title: Growth and safety evaluation of infant formulae containing oligosaccharides derived from bovine milk: a randomized, double-blind, noninferiority trial.
abstract: BACKGROUND
  A limited number of nondigestible oligosaccharides are available for use in infant formula. This study evaluated growth and safety in infants fed formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS). This mixture, which was generated from whey permeate, contains galactooligosaccharides and other oligosaccharides from bovine milk, such as 3'- and 6'-sialyllactose. We hypothesized that growth in infants fed BMOS-supplemented formula would be noninferior to that in infants fed standard formula.
  
  
  METHODS
  Healthy term infants ≤14 days old were randomly assigned to standard formula (control; n = 84); standard formula with BMOS (IF-BMOS; n = 99); or standard formula with BMOS and probiotics (Bifidobacterium longum, Lactobacillus rhamnosus) (IF-BMOS + Pro; n = 98). A breastfed reference group was also enrolled (n = 30). The primary outcome was mean weight gain/day from enrollment to age 4 months (noninferiority margin: -3.0 g/day).
  
  
  RESULTS
  189 (67.3%) formula-fed infants were included in the primary analysis. Mean differences in weight gain between the control and IF-BMOS and IF-BMOS + Pro groups were <1 g/day, with 97.5% confidence intervals above -3.0 g/day, indicating noninferior weight gain in the BMOS formula groups. Compared with control, infants in the BMOS groups had more frequent (p < 0.0001) and less hard (p = 0.0003) stools. No significant differences were observed between the control and BMOS groups in caregivers' reports of flatulence, vomiting, spitting up, crying, fussing, and colic. When based on clinical evaluation by the investigator, the incidence of colic was higher (p = 0.01) in IF-BMOS than in control; the incidence of investigator-diagnosed colic was not significantly different in control and IF-BMOS + Pro (p = 0.15). Stool bifidobacteria and lactobacilli counts were higher with IF-BMOS + Pro compared with control (p < 0.05), whereas Clostridia counts were lower (p < 0.05) in both BMOS groups compared with control.
  
  
  CONCLUSIONS
  Infant formula containing BMOS either with or without probiotics provides adequate nutrition for normal growth in healthy term infants. Further studies are needed to fully explore the digestive tolerance of BMOS formula.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01886898 . Registered 24 June 2013.
authors.affiliation: Dipartimento Materno Infantile, Unità Operativa di Neonatologia, Università degli Studi di Palermo, Palermo, Italy. meliferd@libero.it.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Meli
authors.affiliation: Dipartimento Materno Infantile, Unità Operativa di Neonatologia, Università degli Studi di Palermo, Palermo, Italy. gipuccio@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Puccio
authors.affiliation: Dipartimento Materno Infantile, Unità Operativa di Neonatologia, Università degli Studi di Palermo, Palermo, Italy. ccajozzo@hotmail.com.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cajozzo
authors.affiliation: Dipartimento Materno Infantile, Unità Operativa di Neonatologia, Università degli Studi di Palermo, Palermo, Italy. g.licata@iol.it.
authors.forename: Giovanni Licata
authors.initials: GL
authors.lastname: Ricottone
authors.affiliation: Nestlé Nutrition, Nestec Ltd, 22 av Reller, 1800, Vevey, Switzerland. sophie.pecquet@rdls.nestle.com.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pecquet
authors.affiliation: Nestlé Research Center, Nestec Ltd, Vers-chez-les-Blanc, 1000, Lausanne 26, Switzerland. norbert.sprenger@rdls.nestle.com.
authors.forename: Norbert
authors.initials: N
authors.lastname: Sprenger
authors.affiliation: Nestlé Nutrition, Nestec Ltd, 22 av Reller, 1800, Vevey, Switzerland. philippe.steenhout@nestle.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Steenhout
mesh_terms: D000818:Animals; D000886:Anthropometry; D002417:Cattle; D002657:Child Development; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D005527:Food, Fortified; D005772:Gastrointestinal Transit; D006128:Growth; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry; D007231:Infant, Newborn; D008297:Male; D008892:Milk; D009844:Oligosaccharides / Q000008:administration & dosage*; D019936:Probiotics / Q000008:administration & dosage; D015430:Weight Gain
chemical_list: D009844:Oligosaccharides