Review Article
Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very low-birth-weight infants: an updated meta-analysis of 20 randomized, controlled trials,☆☆

https://doi.org/10.1016/j.jpedsurg.2011.09.064Get rights and content

Abstract

Purpose

Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract in preterm infants, whereas probiotic supplementation might reduce NEC risk and potentially provide benefits to preterm infants. We performed an updated meta-analysis of all relevant randomized, controlled trials to assess the benefits of probiotic supplementation for preterm very low-birth-weight (VLBW) infants.

Methods

We searched in PubMed, Embase, and Chinese BioMedical Literature Database (CBM) databases, and 20 randomized, controlled trials (a total of 3816 preterm VLBW infants) were finally included into this meta-analysis. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model depending on the heterogeneity of the included studies.

Results

Probiotic supplement was associated with a significantly decreased risk of NEC in preterm VLBW infants (RR = 0.33; 95% confidence interval [CI], 0.24-0.46; P < .00001). Risk of death was also significantly reduced in the probiotic group (RR = 0.56; 95% CI, 0.43-0.73; P < .0001). There was no difference in the risk of sepsis between the probiotic group and placebo group (RR = 0.90; 95% CI, 0.71-1.15; P = .40).

Conclusions

Probiotic supplement can reduce risk of NEC and mortality in preterm VLBW infants. However, the optimum type of probiotic supplement and the long-term effects need further study.

Section snippets

Search strategy and selection criteria

We searched PubMed, Embase, and CBM databases for studies published between January 1985 and March 2011, with the search terms “very low birth weight infant” or “low birth weight infant” or “extremely low birth weight infant” or “premature infant” or “preterm infant” and “lactobacillus” or “probiotics” or “saccharomyces” or “bifid bacterium”. No language restriction was applied. The reference lists of identified studies and key review articles were also searched. The inclusion criteria of this

Demographic characteristics of the studies

Our search yielded a total of 150 studies on probiotic supplement for preterm VLBW infants (Fig. 1). After reviewing each abstract or original publication and extracting data from the publications, 7 RCTs were excluded because of an absence of clinically relevant data even after contacting the investigators [23], [24], [25], [26], [27], [28], [29]. Finally, we identified 20 original RCTs (16 in English, 4 in Chinese), including a total of 3816 patients [12], [13], [14], [15], [16], [30], [31],

Discussion

Previous studies investigating probiotic supplement for preterm VLBW infants have provided inconsistent results, and most of those studies involved no more than a few hundred preterm infants, which is too few to assess any effect reliably. Meta-analysis has been recognized as an important tool to define the effect of clinical interventions more precisely and to identify potentially important sources of between-study heterogeneity. A meta-analysis of 11 studies showed the dramatic benefits of

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      The inflammation of the intestine leading to bacterial invasion causing cellular damage and death which causes necrosis of the colon and intestine [62,71]. Compared with term infants, the intestinal microbiota of preterm infants has fewer bacterial species, less diversity, smaller proportions of beneficial bacteria including Lactobacillus and Bifidobacterium species and increased levels of bacteria that can become pathogenic Gammaproteobacteria (i.e. E. coli, Klebsiella pneumoniae) [72,73]. Since then, numerous trials evaluating the efficacy of probiotics in preventing NEC have been conducted, with some demonstrating efficacy [66,74].

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    Conflict of interest statement: We declare that we have no conflict of interest.

    ☆☆

    Role of funding source: None.

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