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Published on: January 27, 2019
Probiotics for prevention of necrotizing enterocolitis in preterm infants
Khalid AlFaleh1, Jasim Anabrees
1Department of Pediatrics (Division of Neonatology), King Saud University, Riyadh, Saudi Arabia. kfaleh@ksu.edu.sa, kmfaleh@hotmail.com.
Insights
Prophylactic enteral probiotics significantly reduce severe necrotizing enterocolitis (NEC) and mortality in preterm infants. This evidence supports a practice change, though further studies are needed on optimal probiotic preparations and therapy duration.
Area of Science:
- Neonatal Medicine
- Gastroenterology
- Microbiology
Background:
- Necrotizing enterocolitis (NEC) and nosocomial sepsis increase morbidity and mortality in preterm infants.
- Enteral probiotics may reduce NEC and associated morbidity by preventing bacterial translocation, excluding pathogens, and enhancing host immunity.
Purpose of the Study:
- To evaluate the efficacy and safety of prophylactic enteral probiotics versus placebo or no treatment in preventing severe NEC or sepsis in preterm infants.
Main Methods:
- Systematic review and meta-analysis of randomized or quasi-randomized controlled trials.
- Included trials enrolled preterm infants (<37 weeks gestational age or <2500g birth weight).
- Data were collected and analyzed using standard Cochrane Collaboration methods.
Main Results:
- Enteral probiotics significantly reduced severe NEC (stage II or more) (RR 0.43, 95% CI 0.33-0.56) and mortality (RR 0.65, 95% CI 0.52-0.81).
- No significant reduction in nosocomial sepsis was observed (RR 0.91, 95% CI 0.80-1.03).
- No systemic infections with probiotic organisms were reported; Lactobacillus and Bifidobacterium combinations were effective.
Conclusions:
- Enteral probiotic supplementation effectively prevents severe NEC and all-cause mortality in preterm infants.
- Evidence strongly supports a change in clinical practice.
- Further head-to-head trials are needed to determine optimal probiotic preparations, timing, and duration of therapy.
Background:
Necrotizing 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 the associated morbidity.
Objectives:
To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants.
Search Methods:
For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013).
Selection Criteria:
Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome.
Data Collection And Analysis:
Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis.
Main Results:
Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective.
Authors' Conclusions:
Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized.
Plain Language Summary:
Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth.
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