Randomized control trials Safety and efficacy of inulin and oligofructose supplementation in infant formula: Results from a randomized clinical trial q R. Closa-Monasterolo a, b , M. Gispert-Llaurado a , V. Luque a, b , N. Ferre a , C. Rubio-Torrents a , M. Zaragoza-Jordana a , J. Escribano a, c, * a Paediatrics Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain b Neonatal Unit, Hospital Universitari Joan XXIII de Tarragona, Spain c Paediatrics Unit, Hospital Universitari Sant Joan de Reus, Spain article info Article history: Received 26 September 2012 Accepted 13 February 2013 Keywords: Inulin Oligofructose Prebiotic Infant formula Safety Efficacy summary Background & aims: The sterile newborn digestive tract is rapidly colonized after birth and feeding type could influence this process. Infant formulas try to mimic the bifidogenic effect of human milk using prebiotic supplementation. The aim of this study was to demonstrate the efficacy, safety and tolerance of a 0.8 g/dL Orafti Ò Synergy1 (oligofructose-enriched inulin) supplemented infant formula during the first 4 months of life. Methods: In a double-blind, randomized, placebo-controlled and parallel trial, formula fed healthy term newborns were randomized to receive a control (controls) or SYN1 supplemented infant formula (SYN1). Breastfed newborns (BF) were also followed for comparison. Anthropometry, water balance, blood pa- rameters, adverse events, stool frequency and characteristics and faecal microbiota were assessed. Results: A total of 252 formula fed infants were randomized at birth (n ¼ 124 controls, n ¼ 128 SYN1) and 131 BF infants were recruited; after 4 months 68 controls, 63 SYN1 and 57 BF completed the study. SYN1 infants showed a microbiota composition closer to that of BF infants, with a trend towards higher Bifi- dobacterium cell counts, softer stools and a higher deposition frequency compared to controls. There were no differences between formulas in anthropometry and relevant adverse events, water balance or blood parameters. Conclusion: A 0.8 g/dL SYN1-supplemented infant formula during the first 4 months of life is safe and effective, promoting a gut microbiota closer to that of breastfeeding. This clinical trial was registered at Clinicaltrials.gov as Study on Fermentable Carbohydrates in Healthy Infants (number NCT00808756). Ó 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. 1. Introduction Prenatally, the gastrointestinal tract is sterile. After birth, massive and rapid colonization of the digestive tract by microor- ganisms occurs as a part of the adaptation to extrauterine life. This colonization process is influenced by factors such as type of de- livery, hygienic measures, prematurity, antibiotic therapy and feeding type. 1 Numerous studies have shown that the intestinal flora of infants fed with human milk includes higher proportions of Bifidobacterium and Lactobacillus than those of formula fed infants, who have a more complex flora with higher proportions of Bac- teroides, Enterobacteriaceae and Clostridium. 2,3 In recent decades, infant formulas have been improved with prebiotic supplementation, such as inulin and oligofructose, to mimic the bifidogenic effect of breastfeeding. Orafti Ò Synergy1 (SYN1) is a commercial combination of oligofructose and long- chain inulin (50:50). 4,5 The beneficial effects of inulin and/or oligofructose on the intes- tinal microbiota have been demonstrated in adults. 6 Many studies that examined the use of formulas supplemented with long-chain fructan polysaccharides (i.e., long-chain inulin and fructooligo- saccharides (FOS)) and galactooligosaccharide mixtures (GOS) in healthy newborns have shown an improvement in the gut flora Abbreviations: BF, breastfeed; FOS, fructooligosaccharides; GOS, gal- actooligosaccharides; SYN1, Orafti Ò Synergy1. q Conference presentation: 61st Anual Congres from the Asociación Espanyola de Pediatria (AEP). Granada 2012. * Corresponding author. Paediatrics Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain. Tel.: þ34 977759364. E-mail addresses: jescribano@grupsagessa.com, joaquin.escribano@urv.cat (J. Escribano). Contents lists available at SciVerse ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu 0261-5614/$ e see front matter Ó 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. http://dx.doi.org/10.1016/j.clnu.2013.02.009 Clinical Nutrition 32 (2013) 918e927