NEC in newborn

Case Presentation

• B/o Sabiya Banu,32 wks,1.7kg,admitted on 2HOL with provisional diagnosis of MPT/LBW/Moderate RDS.

• H/o PPROM>72 hours,no antenatal steroids.

• CPAP started at 2 HOL,recieved late rescue surfactant at 4HOL ,INSURE .

• Removed from CPAP at 48 HOL.

• Initial septic screen was negative.

• Baby on 2nd line Ab as per protocol.

• Baby started with feeds 3ml/3hrly RTF of EBM on D3 of life.• Feeds gradually increased twice daily

increment(30ml/kg/day)• On D7 of life baby on 23ml RTF,developed abdominal

distension,residual feeds.AG-27cm.• Abdomen –Soft,mild distension,non tender,Bowel sounds –

heard.No abdomen wall edema/erythema.• Investigations-TLC-10,590/cumm,

Plt-12,000/cumm.CRP-62.5mg/dl. Serum Na-124mEq/dl.• Stool occult blood-positive• Diagnosis of NEC stage 1A was made .• Baby kept NPO and Ab’s changed to Meropenem &

ofloxacin• In view of broad spectrum Ab’s and other risk factors

Flucanozole was added.

• Surgical consultation –advised for medical line of management.

• After 48hrs of bowel rest,Repeat invetsigations requested showed-TLC-7870/cumm,PLT-40000/cumm and CRP of 94.1mg/L.

• In view of persistent distension and RTA baby was kept NPO for 5days.

• Baby was restarted on feeds after 5 days of bowel rest.(D=9)

• Baby started with 3ml RTF/3hrly and gradually increased with once daily increment.

• After 3 days of feed on 10ml/EBM 3 hrly,baby had repeat bout of feed intolerance.(D=12 )

• Repeat counts D12-Hb-11.3Gm%,TLC-10,720 and platelet -35,000/cumm. CRP-53.2mg/L.

• USG abdomen D15-Minimal turbid ascites,small bowel edema,no pneumobilia.

• Diagnosis was revised to NEC stage 2B.

• Baby kept NBM and continued with same antibiotics.

• On D19 baby noticed to have significant tachycardia 190bpm,bounding periphreal pulses and PSM.Screening echo showed PDA 4mm with L to R shunt.(RFT-WNL,Plt-75,000/cumm)

• Received Oral Ibubrofen for 3days.

• Baby restarted on feeds after 7 days of bowel rest D21 of life RTF EBM 3ml/3hrly.

MODERATE PT(32WK)/LBW/MODERATE RDS/STAGE 2B NEC/HS PDA 4MM L TO R SHUNT.

NEC

• Most common GI emergencies in the newborn infant.

• Defined as:

Transmural coagulative necrosis of the intestinal mucosa,with invasion of enteric gas forming organisms, and dissection of gas into the muscularis and portal venous system .

Epidemology:

• 1 -3 /1000 live births and 1 -7.7 % of admissions to NICUs .

• Rates were inversely related to BW 401 to 750 g – 11.5%751 to 1000 g – 9 %1001 to 1250 g – 6 %1251 to 1500 g – 4 %• Mortality rates range from 15- 30% and are inversely

related to GA and BW.• Approximately 13 % of cases occur in term,have a pre

existing illness- IUGR,congenital heart disease , respiratory distress , sepsis , birth asphyxia , and polycythemia .

Pathology:

• The terminal ileum and colon are MC involved, entire GI tract is affected in severe cases.

• On gross examination- the bowel distended and hemorrhagic. Subserosal collections of gas,gangrenous necrosis and perforation may be present.

• Histologic findings in NEC -mucosal edema, hemorrhage, and transmural coagulativenecrosis.-secondary bacterial infiltration, and collections of gas.

Gross Microscopy

Pathogenesis:Factors implicated in NEC

• Prematurity

• Enteral nutrition

• Circulatory instability of the intestinal tract.

• Microbial bowel overgrowth

• Medications that cause intestinal mucosal injury or enhance microbial overgrowth-Antibiotics,H2 blockers.

• Maternal choriamniotis.

• IUGR with doppler changes.

• Maternal smoking,coccaine use.

• Polycythemia

• Anemia ,PRBC transfusion.

• Umbilical cathetristaion

• Oral indomethacin

Pathogeneis:

Prematurity:

• Immature mucosal barrier with increased permeability

• Immature local host defenses.

• Immature bowel motility and function.

Enteral nutrition

• More than 90 percent of infants who develop NEC have received milk feeding

• Incompletely digested carbohydrates and lipids in the intestine of preterm infants cause mucosal injury .

• Human milk, protective :PAF acetylhydrolase, S IgA, IL-10, IL-11, EGF , nucleotides, glutamine, and antioxidants such as vit E, carotene, and glutathione.

Anemia & RBC transfusion:

• Multicenter observational’ cohort study reported that severe anemia and not RBC transfusion was associated with NEC.

• Clinically-significant anemia is associated with an increased risk for NEC, and that RBC transfusion is only a surrogate marker for anemia

‘Patel RM, Knezevic A, Shenvi N, et al. Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants. JAMA 2016; 315:889

Medications

• Hyperosmolar medications and formulas can cause mucosal injury and may result in NEC-oral theophylline, multivitamins, or phenobarbitone.

• Cimetidine, ranitidine, and famotidine, are associated with higher rates of NEC.

• Antibiotic administration greater than five days duration is associated with an increased risk of NEC or death

Clinical Presentation:

• Majority of premature infants who develop NEC are healthy, feeding well, and growing babies.

• Onset of symptoms varies and is inversely related to gestational age

GA< 26 weeks-23 days,

GA >31 weeks- 11 days.

• Indian data peak age –end of 1stwk to 2nd

week

Systemic Signs

• Apnea,Bradycardia

• Respiratory distress

• Lethargy

• Poor feeding

• Temperature instability.

• Hypotension

• Bleeding diathesis with consumption coagulopathy.

Abdominal Signs

• Gastric retention

• Abdominal Distension

• Abdominal redness & tenderness

• Vomiting.

• Diarrhea.

• Rectal bleeding (hematochezia)

• Bilious drainage from enteral feeding tubes

Modified Bells staging for NEC:

• Bell staging criteria (Walsh & Kleigman) provide a uniform definition of NEC based upon the severity of systemic, intestinal, and radiographic findings.

1. Stage I/suspected NEC

2. Stage II/proven NEC

3. Stage III/advanced NEC

Bells Staging Criteria

Investigations:

Abdomen X ray• Abnormal gas pattern with dilated loops of bowel -ileus, early stages

of NEC.• Bowel wall edema• Pneumatosis intestinalis, the hallmark of NEC, appears as bubbles of

gas in the small bowel wall, stages II and III NEC .• Gasless abdomen indicating ascites.• Pneumoperitoneum bowel perforation occurs , IIIB NEC.

-"football" sign on a supine radiograph,large hypolucent area in the central abdomen with markings from the falciform ligament.

• Sentinel loops, a loop of bowel that remains in fixed position, is suggestive of necrotic bowel and/or perforation in the absence of pneumatosis intestinalis.

In EPT, treatment -clinical suspicion as confirmatory radiographic findings may not be present

USG abdomen:

• USG more sensitive method to detect intramural air and portal venous gas .

• USG can detect intermittent gas bubbles in liver parenchyma and the portal venous system that are not detected by radiographs

• Color Doppler USG more sensitive than abdominal radiography in detecting bowel necrosis and alterations in bowel wall perfusion

Blood and serum studies:• WBC count <1500/cumm –poor prognostic factor

• Thrombocytopenia, persistent metabolic acidosis, and severe refractory hyponatremia triad of signs and help to confirm the diagnosis.

• Serial measurements of CRP - diagnosis and assessment of response to therapy of severe NEC.

• Blood cultures are positive in ˜40% of cases

Analysis of stool:• Grossly bloody stools may be an indication of NEC, routine

testing of stool for occult blood has no value .

• 60% of infants will have Hemoccult-positive stools at any given time during hospitalization without any evidence for NEC

D/D’s

1. Sepsis with Ileus

2. Infectious enteritis

3. Spontaneous intestinal perforation of the newborn

4. Intestinal obstruction –enterocolitis in Hirschsprung disease, ileal atresia, volvulus, meconium ileus, and intussusception.

5. Anal fissures

6. Neonatal appendicitis

7. Cow's milk protein allergy

Management:

• Medical management

-Supportive care

-Antibiotics

-Radilogical and lab monitoring

• Surgical management

-Primary peritonael drainage

-Laprotomy

Supportive Care:

• Bowel rest with gastrointestinal decompression with intermittent nasogastric suction.

• Total parenteral nutrition

• Fluid replacement to correct third space losses

• Support of both the cardiovascular( inotropes) and respiratory systems (O2 & Ventilation as needed).

• Correction of hematologic (DIC) and metabolic abnormalities (metabolic acidosis).

Antibiotics:

• After obtaining appropriate specimens for culture, broad spectrum antibiotic treatment should be initiated for suspected or proven NEC.

• Regimens should provide coverage for pathogens that cause late-onset bacteremia.

• Anaerobic coverage considered-peritonitis or pneumoperitoneum, suggesting intestinal perforation.

• Lack of consensus, and the choice of antibiotic regimen varies among NICU

1. Ampicillin, gentamicin ,and metronidazole

2. Ampicillin, gentamicin, and clindamycin

3. Ampicillin, cefotaxime, and metronidazole

4. Piperacillin.tazobactam and gentamicin

5. Vancomycin, piperacillin-tazobactam, and gentamicin.

6. Meropenem

Surgical management:

Indications

• Perforation on abdominal X ray(pneumoperitoneum)

• Positvie test on paracentesis(stool ,organism)

• Failure of medical management.

• Single fixed bowel loop on radiograph

• Abdominal wall erythema.

• Palpable mass

• Ideally surgery performed after intestinal necrosis but before perfoartion and peritonitis develop.

• Surgical procedures- exploratory laparotomy with resection of the affected intestinal region, or primary peritoneal drainage (PPD).

• PPD may be the preferred initial surgical procedure in extremely low birth weight (ELBW) infants and unstable premature infants.

Complications:

Early:• Infectious complications – Sepsis, meningitis,

peritonitis, and abscess formation• Disseminated intravascular coagulation- intestinal or

extraintestinal bleeding• Respiratory and cardiovascular complications –

Hypotension, shock, and respiratory failure• Metabolic complications – Hypoglycemia and

metabolic acidosisLate:• Stricture formation(9-36%)• Short bowel syndrome.(9% surgical operated cases)

Mortality:71,808 premature infants who were born between January 2005 and

December 2006 -Vermont Oxford NetworkFitzgibbons SC, Ching Y, Yu D, et al. Mortality of necrotizing enterocolitis expressed by birth weight categories. J

Pediatr Surg 2009; 44:1072

BW 501 to 750 g – 42 %

BW 751 to 1000 g – 29 %

BW 1001 to 1250 g – 21 %

BW 1251 to 1500 g – 16 %

• Mortality rate is higher in infants with more severe disease requiring surgical intervention(30.8 versus 6.8 percent).

• Radiographic evidence of portal venous air, an increase in feeding volume that was greater than 20 mL/kg per day, and an increase in the concentration of HMF within 48 hours of developing NEC .

• Hematocrit < 22 % ,I:T ratio > 0.5, and total lymphocyte count below 4000/microlt

Long term outcome:

• Approximately one-half of survivors have no long-term sequel.

• 10% infants will have late gastrointestinal morbidity-persistent loose stools or frequent bowel movements

• Infants with NEC were at increased risk for cerebral palsy, and cognitive and severe visual impairment.

• Patients who were surgically treated had poorer neurodevelopmental outcome than those treated medically.

• ELBW infants who required surgical care were more likely to have significant growth delay and poorer developmental outcome at 18 to 22 months.

Hintz SR, Kendrick DE, Stoll BJ, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005; 115:696.

Prevention of NEC:

• Antenatal corticosteroids reduced the risk for NEC approximately by half.

• Human milk compared with formula is the most important strategy associated with a lower risk of NEC( 2.8 times risk in formula fed)

• TIMING AND ADVANCEMENT OF FEEDING

The optimal timing of initiation of minimal enteral (trophic) feeding remains uncertain and its association with NEC is lacking.

Advancement of enteral feed volumes at daily increments of 30 to 40 mL/kg compared to lower volumes of 15 to 24 mL/kg did not increase the risk of NEC or death in VLBW infants (BW <1500 g)

Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2015; :CD001241

Prevention of NEC:

• Routine use of probiotic –not recomended, the lack of an established regimen of optimal strain and dosing, and the absence of quality control regulation to ensure consistency and safety of product.

• Oral immunoglobulins may reduce NEC by inhibiting the release of proinflammatory cytokines ,meta analysis administration of oral IgGor IgG/IgA combination did not reduce the incidence .

• Lactoferrin,Arginine,Glutamine ,HMO-proven to be beneficaial in some studies but not routinely recommended.

Prevention of NEC:

• Avoidance of histamine 2 blockers:Immunity provided by gastric acid may be important in preventing the cascade of infectious and inflammatory events.

• Avoidance of prolonged empirical antibiotic use :use of prolonged initial empiric antibiotic (≥5 days duration) started in the first three days of life was associated with an increased risk of NEC or death.

• Unproven as measures to prevent NEC:use of feeding protocols, judicious advancement of feeding, avoidance of hypertonic formulas and contrast agents, and prompt treatment of polycythemia.