title: Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis.
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.
authors.affiliation: Neonatology and Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna 40138, Italy. arianna.aceti2@unibo.it.|Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. arianna.aceti2@unibo.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Aceti
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. dedegori27@gmail.com.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna 40138, Italy. dedegori27@gmail.com.
authors.forename: Davide
authors.initials: D
authors.lastname: Gori
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. gbarone85@yahoo.it.|Neonatal Unit, Catholic University, Rome 00168, Italy. gbarone85@yahoo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barone
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. marialuisa.callegari@unicatt.it.|Institute of Microbiology, UCSC, Piacenza 29122, Italy. marialuisa.callegari@unicatt.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Callegari
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. mariapia.fantini@unibo.it.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna 40138, Italy. mariapia.fantini@unibo.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Fantini
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. f.indrio@alice.it.|Department of Pediatrics, Aldo Moro University, Bari 70124, Italy. f.indrio@alice.it.|Study Group of Neonatal Gastroenterology and Nutrition of the Italian Society of Neonatology, Milan 20126, Italy. f.indrio@alice.it.
authors.forename: Flavia
authors.initials: F
authors.lastname: Indrio
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. luca.maggio@fastwebnet.it.|Neonatal Unit, Catholic University, Rome 00168, Italy. luca.maggio@fastwebnet.it.|Study Group of Neonatal Gastroenterology and Nutrition of the Italian Society of Neonatology, Milan 20126, Italy. luca.maggio@fastwebnet.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Maggio
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. fabio.meneghin@asst-fbf-sacco.it.|Division of Neonatology, Children Hospital V. Buzzi, ICP, Milan 20154, Italy. fabio.meneghin@asst-fbf-sacco.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Meneghin
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. lorenzo.morelli@unicatt.it.|Institute of Microbiology, UCSC, Piacenza 29122, Italy. lorenzo.morelli@unicatt.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Morelli
authors.affiliation: Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. gianvincenzo.zuccotti@unimi.it.|Department of Pediatrics, Children Hospital V. Buzzi, University of Milan, Milan 20154, Italy. gianvincenzo.zuccotti@unimi.it.
authors.forename: Gianvincenzo
authors.initials: G
authors.lastname: Zuccotti
authors.affiliation: Neonatology and Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna 40138, Italy. luigi.corvaglia@unibo.it.|Task Force on Probiotics of the Italian Society of Neonatology, Milan 20126, Italy. luigi.corvaglia@unibo.it.|Study Group of Neonatal Gastroenterology and Nutrition of the Italian Society of Neonatology, Milan 20126, Italy. luigi.corvaglia@unibo.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Corvaglia
mesh_terms: D002657:Child Development; D006801:Humans; D041943:Infant Formula; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development* / Q000378:metabolism; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D008895:Milk, Human / Q000378:metabolism*; D010288:Parenteral Nutrition / Q000009:adverse effects; D019936:Probiotics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D013997:Time Factors
keywords: full enteral feeding; human milk; preterm infants; probiotics; systematic review