title: Normal growth of infants receiving an infant formula containing Lactobacillus reuteri, galacto-oligosaccharides, and fructo-oligosaccharide: a randomized controlled trial.
abstract: BACKGROUND
  The safety of an infant formula containing a new mixture of the prebiotics galacto-oligosaccharides (GOS) and fructo-oligosaccharide (FOS) and the probiotic Lactobacillus reuteri needs to be evaluated.
  
  
  METHODS
  Healthy term infants in Singapore were randomly assigned (using computer-generated allocation sequences) to receive exclusively an experimental infant formula containing L. reuteri, GOS (5.50 g/L), and FOS (0.36 g/L) or a control formula containing only L. reuteri from enrollment (7-14 days of age) to 4 months of age. The primary objective of this trial was to demonstrate that weight change between birth and 4 months of age in infants fed the experimental formula was not inferior to World Health Organization (WHO) Child Growth standards. The non-inferiority margin was -0.5 standard deviations (SD). The secondary objectives were to compare changes in anthropometric measurements (weight, length, body mass index, and head circumference), digestive tolerance, stool bacterial counts, urinary D- and L- lactate concentrations, and adverse events in the two formula groups.
  
  
  RESULTS
  The intention-to-treat (ITT) population included all randomized infants stratified by gender, (experimental group, N = 68 and control group, N = 72). The per-protocol (PP) population included 61 infants in the experimental and 62 infants in the control groups. The change in weight-for-age z-score between birth and 4 months was +0.93 (95% confidence interval [CI]: +0.63 to +1.23) SD in the experimental group and +0.92 (95% CI: +0.62 to +1.22) SD in the control group in the PP population, indicating non-inferior weight gain in both formulas groups compared with WHO standards. The ITT population had similar results. Liquid stools occurred more frequently in the experimental compared with the control group and median bifidobacteria, lactobacilli, and enterococci counts were higher in the experimental group (p < 0.05). Other secondary outcomes were not significantly different between groups.
  
  
  CONCLUSIONS
  Infant formula containing L. reuteri + GOS/FOS supports normal growth and is safe.
  
  
  BACKGROUND
  ClinicalTrial.gov: NCT01010113.
authors.affiliation: Department of Neonatology, National University Health System, NUHS Tower Block 1E Kent Ridge Road, Singapore, 119228 Singapore ; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Le Ye
authors.initials: le Y
authors.lastname: Lee
authors.affiliation: Department of Neonatology, National University Health System, NUHS Tower Block 1E Kent Ridge Road, Singapore, 119228 Singapore.
authors.forename: Roshan
authors.initials: R
authors.lastname: Bharani
authors.affiliation: Department of Neonatology, National University Health System, NUHS Tower Block 1E Kent Ridge Road, Singapore, 119228 Singapore ; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Agnihotri
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Department of Neonatology, National University Health System, NUHS Tower Block 1E Kent Ridge Road, Singapore, 119228 Singapore ; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Jiun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Nestle Clinical Development Unit, Nestec Ltd, Vevey, Switzerland.
authors.forename: Liên-Anh
authors.initials: LA
authors.lastname: Tran
authors.affiliation: Nestle Clinical Development Unit, Nestec Ltd, Vevey, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pecquet
authors.affiliation: Nestle Clinical Development Unit, Nestec Ltd, Vevey, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Steenhout
keywords: Fructo-oligosaccharide; Galacto-oligosaccharides; Growth; Infant formula; Lactobacillus reuteri; Probiotic; Safety