Next Article in Journal
Associations of Fat Mass and Fat-Free Mass with Physical Fitness in 4-Year-Old Children: Results from the MINISTOP Trial
Next Article in Special Issue
A Comparison by Milk Feeding Method of the Nutrient Intake of a Cohort of Australian Toddlers
Previous Article in Journal
Beverage Intake Assessment Questionnaire: Relative Validity and Repeatability in a Spanish Population with Metabolic Syndrome from the PREDIMED-PLUS Study
Previous Article in Special Issue
Usual Intake of Key Minerals among Children in the Second Year of Life, NHANES 2003–2012
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 8
Issue 8
10.3390/nu8080471
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

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

by
Arianna Aceti
1,2,
Davide Gori
2,3,
Giovanni Barone
2,4,
Maria Luisa Callegari
2,5,
Maria Pia Fantini
2,3,
Flavia Indrio
2,6,7,
Luca Maggio
2,4,7,
Fabio Meneghin
2,8,
Lorenzo Morelli
2,5,
Gianvincenzo Zuccotti
2,9 and
Luigi Corvaglia
1,2,7,*
1
Neonatology and Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna 40138, Italy
2
Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy
3
Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna 40138, Italy
4
Neonatal Unit, Catholic University, Rome 00168, Italy
5
Institute of Microbiology, UCSC, Piacenza 29122, Italy
6
Department of Pediatrics, Aldo Moro University, Bari 70124, Italy
7
Study Group of Neonatal Gastroenterology and Nutrition of the Italian Society of Neonatology, Milan 20126, Italy
8
Division of Neonatology, Children Hospital V. Buzzi, ICP, Milan 20154, Italy
9
Department of Pediatrics, Children Hospital V. Buzzi, University of Milan, Milan 20154, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2016, 8(8), 471; https://doi.org/10.3390/nu8080471
Submission received: 13 June 2016 / Revised: 17 July 2016 / Accepted: 26 July 2016 / Published: 30 July 2016
(This article belongs to the Special Issue Nutrients in Infancy)
Browse Figures
Versions Notes

Abstract

:
Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD −3.15 days (95% CI −5.25/−1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management.

Graphical Abstract

1. Introduction

Nutrition during critical time windows in early life can affect long-term health [1]. Early provision of optimal enteral nutrition to preterm infants might improve neurodevelopmental outcome by decreasing the rate of several complications of prematurity, such as extrauterine growth restriction, necrotizing enterocolitis (NEC), sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity [2].
Late introduction and slow advancement of enteral feeding may alter gastrointestinal motility and disrupt microbial colonization [3], leading to a delay in establishing full enteral feeding (FEF). The consequent prolonged need for parenteral nutrition can have serious infectious and metabolic complications, which might prolong hospital stay, increase morbidity and mortality, and affect growth and development [4].
Several clinical variables and interventions have been proposed as predictors of the time to FEF achievement in preterm and very-low-birth-weight (VLBW) infants. Among these variables, the influence of type of feeding was also documented, as FEF achievement was delayed in formula-fed infants compared to human milk (HM)-fed infants [5].
Recently, probiotic use has been associated with a reduced time to achieve FEF and better feeding tolerance [6], as well as a reduction of NEC [7,8] and late-onset sepsis [9]. Probiotics are live microorganisms which, when ingested in adequate amounts, confer a health benefit to the host, by modifying the composition and function of gut microbiota and the immunological responses in the host [10]. The role of probiotics in attaining a more rapid achievement of FEF could be related to their favorable effect on the physiological intestinal dysbiosis of preterm infants [11], which is the result of the exposure to a unique environment and to several iatrogenic manipulations, such as broad spectrum antibiotics [12]. It is well known that gut microbiota in HM-fed infants is different compared to formula-fed infants [13]; data from an observational study also suggest a feeding-dependent effect of probiotics, as in that study NEC incidence was reduced in infants treated with probiotics and receiving HM, but not in those exclusively formula-fed [14]. However, the relationship between probiotics and type of feeding in attaining a more rapid achievement of FEF has not been explored yet, even in the most recent meta-analysis on this topic [6].
Thus, the aim of the present paper was to evaluate the effect of probiotics on time to FEF achievement according to type of feeding (exclusive HM vs. formula), by performing a systematic review and meta-analysis of currently available literature on this topic.

2. Materials and Methods

2.1. Literature Search

The study protocol was designed by the members of the Task Force on Probiotics of the Italian Society of Neonatology. PRISMA guidelines [15] were followed in order to perform a systematic review of published studies reporting the relationship between probiotic use and time to FEF achievement in preterm infants according to type of feeding.
In order to be included in the meta-analysis, studies had to meet the following inclusion criteria: randomized or quasi-randomized clinical trials involving preterm infants (gestational age (GA) <37 weeks) who received, within one month of age, any probiotic compared to placebo or no treatment, and reporting on type of feeding. The outcome of interest was time for FEF achievement (any definition). Only English-written studies and studies involving humans were included in the meta-analysis.
A search was conducted for studies published before 2 March 2016 in PubMed [16], the Cochrane Library [17], and Embase [18]. The following search string was used for the PubMed search: ((preterm infant OR pre-term infant) OR (preterm infants OR pre-term infants) OR (preterm neonate OR pre-term neonate) OR (preterm neonates OR pre-term neonates) OR (preterm newborn OR pre-term newborn) OR (preterm newborns OR pre-term newborns) OR (premature infant OR premature infants) OR (premature neonate OR premature neonates) OR (premature newborn OR premature newborns) OR infant, extremely premature (MeSH Heading (MH)) OR premature birth (MH) OR infant, low birth weight (MH) OR infant, very low birth weight (MH)) AND (full enteral* OR feed*) AND (probiotic OR probiotics OR pro-biotic OR pro-biotics OR probio*)) NOT (animals (MH) NOT humans (MH).
The string was built up by combining all the terms related to probiotics and FEF achievement: PubMed MeSH terms, free-text words, and their combinations obtained through the most proper Boolean operators were used. The same criteria were used for searching the Cochrane Library and Embase.
Arianna Aceti and Luigi Corvaglia performed the literature search: relevant studies were identified from the abstract; full-texts of relevant studies were examined, as well as their reference lists in order to identify additional studies.

2.2. Data Extraction and Meta-Analysis

Study details (population, characteristics of probiotic and placebo, type of feeding, and outcome assessment) were evaluated independently by Arianna Aceti and Luigi Corvaglia, and checked by Davide Gori. Study quality was evaluated independently by Arianna Aceti and Davide Gori using the risk of bias tool as proposed by the Cochrane collaboration (Chapter 8 of the Cochrane Handbook of Systematic Reviews) [19].
The corresponding authors of the studies in which days to FEF achievement were not reported as mean ± standard deviation (SD) were contacted by email. When data were not provided, the study was not included in the meta-analysis.
The association between probiotic use and FEF achievement according to type of feeding was evaluated by a meta-analysis conducted by AA and DG using the RevMan software (Cochrane Informatics and Knowledge Management Department, version 5.3.5) downloaded from the Cochrane website [20]. Mean difference (MD) in days to achieve FEF between infants receiving probiotics and those receiving placebo or no treatment was calculated using the inverse variance method, and reported with 95% confidence interval (CI).
For the analysis, we planned to use at first a fixed effect model. Heterogeneity was measured using the I2 test: if significant heterogeneity was present (p < 0.05 from the χ2 test) and/or the number of studies was ≤5, a random-effects model was used instead.

3. Results

Literature Search

Overall, 372 papers were identified through the literature search, 155 in PubMed [16], 73 in the Cochrane Library [17], and 144 in Embase [18].
As shown in Figure 1, 35 studies met the inclusion criteria [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55]. Fourteen additional papers were identified from the reference lists of included studies or by “snowballing” techniques [52,56,57,58,59,60,61,62,63,64,65,66,67,68].
Twenty-four studies were excluded after examining the full-texts [28,29,31,32,33,35,42,43,44,45,46,47,51,53,54,55,57,58,59,62,63,65,69]. 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].
Among them, only eight studies reported FEF achievement according to type of feeding: infants were fed exclusively HM, either own mother’s (OMM) or donor human milk (DHM), in six studies [22,38,50,56,60,70], while two studies reported FEF in exclusively formula-fed infants [41,61].
The corresponding authors of four of these papers were contacted by email, as data for FEF achievement were not suitable for inclusion in the meta-analysis: mean ± SD of days for FEF achievement were provided for one study [22], while data were unavailable for three studies [41,61,70]; these three studies were thus excluded from the meta-analysis.
Overall, five studies were included in the meta-analysis: in all these studies, infants were fed exclusively HM, either OMM or DHM (Figure 1) [22,38,50,56,60].
Data from 359 infants in the probiotic group and 360 infants in the control group were evaluated: probiotic use was associated with a reduction in the time for FEF achievement (MD −3.15 days (95% CI −5.25/−1.05), p = 0.003; Figure 2a). The funnel plot did not show any clear asymmetry (Figure 2b).
Three studies were not included in the meta-analysis because data on FEF were not available as mean ± SD [41,61,70]. One study reported the use of Bacillus clausii in preterm infants with GA < 34 weeks, fed expressed breast milk or DHM [70] and stratified as extreme preterm (GA 27–30 + 6 weeks) and very preterm (GA 31–33 + 6 weeks). In both groups, probiotic use was associated with a reduced time to achieve FEF (risk ratio 0.82 (95% CI 0.74–0.88) and 0.67 (95% CI 0.32–0.77), respectively).
The other two studies reported probiotic use in exclusively formula-fed infants: in the study by Costalos et al., infants born at 28–32 weeks gestation and fed exclusively preterm formula received Saccharomyces boulardii or placebo for approximately 30 days [41]. In the study by Stratiki et al., formula-fed infants with a similar gestational age (27–32 weeks) received Bifidobacterium lactis vs. no treatment [61]. Neither of these two studies reported any significant difference between groups in terms of time to FEF achievement.
All the studies included in the meta-analysis, except one [50], recruited exclusively infants with birth weight <1500 g. The study by Roy et al. [50] reported specific data for extremely low birth weight (ELBW) infants: time to reach FEF in ELBW infants treated with probiotics was significantly lower than in controls (mean ± SD 13.22 ± 5.04 vs. 17.41 ± 8.07, respectively, p = 0.014). None of the studies included in the meta-analysis reported separate data on intrauterine growth restricted (IUGR) infants.
In all the studies, except one [56], a probiotic mix was used: the meta-analysis performed after the exclusion of the study by Manzoni et al., where a single-strain product containing Lactobacillus GG was used, confirmed the results of the overall analysis (MD −3.33 days (95% CI −5.63/−1.04), p ≤ 0.004).

4. Methodological Study Quality

Evaluation of the quality of the studies included in the meta-analysis according to the risk of bias tool as proposed by the Cochrane Collaboration [19] is shown in Table 2.

5. Discussion

The present meta-analysis shows that the use of probiotics in preterm, VLBW infants fed exclusively HM is associated with 3-days reduction in the time to FEF achievement. The only two studies included in the present systematic review in which infants were exclusively formula-fed did not report any difference between the probiotic and the control group.
The single previous meta-analysis investigating FEF as primary outcome showed an overall smaller reduction in the time to FEF achievement, but did not report separate data for HM-fed and formula-fed infants [6]. The studies included in the meta-analysis by Athalye-Jape et al. are almost the same as those included in our systematic review; quite surprisingly, in the majority of the studies included in these two reviews, both HM and formula-fed infants were recruited, but no detailed information on the relationship between type of feeding and outcome was provided.
Type of feeding might modulate the relationship between probiotics and neonatal clinical outcome [14]. It has been previously shown that HM feeding is associated with shorter time to achieve FEF compared to formula feeding [5]. Our meta-analysis, which included only studies where infants were exclusively HM-fed, showed a significant reduction in the time to achieve FEF attributable to probiotics. Despite the limitation given by the small number of studies, a probiotic-related 3-days reduction in time to achieve FEF in preterm infants fed exclusively HM has strong clinical implications and deserves further consideration. When OMM is not available or contraindicated, the use of pasteurized DHM is recommended for preterm infants: pasteurization inactivates most viral and bacterial agents, but at the same time affects some nutritional and immunological properties of HM, including endogenous probiotics [71]. It can be speculated that the beneficial effect of probiotics documented in exclusively HM-fed infants could be attributed to a synergic action exerted by the prebiotic components of HM and the exogenous probiotic, which partially restores the symbiotic properties of naïve HM [72]. In the present meta-analysis, no separate data for OMM-fed and DHM-fed infants were available; for this reason, it is not possible to clarify whether the beneficial effect of HM on FEF achievement applies both to OMM and to DHM.
Heterogeneity among included studies was high; however, given the small number of papers, our ability to explore sources of heterogeneity was limited. In the five included studies, different probiotic strains were used. We aimed to perform strain-specific sub-meta-analyses, in order to clarify whether there was any probiotic product showing a significant benefit in terms of reduction in the time to achieve FEF. However, such analyses were not feasible, as none of the studies used the same probiotic strain or mix. Similarly, it was not possible to explore additional sources of heterogeneity, such as the characteristics of probiotic administration (dose, duration, infant age at probiotic initiation, etc.). In addition, we were unable to test for subgroup differences between HM-fed and formula-fed infants, which might have partially explained the different results in terms of FEF achievement.
Apparently, studies were homogeneous in terms of included populations, as almost all of them recruited only VLBW infants. However, few data on “high-risk” infants, such as ELBW and IUGR infants, could be extrapolated from the main results of the included studies.
The use of probiotics should be weighed against their potential side effects. There are some reports about the occurrence of sepsis in preterm newborns, potentially linked to probiotic administration [73].
However, none of the studies included in the systematic review reported any side effect related to the use of probiotics.

6. Conclusions

According to the results of the present meta-analysis, the use of probiotics is linked to 3-days reduction in time to achieve FEF in preterm VLBW infants fed exclusively HM. If confirmed in further studies, this reduction might have strong clinical implications for this high-risk population.

Acknowledgments

No funding was received to produce the present paper.

Author Contributions

Each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript. Specifically, all the authors, as part of the Task Force on Probiotics of the Italian Society of Neonatology, conceived and designed the study protocol. A.A. and L.C. performed the literature search and assessed study details, which were checked by D.G. A.A. and D.G. evaluated study quality and performed the meta-analyses. A.A. and L.C. wrote the first draft of the paper, which was critically revised by all the other authors.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Faldella, G.; Aceti, A.; Corvaglia, L. Formula milk and neurodevelopmental and cognitive outcomes: Where are we now? Early Hum. Dev. 2011, 87S, S5–S8. [Google Scholar] [CrossRef] [PubMed]
  2. Hsiao, C.-C.; Tsai, M.-L.; Chen, C.-C.; Lin, H.-C. Early optimal nutrition improves neurodevelopmental outcomes for very preterm infants. Nutr. Rev. 2014, 72, 532–540. [Google Scholar] [CrossRef] [PubMed]
  3. Berrington, J.E.; Stewart, C.J.; Embleton, N.D.; Cummings, S.P. Gut microbiota in preterm infants: Assessment and relevance to health and disease. Arch. Dis. Child. Fetal Neonatal Ed. 2013, 98, F286–F290. [Google Scholar] [CrossRef] [PubMed]
  4. The SIFT Investigators Group. Early enteral feeding strategies for very preterm infants: Current evidence from Cochrane reviews. Arch. Dis. Child. Fetal Neonatal Ed. 2013, 98, F470–F472. [Google Scholar]
  5. Corvaglia, L.; Fantini, M.P.; Aceti, A.; Gibertoni, D.; Rucci, P.; Baronciani, D.; Faldella, G. Predictors of full enteral feeding achievement in very low birth weight infants. PLoS ONE 2014, 9. [Google Scholar] [CrossRef] [PubMed]
  6. Athalye-Jape, G.; Deshpande, G.; Rao, S.; Patole, S. Benefits of probiotics on enteral nutrition in preterm neonates: a systematic review. Am. J. Clin. Nutr. 2014, 100, 1508–1519. [Google Scholar] [CrossRef] [PubMed]
  7. Aceti, A.; Gori, D.; Barone, G.; Callegari, M.L.; Di Mauro, A.; Fantini, M.P.; Indrio, F.; Maggio, L.; Meneghin, F.; Morelli, L.; et al. Probiotics for prevention of necrotizing enterocolitis in preterm infants: Systematic review and meta-analysis. Ital. J. Pediatr. 2015, 41, 89. [Google Scholar] [CrossRef] [PubMed]
  8. Alfaleh, K.; Anabrees, J.; Bassler, D. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst. Rev. 2014, CD005496. [Google Scholar] [CrossRef] [PubMed]
  9. Rao, S.C.; Athalye-jape, G.K.; Deshpande, G.C.; Simmer, K.N.; Patole, S.K. Probiotic supplementation and late-onset sepsis in preterm infants: A meta-analysis. Pediatrics 2016, 137, e20153684. [Google Scholar] [CrossRef] [PubMed]
  10. Sanders, M.E.; Guarner, F.; Guerrant, R.; Holt, P.R.; Quigley, E.M.M.; Sartor, R.B.; Sherman, P.M.; Mayer, E.A. An update on the use and investigation of probiotics in health and disease. Gut 2013, 62, 787–796. [Google Scholar] [CrossRef] [PubMed]
  11. Murguía-Peniche, T.; Mihatsch, W.A.; Zegarra, J.; Supapannachart, S.; Ding, Z.-Y.; Neu, J. Intestinal mucosal defense system, Part 2. Probiotics and prebiotics. J. Pediatr. 2013, 162, S64–S71. [Google Scholar] [CrossRef] [PubMed]
  12. Martin, C.R.; Walker, W.A. Probiotics: Role in pathophysiology and prevention in necrotizing enterocolitis. Semin. Perinatol. 2008, 32, 127–137. [Google Scholar] [CrossRef] [PubMed]
  13. Carlisle, E.M.; Morowitz, M.J. The intestinal microbiome and necrotizing enterocolitis. Curr. Opin. Pediatr. 2013, 25, 382–387. [Google Scholar] [CrossRef] [PubMed]
  14. Repa, A.; Thanhaeuser, M.; Endress, D.; Weber, M.; Kreissl, A.; Binder, C.; Berger, A.; Haiden, N. Probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum) prevent NEC in VLBW infants fed breast milk but not formula. Pediatr. Res. 2015, 77, 381–388. [Google Scholar] [CrossRef] [PubMed]
  15. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [PubMed]
  16. PubMed. Available online: http://www.ncbi.nlm.nih.gov/pubmed (accessed on 28 July 2016).
  17. Cochrane Library. Available online: http://www.cochranelibrary.com/ (accessed on 28 July 2016).
  18. Embase. Available online: http://store.elsevier.com/en_US/info/30800006 (accessed on 28 July 2016).
  19. Higgins, J.P.; Green, S. Cochrane Handbook for Systematic Reviews of Interventions; The Cochrane Collaboration: London, UK, 2011. [Google Scholar]
  20. RevMan Software. Available online: http://tech.cochrane.org/revman/download (accessed on 28 July 2016).
  21. Totsu, S.; Yamasaki, C.; Terahara, M.; Uchiyama, A.; Kusuda, S. Bifidobacterium and enteral feeding in preterm infants: Cluster-randomized trial. Pediatr. Int. 2014, 56, 714–719. [Google Scholar] [CrossRef] [PubMed]
  22. Van Niekerk, E.; Kirsten, G.F.; Nel, D.G.; Blaauw, R. Probiotics, feeding tolerance, and growth: A comparison between HIV-exposed and unexposed very low birth weight infants. Nutrition 2014, 30, 645–653. [Google Scholar] [CrossRef] [PubMed]
  23. Patole, S.; Keil, A.D.; Chang, A.; Nathan, E.; Doherty, D.; Simmer, K.; Esvaran, M.; Conway, P. Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates—A randomised double blind placebo controlled trial. PLoS ONE 2014, 9, e89511. [Google Scholar] [CrossRef] [PubMed]
  24. Oncel, M.Y.; Sari, F.N.; Arayici, S.; Guzoglu, N.; Erdeve, O.; Uras, N.; Oguz, S.S.; Dilmen, U. Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: A randomised controlled trial. Arch. Dis. Child. Fetal Neonatal Ed. 2014, 99, F110–F115. [Google Scholar] [CrossRef] [PubMed]
  25. Jacobs, S.E.; Tobin, J.M.; Opie, G.F.; Donath, S.; Tabrizi, S.N.; Pirotta, M.; Morley, C.J.; Garland, S.M. Probiotic effects on late-onset sepsis in very preterm infants: A randomized controlled trial. Pediatrics 2013, 132, 1055–1062. [Google Scholar] [CrossRef] [PubMed]
  26. Serce, O.; Benzer, D.; Gursoy, T.; Karatekin, G.; Ovali, F. Efficacy of saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: A randomised controlled trial. Early Hum. Dev. 2013, 89, 1033–1036. [Google Scholar] [CrossRef] [PubMed]
  27. Demirel, G.; Erdeve, O.; Celik, I.H.; Dilmen, U. Saccharomyces boulardii for prevention of necrotizing enterocolitis in preterm infants: A randomized, controlled study. Acta Paediatr. 2013, 102, 560–565. [Google Scholar] [CrossRef] [PubMed]
  28. Rojas, M.A.; Lozano, J.M.; Rojas, M.X.; Rodriguez, V.A.; Rondon, M.A.; Bastidas, J.A.; Perez, L.A.; Rojas, C.; Ovalle, O.; Garcia-Harker, J.E.; et al. Prophylactic probiotics to prevent death and nosocomial infection in preterm infants. Pediatrics 2012, 130, e1113–e1120. [Google Scholar] [CrossRef] [PubMed]
  29. Sari, F.N.; Eras, Z.; Dizdar, E.A.; Erdeve, O.; Oguz, S.S.; Uras, N.; Dilmen, U. Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? Am. J. Perinatol. 2012, 29, 579–586. [Google Scholar] [CrossRef] [PubMed]
  30. Fernández-Carrocera, L.A.; Solis-Herrera, A.; Cabanillas-Ayón, M.; Gallardo-Sarmiento, R.B.; García-Pérez, C.S.; Montaño-Rodríguez, R.; Echániz-Aviles, M.O.L. Double-blind, randomised clinical assay to evaluate the efficacy of probiotics in preterm newborns weighing less than 1500 g in the prevention of necrotising enterocolitis. Arch. Dis. Child. Fetal Neonatal Ed. 2013, 98, F5–F9. [Google Scholar] [CrossRef] [PubMed]
  31. Havranek, T.; Al-Hosni, M.; Armbrecht, E. Probiotics supplementation increases intestinal blood flow velocity in extremely low birth weight preterm infants. J. Perinatol. 2013, 33, 40–44. [Google Scholar] [CrossRef] [PubMed]
  32. Chrzanowska-Liszewska, D.; Seliga-Siwecka, J.; Kornacka, M.K. The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial. Early Hum. Dev. 2012, 88, 57–60. [Google Scholar] [CrossRef] [PubMed]
  33. Campeotto, F.; Suau, A.; Kapel, N.; Magne, F.; Viallon, V.; Ferraris, L.; Waligora-Dupriet, A.-J.; Soulaines, P.; Leroux, B.; Kalach, N.; Dupont, C.; Butel, M.-J. A fermented formula in pre-term infants: Clinical tolerance, gut microbiota, down-regulation of faecal calprotectin and up-regulation of faecal secretory IgA. Br. J. Nutr. 2011, 105, 1843–1851. [Google Scholar] [CrossRef] [PubMed]
  34. Sari, F.N.; Dizdar, E.A.; Oguz, S.; Erdeve, O.; Uras, N.; Dilmen, U. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: A randomized, controlled trial. Eur. J. Clin. Nutr. 2011, 65, 434–439. [Google Scholar] [CrossRef] [PubMed]
  35. Indrio, F.; Riezzo, G.; Raimondi, F.; Bisceglia, M.; Cavallo, L.; Francavilla, R. Effects of probiotic and prebiotic on gastrointestinal motility in newborns. J. Physiol. Pharmacol. 2009, 60, 27–31. [Google Scholar] [PubMed]
  36. Mihatsch, W.A.; Vossbeck, S.; Eikmanns, B.; Hoegel, J.; Pohlandt, F. Effect of Bifidobacterium lactis on the incidence of nosocomial infections in very-low-birth-weight infants: A randomized controlled trial. Neonatology 2010, 98, 156–163. [Google Scholar] [CrossRef] [PubMed]
  37. Rougé, C.; Piloquet, H.; Butel, M.-J.; Berger, B.; Rochat, F.; Ferraris, L.; Des Robert, C.; Legrand, A.; de la Cochetiere, M.-F.; N’Guyen, J.-M.; et al. Oral supplementation with probiotics in very-low-birth-weight preterm infants: A randomized, double-blind, placebo-controlled trial. Am. J. Clin. Nutr. 2009, 89, 1828–1835. [Google Scholar] [CrossRef] [PubMed]
  38. Samanta, M.; Sarkar, M.; Ghosh, P.; Ghosh, J.K.; Sinha, M.K.; Chatterjee, S. Prophylactic probiotics for prevention of necrotizing enetrocolitis in very low birth weight newborns. J. Trop. Pediatr. 2008, 55, 128–131. [Google Scholar] [CrossRef] [PubMed]
  39. Lin, H.-C.; Hsu, C.-H.; Chen, H.-L.; Chung, M.-Y.; Hsu, J.-F.; Lien, R.; Tsao, L.-Y.; Chen, C.-H.; Su, B.-H. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: A multicenter, randomized, controlled trial. Pediatrics 2008, 122, 693–700. [Google Scholar] [CrossRef] [PubMed]
  40. Bin-Nun, A.; Bromiker, R.; Wilschanski, M.; Kaplan, M.; Rudensky, B.; Caplan, M.; Hammerman, C. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J. Pediatr. 2005, 147, 192–196. [Google Scholar] [CrossRef] [PubMed]
  41. Costalos, C.; Skouteri, V.; Gounaris, A.; Sevastiadou, S.; Triandafilidou, A.; Ekonomidou, C.; Kontaxaki, F.; Petrochilou, V. Enteral feeding of premature infants with Saccharomyces boulardii. Early Hum. Dev. 2003, 74, 89–96. [Google Scholar] [CrossRef]
  42. Dani, C.; Biadaioli, R.; Bertini, G.; Martelli, E.; Rubaltelli, F.F. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. Biol. Neonate 2002, 82, 103–108. [Google Scholar] [CrossRef] [PubMed]
  43. Stansbridge, E.M.; Walker, V.; Hall, M.A.; Smith, S.L.; Millar, M.R.; Bacon, C.; Chen, S. Effects of feeding premature infants with Lactobacillus GG on gut fermentation. Arch. Dis. Child. 1993, 69, 488–492. [Google Scholar] [CrossRef] [PubMed]
  44. Millar, M.R.; Bacon, C.; Smith, S.L.; Walker, V.; Hall, M.A. Enteral feeding of premature infants with Lactobacillus GG. Arch. Dis. Child. 1993, 69, 483–487. [Google Scholar] [CrossRef] [PubMed]
  45. Indrio, F.; Riezzo, G.; Raimondi, F.; Bisceglia, M.; Cavallo, L.; Francavilla, R. The effects of probiotics on feeding tolerance, bowel habits, and gastrointestinal motility in preterm newborns. J. Pediatr. 2008, 152, 801–806. [Google Scholar] [CrossRef] [PubMed]
  46. Al-Hosni, M.; Duenas, M.; Hawk, M.; Stewart, L.A.; Borghese, R.A.; Cahoon, M.; Atwood, L.; Howard, D.; Ferrelli, K.; Soll, R. Probiotics-supplemented feeding in extremely low-birth-weight infants. J. Perinatol. 2012, 32, 253–259. [Google Scholar] [CrossRef] [PubMed]
  47. Savino, F.; Ceratto, S.; Poggi, E.; Cartosio, M.E.; Cordero di Montezemolo, L.; Giannattasio, A. Preventive effects of oral probiotic on infantile colic: A prospective, randomised, blinded, controlled trial using Lactobacillus reuteri DSM 17938. Benef. Microbes 2014. [Google Scholar] [CrossRef]
  48. Saengtawesin, V.; Tangpolkaiwalsak, R.; Kanjanapattankul, W. Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. J. Med. Assoc. Thail. 2014, 97, S20–S25. [Google Scholar]
  49. Dilli, D.; Aydin, B.; Fettah, N.; Özyazıcı, E.; Beken, S.; Zenciroğlu, A.; Okumuş, N.; Özyurt, B.; İpek, M.; Akdağ, A.; et al. The propre-save study: Effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. J. Pediatr. 2015, 28, 1537–1541. [Google Scholar] [CrossRef] [PubMed]
  50. Roy, A.; Chaudhuri, J.; Sarkar, D.; Ghosh, P.; Chakraborty, S. Role of enteric supplementation of Probiotics on late-onset sepsis by Candida species in preterm low birth weight neonates: A randomized, double blind, placebo-controlled trial. N. Am. J. Med. Sci. 2014, 6, 50–57. [Google Scholar] [PubMed]
  51. Oncel, M.Y.; Arayici, S.; Sari, F.N.; Simsek, G.K.; Yurttutan, S.; Erdeve, O.; Saygan, S.; Uras, N.; Oguz, S.S.; Dilmen, U. Comparison of Lactobacillus reuteri and nystatin prophylaxis on Candida colonization and infection in very low birth weight infants. J. Matern. Neonatal Med. 2014, 1–5. [Google Scholar] [CrossRef]
  52. Millar, M.; Wilks, M.; Fleming, P.; Costeloe, K. Should the use of probiotics in the preterm be routine? Arch. Dis. Child. Fetal Neonatal Ed. 2012, 97, F70–F74. [Google Scholar] [CrossRef] [PubMed]
  53. Rinaldi, M.; Manzoni, P.; Meyer, M.; Casa, E.D.; Pugni, L.; Mosca, F.; Stolfi, I.; Messner, H.; Memo, L.; Laforgia, N.; et al. Bovine lactoferrin supplementation for prevention of necrotising enterocolitis in preterm very-low-birth-weight neonates: A randomised trial. Early Hum. Dev. 2012, 88, S102. [Google Scholar] [CrossRef]
  54. Manzoni, P.; Meyer, M.; Stolfi, I.; Rinaldi, M.; Cattani, S.; Pugni, L.; Romeo, M.G.; Messner, H.; Decembrino, L.; Laforgia, N.; et al. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: A randomized clinical trial. Early Hum. Dev. 2014, 90, S60–S65. [Google Scholar] [CrossRef]
  55. Benor, S.; Marom, R.; Tov, A.B.; Domany, K.A.; Zaidenberg-Israeli, G.; Dollberg, S. Probiotic supplementation in mothers of very low birth weight infants. Am. J. Perinatol. 2014, 31, 497–504. [Google Scholar] [PubMed]
  56. Manzoni, P.; Mostert, M.; Leonessa, M.L.; Priolo, C.; Farina, D.; Monetti, C.; Latino, M.A.; Gomirato, G. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: A randomized study. Clin. Infect. Dis. 2006, 42, 1735–1742. [Google Scholar] [CrossRef] [PubMed]
  57. Kitajima, H.; Sumida, Y.; Tanaka, R.; Yuki, N.; Takayama, H.; Fujimura, M. Early administration of Bifidobacterium breve to preterm infants: Randomised controlled trial. Arch. Dis. Child. Fetal Neonatal Ed. 1997, 76, F101–F107. [Google Scholar] [CrossRef] [PubMed]
  58. Mohan, R.; Koebnick, C.; Schildt, J.; Schmidt, S.; Mueller, M.; Possner, M.; Radke, M.; Blaut, M. Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: A double-blind, placebo-controlled, randomized study. J. Clin. Microbiol. 2006, 44, 4025–4031. [Google Scholar] [CrossRef] [PubMed]
  59. Lin, H.-C.; Su, B.-H.; Chen, A.-C.; Lin, T.-W.; Tsai, C.-H.; Yeh, T.-F.; Oh, W. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2005, 115, 1–4. [Google Scholar] [PubMed]
  60. Braga, T.D.; da Silva, G.A.P.; de Lira, P.I.; de Carvalho Lima, M. Efficacy of Bifidobacterium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birth-weight preterm infants: A double-blind, randomized, controlled trial. Am. J. Clin. Nutr. 2011, 93, 81–86. [Google Scholar] [CrossRef] [PubMed]
  61. Stratiki, Z.; Costalos, C.; Sevastiadou, S.; Kastanidou, O.; Skouroliakou, M.; Giakoumatou, A.; Petrohilou, V. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Early Hum. Dev. 2007, 83, 575–579. [Google Scholar] [CrossRef] [PubMed]
  62. Manzoni, P.; Rinaldi, M.; Cattani, S.; Pugni, L.; Romeo, M.G.; Messner, H. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates. JAMA 2009, 302, 1421–1428. [Google Scholar] [CrossRef] [PubMed]
  63. Li, Y.; Shimizu, T.; Hosaka, A.; Kaneko, N.; Ohtsuka, Y.; Yamashiro, Y. Effects of bifidobacterium breve supplementation on intestinal flora of low birth weight infants. Pediatr. Int. 2004, 46, 509–515. [Google Scholar] [CrossRef] [PubMed]
  64. Costeloe, K.; Hardy, P.; Juszczak, E.; Wilks, M.; Millar, M.R. Bifidobacterium breve BBG-001 in very preterm infants: A randomised controlled phase 3 trial. Lancet 2015, 387, 649–660. [Google Scholar] [CrossRef]
  65. Dutta, S.; Ray, P.; Narang, A. Comparison of stool colonization in premature infants by three dose regimes of a probiotic combination: A randomized controlled trial. Am. J. Perinatol. 2015, 32, 733–740. [Google Scholar] [PubMed]
  66. Hays, S.; Jacquot, A.; Gauthier, H.; Kempf, C.; Beissel, A.; Pidoux, O.; Jumas-Bilak, E.; Decullier, E.; Lachambre, E.; Beck, L.; et al. Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO study. Clin. Nutr. 2014. [Google Scholar] [CrossRef] [PubMed]
  67. Romeo, M.G.; Romeo, D.M.; Trovato, L.; Oliveri, S.; Palermo, F.; Cota, F.; Betta, P. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: Incidence of late-onset sepsis and neurological outcome. J. Perinatol. 2011, 31, 63–69. [Google Scholar] [CrossRef] [PubMed]
  68. Hikaru, U.; Koichi, S.; Yayoi, S.; Hiromici, S.; Hiroaki, S.; Yoshkazu, O.; Seigo, A.; Satoru, N.; Toshiaki, S.; Yuichiro, Y. Bifidobacteria prevents preterm infants from developing infection and sepsis. Int. J. Probiotics Prebiotics 2010, 5, 33–36. [Google Scholar]
  69. Patole, S.K.; Keil, A.D.; Nathan, E.; Doherty, D.; Esvaran, M.; Simmer, K.N.; Conway, P. Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in growth restricted very preterm infants -analysis from a randomised trial. J. Matern. Fetal Neonatal Med. 2016. [Google Scholar] [CrossRef] [PubMed]
  70. Tewari, V.V.; Dubey, S.K.; Gupta, G. Bacillus clausii for prevention of late-onset sepsis in preterm infants: A randomized controlled trial. J. Trop. Pediatr. 2015, 61, 377–385. [Google Scholar] [CrossRef] [PubMed]
  71. Bertino, E.; Giuliani, F.; Baricco, M.; Di Nicola, P.; Peila, C.; Vassia, C.; Chiale, F.; Pirra, A.; Cresi, F.; Martano, C.; Coscia, A. Benefits of donor milk in the feeding of preterm infants. Early Hum. Dev. 2013, 89, S3–S6. [Google Scholar] [CrossRef] [PubMed]
  72. Zivkovic, A.M.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc. Natl. Acad. Sci. USA 2011, 108, 4653–4658. [Google Scholar] [CrossRef] [PubMed]
  73. Bertelli, C.; Pillonel, T.; Torregrossa, A.; Prod’hom, G.; Fischer, C.J.; Greub, G.; Giannoni, E. Bifidobacterium longum bacteremia in preterm infants receiving probiotics. Clin. Infect. Dis. 2015, 60, 924–927. [Google Scholar] [CrossRef] [PubMed]
Nutrients 08 00471 g001 1024
Figure 1. Flow chart of the search strategy used for the systematic review. The relevant number of papers at each point is given.
Figure 1. Flow chart of the search strategy used for the systematic review. The relevant number of papers at each point is given.
Nutrients 08 00471 g001
Nutrients 08 00471 g002 1024
Figure 2. Forest plot (2a) and funnel plot (2b) showing the association between the use of probiotics and achievement of full enteral feeding in exclusively human milk-fed preterm infants. IV: inverse variance method.
Figure 2. Forest plot (2a) and funnel plot (2b) showing the association between the use of probiotics and achievement of full enteral feeding in exclusively human milk-fed preterm infants. IV: inverse variance method.
Nutrients 08 00471 g002
Table
Table 1. Studies included in the systematic review.
Table 1. Studies included in the systematic review.
Author, YearStudy DetailsStudy PopulationIntervention SpecieMilkPlaceboFEF Definition
Dose (D)
Start of Treatment (S)
End of Treatment (E)
Bin-Nun, 2005 [40]PPreterm infants with BW < 1500 g, who began enteral feeding on a weekdayB. infantis, Str. thermophilus, B. bifidusOMM, PFMHM or FM100 mL/kg/day
BD: 0.35 × 109 CFU each, OD
RS: start of enteral feeding
CE: 36 w postconceptual age
Braga, 2011 [60]PInborn infants with BW 750–1499 gL. casei, B. BreveHM (± PFM from w3)Extra HM150 mL/kg/day
DBD: 3.5 × 107 CFU to 3.5 × 109 CFU OD
RS: day 2
CE: day 30, NEC diagnosis, discharge, death, whichever occurred first
Costalos, 2003 [41]PGA 28–32 wSaccharomyces boulardiiPFMMDXNot defined
RNo major GI problemD: 1 × 109 CFU BD
CNot receiving antibioticsS: non-specified
Not receiving breast milkMedian duration of probiotic supplementation: 30 days
Costeloe, 2015 [64]PPreterm infants with GA 23–30 + 6 weeks, without any lethal malformation or any malformation of the GI tractBifidobacterium breve BBG-001OMM, DHM, FMCorn starch powder150 mL/kg/day
DBD: 8 · 3–8 · 8 log10 CFU/day
RS: as soon as possible after randomisation
CE: 36 w PMA or discharge if sooner
Multic.
Demirel, 2013 [27]PPreterm infants with GA ≤ 32 weeks and BW ≤ 1500 g, who survived to feed enterallyS. boulardiiHM, FMNoneNot defined
BD: 5 × 109 CFU OD
RS: first feed
CE: discharge
Dilli, 2015 [49]PPreterm infants with GA < 32 weeks and BW < 1500 g, born at or transferred to the NICU within the first week of life and fed enterally before inclusionB. lactisHM, FMMDX powder100 mL/kg/day (FEF for hydration)
DBD: 5 × 109 CFU150 mL/kg/day (FEF for growth)
RS: beyond d7 after birth
CE: death or discharge (max 8 weeks)
Multic.
Fernández-Carrocera, 2013 [30]PPreterm infants withL. acidophilus 1 × 109 CFU/g, L. rhamnosus 4.4 × 108 CFU/g, L. casei 1 × 109 CFU/g, L. plantarum 1.76 × 108 CFU/g, B. infantis 2.76 × 107 CFU/g, Str. thermophilus 6.6 × 105 CFU/gOMM, PFMNoneNot defined
DBBW < 1500 gTotal D: 1 g powder OD
RInfants with NEC stage IA and stage IB were excludedS: start of enteral feeding
C E: non specified
Hays, 2014 [66]PPreterm infants with GA 25–31 weeks, BW 700–1600 g, AGA, enteral feeding initiated before day 5Probiotic group composed of 3 subgroups:OMM, DM or PFMMDXNot defined
DBInfants with NEC stage ≥ IB, malformations or severe medical or surgical conditions were excludedP1 B. lactis
RP2 B. longum
CP3 B. lactis + longum
Multic.D: 1 × 109 CFU each probiotic daily
Duration: 4 weeks for infants ≥29 w/6 weeks for infants ≤28 w GA
Hikaru, 2010 [68]PExtremely low birth weight and very low birth weight infantsB. breveOMM, PFMNoneNot defined
RD: 0.5 × 109 CFU BD
CS: birth
E: discharge from NICU
Jacobs, 2013 [25]PPreterm infants with GA <32 weeks and BW < 1500 gB. infantis BB-02 300 CFU × 106, Str. thermophilus Th-4 350 CFU × 106, B. lactis BB-12 350 CFU × 106HM, FMMDX powderEnteral feeds of 120 mL/kg for ≥3 days
DBTotal D: 1 × 109 CFU × 1.5 g MDX powder OD
RS: enteral feed ≥ 1 mL every 4 h
CE: discharge or term corrected age
Multic.
Lin, 2008 [39]PPreterm infants with GA < 34 weeks and BW ≤ 1500 g, who survived to feed enterallyL. acidophilus NCDO 1746, B. bifidum NCDO 1453 109 CFUHM, FMNoneOral intake of 100 mL/kg/day
BD: 1 × 109 CFU each probiotic (= 125 mg/kg) BD
RS: day 2 of age
CDuration: 6 weeks
Multic.
Manzoni, 2006 [56]PInfants with BW < 1500 g, ≥3 day of life, who started enteral feeding with HML. casei subspecies rhamnosus LGGOMM, DMNoneNot defined
DBD: 6 × 109 CFU/day
RS: day 3 of life
CE: end of the 6th week or discharge
Mihatsch, 2010 [36]PPreterm infants with GA < 30 weeks and BW ≤ 1500 gB. lactis BB12OMM, PFMIndistinguishable powder150 mL/kg/day
RD: 2 × 109 CFU/kg 6 times a day
CS: start of enteral feeding
E: non specified
Oncel, 2014 [24]PPreterm infants with GA ≤ 32 weeks and BW ≤ 1500 g, who survived to feed enterallyL. reuteri DSM 17938HM, FMOil baseNot defined
DBD: 1 × 108 CFU OD
RS: first feed
CE: death or discharge
Patole, 2014 [23]PPreterm infants with GA < 33 weeks and BW < 1500 gB. breveHM, FMDextrin150 mL/kg/day enteral feeding
DBD: 3 × 109 CFU OD (1.5 × 109 CFU OD for newborn ≤ 27 w until they reached 50 mL/kg/day enteral feeds)
RS: start of enteral feed
CE: corrected age of 37 w
Rougé, 2009 [37]PPreterm infants with GA < 32 weeks and BW < 1500 g, ≤2 weeks of age, without any disease other than those linked to prematurity, who started enteral feeding before inclusionB. longum BB536, L. rhamnosus GG BB536-LGGOMM, DM or PFMMDXNot defined
DBTotal D: 1 × 108 CFU/day
RS: start of enteral feeding
CE: discharge
Bic.
Roy, 2014 [50]PPreterm infants (GA < 37 weeks) and BW < 2500 g, with stable enteral feeding within 72 h of birthL. acidophilus 1.25 × 109 CFU × 1 g, B. longum 0.125 × 109 CFU × 1 g, B. bifidum 0.125 × 109 CFU × 1 g, B. lactis 1 × 109 CFU × 1 gHMSterile water120 mL/kg/day for ≥3 d
DBD: half a 1 g sachet
RS: from 72 h of life
CE: after 6 w or at discharge
Saengtawesin, 2014 [48]PPreterm infants with GA ≤ 34 weeks and BW ≤ 1500 gL. acidophilus 1 × 109 CFU, B. bifidum 1 × 109 CFUHM, PFMNone150 mL/kg/day
RD: 125 mg/kg BD
CS: start of feeding
E: 6 w of age or discharge.
Samanta, 2008 [38]PPreterm infants with GA < 32 weeks and BW < 1500 g, who started enteral feeding and survived beyond 48 h of ageB. infantis, B. bifidum, B. longum, L. acidophilusHMNoneNot defined
DB
RD: 2.5 × 109 CFU each probiotic, BD
CS: start of enteral feeding
E: discharge
Sari, 2011 [34]PPreterm infants with GA < 32 weeks or BW < 1500 g, who survived to feed enterallyL. sporogenesHM, FMNoneNot defined
BD: 0.35 × 109 CFU OD
RS: first feed
CE: discharge
Serce, 2013 [26]PPreterm infants with GA ≤ 32 weeks and BW ≤ 1500 g, who survived to feed enterallyS. boulardiiHM, FMDistilled water100 mL/kg/day
MD: 0.5 × 109 CFU/kg BDenteral feeding
RS: non specified
CE: non specified
Stratiki, 2007 [61]PPreterm infants with GA 27–32 weeks, formula-fed, without major congenital anomaliesBifidobacterium lactisFMNone150 mL/kg/day
BD: 2 × 107 CFU/g of milk powder
RS: start of enteral feeding
CE: not specified
Tewari, 2015 [70]PPreterm infants with GA < 34 weeksBacillus clausiiOMM, DHMSterile water180 mL/kg/day
DBExcluded if: NEC, congenital anomaly , outborn and >10 days of with sepsisD: 2.4 × 109 CFU/day
RStratified as extreme preterm (GA 27–30 + 6) and very preterm (GA 31–33 + 6)S: by day 5 in asymptomatic and by day 10 in symptomatic infants
C E: 6 weeks of age, discharge or death (whichever occurred first)
Totsu, 2014 [21]PInfants with BW < 1500 gB. bifidumHM, FMDextrinPostnatal day at which the amount of enteral feeding exceeded 100 mL/kg/day
DBD: 2.5 × 109 CFU, divided in two doses
CLRS: within 48 h after birth
CE: body weight 2000 g
Multic.
Van Niekerk, 2014 [22]PPreterm infants with GA < 34 weeks and BW < 1250 g, exposed and non-exposed to HIV (only infants unexposed to HIV are included in the meta-analysis)L. rhamnosus, B. infantisHMMCT oil“when infants no longer required the use of IV fluids”
DBD: 0.35 × 109 CFU each probiotic
RS: start of enteral feeding
CE: day 28 postconceptual age
P: prospective; B: blinded; R: randomized; C: controlled; DB: double-blinded; Multic: multicentric; M: masked; CLR: cluster-randomized; BW: birth weight; GA: gestational age; HM: human milk; L.: Lactobacillus; B.: Bifidobacterium; Str.: Streptococcus; S.: Saccharomyces; CFU: colony forming unit; OD: once daily; NEC: necrotizing enterocolitis; BD: twice daily; OMM: own mother’s milk; PFM: preterm formula; FM: formula; MDX: maltodextrin; PMA: postmenstrual age; AGA: appropriate for gestational age.
Table
Table 2. Evaluation of the quality of the studies included in the meta-analysis according to the risk of bias tool as proposed by the Cochrane collaboration.
Table 2. Evaluation of the quality of the studies included in the meta-analysis according to the risk of bias tool as proposed by the Cochrane collaboration.
StudyRandom Sequence GenerationAllocation ConcealmentBlindingIncomplete Outcome DataSelective Outcome ReportingOther Sources of Bias
Braga, 2011 [60]LowLowLowLowUnclearLow
Manzoni, 2006 [56]LowLowLowUnclearUnclearLow
Roy, 2014 [50]LowUnclearLowLowUnclearUnclear
Samanta, 2008 [38]LowLowLowUnclearUnclearUnclear
Van Niekerk, 2014 [22]LowUnclearLowUnclearUnclearUnclear

Share and Cite

MDPI and ACS Style

Aceti, A.; Gori, D.; Barone, G.; Callegari, M.L.; Fantini, M.P.; Indrio, F.; Maggio, L.; Meneghin, F.; Morelli, L.; Zuccotti, G.; et al. Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis. Nutrients 2016, 8, 471. https://doi.org/10.3390/nu8080471

AMA Style

Aceti A, Gori D, Barone G, Callegari ML, Fantini MP, Indrio F, Maggio L, Meneghin F, Morelli L, Zuccotti G, et al. Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis. Nutrients. 2016; 8(8):471. https://doi.org/10.3390/nu8080471

Chicago/Turabian Style

Aceti, Arianna, Davide Gori, Giovanni Barone, Maria Luisa Callegari, Maria Pia Fantini, Flavia Indrio, Luca Maggio, Fabio Meneghin, Lorenzo Morelli, Gianvincenzo Zuccotti, and et al. 2016. "Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis" Nutrients 8, no. 8: 471. https://doi.org/10.3390/nu8080471

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop