**11. Long-term outcomes**

Approximately half of all cases of NEC display no long-term sequelae. This includes cases of stage I NEC from Bell's criteria. NEC is associated with significant impairment of growth and neurodevelopment [56–58]. Ten to thirteen percent of patients suffer from late gastrointestinal morbidity if resection is performed. Majority of infants who have had no extensive intestinal resection have normal gastrointestinal function at 1–10 years of age.

#### **11.1 Growth and neurodevelopment**

In a large multicenter study from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, extremely low birth weight (ELBW) infants (BW <1000 g) who required surgical care were more likely to have significant growth delay and poorer developmental outcome at 18–22 months compared with infants without NEC [56]. ELBW treated medically or surgically suffer from significant growth failure until 22 months, and in a lesser percentage beyond that age [57], while those who were medically treated do not differ in growth or developmental testing compared with those without NEC [58]. Infants with NEC are at increased risk for cerebral palsy and cognitive and severe visual impairment. At 7 years of age, survivors with NEC compared to controls demonstrate a higher rate of neurologic functional impairment.

### **11.2 Mortality**

Overall survival in cases with NEC is 70–80%, being >95% in medical and 70–75% in surgical NEC [59]. Lower BW and GA and surgical intervention, such as laparotomy and peritoneal drainage, are independent predictors for mortality.

**41**

**13. Future directions**

*Necrotizing Enterocolitis*

center study [61].

**12. Prevention**

**11.3 Financial burden of NEC**

*DOI: http://dx.doi.org/10.5772/intechopen.85784*

Other risk factors associated with death from NEC are mechanical ventilation, treatment with vasopressor agents, surgical intervention, and black ethnicity as per a retrospective multicenter review of data [60]. Two thirds of NEC deaths occur within 7 days of diagnosis, with a median time of death being 1 day from the day of onset. Infants who die within 7 days of diagnosis have higher BW, and more often they are on vasopressors and high-frequency ventilation at the time of diagnosis. Risk factors for fulminant NEC, defined as death within 48 h of onset, are presence of portal venous air, increase in feeding volume by >20 mL/kg per day, HCT <22%, I/T ratio > 0.5, and total lymphocyte count <4000/μL as demonstrated in a multi-

The average total treatment cost of one case of NEC is US \$500,000 [62, 63]. Total annual estimated cost of care of NEC in the United States is between \$500 million and \$1 billion. Infants with NEC are hospitalized for 60 days longer than unaffected preterm infants if surgery is performed and >20 days longer if surgery is not required. Bowel resection—one of the most severe complications of NEC—is the major cause of short bowel syndrome in pediatric patients, making 95% of all such cases. The total mean cost of care over a 5-year period for a child with the short

Prevention is the primary strategy in this devastating disease with undetermined etiology. Breast milk feeding, prolonging gestation to avoid prematurity, antenatal steroid, and the use of probiotics/prebiotics are established prevention strategies in NEC [16]. Nonaggressive feeding is evidenced to be efficacious. The rate of advancement of feeding under 20 ml/kg/day is considered to be safe. Newer strategies, such as use of toll-like receptor agonist, glutamine, n-3 fatty acids, anti-cytokines, and growth factors are proposed preventive interventions, but most of these either lack evidence or have questionable safety. Compound CpG-DNA inhibit TLR4 signaling, thereby dramatically reducing the severity of NEC in mice. Clinically, the following measures are suggested to be practiced in order to reduce the risk of NEC: human milk (both mother's and donor's); standardized feeding guidelines, including early initiation with trophic feeds; the use of probiotics; antibiotic stewardship; optimization of enteral nutrition and growth; elimination of H2 blockers and acid pump suppressors; elimination of cow's milk products; transfusion protocols; and transfusion outcome monitoring. Avoidance of hyperosmolar agents, treatment of polycythemia, and delayed cord clamping are other interventions that are suggested to be followed. Prophylactic probiotics, although not yet universally applied due to uncertainties about its dose and duration of therapy, have been documented to reduce the incidence of NEC, especially that of severe cases (RR 0.75 95% CI −0.57 to 0.92) in infants <1500 g in multiple studies [64]. There are concerns about bactere-

NEC remains a major unsolved medical challenge for which no specific therapy exists. Recent research is concentrated on the role of TLR4 signaling within the intestinal epithelium and intestinal stem cells and modulation of the genetics and

bowel syndrome has been estimated to be nearly \$1.5 million.

mia and some aspects of quality control which restrict its use.

*Necrotizing Enterocolitis DOI: http://dx.doi.org/10.5772/intechopen.85784*

*Pediatric Surgery, Flowcharts and Clinical Algorithms*

of independence from PN.

**11. Long-term outcomes**

gastrointestinal function at 1–10 years of age.

**11.1 Growth and neurodevelopment**

**10. Complications**

interventions. The approach is associated with improved survival and achievement

The acute complications of NEC are sepsis, meningitis, peritonitis, intraabdominal abscess formation, DIC, thrombocytopenia, hypotension, shock, respiratory failure, metabolic or combined acidosis, hyponatremia, hyperglycemia, or less often hypoglycemia. Late complications are stricture formation, short bowel syndrome, and intestinal failure [55]. Rarely enterocele, enterocolic fistula, and intraabdominal abscess formation may be encountered. About 24% (95% CI 17–31%) of infants treated medically or surgically develop strictures in bowel which is unrelated to the severity of NEC or gestational age. The commonest location is in the colon, followed by the ileum and jejunum. Multiple sites strictures are seen. It can appear within 2 to 3 months of the acute episode and as late as 20 months. Stricture may lead to local bacterial overgrowth resulting in repeated infections, bloody stools, failure to thrive, and symptoms of bowel obstruction. Strictures are more common following enterostomy; therefore contrast enemas should be performed 4–6 weeks after the occurrence of NEC and prior to surgical closure of enterostomy with reanastomosis or if and when feeding intolerance develops. Recurrent NEC may occur in 8% and adhesion ileus in 6% cases of NEC. Overall intestinal failure happens in 13% of all

cases of NEC, inclusive of medically and surgically treated infants.

demonstrate a higher rate of neurologic functional impairment.

Approximately half of all cases of NEC display no long-term sequelae. This includes cases of stage I NEC from Bell's criteria. NEC is associated with significant impairment of growth and neurodevelopment [56–58]. Ten to thirteen percent of patients suffer from late gastrointestinal morbidity if resection is performed. Majority of infants who have had no extensive intestinal resection have normal

In a large multicenter study from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, extremely low birth weight (ELBW) infants (BW <1000 g) who required surgical care were more likely to have significant growth delay and poorer developmental outcome at 18–22 months compared with infants without NEC [56]. ELBW treated medically or surgically suffer from significant growth failure until 22 months, and in a lesser percentage beyond that age [57], while those who were medically treated do not differ in growth or developmental testing compared with those without NEC [58]. Infants with NEC are at increased risk for cerebral palsy and cognitive and severe visual impairment. At 7 years of age, survivors with NEC compared to controls

Overall survival in cases with NEC is 70–80%, being >95% in medical and 70–75% in surgical NEC [59]. Lower BW and GA and surgical intervention, such as laparotomy and peritoneal drainage, are independent predictors for mortality.

**40**

**11.2 Mortality**

Other risk factors associated with death from NEC are mechanical ventilation, treatment with vasopressor agents, surgical intervention, and black ethnicity as per a retrospective multicenter review of data [60]. Two thirds of NEC deaths occur within 7 days of diagnosis, with a median time of death being 1 day from the day of onset. Infants who die within 7 days of diagnosis have higher BW, and more often they are on vasopressors and high-frequency ventilation at the time of diagnosis. Risk factors for fulminant NEC, defined as death within 48 h of onset, are presence of portal venous air, increase in feeding volume by >20 mL/kg per day, HCT <22%, I/T ratio > 0.5, and total lymphocyte count <4000/μL as demonstrated in a multicenter study [61].
