Probiotics and prebiotics in preterm infants: Where are we? Where are we going?

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Abstract

Background

Uncertainty exists regarding the efficacy and safety of using probiotics and prebiotics in preterm infants.

Aim

To review the evidence on the effects of administering probiotics and/or prebiotics to preterm infants.

Methods

MEDLINE and the Cochrane Library were searched in August 2008. A supplemental search was conducted in July 2009. Only systematic reviews/meta-analyses and randomized controlled trials (RCTs) that evaluated the effects of probiotics and/or prebiotics on relevant short- and long-term primarily clinically important health outcomes published in the English language were included.

Results

One systematic review and 2 well-performed meta-analyses suggest that probiotics reduce the risk of necrotizing enterocolitis (NEC) (stage ≥ 2). One subsequently published RCT reported similar results. The 2 meta-analyses also demonstrated that probiotics reduce the risk of death due to all causes, but do not have an effect on the risk of sepsis or death due to NEC. Regarding prebiotics, one meta-analysis of 4 RCTs demonstrated that prebiotic-supplemented formula increases stool colony counts of bifidobacteria and lactobacilli in preterm neonates without adversely affecting weight gain. Because of the limited data regarding synbiotics, the relationship between their use and clinical outcomes in preterm infants remains unclear.

Conclusions

The findings from the 2 meta-analyses of the effects of probiotic administration on the prevention of NEC show potential for such dietary supplementation. However, they must be interpreted with caution because the beneficial effects of probiotics seem to be strain specific, thus, pooling data from different strains may result in misleading conclusions. Before the routine use of probiotics and/or prebiotics in preterm infants, data regarding which products should be administered, at what dose, and for how long are needed.

Introduction

Over the past decade or so, we have witnessed an explosion of new information pertaining to the possible role of gut microbiota in health and disease. This has led to an interest in the development of strategies aimed at manipulating bacterial colonization, including the administration of probiotics or prebiotics or a combination of both (synbiotics). These products are currently gaining worldwide popularity and are increasingly being used in the pediatric population. However, uncertainty exists regarding the efficacy and safety of their use in preterm infants.

The purpose of this paper is to summarize the literature concerning the effects of administering probiotics and/or prebiotics to preterm infants primarily on clinically relevant health outcomes. Literature searches of MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Trials Register were performed in August 2008. Search terms included subject headings and text words relevant to probiotics and/or prebiotics and preterm infants. Supplemental searches were conducted through July 2009. The searches were limited to randomized controlled trials (RCTs) or their systematic reviews or meta-analyses. For outcomes of interest that have previously been reviewed systematically, a summary of the findings from those reviews is presented. In addition, data from primary studies published subsequent to those reviews are assessed.

Section snippets

Probiotics

Probiotics are defined as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host’ [1]. The rationale for probiotic supplementation of preterm infants is based on data demonstrating differences in the establishment of the intestinal microbiota in preterm infants [2], [3], [4], [5], [6]. Compared with healthy, full-term infants, the intestinal microbiota in preterm infants features a low number of species, with typically only 3 bacterial species found

Prebiotics

The term ‘prebiotic’ was introduced by Gibson and Roberfroid in 1995, who defined prebiotics as ‘nondigestible food components that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon and thereby improving host health’ [40]. Oligosaccharides that are contained in human breast milk are considered to be the prototype of prebiotics, since they have been shown to facilitate the growth of bifidobacteria and

Synbiotics

The term ‘synbiotic’ is used ‘when a product contains both probiotics and prebiotics’ [53]. In a recently published RCT [54], 90 preterm infants received a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides, a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides, or placebo (a dilute preparation of Pregestamil formula) twice daily for 28 days or until discharge if earlier. The study found that preterm infants who

Safety issues

In 2004, the ESPGHAN Committee on Nutrition commented on the probiotic bacteria in dietetic products for infants and stated that the probiotics used thus far in clinical trials can be generally considered as safe. However surveillance regarding the detection of possible side effects, such as cases of infection in high-risk groups for which there is very little systematic evidence available, is needed. The Committee concluded that the available data are not sufficient to support the safety of

Conclusions

So where are we now, and where are we going? The magnitude of the problem of prematurity worldwide justifies any attempt at the prevention of morbidity and mortality in preterm infants. Probiotics and prebiotics have the potential to prevent and treat many disorders in preterm infants. To date, the most promising application is the prevention of NEC by the administration of probiotics. Many other benefits of administering probiotics and/or prebiotics to preterm infants are, however, largely

Role of the funding source

No funding source was involved in this study.

Conflict of interest

None declared.

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  • Cited by (27)

    • Bacterial colonization and gut development in preterm neonates

      2012, Early Human Development
      Citation Excerpt :

      Despite limited evidence for a role of specific bacteria in NEC development, numerous attempts have been made to modify intestinal colonization with probiotic bacteria to decrease the risk of NEC. Several meta analyses [76–79] and a recently updated Cochrane analysis [80,81] claim that interventions with probiotics mostly from the genera of Lactobacilli and Bifidobacteria are safe for preterm infants and reduce the risk of NEC. Based on animal studies [27,82,83], these probiotics are hypothesized to exert their effect through competitive exclusion of potential pathogens and stimulation of the host immune system [4,5,84], improved regulation of apoptosis and cyto-protective responses [85] and better gut barrier functions [82,83].

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    Presented at the 2nd International Conference on ‘Nutrition of the preterm infant: current issues’, Rome, 18–19 September 2008. The Symposium Director was Professor Vittorio Vigi.

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