PICO Summary: Does Prophylactic enteral probiotic administration prevent severe necrotizing enterocolitis (NEC) in preterm infants?

BackgroundNecrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and associated morbidity.
ParticipantsPreterm infants < 37 weeks and/or birth weight < 2500 g.
InterventionEnteral administration of any live microbial supplement (probiotics) at any dose for more than 7 days.
ComparisonPlacebo or no treatment.
Outcome(s)Primary outcomes
 • Severe NEC (stage II or more) as per Bell's criteria (Bell et al., 1978), diagnosed prior to discharge
 • Nosocomial sepsis, defined as positive blood or cerebrospinal fluid cultures taken beyond 5 days of age
 Secondary outcomes
 • All cause neonatal mortality
 • Any NEC (according Bell's criteria)
 • The composite of nosocomial sepsis or NEC or death
 • Systemic infection with the supplemented organism
 • Duration of total parenteral nutrition (days)
 • Time to establish full enteral feeds (days)
 • Duration of hospitalization (days)
 • Neurodevelopmental impairment, i.e. rates of cerebral palsy, cognitive delay, deafness, blindness or their composite reported at 18 months corrected age or later
StudiesRandomized or quasi-randomized controlled trials.
Study description and settingThe review of AlFaleh and coworkers (AlFaleh 2008) included nine eligible trials randomizing 1425 infants. Included trials were highly variable with regard to enrollment criteria (i.e. birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. Data regarding extremely low birth weight infants (ELBW) could not be extrapolated.
ResultsEnteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical RR 0.32, 95% CI 0.17, 0.60, NNT 25(16–50)) and mortality (typical RR 0.43, 95% CI 0.25, 0.75, NNT 25(16–100)). There was no evidence of significant reduction of nosocomial sepsis [typical RR 0.93 (95% CI 0.73, 1.19)] or days on total parenteral nutrition (TPN) [WMD −1.9, 95% CI −4.6, 0.77). The included trials reported no systemic infection with the probiotics supplemental organism. The statistical test of heterogeneity for NEC, mortality and sepsis was insignificant.
Confidence in resultsHigh quality evidence for all primary outcomes reported.
Key figure(s)Thumbnail image of
Figure captionSevere Necrotising Enterocolitis (stage II-III)
Search for eligible studiesCENTRAL, MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched through December 2006.
ConclusionsEnteral probiotics supplementation significantly reduced the incidence of severe NEC and mortality in preterm infants. Insufficient data is available to determine the effects of probiotics in infants at greatest risk of NEC (infants less than 100 grams at birth). Multiple agents were used in these trials, leaving it unclear which product should be considered for use.
CitationAlFaleh K, Bassler D. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD005496. DOI: 10.1002/14651858.CD005496.pub2.
Date completed23 February 2010
People who helped prepare this Cochrane PICO:Roger Soll and Martin Offringa, editors