title: Safety, growth, and support to healthy gut microbiota by an infant formula enriched with functional compounds.
abstract: Safety and growth adequacy of infant formulae enriched by functional ingredients need stringent evaluation by means of randomized controlled trials (RCTs), therefore we performed a double-blind RCT to evaluate an infant formula enriched with galacto-oligosaccharides, beta-palmitate, and acidified milk vs. a standard infant formula.
  
  
  
  Weight, length, head circumference and fecal bacteria (Bifidobacteria, BIF/Clostridia, CLO) were measured in healthy full term infants, at baseline - as before 21 days of life - at 60 and 135 days thereafter. A group of 51 neonates received the enriched formula (ENR), 59 the standard one (ST). Parents were trained to daily register gastrointestinal diseases.
  
  
  
  All the infants grew homogeneously increasing the anthropometric parameters and complying with WHO and Italian standards: the mean (SD) difference in daily weight between ENR and ST groups was -0.74 (1.13) g/day, corresponding to a 90% CI of -2.62 to 1.13 g/day, well within the postulated interval of equivalence of -3.9 to +3.9 g/day. A statistical improvement in BIF concentration in the microbiota of infants fed by ENR was recorded. There was no between-group change in log10CLO, but log10BIF increase was higher at T2 vs. T0 in ENR (treatment × time interaction = 0.71, 95% CI 0.08-1.34, p = 0.028) than in ST neonates. This corresponds to estimated mean (95% CI) values of 8.37 (8.04-8.69) log10-units for ENR vs. 8.08 (7.77-8.39) log10-units for ST neonates. Gastrointestinal effects were mild and similar, with no statistical difference between two groups.
  
  
  
  Safety and growth ability of the enriched formula has been confirmed. A positive effect on neonatal gut microbiota, consisting of increased fecal BIF counts at T2 vs. baseline has been shown too. Nonetheless, larger RCTs are needed to estimate with greater precision the effective potential attributable to the enriched formula on neonatal microbiota, with particular reference to the mode of delivery.
authors.affiliation: Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Civardi
authors.affiliation: Neonatal Immunology Laboratory, Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: lab.immunoneo@smatteo.pv.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Garofoli
authors.affiliation: Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Longo
authors.affiliation: Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Mongini
authors.affiliation: Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Grenci
authors.affiliation: Neonatal Immunology Laboratory, Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Mazzucchelli
authors.affiliation: Neonatal Immunology Laboratory, Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Micol
authors.initials: M
authors.lastname: Angelini
authors.affiliation: Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Castellazzi
authors.affiliation: R&D Heinz Italia S.p.A, 04100 Latina, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fasano
authors.affiliation: R&D Heinz Italia S.p.A, 04100 Latina, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Grinzato
authors.affiliation: Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, University of Cagliari, Cagliari, Italy.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Fanos
authors.affiliation: R&D Heinz Italia S.p.A, 04100 Latina, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Budelli
authors.affiliation: Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Neonatal Immunology Laboratory, Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Stronati
mesh_terms: D001644:Bifidobacterium; D003013:Clostridium; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004043:Dietary Fiber / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D004311:Double-Blind Method; D059022:Food Safety; D055951:Functional Food / Q000032:analysis*; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry* / Q000382:microbiology; D018977:Micronutrients / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004043:Dietary Fiber; D004044:Dietary Proteins; D018977:Micronutrients
keywords: Bifidobacteria; Formula; Microbiota; Neonate