Effects of Probiotics on Necrotizing Enterocolitis, Sepsis, Intraventricular Hemorrhage, Mortality, Length of Hospital Stay, and Weight Gain in Very Preterm Infants: A Meta-Analysis

Abstract

Probiotics are increasingly used as a supplement to prevent adverse health outcomes in preterm infants. We conducted a systematic review, meta-analysis, and subgroup analysis of findings from randomized controlled trials (RCTs) to assess the magnitude of the effect of the probiotics on health outcomes among very-low-birth-weight (VLBW) infants. Relevant articles from January 2003 to June 2017 were selected from a broad range of databases, including Medline, PubMed, Scopus, and Embase. Studies were included if they used an RCT design, involved a VLBW infant (birthweight <1500 g or gestational age <32 wk) population, included a probiotic intervention group, measured necrotizing enterocolitis (NEC) as a primary outcome, and measured sepsis, mortality, length of hospital stay, weight gain, and intraventricular hemorrhage (IVH) as additional outcomes. The initial database search yielded 132 potentially relevant articles and 32 ( = 8998 infants) RCTs were included in the final meta-analysis. Subgroup analysis was used to evaluate the effects of the moderators on the outcome variables. In the probiotics group, it was found that NEC was reduced by 37% (95% CI: 0.51%, 0.78%), sepsis by 37% (95% CI: 0.72%, 0.97%), mortality by 20% (95% CI: 0.67%, 0.95%), and length of hospital stay by 3.77 d (95% CI: -5.94, -1.60 d). These findings were all significant when compared with the control group. There was inconsistent use of strain types among some of the studies. The results indicate that probiotic consumption can significantly reduce the risk of developing medical complications associated with NEC and sepsis, reduce mortality and length of hospital stay, and promote weight gain in VLBW infants. Probiotics are more effective when taken in breast milk and formula form, consumed for <6 wk, administered with a dosage of <10 CFU/d, and include multiple strains. Probiotics are not effective in reducing the incidence of IVH in VLBW infants.

What do Cochrane systematic reviews say about probiotics as preventive interventions?

“…7 Indeed, many trials assessing the effects of probiotics (including using different species of microorganisms) as preventive or therapeutic options for a range of diseases have been conducted and published. 2,5 Consequently, a considerable amount of published data is currently available through MEDLINE. Corroborating this, a search in this database carried out on July 26, 2017, using the MeSH (medical subheading) term probiotics, retrieved 12,370 records, which corresponded to an increase of 278% in the number of records over the last ten years (from December 2007 to July 2017).…”

“…3,4 Some research has shown that use of probiotics can confer some health benefits, such as treatment for diarrheal disease, prevention of systemic infections and other effects. 2,5 The 2001 definition from the World Health Organization (WHO) states that probiotics are "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host". 6 They are currently presented by media sources as an attractive health promotion method that prevents or cures a range of clinical situations.…”

Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk

“…Previous studies revealed inconsistent results that were not necessarily adjusted for the type of feeding [27][28][29][30]. A meta-analysis of 15 studies including 3751 infants <32 weeks and <1500 g birth weight demonstrated no significant effects of probiotics on weight gain [31]. In comparison to our cohort, the gestational age in this pooled study cohort analysis was higher while mean weight gain/day was lower (16 g/day vs. 21 g/day) indicating that the effects of probiotics are context sensitive.…”

Probiotics and Prebiotics in Infant Formulae

“…In a review on the effects of a variety of immunonutrients in the prevention of necrotizing enterocolitis [35], the authors gathered sufficient data supporting supplementation of infant formulae with probiotics. Several meta-analyses combined these randomized controlled trials and observational studies demonstrated that the use of probiotics was beneficial for the prevention of severe necrotizing enterocolitis, late-onset sepsis, and all-cause mortality in very-low-birth-weight infants, as well as the time to achieve full enteral feeding in preterm infants [36][37][38]. By contrast, no differences were observed in a multicenter study involving 1315 preterm newborns fed with a hydrolyzed formula supplemented and nonsupplemented with the probiotic Bifidobacterium breve BBG-001 [39]; the results of this trial provide no evidence of benefit of this probiotic intervention in reducing late-onset sepsis and necrotizing enterocolitis or death.…”