Wednesday, May 5, 2010

Necrotizing Enterocolitis and the Preterm Infant

Necrotizing Enterocolitis (NEC) is an inflammatory bowel disease affecting three to ten percent of neonates in intensive care units (ICU) (Bisquera et al., 2002: Guthrie et al., 2003) and results in necrosis of the intestinal tissue and possible perforation of the bowel (Kafetzis et al., 2003; MedlinePlus, 2009). NEC predominantly affects low birth weight (LBW) and very low birth weight (VLBW) neonates (Kafetzis et al., 2003; Martin et al., 2008) and plays a significant role in the morbidity and mortality (rates reported between 13%-25%) of these infants (Guner et al., 2009; Henry et al., 2009; Lambert et al., 2007). A Canadian survey of 18,234 infants, in 17 neonatal intensive care units (NICU), reported the incidence of NEC among VLBW infants ( less than 1500g ) as 6.6 percent (Sankaran et al., 2004).

The etiology of NEC (with severity classified on a scale of I (mild) to III (severe, including GI hemorrhage and septic shock) (Bell et al., 1978)) is multifactorial. Many pathogenic factors play a role, including, immaturity and ischemia of the gastrointestinal (GI) tract, and changes in commensal gut microflora (normal, indigenous bacteria) accompanied by increases in pathogenic bacteria as well intestinal inflammation (Hsueh et al., 2003; Panigrahi, 2006; Thompson et al., 2008). Treatment includes medically and surgically invasive procedures such as intravenous fluids, orogastric and peritoneal drainage and laparotomy (Panigrahi, 2006; Thompson et al., 2008). It is therefore important to prevent and manage the disease so that this already vulnerable population is not placed under even greater risk for complications.

Are There Alternative Treatments?

Reviews of the use of probiotics (defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” (FAO/WHO, 2001, pg. 5)) for the treatment of acute and antibiotic associated diarrhea and atopic dermatitis in infants have suggested that for these conditions, probiotics are tolerated well, and are beneficial and safe for infants (Kullen et al., 2005; Saavedra, 2007).

Although not as extensive, research regarding administration of prophylactic probiotics to VLBW neonates shows a decrease in the incidence a nd severity of NEC. The rationale for supplementation of probiotics for prevention and management of NEC in infants is that the bacteria will restore microbial balance to the immature gut by competing with pathogens, thereby improving the gut barrier and decreasing inflammatory responses (Costalos et al., 2003; Cucchiara et al., 2002; Martin et al., 2008).

Relevance to Practice

Clinical trials conducted in NICUs using various probiotics are promising. Dani et al. (2002) conducted a prospective, multi-centre, double-blind, randomized study of VLBW preterm infants. The probiotic group (PG) received a dose of 6 x 109 colony-forming units (CFU) of Lactobacillus GG each day (in pasteurized breastmilk or infant formula) until discharge. The incidence of NEC was lower in the PG (1.4 compared to 2.8 percent) but not significant. Bin-Nun et al. (2005) conducted a blinded randomized trial using a different probiotic supplement (ABC Dophilus: Bifidobacteria infantis, Streptococcus thermophilus and Bifidobacteria bifidus at a dose of 1.05 x 109 CFU per day added to breastmilk or enteral formula). Incidence of NEC in the PG was significantly lower (4 percent) than the placebo group (16.4 percent; p=0.03), as was the severity. Two randomized controlled trials, using Infloran (Lactobacillus acidophilus and Bifidobacterium infantis; dosage of 125 mg/kg per dose of 109 CFU twice daily added to breastmilk or formula) on VLBW infants, demonstrated a significantly lower incidence and severity of NEC in the PG (Lin et al., 2005; Lin et al., 2008). Lastly, a historic control group was compared to a newborn PG (treated with Lactobacillus acidophilus and Bifidobacterium infantis, 250 x 106 CFU, in sterilized water or 5 percent dextrose, via orogastric tube or drops into the mouth) admitted to the ICU during one year. Although the dose was smaller than other studies, this trial demonstrated a significant reduction in NEC (Hoyos, 1999). No significant adverse reactions were reported in these studies.

Probiotics are potentially beneficial in preventing NEC in neonates. However, evidence is lacking to recommend the most beneficial probiotics, the best time to initiate prophylaxis, the optimal dose, or the duration of treatment. A predictive model using United States NEC statistics estimated an increase length of stay (where surgical NEC infants exceeded controls by 60 days and medical NEC infants exceeded controls by 22 days), and an additional $6.5 million in hospital charges per year, or $216,666 per NEC survivor (Bisquera et al., 2002). As technology and health care practices improve, survival of VLBW neonates will increase possibly increasing the incidence of NEC. This should be taken as a call to action. The ‘cost’ of NEC on the neonatal community (financially for the health care system, and emotionally for parents aware of the bleak statistics) is arguably far greater than the ‘price’ of using health care dollars to research best practices for the use of probiotics for the prevention of NEC in neonates.

REFERENCES available from Andrea Buchholz.


Deborah Van Dyke
4th year student (visiting from U of A)

Andrea Buchholz, PhD, RD
Faculty Advisor
Dept of Family Relations and Applied Nutrition
University of Guelph