title: Probiotics for prevention of necrotizing enterocolitis in preterm infants: systematic review and meta-analysis.
abstract: Necrotizing enterocolitis (NEC) affects predominantly preterm infants, who have specific risk factors leading to intestinal dysbiosis. Manipulations of gut microbiota through probiotics have the potential to prevent NEC.The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics for NEC prevention in preterm infants, with a focus on specific strains, microbiological strength of currently available studies, and high-risk populations. PubMed and the Cochrane Library were searched for trials published within 4th February 2015. Randomized-controlled trials reporting on NEC and involving preterm infants who were given probiotics in the first month of life were included in the systematic review.Twenty-six studies were suitable for inclusion in the meta-analysis.Data about study design, population, intervention and outcome were extracted and summarized independently by two observers. Study quality and quality of evidence were also evaluated.Fixed-effects models were used and random-effects models where significant heterogeneity was present. Subgroup analyses were performed to explore sources of heterogeneity among studies. Results were expresses as risk ratio (RR) with 95 % confidence interval (CI). The main outcome was incidence of NEC stage ≥2 according to Bell's criteria. Probiotics prevented NEC in preterm infants (RR 0.47 [95 % CI 0.36-0.60], p < 0.00001). Strain-specific sub-meta-analyses showed a significant effect for Bifidobacteria (RR 0.24 [95 % CI 0.10-0.54], p = 0.0006) and for probiotic mixtures (RR 0.39 [95 % CI 0.27-0.56], p < 0.00001). Probiotics prevented NEC in very-low-birth-weight infants (RR 0.48 [95 % CI 0.37-0.62], p < 0.00001); there were insufficient data for extremely-low-birth-weight infants. The majority of studies presented severe or moderate microbiological flaws.Probiotics had an overall preventive effect on NEC in preterm infants. However, there are still insufficient data on the specific probiotic strain to be used and on the effect of probiotics in high-risk populations such as extremely-low-birth-weight infants, before a widespread use of these products can be recommended.
authors.affiliation: Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy. arianna.aceti2@unibo.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Aceti
authors.affiliation: Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. dedegori27@gmail.com.
authors.forename: Davide
authors.initials: D
authors.lastname: Gori
authors.affiliation: Neonatal Unit, Catholic University, Rome, Italy. gbarone85@yahoo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barone
authors.affiliation: Institute of Microbiology, UCSC, Piacenza, Italy. marialuisa.callegari@unicatt.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Callegari
authors.affiliation: Department of Pediatrics, Aldo Moro University, Bari, Italy. dimauroantonio@msn.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Mauro
authors.affiliation: Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. mariapia.fantini@unibo.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Fantini
authors.affiliation: Department of Pediatrics, Aldo Moro University, Bari, Italy. f.indrio@alice.it.
authors.forename: Flavia
authors.initials: F
authors.lastname: Indrio
authors.affiliation: Neonatal Unit, Catholic University, Rome, Italy. luca.maggio@fastwebnet.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Maggio
authors.affiliation: Department of Pediatrics, University of Milan, Luigi Sacco Hospital, Milan, Italy. meneghin.fabio@hsacco.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Meneghin
authors.affiliation: Institute of Microbiology, UCSC, Piacenza, Italy. lorenzo.morelli@unicatt.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Morelli
authors.affiliation: Department of Pediatrics, University of Milan, Luigi Sacco Hospital, Milan, Italy. gianvincenzo.zuccotti@unimi.it.
authors.forename: Gianvincenzo
authors.initials: G
authors.lastname: Zuccotti
authors.affiliation: Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy. luigi.corvaglia@unibo.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Corvaglia
mesh_terms: D020345:Enterocolitis, Necrotizing / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D019936:Probiotics / Q000627:therapeutic use*; D016896:Treatment Outcome