An infant was born weighing 1,250g at 30 weeks gestation due to premature rupture of membranes.  Pregnancy complications included maternal cocaine use and intrauterine growth restriction.  As feeds were introduced with donor breast milk, the infant appeared to have increased discomfort with feeds.  The baby went on to develop necrotizing enterocolitis, also known as NEC, at 20 days of life.  Which of the following is NOT a risk factor for the development of NEC?

A. Pre-term birth

B. Very low birth weight (defined as < 1,500g)

C. Intrauterine growth restriction

D. Maternal cocaine use

E. Feeding with donor breast milk

 

The correct answer is E, Feeding with donor breast milk is NOT a risk factor for the development of Necrotizing Enterocolitis (NEC).

 

Before we get into the risk factors, let’s learn a little more about NEC.  Infants present with poor feeding tolerance, increasing gastric residuals, increasing abdominal distension, and blood bowel movements.  The pathognomonic finding on abdominal X-ray is pneumatosis intestinalis which has been described as a “bubbly appearance” throughout the bowel.  Pneumatosis intestinalis results from intramural gas generated from anaerobic bacteria becoming trapped in the submucosal layer of the bowel wall.  Serial abdominal x-rays are the current gold standard to evaluate for disease progression.  Treatment includes making the infant NPO, placing a gastric tube for decompression, empiric antibiotics, and providing nutrition via TPN.  A surgical consult is also appropriate as approximately 30% of infants will progress to surgical disease. 

Now you may be wondering what antibiotics you should start… unfortunately there is no consensus recommendation on empiric antibiotics.  What the experts do agree on is that coverage should be broad and should target gram negative and anaerobic bacteria.  Typically, empiric coverage should last somewhere between 7-14 days.  A Cochrane systematic review completed in 2012 looked at various antibiotic regimens and concluded that there was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC.  A randomized control trial would be needed to address this issue.  Most NICU’s will have standard empiric antibiotics based on provider preference and the local antibiogram.  Complications include intestinal perforation, intestinal stricture formation, intestinal malabsorption and short bowel syndrome, cholestatic liver disease, and neurodevelopmental delay.

 

So now that we have heard about a quick overview, let’s get back to our question. Feeding with breast milk, including donor breast milk, has been identified as the only consistent intervention for the prevention of NEC.  It is currently recommended that infants at risk for NEC, specifically those born with very low birth weight and born premature, receive feeds with breast milk or with donor breast milk if their own mother’s milk is not available.  Additionally, if fortification is needed, human milk derived fortifiers decrease the rate of NEC, specifically NEC which requires surgical treatment.  Formula feeding is a known risk factor for the development of NEC in both preterm and term infants.

 

The biggest risk factors for the development of NEC are prematurity and low birthweight.  Most NEC occurs in infants born at less than 32 weeks gestational age, and NEC affects 5-9% of all very low birth weight infants. About 90% of all NEC cases occur in pre-term infants.

 

Some additional risk factors to keep in mind are the need for packed red blood cell transfusion, a patent ductus arteriosus or other congenital heart disease, birth asphyxia or hypoxia, intrauterine growth restriction, polycythemia, chorioamnionitis, premature rupture of membranes, maternal cocaine use, chromosomal abnormalities, sepsis, gastroschisis, hypothyroidism, maternal pre- eclampsia, and maternal gestational diabetes.

 

The onset of NEC is inversely related to gestational age, the earlier the baby is born, the later the onset of NEC.  This is believed to be due to the fact that the timing of the onset of NEC often correlates with the initiation or advancement of feeds.  Typically, infants born near or at term are introduced to feeds sooner than their preterm counterparts therefore the onset of NEC is typically seen at an earlier post gestational age.

 

Again, the biggest risk factors to keep in mind are prematurity and low birth weight.  NEC onset is usually associated with the initiation or advancement of feeds.  While formula feeding is a known risk factor for the development of NEC, breast milk is protective.

 

Resources

  1. Samuels N, van de Graaf RA, de Jonge RCJ, Reiss IKM, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017 Apr 14;17(1):105. doi: 10.1186/s12887-017-0847-3. PMID: 28410573; PMCID: PMC5391569.
  2. Chu A, Hageman JR, Caplan MS. Necrotizing Enterocolitis. NeoReviews Mar 2013, 14 (3) e113-e120; DOI: 10.1542/neo.14-3-e113.
  3. Rich BS, Dolgin SE. Necrotizing Enterocolitis. Pediatrics in Review Dec 2017, 38 (12) 552-559; DOI: 10.1542/pir.2017-0002.
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  5. Ross A, LeLeiko NS. Pediatrics in Review Apr 2010, 31 (4) 135-144; DOI: 10.1542/pir.31-4-135.
  6. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364(3):255-264. doi:10.1056/NEJMra1005408.
  7. Kim SS, Albanese CT. Necrotizing Enterocolitis. Pediatric Surgery. 2006;1427-1452. doi:10.1016/B978-0-323-02842-4.50095-4.
  8. Gregory KE, Deforge CE, Natale KM, Phillips M, Van Marter LJ. Necrotizing enterocolitis in the premature infant: neonatal nursing assessment, disease pathogenesis, and clinical presentation. Adv Neonatal Care. 2011;11(3):155-166. doi:10.1097/ANC.0b013e31821baaf.
  9. Shah D, Sinn JK. Antibiotic regimens for the empirical treatment of newborn infants with necrotising enterocolitis. Cochrane Database Syst Rev. 2012 Aug 15;(8):CD007448. doi: 10.1002/14651858.CD007448.pub2. PMID: 22895960.

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