Necrotizing Enterocolitis & Feeding ...An Update

Volume 1 Issue 3 Introduction I. Epidemiology II. Pathophysiology III. Diagnosis IV. Management V. Prevention The Case Begins a) RK is a male baby (31+6wks. gestation), born to a 29 years old woman, Primipara, A positive, with negative serology and her antenatal scan revealed twins. b) Three days prior to delivery she was given Betamethasone because of preterm labor. c) The baby was delivered by preterm NVD. d) Cried soon after birth but owing to poor respiratory efforts, needed intubation and ventilation. e) APGAR scores of 6 and 8 at 1 & 5 minutes respectively. f) He was admitted to the NICU for management of prematurity and respiratory support (Figure 1).

The Case Begins a) RK is a male baby (31+6wks. gestation), born to a 29 years old woman, Primipara, A positive, with negative serology and her antenatal scan revealed twins. b) Three days prior to delivery she was given Betamethasone because of preterm labor.
c) The baby was delivered by preterm NVD. d) Cried soon after birth but owing to poor respiratory efforts, needed intubation and ventilation. e) APGAR scores of 6 and 8 at 1 & 5 minutes respectively. f) He was admitted to the NICU for management of prematurity and respiratory support ( Figure 1).

Figure 1
g) His initial chest x-ray was unremarkable. Started on IV Ampicillin and Gentamicin owing to high risk of infection but were discontinued after 48 hours as he remained well and sepsis screen was normal along with sterile blood culture. h) He could be extubated to non invasive ventilator.
i) He could be trialled off to room air by day 5 of life and remained on room air that well tolerated.
j) The baby could be commenced on feeds and could be graded up to nearly full feeds (4ml per kg per hour) by day 5 of life. Feeds were well tolerated. k) On day 7 of life, he was noted to have abdominal distension that was rapidly progressive to a shiny red abdomen with increased gastric aspirates (Figure 2    So, baby was kept NPO and commenced on antibiotics but as there was rapid deterioration in his clinical condition, over a In the subsequent 72hours, due to features of DIC, he needed blood and fresh frozen plasma along with platelet concentrates infusion. Supportive treatment with immunoglobulin was given. He needed inotropes support with Dopamine for a period of 72hours and could be weaned down. There was hypoalbuminemia noted and was treated with Albumin infusion. Acidosis, Hyperglycemia and raised lactate were also noted and treated. All these features were suggestive of Multi organ Dysfunction. 24hours later, baby was noted to have pneumo-peritoneum that was treated by insertion of a multi drain (too sick to be exposed to surgical exploration).
His abdominal distension was noted to gradually resolve and once he was noted to be hemodynamically stable along with improving platelet counts, normalized coagulation profile with declining CRP levels and sterile blood culture ( Figure 4).  Baby underwent laparotomy with resection and Anastomosis of his intestine and formation of ileostomy on (day 13 of life and 6 days following drain insertion).One perforation was noted at DJ junction and multiple perforations were noted proximal to ileocecal valve and approx. 15cms of bowel resection was performed followed by end to end anastomosis. The histopathology of the bowel specimen sent revealed Necrotizing Enterocolitis ( Figure 5).
Widely varying incidence between centers. c.
Incidence inversely related to degree of prematurity.

d.
No seasonal or sex predilection.
e. There are inverse correlations between gestational age or birth weight and the incidence of NEC, as demonstrated in multicenter and large population-based studies, its prevalence being 7%-11% in very low birth weight infants who weight less than 1,500g.
Age at diagnosis is inversely related to gestational age and degree of prematurity [

Factors that alter patterns of bacterial colonization in ill premature infants
a. Widespread use of broad-spectrum antimicrobials promotes colonization by invasive and opportunistic microbial pathogens.
b. Clinical illness reduces enteral feeding, influencing intestinal bacterial colonization, immune system maturation and barrier function. c. Reduction in BM feeding due infants' clinical illness, reduced availability BM, or alterations due to freeze/thawing of BM.
d. Despite this progress in technologies there has been no method to identify infants who would be ideal candidates for therapy or those who will progress to more severe stages of disease.

Classification of NEC
Stage 1: suspect NEC -signs of sepsis, feeding intolerance ± bright red blood per rectum Stage 2: Proven NEC-all of the above, pneumatosis, ± portal vein gas ± metabolic acidosis ± ascites  Serial physical examination.

Abdominal x-rays.
Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets

•
A major objective of necrotizing enterocolitis (NEC) research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model.
• Concluded that abdominal near-infrared spectroscopy is capable of detecting alterations in intestinal oxygenation and perfusion in neonatal piglets and may allow early detection of neonates at risk for NEC [2].
Abdominal near-infrared spectroscopy measurements are lower in preterm infants at risk for necrotizing enterocolitis • Near-infrared spectroscopy is a noninvasive method of measuring local tissue oxygenation (StO2).

•
Abdominal StO2 measurements in preterm piglets are

Volume 1 -Issue -3
directly correlated with changes in intestinal blood flow and markedly reduced by necrotizing enterocolitis.
• The objectives of this study were to use near-infrared spectroscopy to establish normal values for abdominal StO2 in preterm infants and test whether these values are reduced in infants who develop necrotizing enterocolitis.
• This study establishes normal values for abdominal StO2 in preterm infants and demonstrates decreased values and increased variability in those with necrotizing enterocolitis. Abdominal nearinfrared spectroscopy monitoring of preterm infants may be a useful tool for early diagnosis and guiding treatment of necrotizing enterocolitis [3].

Newly emerging therapeutic strategies
There are many evidence-based approaches to prevent NEC, these includes:

3.
Feeding the infant with the mother's expressed breast milk.
Nutritional support to preserve the epithelial barrier 1. Human milk is able to protect against the development of NEC via induction of intestinal maturation and healing.
2. This is attributed to several factors that influence host immunity, inflammation, and mucosal protection, but a specific component to transfer in preterm formula has not been definitively identified, still no evidence between premature formula and NEC.

Feeding Practices and NEC
1. The evidence is convincing that human milk feeding, as compared to formula feeding, reduces the incidence of NEC in preterm infants.
2. Minimal enteral nutrition is a safe alternative to complete fasting before initiation of progressive feedings and does not increase the incidence of NEC in extremely preterm infants.

NEC Management Updates
• There is no evidence that trophic feeding has adverse effects for necrotizing enterocolitis [4].

Feeding Practices and NEC
1. In clinically stable VLBW infants, early introduction of progressive feeds and advancement of feeds at a faster rate (30-35ml/kg/day) is safe and does not increase the incidence of NEC.
2. There is no evidence supporting continuous over intermittent tube feedings in preterm infants.

Slow Advancement of Enteral Feed Volumes to Prevent
Necrotising Enterocolitis in very Low Birth Weight Infants 1. Data suggest that advancing enteral feed volumes at daily increments of up to 30 to 40 mL/kg does not increase the risk of feed intolerance, necrotizing enterocolitis (NEC), or death in (VLBW) infants.
2. Increasing the volume of enteral feeds at slow rates (less than 24mL/kg/day) resulted in several days of delay in the time taken to regain birth weight and establish full enteral feeds, and increased the risk of late-onset invasive infection [5].
3. In a feed-intolerant preterm infant without any other clinical and radiological evidence of NEC, minimal enteral nutrition rather than complete suspension of enteral feeding may be alternative.

4.
Human milk-based fortifier as compared to bovine-based fortifier may reduce the incidence of NEC but additional studies are required [6].
Nutritional support to preserve the epithelial barrier 1. The Cochrane review (2014) by Kuschel and Harding, presents the result of 13 randomized controlled trials that examined the long and short-term outcomes of preterm infants fed on a diet of fortified expressed breast milk.
2. They found that the use of a fortifier was associated with improved growth, with no significant increase in the adverse outcomes, including NEC.

Modification of gut microbiota composition
I. Probiotic colonization improves GI health and prevents proinflammatory signaling and disease progression by: a) Increasing mucosal barrier function and by up-regulating the immune system. b) Reduces mucosal colonization of potential pathogens.

c)
Alters the key components of intestinal inflammation.
II. Several studies have demonstrated the efficacy and safety of prophylactic enteral probiotic administration in the prevention of NEC in infants with very low birth weight.
III. In these studies, the administered probiotics were Lactobacillus alone or in combination with Bifidobacterium.
1. Surgically treated NEC can be very devastating. Surviving infants require attentive healthcare and often need invasive catheters for parenteral nutrition. Our current ability to medically treat NEC is limited.
2. A scoring system to predict surgical NEC and mortality needs to be established in order to achieve this goal [9]. Conclusion a. Prematurity is the single greatest risk factor for NEC & avoidance of premature birth is the best way to prevent NEC. b. The role of feeding in the pathogenesis of NEC is uncertain, but it seems prudent to use breast milk (when available) and advance feedings slowly and cautiously.

Firm Indications for Surgical Intervention
c. NEC is one of the leading causes of mortality, and the most common reason for emergent GI surgery in newborns.
d. NEC remains a major unsolved medical challenge, for which no specific therapy exists, and its pathogenesis remains controversial. e. A better understanding of the pathophysiology will offer new and innovative therapeutic approaches, and future studies should be focused on the roles of the epithelial barrier, innate immunity, and microbiota in this disorder.
f. Bioinformatics modeling is a new emerging strategy aimed at understanding the dynamics of various inflammatory markers and their application in early diagnosis and treatment.