Efficacy of saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: A randomised controlled trial
Introduction
Necrotizing enterocolitis (NEC) is the most serious acquired disease of the gastrointestinal tract characterized by bowel wall necrosis in very low birth weight infants (VLBW) [1]. The incidence varies among centers [2]. Recent studies report up to 9000 cases of NEC in the United States every year, with a case fatality rate of 15% to 30% [3]. The pathogenesis of NEC remains incompletely understood but it is considered to be due to a complex interaction of factors such as; prematurity, enteral feeding, intestinal hypoxia–ischemia, and bacterial colonization causing mucosal injury through a final, common, inflammatory pathway [2], [4], [5]. VLBW infants at risk of NEC have abnormal fecal colonization, demonstrate a paucity of normal enteric bacterial species, and have delayed onset of bacterial colonization [5].
Nosocomial infection is also a frequent complication in VLBW infants. Twenty five percent of these infants have at least one or more positive blood cultures over the course of their hospitalization [6]. Late onset sepsis is associated with an increased risk of death, neonatal morbidity and prolonged hospitalization [7].
Probiotic bacteria are live microbial supplements that colonize the gastrointestinal tract and potentially provide benefit to the host. Probiotics may prevent NEC by promoting colonization of the gut with beneficial organisms, preventing colonization by pathogens, improving the maturity and function of gut mucosal barrier, and modulating the immune system [1]. Many clinical trials have evaluated the safety and benefits of probiotic supplementation in VLBW neonates. It is important to note that there are many different mechanisms producing the benefits of probiotics and there are also strain-specific effects [8]. Researchers have generally selected strains belonging to bacterial species naturally present in the intestinal flora. Saccharomyces boulardii (SB) is a yeast which acts both as a probiotic and polyamine producer [9]. Polyamines which are essential for cell growth and differentiation enhance intestinal maturation [9]. SB is used for the treatment of a number of gastrointestinal disorders related to abnormal bacterial growth [9]. Therefore, we hypothesized that SB may be an attractive candidate for the prevention of NEC which is characterized by bacterial colonization causing mucosal injury, and sepsis by overwhelming bacterial translocation with affects on intestinal maturation. SB can be a better strategy than other bacterial strains due to the ability to produce polyamines. We therefore designed a randomized, double-blind placebo controlled clinical trial to evaluate the influence of SB supplementation on the incidence and severity of NEC and sepsis in VLBW infants.
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Patients and method
A prospective, masked, randomized, controlled trial was conducted from October 1, 2010 to November 30, 2011, in Zeynep Kamil Maternity and Children's Research and Training Hospital, Neonatal Intensive Care Unit (NICU) after the approval from ethical committee. VLBW infants (gestational age ≤ 32 weeks; birth weight ≤ 1500 g) who survived to feed enterally were eligible for the trial. Infants who had severe asphyxia (stage III), major congenital anomalies, those who had been fasted for more than 3
Results
Infants assessed for eligibility were 292; 48 of them were excluded because of major congenital malformation (n = 9), severe asphyxia (n = 4), death occurred in 24 h (n = 10), and lack of parental consent (n = 25). A total of 244 infants were enrolled in the study. Three infants were excluded due to fasting more than 3 weeks. Eleven infants were lost to follow up due to family withdraw, and a total of 19 infants died during the first 2 week period after enrollment. Finally, 104 infants per group completed
Discussion
Probiotics have become a hope for NEC prophylaxis and treatment and many trials have been performed. Cochrane meta-analysis indicates that enteral probiotic supplementation such as Lactobacillus and Bifidobacterium species which are members of the normal flora of gut significantly reduces the incidence of stage ≥ 2 NEC and mortality in preterm infants [13]. Probiotics act through many different mechanisms which are strain-specific. The use of probiotic bacteria to inhibit pathogenic bacteria has
Funding and competing interests
The drugs were supplied by Biocodex.
Ethics approval
The trial was approved by the central ethical committee in Ankara, Turkey.
Registration
This trial was registered by IRCT with ID as IRCT2012071410279N1.
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