Probiotics for Prevention of Necrotising Enterocolitis: An Updated Meta-analysis

Abstract

Several randomized controlled trials (RCTs) have investigated the prophylactic use of probiotics in preterm infants aimed at reducing the rate of necrotising enterocolitis (NEC). There are 4 meta-analyses on this subject. 2 more RCTs have been published since these meta-analyses were completed. Each meta-analysis, as well as the 2 recent RCTs, document reduced rates of NEC and mortality with the use of prophylactic probiotics. We calculated meta-analyses based on 3 approaches: A - RCTs common to all meta-analyses, B - RCTs ever accounted for in a meta-analysis but not common to all, and C - the 2 recent RCTs. The 3 subgroups yield similar results, with an overall reduction in the relative risk (RR) of NEC (Bell > or =2) to 0.35 (95% CI 0.23-0.55) and of mortality to 0.41 (0.28-0.60). NEC rates and mortalities in the dominant RCTs are in the range reported from North American and European networks. Best results appear to be achieved with probiotics based on 2 or more probiotic species and/or with a combination of Bifidusbacterium spp. and Lactobacillus acidophilus. No unwanted side effects have been reported among 1 117 infants randomized to receive probiotics. We conclude that probiotics are safe and beneficial in preterm infants at risk for NEC.

Probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum) prevent NEC in VLBW infants fed breast milk but not formula

“…Death was significantly lower in infants who received probiotics in our study, but the positive effect on survival even exceeded the reduction of NEC, which is not seen in the meta-analyses (13,14). Consequently, it can be assumed that other factors besides a reduction of NEC improved the survival in these infants.…”

“…We anticipated a reduction of NEC by 65%, as published in the metaanalyses (13,14) and calculated a sample size of 226 patients per group (α-error < 0.05; power 80%), based on a baseline NEC incidence of 10.3%. Statistical analysis was performed using the χ 2 test for categorical data; Student's t-test and Mann-Whitney U-test were used for continuous variables.…”

“…In the recent past, a preventive effect against NEC was assumed (12), and a variety of probiotic preparations were studied in randomized trials. Meta-analyses of these trials reported on a reduction of NEC in very-low-birth-weight (VLBW) infants by 65% (13,14), and the use of probiotics in clinical routine was recommended. Based on these suggestions, we decided to introduce probiotics for NEC prophylaxis as standard of care at our department.…”

“…Based on these suggestions, we decided to introduce probiotics for NEC prophylaxis as standard of care at our department. The probiotic preparation Infloran (Laboratorio Farmaceutico, Mede, Italia) consists of a mixture of Lactobacillus acidophilus and Bifidobacterium infantis and was chosen as its use was suggested by European experts (14) and it was available in sufficient quantities for routine application. Infloran (Laboratorio Farmaceutico) was highly effective (−80% NEC incidence) in a prospective randomized trial performed by Lin et al (15) in China.…”

“…Infloran (Laboratorio Farmaceutico) was highly effective (−80% NEC incidence) in a prospective randomized trial performed by Lin et al (15) in China. Despite the high efficacy in this trial (14), we felt that it was important to evaluate the effect in our mainly European population of VLBW infants, as there are no published data on its use outside Asia. Furthermore, there is a lack of data on possible interactions of feeding breast milk vs. formula on the protective effect of probiotics.…”