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Prebiotics in infants for prevention of allergy

  1. David A Osborn1,*,
  2. John KH Sinn2

Editorial Group: Cochrane Neonatal Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 23 AUG 2012

DOI: 10.1002/14651858.CD006474.pub3

How to Cite

Osborn DA, Sinn JKH. Prebiotics in infants for prevention of allergy. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD006474. DOI: 10.1002/14651858.CD006474.pub3.

Author Information

  1. 1

    University of Sydney, Central Clinical School, Discipline of Obstetrics, Gynaecology and Neonatology, Sydney, NSW, Australia

  2. 2

    Royal North Shore Hospital, The University of Sydney, Department of Neonatology, Sydney, New South Wales, Australia

*David A Osborn, Central Clinical School, Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney, Sydney, NSW, 2050, Australia. david.osborn@email.cs.nsw.gov.au.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 28 MAR 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Gruber 2010 {unpublished data only}
  • Boehm G, Jelinek J. Double-blind, controlled and randomised study with a parallel group design on the effect of formula feeding (IF and FOF) supplemented with a mixture of immunological active neutral and acidic oligosaccharides on the incidence of febrile respiratory and gastrointestinal infections in healthy term born infants during the first year of life. German Clinical Trials Register 2009; Vol. DRKS00000201.
  • Boehm G. European Immuno Programming Study Group. First results of a randomised controlled double blind European multi-centre study with an infant formula supplemented with immunoactive prebiotics. Part II: Effect on atopic dermatitis in healthy infants in the first year of life. 2008. World Congress of Pediatric Gastroenterology, Hepatology and Nutrition:P0874.
  • Eisses AM. Multi-centre Immuno-Programming Study (MIPS). First results of a randomised controlled double blind European multi-centre study with an infant formula supplemented with immunoactive prebiotics. Part I: Effect on frequency of febrile episodes in healthy infants in the first year of life. World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. 2008:P0797.
  • Gruber C, Arslanoglu S, Piemontese P, Eisses A, Macheiner M, Stricker T, et al. Prevention of early atopic dermatitis by an infant formula supplemented with immunoactive prebiotics in low atopy risk infants. Munksgaard Allergy. 2008; Vol. 63 Suppl 88:612–21.
  • Gruber C, van Stuijvenberg M, Mosca F, Moro G, Chirico G, Braegger CP, et al. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Journal of Allergy and Clinical Immunology 2010;126(4):791-7.
  • Gruber C, van Stuijvenberg M, Mosca F, Moro G, Chirico G, Braegger CP, et al. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Journal of Allergy and Clinical Immunology 2010;126(4):791-7.
  • Piemontese P, Gianni ML, Braegger CP, Chirico G, Gruber C, Riedler J, et al. Tolerance and safety evaluation in a large cohort of healthy infants fed an innovative prebiotic formula: a randomized controlled trial. PLoS One 2011;6(11):e28010.
  • Roggero P, Boehm G, Braegger C, Chirico G, Grüber C, Moro G, et al. First results of a randomised controlled double blind Europeanmulti-centre study with an infant formula supplemented with immunoactive prebiotics Part II:Effect on atopic dermatitis in healthy infants in the first year of life. 1st International Congress of UENPS. 2008.
  • Stam J, van Stuijvenberg M, Garssen J, Knipping K, Sauer PJ. A mixture of three prebiotics does not affect vaccine specific antibody responses in healthy term infants in the first year of life. Vaccine 2011;29(44):7766-72.
  • van Stuijvenberg M, Eisses AM, Gruber C, Mosca F, Arslanoglu S, Chirico G, et al. Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial. The British Journal of Nutrition 2011;106(11):1740-8.
Moro 2006 {published data only}
  • Arslanoglu S, Moro GE, Boehm G. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. Journal of Nutrition 2007;137(11):2420-4.
  • Arslanoglu S, Moro GE, Schmitt J, Tandoi L, Rizzardi S, Boehm G. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. Journal of Nutrition 2008;138(6):1091-5.
  • Moro G, Arslanoglu S, Stahl B, Jelinek J, Wahn U, Boehm G. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Archives of Disease in Childhood 2006;91(10):814-9.
  • Schouten B, Van Esch BC, Kormelink TG, Moro GE, Arslanoglu S, Boehm G, et al. Non-digestible oligosaccharides reduce immunoglobulin free light-chain concentrations in infants at risk for allergy. Pediatric Allergy and Immunology 2011;22(5):537-42.
  • van Hoffen E, Ruiter B, Faber J, M'Rabet L, Knol EF, Stahl B, et al. A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy. Allergy 2009;64(3):484-7.
Westerbeek 2010 {published data only}
  • Niele N, Van Zwol A, Boehm G, Westerbeek EAM, Lafeber HN, Van Elburg RM. Effect of enteral supplementation of neutral and acidic oligosaccharides in preterm infants on allergic and infectious diseases during the first year of life. Journal of Pediatric Gastroenterology and Nutrition 2011;52 Suppl 1:E115-6.
  • Niele N, Westerbeek EAM, Van Zwol A, Lafeber HN, Van Elburg RM. Effect of enteral supplementation of neutral and acidic oligosaccharides in preterm infants on allergic diseases during the first year of life. European Journal of Pharmacology 2011;668 Suppl 1:e14.
  • Westerbeek EA, Hensgens RL, Mihatsch WA, Boehm G, Lafeber HN, van Elburg RM. The effect of neutral and acidic oligosaccharides on stool viscosity, stool frequency and stool pH in preterm infants. Acta Paediatrica 2011;100(11):1426-31.
  • Westerbeek EA, Morch E, Lafeber HN, Fetter WP, Twisk JW, Van Elburg RM. Effect of neutral and acidic oligosaccharides on fecal IL-8 and fecal calprotectin in preterm infants. Pediatric Pesearch 2011;69(3):255-8.
  • Westerbeek EA, van den Berg A, Lafeber HN, Fetter WP, van Elburg RM. The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants. British Journal of Nutrition 2011;105(1):268-74.
  • Westerbeek EA, van den Berg JP, Lafeber HN, Fetter WP, Boehm G, Twisk JW, et al. Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial. American Journal of Clinical Nutrition 2010;91(3):679-86.
  • Westerbeek EA, van Elburg RM, van den Berg A, van den Berg J, Twisk JW, Fetter WP, et al. Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants:carrot study. BMC Pediatrics 2008;8:46.
  • Westerbeek EAM, Van Esch BCA, Garssen J, Van Elburg RM. The effect of enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides on immunoglobulin free light chains in preterm infants. Journal of Pediatric Gastroenterology and Nutrition 2011;52 Suppl 1:e105-6.
  • Westerbeek EAM, Van Esch ECAM, Garssen J, Van Elburg RM. The effect of enteral supplementation of neutral and acidic oligosaccharides on immunoglobulin free light chains in preterm infants. European Journal of Pharmacology 2011;668 Suppl 1:e46-7.
Ziegler 2007 {published and unpublished data}
  • Vanderhoof JA, Mitmesser SH, Harris CL, Stolz SI, Berseth CL. Formula supplemented with specific prebiotic blends is well tolerated by term infants. EPAS. 2007:8431.4.
  • Ziegler E, Vanderhoof JA, Petschow B, Mitmesser SH, Stolz SI, Harris CL, et al. Term infants fed formula supplemented with selected blends of prebiotics grow normally and have soft stools similar to those reported for breast-fed infants. Journal of Pediatric Gastroenterology and Nutrition 2007;44(3):359-64.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Alliet 2007 {published data only}
  • Alliet P, Scholtens P, Raes M, Hensen K, Jongen H, Rummens JL, et al. Effect of prebiotic galacto-oligosaccharide, long-chain fructo-oligosaccharide infant formula on serum cholesterol and triacylglycerol levels. Nutrition 2007;23(10):719-23.
  • Raes M, Scholtens PA, Alliet P, Hensen K, Jongen H, Boehm G, et al. Exploration of basal immune parameters in healthy infants receiving an infant milk formula supplemented with prebiotics. Pediatric Allergy and Immunology 2010;21(2 Pt 2):e377-85.
  • Scholtens PA, Alliet P, Raes M, Alles MS, Kroes H, Boehm G, et al. Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. Journal of Nutrition 2008;138(6):1141-7.
Ashley 2008 {unpublished data only}
  • Ashley C, Johnston WH, Harris CL, Stolz SI, Wampler JL, Berseth CL. Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial. Nutrition Journal 2012;11:38.
  • Berseth CL. The Evaluation of Cow's Milk Formula - Study B. ClinicalTrials.gov identifier: NCT00712608 2008.
Bakker-Zierikzee 2005 {published data only}
  • Bakker-Zierikzee AM, Alles MS, Knol J, Kok FJ, Tolboom JJ, Bindels JG. Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora during the first 4 months of life. British Journal of Nutrition 2005;94:783-90.
  • Bakker-Zierikzee AM, Tol EA, Kroes H, Alles MS, Kok FJ, Bindels JG. Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Pediatric Allergy and Immunology 2006;17:134-40.
Ben 2004 {published data only}
  • Ben XM, Li J, Feng ZT, Shi SY, Lu YD, Chen R, et al. Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. World Journal of Gastroenterology 2008;14(42):6564-8.
  • Ben XM, Zhou XY, Zhao WH, Yu WL, Pan W, Zhang WL, et al. Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. Chinese Medical Journal 2004;117(6):927-31.
  • Cai JW, Lu YD, Ben XM. Effects of infant formula containing galacto-oligosaccharides on the intestinal microflora in infants. Zhongguo Dangdai Erke Zazhi 2008;10(5):629-32.
Bisceglia 2009 {published data only}
Boehm 2002 {published data only}
  • Boehm G, Lidestri M, Casetta P, Jelinek J, Negretti F, Stahl B, Marini A. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2002;86(3):F178-81.
  • Knol J, Boehm G, Lidestri M, Negretti F, Jelinek J, Agosti M, et al. Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants. Acta Paediatrica Supplement 2005;94(449):31-3.
  • Lidestri M, Agosti M, Marini A, Boehm G. Oligosaccharides might stimulate calcium absorption in formula-fed preterm infants. Acta Paediatrica Supplement 2003;91(441):91-2.
  • Marini A, Negretti F, Boehm G, Li Destri M, Clerici-Bagozzi D, Mosca F, et al. Pro- and pre-biotics administration in preterm infants: colonization and influence on faecal flora. Acta Paediatrica Supplement 2003;91(441):80-1.
Bongers 2007 {published data only}
  • Bongers ME, de Lorijn F, Reitsma JB, Groeneweg M, Taminiau JA, Benninga MA. The clinical effect of a new infant formula in term infants with constipation: a double-blind, randomized cross-over trial. Nutrition Journal 2007;6:8.
Brunser 2006 {published data only}
  • Brunser O, Figueroa G, Gotteland M, Haschke-Becher E, Magliola C, Rochat F, et al. Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Asia Pacific Journal of Clinical Nutrition 2006;15(3):368-76.
Bruzzese 2009 {published data only}
  • Bruzzese E, Volpicelli M, Squeglia V, Bruzzese D, Salvini F, Bisceglia M, et al. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. Clinical Nutrition 2009;28(2):156-61.
Chouraqui 2008 {published data only}
  • Chouraqui JP, Grathwohl D, Labaune JM, Hascoet JM, de Montgolfier I, Leclaire M, et al. Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial. American Journal of Clinical Nutrition 2008;87(5):1365-73.
  • Hascoet JM, Chouraqui JP, Putet G, Gold F, Simeoni U. Evaluation of growth and incidence of diarrhea with a starter infant formula containing Bifidobacterium longum, Lactobacillus rhamnosus or Lactobacillus paracasei and a mixture of prebiotics. EPAS. 2007:7355.6.
Costalos 2008 {published data only}
Decsi 2005 {published data only}
  • Decsi T, Arato A, Balogh M, Dolinay T, Kanjo AH, Szabo E, et al. Randomised placebo controlled double blind study on the effect of prebiotic oligosaccharides on intestinal flora in healthy infants [Prebiotikus hatasu oligoszacharidok egeszseges csecsemok szekletflorajara gyakorolt hatasanak randomizalt, placeboval kontrollalt vizsgalata]. Orvosi Hetilap 2005;146(48):2445-50.
Euler 2005 {published data only}
  • Euler AR, Mitchell DK, Kline R, Pickering LK. Prebiotic effect of fructo-oligosaccharide supplemented term infant formula at two concentrations compared with unsupplemented formula and human milk. Journal of Pediatric Gastroenterology and Nutrition 2005;40(2):157-64.
Fanaro 2005 {published data only}
  • Fanaro S, Jelinek J, Stahl B, Boehm G, Kock R, Vigi V. Acidic oligosaccharides from pectin hydrolysate as new component for infant formulae: effect on intestinal flora, stool characteristics, and pH. Journal of Pediatric Gastroenterology and Nutrition 2005;41(2):186-90.
Fanaro 2009 {published data only}
  • Fanaro S, Marten B, Bagna R, Vigi V, Fabris C, Pena-Quintana L, et al. Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study. Journal of Pediatric Gastroenterology and Nutrition 2009;48(1):82-8.
Indrio 2009a {published data only}
  • Indrio F, Riezzo G, Raimondi F, Bisceglia M, Cavallo L, Francavilla R. Effects of probiotic and prebiotic on gastrointestinal motility in newborns. Journal of Physiology and Pharmacology 2009;60 Suppl 6:27-31.
Indrio 2009b {unpublished data only}
  • Indrio F, Raimondi F, Bisceglia M, Riezzo G, Delvecchio M, Francavilla R, et al. Effects of prebiotic supplementation in the prevention of obesity in early infancy. EPAS. 2009:5500.8.
Indrio 2009c {published data only}
  • Indrio F, Riezzo G, Raimondi F, Francavilla R, Montagna O, Valenzano ML, et al. Prebiotics improve gastric motility and gastric electrical activity in preterm newborns. Journal of Pediatric Gastroenterology and Nutrition 2009;49(2):258-61.
Kapiki 2007 {published data only}
  • Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Human Development 2007;83:335-9.
Kim 2007 {published data only}
  • Kim SH, Lee da H, Meyer D. Supplementation of baby formula with native inulin has a prebiotic effect in formula-fed babies. Asia Pacific Journal of Clinical Nutrition. 2007;16(1):172-7.
Knol 2005 {published data only}
  • Haarman M, Knol J. Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium species in infants receiving a prebiotic infant formula. Applied and Environmental Microbiology 2005;71(5):2318-24.
  • Knol J, Scholtens P, Kafka C, Steenbakkers J, Gro S, Helm K, et al. Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants. Journal of Pediatric Gastroenterology and Nutrition 2005;40(1):36-42.
Kukkonen 2006 {published data only}
  • Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, et al. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Journal of Allergy and Clinical Immunology 2009;123(2):335-41.
  • Kuitunen M, Kukkonen K, Savilahti E. Pro- and prebiotic supplementation induces a transient reduction in hemoglobin concentration in infants. Journal of Pediatric Gastroenterology and Nutrition 2009;49(5):626-30.
  • Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatric Allergy and Immunology 2010;21(1 Pt 1):67-73.
  • Kukkonen K, Nieminen T, Poussa T, Savilahti E, Kuitunen M. Effect of probiotics on vaccine antibody responses in infancy--a randomized placebo-controlled double-blind trial. Pediatric Allergy and Immunology 2006;17(6):416-21.
  • Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, et al. Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial. Pediatrics 2008;122(1):8-12.
  • Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology 2007;119(1):192-8.
  • Marschan E, Honkanen J, Kukkonen K, Kuitunen M, Savilahti E, Vaarala O. Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with IgE sensitization. Pediatric Allergy and Immunology 2008;19(2):132-9.
  • Marschan E, Kuitunen M, Kukkonen K, Poussa T, Sarnesto A, Haahtela T, et al. Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation. Clinical and Experimental Allergy 2008;38(4):611-8.
Magne 2008 {published data only}
  • Magne F, Hachelaf W, Suau A, Boudraa G, Bouziane-Nedjadi K, Rigottier-Gois L, et al. Effects on faecal microbiota of dietary and acidic oligosaccharides in children during partial formula feeding. Journal of Pediatric Gastroenterology and Nutrition 2008;46(5):580-8.
Manzoni 2009 {unpublished data only}
  • Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 2009;302(13):1421-8.
  • Manzoni P, Stolfi I, Cattani S, Messner H, Laforgia N, Romeo MG, et al. Bovine Lactoferrin supplementation prevents invasive fungal infections in preterm VLBW neonates: Data from a multicenter, randomized, double-blind, placebo-controlled study. E-PAS. 2009:2155.4.
Mihatsch 2006 {published data only}
  • Mihatsch WA, Hoegel J, Pohlandt F. Oligosaccharides reduce stool viscosity and accelerate the gastro-intestinal transport in preterm infants. EPAS. 2005:1302.
  • Mihatsch WA, Hoegel J, Pohlandt F. Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Acta Paediatrica 2006;95(7):843-8.
Modi 2010 {published data only}
  • Modi N, Uthaya S, Fell J, Kulinskaya E. A randomised, double-blind, controlled trial of the effect of prebiotic oligosaccharides on enteral tolerance in preterm infants. Pediatric Research 2010;68:440-5.
Moro 2002 {published data only}
  • Moro G, Minoli I, Mosca M, Fanaro S, Jelinek J, Stahl B, et al. Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. Journal of Pediatric Gastroenterology and Nutrition 2002;34(3):291-5.
  • Moro GE, Mosca F, Miniello V, Fanaro S, Jelinek J, Stahl B, et al. Effects of a new mixture of prebiotics on faecal flora and stools in term infants. Acta Paediatrica Supplement 2003;91(441):77-9.
  • Moro GE, Stahl B, Fanaro S, Jelinek R, Boehm G, Coppa GV. Dietary prebiotic oligosaccharides are detectable in the faeces of formula-fed infants. Acta Paediatrica 2005;94(449):27-30.
Nakamura 2009 {published data only}
  • Nakamura N, Gaskins HR, Collier CT, Nava GM, Rai D, Petschow B, et al. Molecular ecological analysis of fecal bacterial populations from term infants fed formula supplemented with selected blends of prebiotics. Applied and Environmental Microbiology 2009;75(4):1121-8.
Panigrahi 2008 {published data only}
  • Chandel DS, Tulapurkar ME, Braileanu GT, Panigrahi P. Long-term impact of synbiotic treatment on the developing gut flora of Indian infants. PAS Annual Meeting. 2010.
  • Panigrahi P, Parida S, Pradhan L, Mohapatra SS, Misra PR, Johnson JA, et al. Long-term colonization of a Lactobacillus plantarum synbiotic preparation in the neonatal gut. Journal of Pediatric Gastroenterology and Nutrition 2008;47(1):45-53.
  • Panigrahi P, Parida S, Satpathy R, Pradhan L, Mohapatra SS, Misra PR, et al. Long term colonization of a synbiotic Lactobacillus preparation in the newborn gut. EPAS. 2006:4812.50.
Puccio 2007 {published data only}
  • Puccio G, Cajozzo C, Meli F, Rochat F, Grathwohl D, Steenhout P. Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics. Nutrition 2007;23(1):1-8.
Rinne 2005 {published data only}
Riskin 2010 {unpublished data only}
  • Riskin A, Hochwald O, Bader D, Srugo I, Kugelman A, Shaoul R. The effects of lactulose supplementation to enteral feedings in premature infants. A pilot study. EPAS. 2007:6282.10.
  • Riskin A, Hochwald O, Bader D, Srugo I, Naftali G, Kugelman A, et al. The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study. Journal of Pediatrics 2010;156(2):209-14.
  • Shaoul R. Lactulose for the Prevention of Nosocomial Infections in Children. ClinicalTrials.gov identifier: NCT00273949 2006.
Salvini 2011 {published data only}
  • Salvini F, Riva E, Salvatici E, Boehm G, Jelinek J, Banderali G, et al. A specific prebiotic mixture added to starting infant formula has long-lasting bifidogenic effects. The Journal of Nutrition 2011;141(7):1335-9.
Savino 2003 {published data only}
  • Savino F, Cresi F, Maccario S, Cavallo F, Dalmasso P, Fanaro S, et al. "Minor" feeding problems during the first months of life: effect of a partially hydrolysed milk formula containing fructo- and galacto-oligosaccharides. Acta Paediatrica Supplement 2003;91(441):86-90.
Savino 2005 {published data only}
  • Savino F, Maccario S, Castagno E, Cresi F, Cavallo F, Dalmasso P, et al. Advances in the management of digestive problems during the first months of life. Acta Paediatrica Supplement. 2005;94(449):120-4.
  • Savino F, Palumeri E, Castagno E, Cresi F, Dalmasso P, Cavallo F, et al. Reduction of crying episodes owing to infantile colic: A randomized controlled study on the efficacy of a new infant formula. European Journal of Clinical Nutrition 2006;60(11):1304-10.
Scholtens 2006 {published data only}
  • Scholtens PA, Alles MS, Bindels JG, van der Linde EG, Tolboom JJ, Knol J. Bifidogenic effects of solid weaning foods with added prebiotic oligosaccharides: a randomised controlled clinical trial. Journal of Pediatric Gastroenterology and Nutrition 2006;42(5):553-9.
Shadid 2007 {published data only}
  • Shadid R, Haarman M, Knol J, Theis W, Beermann C, Rjosk-Dendorfer D, et al. Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study. American Journal of Clinical Nutrition 2007;86(5):1426-37.
Singhal 2008 {published data only}
  • Singhal A, Kennedy K, Lanigan J, Clough H, Jenkins W, Elias-Jones A, et al. Dietary nucleotides and early growth in formula-fed infants: A randomized controlled trial. Pediatrics 2010;126(4):e946-53.
  • Singhal A, Macfarlane G, Macfarlane S, Lanigan J, Kennedy K, Elias-Jones A, et al. Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial. American Journal of Clinical Nutrition 2008;87(6):1785-92.
Underwood 2009 {published data only}
  • Underwood MA, Salzman NH, Bennett SH, Barman M, Mills DA, Marcobal A, et al. A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations in preterm infants: impact on weight gain, intestinal microbiota, and fecal short-chain fatty acids. Journal of Pediatric Gastroenterology and Nutrition 2009;48(2):216-25.
van den Berg 2004 {published data only}
  • van den Berg A, Fetter WP, Westerbeek EA, van der Vegt IM, van der Molen HR, van Elburg RM. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: a randomized controlled trial. JPEN, Journal of Parenteral and Enteral Nutrition 2006;30(5):408-14.
  • van den Berg A, van Elburg RM, Teerlink T, Lafeber HN, Twisk JW, Fetter WP. A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations. Journal of Pediatric Gastroenterology and Nutrition 2005;41(1):66-71.
  • van den Berg A, van Elburg RM, Twisk JW, Fetter WP. Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583]. BMC Pediatrics 2004;4:17.
  • van den Berg A, van Elburg RM, Vermeij L, van Zwol A, van den Brink GR, Twisk JW, et al. Cytokine responses in very low birth weight infants receiving glutamine-enriched enteral nutrition. Journal of Pediatric Gastroenterology and Nutrition 2009;48(1):94-101.
  • van den Berg A, van Elburg RM, Westerbeek EA, Twisk JW, Fetter WP. Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial. American Journal of Clinical Nutrition 2005;81(6):1397-404.
  • van den Berg A, van Elburg RM, Westerbeek EA, van der Linde EG, Knol J, Twisk JW, et al. The effect of glutamine-enriched enteral nutrition on intestinal microflora in very low birth weight infants: a randomized controlled trial. Clinical Nutrition 2007;26(4):430-9.
  • van den Berg A, van Zwol A, Moll HA, Fetter WP, van Elburg RM. Glutamine-enriched enteral nutrition in very low-birth-weight infants: effect on the incidence of allergic and infectious diseases in the first year of life. Archives of Pediatrics and Adolescent Medicine 2007;161(11):1095-101.
  • van Zwol A, van den Berg A, Huisman J, Vermeulen RJ, Fetter WP, Twisk JW, et al. Neurodevelopmental outcomes of very low-birth-weight infants after enteral glutamine supplementation in the neonatal period. Acta Paediatrica 2008;97(5):562-7.
  • van Zwol A, van den Berg A, Nieuwenhuis EE, Twisk JW, Fetter WP, van Elburg RM. Cytokine profiles in 1-yr-old very low-birth-weight infants after enteral glutamine supplementation in the neonatal period. Pediatric Allergy and Immunology 2009;20(5):467-70.
Vivatvakin 2010 {published data only}
  • Vivatvakin B, Mahayosnond A, Theamboonlers A, Steenhout PG, Conus NJ. Effect of a whey-predominant starter formula containing LCPUFAs and oligosaccharides (FOS/GOS) on gastrointestinal comfort in infants. Asia Pacific Journal of Clinical Nutrition 2010;19(4):473-80.
Vlieger 2009 {published data only}
  • Vlieger AM, Robroch A, van Buuren S, Kiers J, Rijkers G, Benninga MA, et al. Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial. British Journal of Nutrition 2009;102(6):869-75.
Ziegler 2007a {unpublished data only}
  • Ziegler EE, Black B, Lessin H, Jones S, Sun S. Assessment of growth of infants fed a starter infant formula containing prebiotics and probiotics. EPAS. 2007:5888.8.

References to studies awaiting assessment

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Campeotto 2011 {unpublished data only}
  • Campeotto F. Evaluation of a Fermented Formula Without Live Bacteria for Preterm Infants: Effects on Microbiota Species and Intestinal Inflammatory Markers. ClinicalTrials.gov identifier: NCT00711633 2008.
  • Campeotto F, Suau A, Kapel N, Magne F, Viallon V, Ferraris L, et al. A fermented formula in pre-term infants: clinical tolerance, gut microbiota, down-regulation of faecal calprotectin and up-regulation of faecal secretory IgA. The British Journal of Nutrition 2011;March 22:1-10 [Epub ahead of print].
Hicks 2010 {unpublished data only}
  • Heubi J. Evaluation of Mineral Absorption in Infants Fed Infant Formula. ClinicalTrials.gov identifier: NCT00366873 2006.
  • Hicks PD, Hawthorne KM, Marunycz J, Berseth CL, Heubi J, Abrams SA. Similar calcium status is present in infants fed formula with and without prebiotics [abstract]. Annual Meeting of the Pediatric Academic Society. 2010; Vol. E-PAS2010:1665.7.
Holscher 2012 {unpublished data only}
  • Faust K, Litov R, Ziegler EE, Lessin H, Hatch T, Sun S, Tappenden KA. Effects of prebiotic-containing infant formula on commensal microbiota [abstract]. Annual Meeting of the Pediatric Academic Societies. 2008; Vol. EPAS:5820.4.
  • Holscher HD, Faust KL, Czerkies LA, Litov R, Ziegler EE, Lessin H, et al. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. Journal of Parenteral and Enteral Nutrition 2012;36(1 Suppl):95S-105S.
Nyankovskyy 2008 {unpublished data only}
  • Nyankovskyy SL, Ivakhnenko OS, Dobryanskyy DD, Shadrin OG, Berezhnyy VV, Aryaev ML. Multicentre open randomized study of the effect of prebiotic infant formula on some immune markers in term infants. World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. 2008:P0996.
Scalabrin 2012 {unpublished data only}
  • Scalabrin D, Harris C, Marunycz J, Mitmesser S. Stooling patterns of infants fed an infant formula supplemented with a novel prebiotic blend. Allergy 2010;65 Suppl 92:313-4.
  • Scalabrin D, Mitmesser S, Harris C, Marunycz J, Walker D, Tolkko S, Salminen S. A more diverse bifidobacterium profile is observed in infants when fed a formula supplemented with polydextrose (PDX) and galactooligosaccharides (GOS). Allergy 2010;65 Suppl 92:751.
  • Scalabrin DM, Harris C, Marunycz J, Mitmesser SH. Positive impact of a novel prebiotic blend on infant stooling patterns and growth. Pediatric Academic Societies Annual Meeting. 2010; Vol. EPAS2010373.
  • Scalabrin DM, Mitmesser SH, Welling GW, Harris CL, Marunycz JD, Walker DC, et al. New prebiotic blend of polydextrose and galacto-oligosaccharides has a bifidogenic effect in young infants. Journal of Pediatric Gastroenterology and Nutrition 2012;54(3):343-52.
  • Walker DC, Scalabrin DMF, Mitmesser SH, Harris C, Marunycz JD, Tölkkö S, et al. A bifidogenic effect is observed in young infants fed infant formula supplemented with galactooligosaccharide (GOS) and polydextrose (PDX). FASEB Journal. 2010; Vol. Meeting Abstracts:24.
Vanderhoff 2010 {published data only}
  • Vanderhoof JA, Mitmesser SH, Harris C, Stolz S, Berseth C. Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or Galacto Oligo Saccharides (GOS). Journal of Pediatric Gastroenterology and Nutrition 2010;50 Suppl 2:E200-1.
Veereman-Wauters 2008 {unpublished data only}
  • Veereman-Wauters G, Assam P, Van de Broek H, Plaskie K, Wesling F, McCartney A. Safety, tolerance and bifidogenic effect of prebiotic supplements in infant formula. World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. 2008:P0797.
  • Veereman-Wauters G, Staelens S, Van de Broek H, Plaskie K, Wesling F, Roger LC, et al. Physiological and bifidogenic effects of prebiotic supplements in infant formulae. Journal of Pediatric Gastroenterology and Nutrition 2011;52(6):763-71.
Zoeren-Grobben 2009 {published data only}
  • van Zoeren-Grobben D. The role of pre- and probiotics in infections in term infants (De role van pre- en probiotica in infecties in a terme geboren kinderen). controlled-trials.com: ISRCTN65140085 2009.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Agostoni 2006 {unpublished data only}
  • Agostoni C. Randomized, Double Blind Study to Evaluate the Safety and Efficacy of an Infant Formula Supplemented With Galacto-oligosaccharides (GOS) in Healthy, Full Term Infants. ClinicalTrials.gov identifier: NCT00486148 2006.
Hammerman 2007 {unpublished data only}
  • Hammerman C, Bin-nun A. Prebiotics vs. Placebo in the Prevention of Necrotizing Enterocolitis in Premature Neonates. ClinicalTrials.gov identifier: NCT00437567 2007.
Materna Laboratories 2010 {published data only}
  • Materna Laboratories. Evaluation of the Effect of Milk Based Infant Formula Supplemented Either With Probiotic Microorganisms and/or With Prebiotic on the Intestinal Microflora During the First 4 Months of Life of Healthy, Full Term Infants and it's Long Term Effect on Morbidity up to the Age of 9 Months. ClinicalTrials.gov Identifier: NCT00836771 2010.
Stronati 2010 {unpublished data only}
  • Stronati M. Double-blind Randomized Controlled Study for the Evaluation of Nutritional Outcomes of a Cow's Milk Based Infant Formula Containing Galacto-oligosaccharides, Beta-palmitate and Acidified Milk. ClinicalTrials.gov identifier: NCT01197365 2010.
Underwood 2009a {unpublished data only}
  • Underwood M. Phase 1A Study of Impact of Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Premature Infants. ClinicalTrials.gov identifier: NCT00810160 2009.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Agostoni 2004
  • Agostoni C, Axelsson I, Goulet O, Koletzko B, Michaelsen KF, Puntis JW, et al. Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition. Journal of Pediatric Gastroenterology and Nutrition 2004;39(5):465-73.
Arshad 2005
Asher 2004
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Bergmann 1997
Bernsen 2005
Bjorksten 2001
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Burr 1989
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Hansen 1993
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Kalliomaki 2001
  • Kalliomaki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. Journal of Allergy and Clinical Immunology 2001;107(1):129-34.
Kjellman 1977
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Osborn 2007a
  • Osborn DA, Sinn JKH. Probiotics in infants for prevention of allergy. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006475.pub2]
Osterballe 2005
Prescott 2005
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Raby 2004
Rao 2009
  • Rao S, Srinivasjois R, Patole S. Prebiotic supplementation in full-term neonates: a systematic review of randomized controlled trials. Archives of Pediatric and Adolescent Medicine 2009;163(8):755-64.
RevMan 2011
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Sampson 2004
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Schmelzle 2003
  • Schmelzle H, Wirth S, Skopnik H, Radke M, Knol J, Bockler HM, et al. Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolyzed protein, a high beta-palmitic acid level, and nondigestible oligosaccharides. Journal of Pediatric Gastroenterology and Nutrition 2003;36(3):343-51.
Schultz Larsen 1996
Srinivasjois 2009
  • Srinivasjois R, Rao S, Patole S. Prebiotic supplementation of formula in preterm neonates: a systematic review and meta-analysis of randomised controlled trials. Clinical Nutrition 2009;28(3):237-42.
Sudo 1997
  • Sudo N, Sawamura S, Tanaka K, Aiba Y, Kubo C, Koga Y. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. Journal of Immunology 1997;159(4):1739-45.

References to other published versions of this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Osborn 2007b
  • Osborn DA, Sinn JKH. Prebiotics in infants for prevention of allergy. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006474.pub2]