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COMMENTARY |
Department of Pediatrics,
Carver College of Medicine,
University of Iowa,
Iowa City, IA 52242
Abbreviations: NEC, necrotizing enterocolitis • VLBW, very low birth weight
Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among premature infants, affecting 4% to 13% of very low birth weight (VLBW) infants.1 The incidence varies among institutions and over time within each institution, occurring at times in outbreaks suggesting transmission among patients. The incidence of NEC varies inversely with pregnancy length, being more common in infants of younger gestational age. Reports of cases identified as NEC appeared in the 1960s,2 although apparent cases were reported much earlier, in the 19th century.3 A single cause has not been identified, suggesting that NEC results from various triggering events under certain predisposing conditions: a final common pathway. The leading theory is that NEC requires 3 coexisting elements: inadequate oxygen transport to the gut, potentially invasive pathogenic bacteria, and substrate in the form of enteral feedings.4 Early animal models of NEC are consistent with this theory.5 More recent thought adds the possible role of vasoconstriction in response to inflammatory or other stimuli.6
Despite our limited knowledge of the pathogenesis of NEC, various strategies have been tried in an effort to prevent NEC in high-risk infants (Table 1). Among these strategies is the enteral administration of probiotics, which are defined as live microorganisms that survive in the gastrointestinal tract and have beneficial effects on the host.7 Probiotics have been advocated for prevention or treatment of a variety of disorders including rotavirus infection, antibiotic-associated diarrhea, and traveler’s diarrhea. In this issue of Pediatrics, Lin et al report a randomized, clinical trial in which prophylactic administration of probiotics to VLBW infants reduced the incidence of NEC from 5.3% to 1.1%, a relative risk reduction of 79%.8 The probiotic group was given a commercial preparation (Infloran, Berna Biotech Ltd, Berne, Switzerland) containing Lactobacillus acidophilus and Bifidobacterium infantis. The absolute risk reduction was 4.2%, which means that 24 infants would need to be given probiotics to prevent 1 case of NEC.9
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Other strategies that have been shown to reduce the risk of NEC are enteral antibiotics,13–18 judicious administration of parenteral fluids,19 human milk feeding,20,21 enteral administration of IgG and IgA together22 but not IgG alone,23–25 and antenatal corticosteroids26 (Table 1). Delayed or slow feeding has not been shown to reduce the incidence of NEC.27,28 In evaluating each of these strategies, it is necessary to look at the number needed to treat as a measure of the size of treatment effect but also at the risks and the size of these potentially harmful effects: the number needed to harm. Although the risks of enteral antibiotics have not been quantified, this strategy has never been widely adopted, despite its efficacy, because of concerns about the emergence of resistant bacteria and absorption of antibiotics from the gut.18 Human milk feeding, avoidance of excess fluid administration, and antenatal corticosteroid use are widely practiced. Combined use of enteral IgG and IgA has been examined in only 1 placebo-controlled trial. Replication of this result and more data on safety would help to clarify the role of this strategy for preventing NEC. Studies of IgG alone have not shown protection against NEC.
Enteral administration of probiotics is an appealing strategy for preventing NEC. Colonization of the gut with Lactobacillus and Bifidobacterium species is thought to be promoted by the feeding of human milk,29 which also decreases the risk of NEC in premature infants.20,21 This observation suggests that promotion of probiotic colonization may be among the mechanisms by which human milk protects against NEC. Milk leukocytes, immunoglobulins, and growth factors are other components proposed to contribute to the protective effect of human milk. The 3 clinical studies of probiotic administration to infants have reported no adverse effects including no cases of pathogenic infection caused by a probiotic organism.8,11,12 Bloodstream infection with Lactobacillus or Bifidobacterium species is rare.30
The human gut is a hospitable environment for bacteria and other microorganisms, most of which live there peacefully for the entire life of the host. The microbial flora are affected by what we eat and certain medications we take, both probiotics and antibiotics. Some of our healthiest and tastiest foods are produced with the help of bacteria or yeast (eg, yogurt, cheese, and wine). The study by Lin et al8 suggests that we may be able to help our premature infant patients by manipulating their intestinal flora with enterally administered probiotics. This promising intervention warrants additional examination of its safety and efficacy through larger clinical trials so that both the benefits and the risks of probiotics for premature infants can be better defined.
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FOOTNOTES |
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Address correspondence to Edward F. Bell, MD, Department of Pediatrics, Carver College of Medicine, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242. E-mail: edward-bell{at}uiowa.edu
No conflict of interest declared.
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