised controlled trials of oral IgA alone for the prevention of NEC. 47 47 Foster J et al, Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth- weight neonates. Cochrane Database Syst Rev. 2004;(1):CD001816.
    • Prevention: Probiotics Probiotics might reduce the risk of necrotising enterocolitis in preterm neonates with less than 33 weeks' gestation (relative risk 0.36, 95% CI 0.20-0.65) the short-term and long-term safety of probiotics needs to be assessed in large trials Unanswered questions include the dose, duration, and type of probiotic agents (species, strain, single or combined, live or killed) used for supplementation. 48 48 Deshpande G et al. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet. 2007 May 12;369(9573):1614-20 .
    • Prevention: Feeding Strategies Pietz et al. reported 20-year experience, in Fairview Hospital, Cleveland, Ohio, with 1239 very low birth weight infants suggests strongly that the late-onset, slow, continuous drip feeding protocol and avoidance of indomethacin and early dexamethasone treatment contribute to the prevention of necrotizing enterocolitis. 49 49 Pietz J et al. Prevention of necrotizing enterocolitis in preterm infants: a 20-year experience. Pediatrics. 2007 Jan;119(1):e164-70 .
    • Prevention: Glutamine The available data from good quality randomised controlled trials suggest that glutamine supplementation does not confer clinically significant benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority. 50 50 Tubman TR et al, Dalziel S. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001457.
    • Prevention: Arginine The data are insufficient at present to support a practice recommendation. A multicentre randomized controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly the more severe stages (2 or 3). 51 51 ShahP, Shah V., Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004339 .
    • References Manual of Neonatal Care, Cloherty, 5th ed, 2004, Lippincott Williams & Wilkins Neonatology, Tricia Gomella, 5th ed, 2004, McGraw Hill A Manual of Neonatal Intensive Care, Rennie & Roberton, 4th ed, 2002, Arnold