Effect of Bifidobacterium breve M-16V Supplementation on Fecal Bifidobacteria in Preterm Neonates - A Randomised Double Blind Placebo Controlled Trial

Abstract

BackgroundProbiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC) and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort.AimTo assess product quality, and confirm that Bifidobacterium breve (B. breve) M-16V supplementation will increase fecal B. breve counts without adverse effects.Methods and ParticipantsStrain identity (16S rRNA gene sequencing), viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation <33 weeks) ready to commence or on feeds for <12 hours were randomly allocated to either B. breve M-16V (3×109 cfu/day) or placebo (dextrin) supplementation until the corrected age 37 weeks. Stool samples were collected before (S1) and after 3 weeks of supplementation (S2) for studying fecal B. breve levels using quantitative PCR (Primary outcome). Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons.ResultsA total of 159 neonates (Probiotic: 79, Placebo: 80) were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%), S2: 25/66 (38%), p<0.001] Probiotic: [S1: 29/74 (40%), S2: 67/74 (91%), p<0.001].Median S1 B. breve counts in both groups were below detection (<4.7 log cells.g−1), increasing significantly in S2 for the probiotic group (log 8.6) while remaining <4.7 log in the control group (p<0.001). There were no adverse effects including probiotic sepsis and no deaths. NEC≥Stage II occurred in only 1 neonate (placebo group).Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates.Trial RegistrationAustralia New Zealand Clinical Trial Registry ACTRN 12609000374268

The “Golden Age” of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants

“…Twenty-eight trials [19,20,21,22,23,24,25,26,28,29,30,31,32,33,34,35,37,38,39,40,41,42,43,44,45,46,47] reported on late-onset sepsis. The administration of probiotics reduced the rate of sepsis in the pooled effect by 12% (typical RR 0.88, 95% CI 0.80-0.97, p = 0.01; Fig.…”

“…The administration of Lactobacillus GG [23,34,35,36] and Bifidobacterium lactis [25,37,29] species alone significantly reduced the incidence of severe stage II-III NEC (RR 0.31, 95% CI 0.12-0.76, and RR 0.24, 95% CI 0.10-0.58, respectively). The pooled effect of the included trials that utilized L. reuteri [38,40], B. breve [22,39] and Saccharomyces boulardii alone [24,45,62] showed a lack of significant reduction of severe NEC stage II-III (RR 0.71, 95% CI 0.37-1.39, and RR 0.92, 95% CI 0.67-1.28; RR 0.82, 95% CI 0.44-1.50, respectively). Subgroup analysis identified that mixtures of 2 types and mixtures of more than 2 types of probiotics were most beneficial in reducing the risk of NEC (RR = 0.34; 95% CI 0.17-0.67, p = 0.002, and RR = 0.40; 95% CI 0.26-0.64, p < 0.0001, respectively; online suppl.…”

Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis

“…Twenty-five studies were then suitable for inclusion in the systematic review (Table 1) [21,22,23,24,25,26,27,30,34,36,37,38,39,40,41,48,49,50,56,60,61,64,66,68,70]. …”

Probiotics and antimicrobial protein and peptide levels in preterm infants

“…Probiotic supplementation resulted in high intestinal colonisation rates, comparable to other probiotic trials . There are limited published data on faecal levels of APP; human beta‐defensin 2 was detected in faeces of both term and preterm infants during the first weeks of life; however, the potential relationship with specific intestinal bacteria was not investigated .…”