Prophylactic Use of Lactobacillus acidophilus/Bifidobacterium infantis Probiotics and Outcome in Very Low Birth Weight Infants

16,435

137

Background: Over the last few years, probiotics have been one of the most studied interventions in neonatal medicine. Objectives: The aim of this work was to analyse all studies (randomized controlled trials, RCTs, and observational studies) assessing the use of probiotics in very low birth weight (VLBW) preterm infants. Search Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, and Web of Science. The data from RCTs and observational studies were pooled and analysed separately. Selection Criteria: RCTs and observational studies that enrolled VLBW infants with enteral administration of probiotics were considered. Extracted study data included probiotic characteristics and at least 1 clinical outcome (necrotizing enterocolitis [NEC], late-onset sepsis or all-cause mortality). Data Collection and Analysis: Forty-four studies were eligible for our review: 30 RCTs and 14 observational studies. Severe NEC rates (stage II or more) and all-cause mortality were reduced among the probiotic groups in both the RCTs (RR 0.57, 95% CI 0.47-0.70, and RR 0.77, 95% CI 0.65-0.92, respectively) and the observational studies (RR 0.51, 95% CI 0.37-0.70, and RR 0.71, 95% CI 0.62-0.81, respectively). Furthermore, there was a 12% reduction in the risk of sepsis in RCTs and a 19% reduction in observational studies. The meta-analysis of observational studies showed a reduction in the risk of NEC in extremely low birth weight infants. However, this was not statistically significant. Conclusions: This meta-analysis of RCT and observational studies found that the use of probiotics was beneficial for the prevention of severe NEC, late-onset sepsis, and all-cause mortality in VLBW infants.

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Dermyshi

Wang²,

Yan³

et al. 2017

16,435

137

“…Two studies [13,14] had insufficient data presentation (only on preterm neonates) and were therefore not included in the meta-analysis calculation. Hence, 12 studies were pooled in the meta-analysis, including a total of 10,800 neonates [15,16,17,18,19,20,21,22,23,24,25,26]. Details of the selection process are shown in figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…All included studies were longitudinal cohort studies, either retrospective [15,16,19,22,23], prospective [17,18,20,21,24,26] or with a historical control group [25]. Ten of the included studies were single-center studies and 2 were multicenter [17,23]. With the exception of 2 studies [16,18], all studies classified NEC according to Bell's criteria ≥stage II [10].…”

Section: Resultsmentioning

confidence: 99%

Prophylactic Probiotics for Preterm Infants: A Systematic Review and Meta-Analysis of Observational Studies

Olsen

Greisen²,

Schrøder³

et al. 2015

115

Background: Necrotizing enterocolitis (NEC) is a major morbidity and cause of mortality in preterm neonates. Probiotics seem to have a beneficial role in preventing NEC, which is confirmed in meta-analyses of randomized controlled trials (RCTs). We therefore aimed to review and confirm the efficacy of probiotics in preterm neonates obtained in observational studies. Objective: To assess the effects of prophylactic probiotics in preterm infants. Methods: A meta-analysis was performed searching PubMed, EMBASE, CENTRAL (the Cochrane Library) and www.clinicaltrials.gov. Reference lists of reviews of RCTs were also searched. Included studies were observational studies that enrolled preterm infants <37 weeks of gestational age. Trials were included if they administered any probiotics and measured at least one clinical outcome (e.g. NEC, all-cause mortality, sepsis or long-term development scores). Two authors extracted characteristics and outcomes from included studies. The Newcastle-Ottawa Scale was used for quality assessment. A random-effects meta-analysis model was used, and heterogeneity was assessed by the I² test. Results: We included 12 studies with 10,800 premature neonates (5,144 receiving prophylactic probiotics and 5,656 controls). The meta-analysis showed a significantly decreased incidence of NEC (risk ratio, RR = 0.55, 95% confidence interval, 95% CI, 0.39-0.78; p = 0.0006) and mortality (RR = 0.72, 95% CI, 0.61-0.85; p < 0.0001). Sepsis did not differ significantly between the two groups (RR = 0.86, 95% CI, 0.74-1.00; p = 0.05). Conclusions: Probiotic supplementation reduces the risk of NEC and mortality in preterm infants. The effect sizes are similar to findings in meta-analyses of RCTs. However, the optimal strain, dose and timing need further investigation.

“…Moreover, Härtel et al [8 ]demonstrated the benefit of probiotics in the VLBW infant population for reducing the gastrointestinal morbidity. In both studies, no probiotic systemic infections were observed; however, in the absence of clinical signs, an asymptomatic transient bacteremia with probiotic microorganisms could have been missed.…”

Section: Discussionmentioning

confidence: 99%

Case Series of<b><i> Bifidobacterium longum</i></b> Bacteremia in Three Preterm Infants on Probiotic Therapy

Zbinden

Berger

et al. 2014

Background: The use of probiotics as prophylaxis for necrotizing enterocolitis (NEC) in preterm infants is being increasingly practised. Objective: We report, for the first time, a case series of 3 preterm, very-low-birth-weight (VLBW) infants who developed bacteremia with Bifidobacterium longum on probiotic therapy with Infloran® containing viable B. longum. Methods: We retrospectively reviewed data of3 infants (of gestational age <30 weeks and birth weight <1,230 g). They were admitted to the neonatal intensive care unit. Clinical data were retrieved from their medical records. Results: In infants 1 and 2, B. longum was isolated from the blood cultures when they were on probiotic therapy with Infloran or shortly after, respectively, and was interpreted as transient bacteremia. The clinical presentation of these infants did not require antibiotic treatment after the isolation of B. longum. Infant 3 developed an NEC despite probiotic therapy with Infloran and the blood cultures showed B. longum growth. This infant required explorative laparotomy and antibiotic treatment. The clinical isolates of B. longum and the strain of the Infloran capsule showed an identical profile on biochemical, mass-spectrometric and molecular analyses, suggesting a direct correlation between the administration of probiotics and bacteremia with B. longum in all 3 infants. Conclusions: The occurrence of bacteremia with bifidobacteria after its prophylactic administration in VLBW infants and its possible clinical consequences are a matter of concern. In the interests of safety, the use of probiotics in such a population should be indicated with caution and requires further investigation.