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. The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. 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. A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants Synbiotics-supplemented amino acid-based formula supports adequate growth in cow's milk allergic infants. Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. The effect of a prebiotic supplemented formula on growth and stool microbiology of term infants. The effect of early nutritional supplementation with a mixture of probiotic, prebiotic, fiber and micronutrients in infants with acute diarrhea in Indonesia. Effects of probiotic and prebiotic on gastrointestinal motility in newborns. Long-term Colonization of a Lactobacillus plantarum Synbiotic Preparation in the Neonatal Gut Tolerance and Safety Evaluation in a Large Cohort of Healthy Infants Fed an Innovative Prebiotic Formula: A Randomized Controlled Trial 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 Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. 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. Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial. Effect of a Probiotic Infant Formula on Infections in Child Care Centers: Comparison of Two Probiotic Agents Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast-fed Infants Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1-6 months of age: a randomized controlled trial. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. [Randomised placebo controlled double blind study on the effect of prebiotic oligosaccharides on intestinal flora in healthy infants]. Prebiotic Effect of an Infant Formula Supplemented with Galacto-Oligosaccharides: Randomized Multicenter Trial Growth and Tolerance of Term Infants Fed Formula With Probiotic Lactobacillus reuteri Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition Effect of a New Synbiotic Mixture on Atopic Dermatitis in Children: a Randomized-Controlled Trial Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Non-digestible oligosaccharides reduce immunoglobulin free light-chain concentrations in infants at risk for allergy. Long-term safety of early consumption of Lactobacillus fermentum CECT5716: A 3-year follow-up of a randomized controlled trial. Quantitative Real-Time PCR Assays To Identify and Quantify Fecal Bifidobacterium Species in Infants Receiving a Prebiotic Infant Formula Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial. Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age
BACKGROUND Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants . OBJECTIVE The objective was to evaluate infant formulas containing probiotics and synbiotics ( combinations of probiotics and prebiotics ) for safety and tolerance . DESIGN In a prospect i ve , controlled , double-blind , r and omized trial , healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 ( BL999 ) + Lactobacillus rhamnosus LPR ( LPR ) , BL999 + LPR + 4 g/L of 90 % galactooligosaccharide/10 % short-chain fructooligosaccharide ( GOS/SCFOS ) , or BL999 + Lactobacillus paracasei ST11 ( ST11 ) + 4 g/L GOS/SCFOS from < or = 2 to 16 wk of age ( treatment period ) . Safety and tolerance were assessed based on weight gain during the treatment period ( primary outcome ) as well as recumbent length , head circumference , digestive tolerance , and adverse events ( secondary outcomes ) , which were evaluated at 2 , 4 , 8 , 12 , 16 , and 52 wk of age . RESULTS Two hundred eighty-four infants were enrolled . During the treatment period , difference in mean weight gain between control and study formula groups in both the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d , indicating equivalent weight gain . Secondary outcomes did not show significant differences between groups during the treatment period . CONCLUSION Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P < .001 ) . The times to reach full enteral feeding were faster ( P < .001 ) , the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants  , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC The addition of probiotics to infant formula has been shown to be an efficient way to increase the number of beneficial bacteria in the intestine in order to promote a gut flora resembling that of breast-fed infants . The objective of the present study was to evaluate the safety and tolerance of a combination of two probiotic strains in early infancy . A group of 126 newborns were r and omised to receive a prebiotic-containing starter formula supplemented with Lactobacillus paracasei ssp . paracasei and Bifidobacterium animalis ssp . lactis or the same formula without probiotics for the first 3 months of life . A total of eighty infants continued the study until they were aged 6 months .  Growth measurements were taken monthly at healthy baby clinics . Diaries were used to monitor behaviour , infections , use of antibiotics , as well as stool characteristics . Normal growth occurred in all infants and no statistically significant differences were detected between the probiotics group and the control group for gain in weight , length and head circumference . Infants in the probiotics group produced softer and more frequent stools during the first 3 months of life . No differences were found in crying and sleeping hours , number of parent-diagnosed infections , antibiotic use , visits to the general practitioner and number of adverse events . The use of a prebiotic-containing starter formula supplemented with L. paracasei ssp . paracasei and B. animalis ssp . lactis in early infancy is safe , well tolerated and has no adverse effects on growth and infant behaviour Background Prebiotics and probiotics ( synbiotics ) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula ( AAF ) for infants with cow ’s milk allergy ( CMA ) . Methods This multicenter , double-blind , r and omized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group ( ER/CC ) in feces from infants with suspected non-IgE-mediated CMA . Feces from age-matched healthy breastfed infants were used as reference ( healthy breastfed reference ( HBR ) ) for primary outcomes . The CMA subjects were r and omized and received test or control formula for 8 weeks . Test formula was a hypoallergenic , nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V . Control formula was AAF without synbiotics . Results A total of 35 ( test ) and 36 ( control ) subjects were r and omized ; HBR included 51 infants . At week 8 , the median percentage of bifidobacteria was higher in the test group than in the control group ( 35.4 % vs. 9.7 % , respectively ; P<0.001 ) , whereas ER/CC was lower ( 9.5 % vs. 24.2 % , respectively ; P<0.001 ) . HBR levels of bifidobacteria and ER/CC were 55 % and 6.5 % , respectively . Conclusion AAF including specific synbiotics , which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group , improves the fecal microbiota of infants with suspected non-IgE-mediated CMA BACKGROUND Children with cow 's milk allergy ( CMA ) are at risk for inadequate nutritional intake and growth . Dietary management of CMA , therefore , requires diets that are not only hypoallergenic but also support adequate growth in this population . This study assessed growth of CMA infants when using a new amino acid-based formula ( AAF ) with prebiotics and probiotics ( synbiotics ) and evaluated its safety in the intended population . METHODS In a prospect i ve , r and omized , double-blind controlled study , full-term infants with diagnosed CMA received either an AAF ( control ; n = 56 ) or AAF with synbiotics ( oligofructose , long-chain inulin , acidic oligosaccharides , Bifidobacterium breve M-16V ) ( test ; n = 54 ) for 16 wk . Primary outcome was growth , measured as weight , length and head circumference . Secondary outcomes included allergic symptoms and stool characteristics . RESULTS Average age ( ±SD ) of infants at inclusion was 4.5 ± 2.4 months . Both formulas equally supported growth according to WHO 2006 growth charts and result ed in similar increases of weight , length and head circumference . At week 16 , differences ( 90 % CI ) in Z-scores ( test-control ) were as follows : weight 0.147 ( -0.10 ; 0.39 , p = 0.32 ) , length -0.299 ( -0.69 ; 0.09 , p = 0.21 ) and head circumference 0.152 ( -0.15 ; 0.45 , p = 0.40 ) . Weight-for-age and length-for-age Z-scores were not significantly different between the test and control groups . Both formulas were well tolerated and reduced allergic symptoms ; the number of adverse events was not different between the groups . CONCLUSIONS This is the first study that shows that an AAF with a specific synbiotic blend , suitable for CMA infants , supports normal growth and growth similar to the AAF without synbiotics . This clinical trial is registered as NCT00664768 Secretory immunoglobulin A ( SIgA ) plays an important role in the defence of the gastrointestinal tract . The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses . Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aim ed at study ing the effects of st and ard , prebiotic and probiotic infant formulas on the faecal SIgA levels . At birth , infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a r and omized , double-blind fashion . Nineteen infants received st and ard infant formula ; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 x 10(9 ) cfu Bifidobacterium animalis/100 ml formula . Faecal sample s were taken on postnatal day 5 , day 10 , wk 4 and every 4 wk thereafter until wk 32 . SIgA in faeces was determined by an enzyme-linked immunosorbent assay . During the intervention , infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the st and ard formula-fed infants reaching statistical significance at the age of 16 wk . In contrast , infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the st and ard formula group . Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion . Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend OBJECTIVE . Live probiotic bacteria and dietary prebiotic oligosaccharides ( together termed synbiotics ) increasingly are being used in infancy , but evidence of long-term safety is lacking . In a r and omized , placebo-controlled , double-blind trial , we studied the safety and long-term effects of feeding synbiotics to newborn infants . METHODS . Between November 2000 and March 2003 , pregnant mothers carrying infants at high risk for allergy were r and omly assigned to receive a mixture of 4 probiotic species ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve Bb99 , and Propionibacterium freudenreichii ssp shermanii ) or a placebo for 4 weeks before delivery . Their infants received the same probiotics with 0.8 g of galactooligosaccharides , or a placebo , daily for 6 months after birth . Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3 , 6 , and 24 months and from question naires at ages 3 , 6 , 12 , and 24 months . Growth data were collected at each time point . RESULTS . Of the 1018 eligible infants , 925 completed the 2-year follow-up assessment . Infants in both groups grew normally . We observed no difference in neonatal morbidity , feeding-related behaviors ( such as infantile colic ) , or serious adverse events between the study groups . During the 6-month intervention , antibiotics were prescribed less often in the synbiotic group than in the placebo group ( 23 % vs 28 % ) . Throughout the follow-up period , respiratory infections occurred less frequently in the synbiotic group ( geometric mean : 3.7 vs 4.2 infections ) . CONCLUSION . Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life Background The prevalence of allergic diseases in infants , whose parents and siblings do not have allergy , is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative . Intestinal microbiota may modulate immunologic and inflammatory systemic responses and , thus , influence development of sensitization and allergy . Prebiotics – non-digestible oligosaccharides that stimulate growth of probiotic bacteria – have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations about the use of prebiotics in the prevention of allergy . Methods The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy . We performed a systematic review of r and omized controlled trials of prebiotics , and review ed the evidence about patient values and preferences , and re source requirements ( up to January 2015 , with an up date on July 29 , 2015 ) . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . Results Based on GRADE evidence to decision frameworks , the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants . Both recommendations are conditional and based on very low certainty of the evidence . We found no experimental or observational study of prebiotic supplementation  in pregnant women or in breastfeeding mothers . Thus , the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding , at this time . Conclusions WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy , term infants BACKGROUND : Eczema is the most common inflammatory skin disease of childhood , characterized by an itchy red rash that usually involves the face and skin folds . There is currently no curative treatment for eczema , so the reduction of eczema incidence through disease prevention is a desirable goal . Potential interventions for preventing eczema include exclusive breastfeeding , hydrolysed protein formulas and soy formulas when bottle feeding , maternal antigen avoidance , omega oil supplementation , prebiotics and probiotics . OBJECTIVES : This overview of review s aims to present the current body of data from Cochrane and non-Cochrane review s to provide the most up-to- date evidence on the efficacy and safety of interventions to prevent eczema in infants and children at different risk levels for developing allergic disease . METHODS : Our pool of Cochrane and non-Cochrane review s came from the 2010 United Kingdom National Health Service ( NHS ) Evidence Skin Disorders Annual Evidence Up date s Mapping Exercise on Atopic Eczema . This group used a comprehensive search strategy last conducted in August 2010 to identify all systematic review s on eczema prevention . We identified all review s that met our pre-specified inclusion criteria , and data were extracted , analysed , compiled into tables and synthesized using quantitative and qualitative methods . MAIN RESULTS : Seven systematic review s containing 39 relevant trials with 11 897 participants were included in this overview . Overall , there was no clear evidence that any of the main interventions review ed reduced eczema incidence . In subgroup analyses of infants at high risk of allergic disease , an observational study found that exclusive breastfeeding for at least six months compared with introduction of solids at three to six months decreased the incidence of eczema by 60 % ( risk ratio ( RR ) : 0.40 ; 95 % confidence interval ( CI ) : 0.21 , 0.78 ) , and a r and omized controlled trial found that prebiotics compared with no prebiotics  decreased incidence by 58 % ( RR : 0.42 ; 95 % CI : 0.21 , 0.84 ) . However , each of these findings was based on the results of a single small trial , and no intervention reduced eczema incidence beyond the first two years of life . Although we pre-specified incidence of atopic eczema ( i.e. eczema associated with immunoglobulin E ( IgE ) sensitization ) as a primary outcome , data on whether participants diagnosed with eczema were truly atopic were largely lacking from systematic review s. Similarly , data on atopy , measured using skin prick tests or specific IgE tests to allergens , were not reported in many review s. No interventions were found to decrease atopy when reported . Adverse events data were generally lacking , but data from a trial of probiotics versus no probiotics showed significantly more spitting up in the first one ( RR : 1.88 ; 95 % CI : 1.03 , 3.45 ) and two ( RR : 1.69 ; 95 % CI : 1.02 , 2.80 ) months of life , but no overall increase in risk of gastrointestinal symptoms in the first year . AUTHORS # ENTITYSTARTX02019 ; CONCLUSIONS : Although there is currently no clear evidence showing that any of the interventions examined in this overview prevent eczema in participants not selected for risk of allergic disease , there is some evidence that exclusive breastfeeding for at least six months and prebiotics might reduce eczema incidence in high-risk participants . However , these conclusions are based on limited evidence with method ological shortcomings . Future research on prevention of eczema is needed and should examine different types of hydrolysed formulas , prebiotics and probiotics , as well as enhancement of the skin barrier and other novel approaches in infants at different risk levels for developing allergic disease BACKGROUND The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various compounds of breast milk including prebiotic substances . AIM This prospect i ve , double blind , study compared the growth , acceptability and the proportion of bifidobacteria and clostridia in the stool flora of bottle-fed infants r and omized to receive a formula with a specific mixture of 0.4 g/100 ml prebiotic galacto- and long-chain fructooligosaccharides or the same formula without added prebiotics . METHODS Within 0 - 14 days after birth at term , healthy bottle-fed infants were enrolled to receive either a prebiotic formula or a st and ard formula . At recruitment anthropometric measurements were done . These were repeated at the age of 6 and 12 weeks . Stool sample s were taken at inclusion and at the age of 6 weeks . The number of bifidobacteria and clostridia was determined by fluorescent in situ hybridization . RESULTS There was good tolerance of the prebiotic formula . Somatic growth was similar in the two groups . Stool frequency was significantly higher in the prebiotic group ( P=0.031 ) . Infants in the prebiotic group had also softer stools as compared to the control group ( P=0.026 ) . Baseline values of microorganisms at study entry were similar . The percentage of faecal clostridia at the completion of the study was significantly lower in the prebiotic group ( P=0.042 ) , while the proportion of faecal bifidobacteria was higher in the prebiotic group as compared to the control group . However this difference did not reach statistical significance ( P=0.262 ) . The percentage of E. coli was lower in the prebiotic group but again this did not reach statistical significance ( P=0.312 ) . CONCLUSION An infant formula containing prebiotic oligosaccharides is well tolerated , leads to normal somatic growth and suppresses the numbers of clostridia in the faeces with a trend for higher percentage of stool bifidobacteria and lower percentage of E. coli A r and omized double blind clinical trial was conducted to assess the efficacy of a special infant formula containing Lactobacillus rhamnosus LMG P-22799 ( probiotic : 5 x 10(8 ) CFU/100mL ) , inulin ( prebiotic : 0.15 g/100mL ) , dietary fiber ( soy polysaccharides : 0.2 g/100mL ) and increased amounts of zinc+iron ( + 0.4 and + 0.6 mg/100mL , respectively ) as active ingredients for the early dietary management of 58 Indonesian well-nourished male infants aged 3 - 12 months suffering from acute diarrhea with moderate dehydration . After adequate oral rehydration , the patients were r and omly assigned to receive either a low lactose infant formula supplemented with added precooked rice ( 1.5 g/100mL ) with the above active ingredients ( study group ) or a low lactose infant formula with added precooked rice without the above active ingredient supplement ( control group ) . No antibiotic , anti-secretory drug or antiemetic was given at all . Both study and control groups showed similar outcomes for weight gain and stool weight . The duration of diarrhea was significantly shorter in the study group than in the control group ( 1.63 versus 2.45 days ; p<0.05 ; for the study and control group respectively ) . No treatment failure or other side effects were observed during the course of the study . The present study supports the evidence for the efficacy of a special anti-diarrhea infant formula containing probiotic , prebiotic , fiber and iron+zinc after oral rehydration by shortening the duration of infantile diarrhea in developing countries . However , from the results of our study we can not discern the individual contribution of the active ingredients and also not whether they may act independent from each other or in a synergistic way To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk . The aim of this study was to evaluate the effects of prebiotic , probiotic added to a st and ard formula on gastrointestinal motility respect to placebo-formula .  Cutaneous electrogastrography ( EGG ) and ultrasound gastric emptying ( GE ) were performed in 49 preterm newborns . 17 newborns were exclusively breast-fed ; 32 were r and omly assigned to receive prebiotic-added formula ( 0.8 g/dl of a mixture from scGOS and lcFOS , ratio 9:1 ) ( 10 ) , a probiotic-added formula ( L. reuteri at dose of 1x10(8 ) colony forming units ( CFU ) per day ) ( 10 ) , a formula with placebo ( 12 ) for 30 days . No difference was seen in the nutritional parameters and no adverse events were reported . After the intervention period , the prebiotic , probiotic , and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group ( ANOVAon ranks p<0.001 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 ; and ANOVA on ranks p=0.005 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 , respectively ) . Feeding preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk Background : Probiotic , prebiotic , and synbiotic ( a combination of pro- and prebiotic ) supplements increasingly are being used to prevent and treat a variety of health conditions . Although colonization is considered a key element in the success of such treatments , few clinical studies have addressed colonizing ability . Studies are even more limited in neonates and infants , who may benefit most from such treatment . The present study was conducted to determine the colonizing ability , tolerance , and impact on the stool flora of 7 days of administration of a synbiotic supplement to a neonatal cohort , in preparation for a larger hospital-based trial . Patients and Methods : In this r and omized , double-masked , controlled trial , healthy inborn newborns > 35 weeks of gestational age and > 1800 g birth weight were r and omized between 1 and 3 days after birth to receive an oral synbiotic preparation ( Lactobacillus plantarum and fructooligosaccharides ) or a dextrose saline placebo .  Two babies were treated with the synbiotic preparation for every 1 baby treated with the placebo . Duration of therapy was 7 days . Comprehensive stool cultures were done at baseline and on days 3 , 7 , 14 , 21 , and 28 . Results : Nineteen infants received the active study supplement and 12 infants received the placebo for 7 days . L plantarum was cultured from the stools of 84 % of the treated infants after 3 days of treatment , and from 95 % of infants on day 28 after birth . Of the infants , 100 % , 94 % , 88 % , 56 % , and 32 % remained colonized at months 2 , 3 , 4 , 5 , and 6 , respectively . In both groups , the total mean number of species and the mean log colony counts increased over time . The number of bacterial species was significantly higher on days 21 and 28 in the synbiotic preparation group compared with placebo ( P = 0.002 and 0.03 , respectively ) . There was a linear increase in the mean log gram-negative colony counts in the placebo group during the 4-week period that was significantly higher than that in the Lactobacillus group on days 14 , 21 , and 28 ( P < 0.001 for each ) . In contrast , the supplement group had significantly higher gram-positive colony counts on days 14 ( P = 0.002 ) and 28 ( P = 0.04 ) . Only 1 infant in the placebo group was colonized with L fermentum during the first 28 days of life . No difference was found in the percent increase in weight between baseline and day 7 , but on day 28 and months 2 , 3 , and 6 , the percent increase from baseline was higher in the probiotic-treated group ( P ≤ 0.05 ) . The supplement was tolerated well . Conclusions : The synbiotic preparation colonized quickly after 3 days of administration and the infants stayed colonized for several months after therapy was stopped . There was an increase in bacterial diversity and gram-positive organisms and a reduction of gram-negative bacterial load in the treatment group . Because a combination preparation was used , it is difficult to specifically attribute the colonization to either the probiotic or prebiotic component in this study . Larger efficacy trials are warranted to examine the mechanism of action and precise effects of these supplements Background the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk . The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy . Methodology /Principal Findings this study was performed as a multi-center , r and omized , double-blind , placebo-controlled trial including healthy term infants . Infants were recruited before the age of 8 weeks , either having started with formula feeding or being fully breast-fed ( breastfeeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . Growth , tolerance and adverse events were assessed at 8 , 16 , 24 and 52 weeks of age . The prebiotic and control groups showed similar mean weight , length and head circumference , skin fold thicknesses , arm circumference gains and stool frequency at each study point . As far as the anthropometric parameters are concerned , the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point . The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants , whereas at 52 weeks were strikingly smaller . The stool consistency in the prebiotic group was softer than in the control group at 8 , 16 and 24 weeks ( p<0.001 ) and closer to that of the breastfeeding group . There was no difference in the incidence of adverse events between the two formula groups . Conclusions our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants . Trial Registration : drks-neu.uniklinik-freiburg.de DRKS Objective : To compare the effect of 2 prebiotic/probiotic products on weight gain , stool microbiota , and stool short-chain fatty acid ( SCFA ) content of premature infants . Patients and Methods : This r and omized , blinded , placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides ( CUL , Culturelle , ConAgra , Omaha , NE ) , a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides ( PBP  , ProBioPlus DDS , UAS Laboratories , Eden Prairie , MN ) , or placebo ( a dilute preparation of Pregestamil formula ) twice daily for 28 days or until discharge if earlier . The primary outcome was weight gain . Secondary outcomes were stool bacterial analysis by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA content measured by high performance liquid chromatography . Results : Both prebiotic/probiotic combinations contained more bacterial species than noted on the label . No significant effect on infant growth of either prebiotic/probiotic supplement was observed . By cultures , 64 % of infants receiving PBP became colonized with bifidobacteria , compared with 18 % of infants receiving CUL and 27 % of infants receiving placebo ( chi-square , P = 0.064 ) . No differences were noted between groups in colonization rates for lactobacilli , Gram-negative enteric bacteria , or staphylococci . By 16S rDNA polymerase chain reaction analysis , the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo ( Kruskal-Wallis , P = 0.011 ) . No significant differences in stool SCFA content were detected between groups . No adverse reactions were noted . Conclusions : Infants receiving PBP were more likely to become colonized with bifidobacteria . No significant differences in weight gain or stool SCFA content were detected OBJECTIVE To evaluate the impact of early prebiotic and probiotic intervention on  preterm infants ' well-being , crying , growth , and microbiological programming . STUDY DESIGN Ninety-four preterm infants ( gestational age 32 - 36 weeks and birth weight > 1500 g ) r and omized to receive prebiotics ( mixture of galacto-oligosaccharide and polydextrose 1:1 ) , probiotics ( Lactobacillus rhamnosus GG ) , or placebo during the first 2 months of life were followed up for 1 year . Infants were categorized based on the extent of crying and irritability during the first 2 months of life , and their gut microbiota was investigated by fluorescence in situ hybridization ( n = 66 ) and quantitative polymerase chain reaction ( n = 63 ) . RESULTS A total of 27 of 94 infants ( 29 % ) infants were classified as excessive criers , significantly less frequently in the prebiotic and the probiotic groups than in the placebo group ( 19 % vs 19 % vs 47 % , respectively ; P = .02 ) . The placebo group had a higher percentage of Clostridium histolyticum group bacteria in their stools than did the probiotic group ( 13.9 % vs 8.9 % , respectively ; P = .05 ) . There were no adverse events related to either supplementation . CONCLUSIONS Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants . This original finding may offer new therapeutic and preventive measures for this common disturbance in early life BACKGROUND The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system . Probiotics , live health-promoting microbes , might offer such stimulation . OBJECTIVE We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases . METHODS We r and omized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery . Their infants received the same probiotics plus galacto-oligosaccharides ( n = 461 ) or a placebo ( n = 464 ) for 6 months . At 2 years , we evaluated the cumulative incidence of allergic diseases ( food allergy , eczema , asthma , and allergic rhinitis ) and IgE sensitization ( positive skin prick test response or serum antigen-specific IgE level > 0.7 kU/L ) . Fecal bacteria were analyzed during treatment and at age 2 years . RESULTS Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated ( atopic ) diseases ( odds ratio [ OR ] , 0.71 ; 95 % CI , 0.50 - 1.00 ; P = .052 ) . Probiotic treatment reduced eczema ( OR , 0.74 ; 95 % CI , 0.55 - 0.98 ; P = .035 ) and atopic eczema ( OR , 0.66 ; 95 % CI , 0.46 - 0.95 ; P = .025 ) . Lactobacilli and bifidobacteria more frequently ( P < .001 ) colonized the guts of supplemented infants . CONCLUSION Probiotic treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema . The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics . CLINICAL IMPLICATION S The prevention of atopic eczema in high-risk infants is possible by modulating the infant 's gut microbiota with probiotics and prebiotics Adding prebiotics or probiotics to infant formula to improve the intestinal flora of formula-fed infants is considered to be a major innovation . Several companies have brought relevant formulations onto the market . However , comparative data on the effects of pre- and probiotics on the intestinal microflora of infants are not available . The present study aim ed to compare the effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the composition and metabolic activity of the intestinal microflora . Before birth , infants were r and omised and double blindly allocated to one of three formulas . The prebiotic ( GOS/FOS ) group ( n 19 ) received regular infant formula supplemented with a mixture of galacto-oligosaccharides and fructo-oligosaccharides ( 6 g/l ) . The probiotic ( Bb-12 ) group ( n 19 ) received the same formula supplemented with 6.0x10(10 ) viable cells of B. animalis per litre . The st and ard group ( n 19 ) received non-supplemented regular formula .  A group of sixty-three breast-fed infants was included as a reference group . Faecal sample s were taken at postnatal day 5 and 10 , and week 4 , 8 , 12 and 16 . Compared with the groups fed Bb-12 and st and ard formula , the GOS/FOS formula group showed higher faecal acetate ratio ( 69.7 % ( sem 2.7 ) , 69.9 % ( sem 3.9 ) and 82.2 % ( sem 5.3 ) ; P<0.05 ) and lactate concentration ( 11.3 ( sem 7.9 ) , 3.1 ( sem 2.3 ) and 34.7 ( sem 10.7 ) mmol/kg faeces ) and lower pH ( 6.6 ( sem 0.2 ) , 7.1 ( sem 0.2 ) and 5.6 ( sem 0.2 ) ; P<0.05 ) at 16 weeks . Differences in percentage of bifidobacteria between the GOS/FOS ( 59.2 % ( sem 7.7 ) ) , Bb-12 ( 52.7 % ( sem 8.0 ) ) and the st and ard ( 51.8 % ( sem 6.4 ) ) groups were not statistically significant at 16 weeks . Feeding infants GOS/FOS formula result ed in a similar effect on metabolic activity of the flora as in breast-fed infants . In the Bb-12 group , composition and metabolic activity of the flora were more similar to those of the st and ard group The aim of the study was to evaluate whether supplementation of milk-formulas with prebiotic fructo-oligosaccharides or a probiotic , Lactobacillus johnsonii La1 ( La1 ) , could modulate the composition of the fecal microbiota of formula-fed infants , compared to breastfed ( BF ) infants . Ninety infants close to 4 months of age were r and omized into one of three groups to be blindly assigned to receive for 13 weeks : a ) an infant formula ( Control ) , b ) the same formula with fructo-oligosaccharides ( Prebio ) , or c ) with La1 ( Probio ) . At the end of this period , all infants received the control formula for 2 additional weeks . Twenty-six infants , breastfed throughout the study , were recruited to form group BF . Fecal sample s were obtained upon enrolment and after 7 and 15 weeks . Bacterial population s were assessed with classical culture techniques and fluorescent in situ hybridisation ( FISH ) . Seventy-six infants completed the study . On enrolment , higher counts of Bifidobacterium and Lactobacillus and lower counts of enterobacteria were observed in BF compared to the formula-fed infants ; these differences tended to disappear at weeks 7 and 15 . No major differences for Clostridium , Bacteroides or Enterococcus were observed between the groups or along the follow up . Probio increased fecal Lactobacillus counts ( p<0.001 ) ; 88 % of the infants in this group excreted live La1 in their stools at week 7 but only 17 % at week 15 . Increased Bifidobacterium counts were observed at week 7 in the 3 formula groups , similar to BF infants . These results confirm the presence of higher counts of bifidobacteria and lactobacilli in the microbiota of BF infants compared to formula-fed infants before dietary diversification , and that La1 survives in the infant digestive tract BACKGROUND Prebiotic-containing infant formula may beneficially affect gastrointestinal tolerance and commensal microbiota composition . OBJECTIVE Assess gastrointestinal tolerance and fecal microbiota , pH , and short-chain fatty acid ( SCFA ) concentrations of infants consuming formula with or without prebiotics .  DESIGN Full-term formula-fed infants were studied to a breastfed comparison group ( BF ) . Formula-fed infants ( FF ) were r and omized to consume a partially hydrolyzed whey formula with ( PRE ) or without ( CON ) 4 g/L of galacto-oligosaccharides and fructo-oligosaccharides ( 9:1 ) . Fecal bacteria , pH , and SCFA were assessed at baseline , 3 weeks , and 6 weeks . Caregivers of patients recorded stool characteristics and behavior for 2 days before the 3- and 6-week visits . RESULTS Feces from infants fed PRE had a higher absolute number ( P = .0083 ) and proportion ( P = .0219 ) of bifidobacteria than CON-fed infants and did not differ from BF . BF had a higher proportion of bifidobacteria than CON ( P = .0219 ) and lower number of Clostridium difficile than FF ( P = .0087 ) . Feces from formula-fed infants had higher concentrations of acetate ( P < .001 ) , butyrate ( P < .001 ) , propionate ( P < .001 ) , and total SCFAs ( P = .0230 ) than BF ; however , fecal pH was lower ( P = .0161 ) in PRE and BF than CON . Prebiotic supplementation did not alter stool patterns , tolerance , or growth . BF had more frequent stools that were yellow ( P < .0001 ) and more often liquid than FF ( P < .0001 ) . CONCLUSIONS Infant formula containing the studied oligosaccharides was well tolerated , increased abundance and proportion of bifidobacteria , and reduced fecal pH in healthy infants BACKGROUND Most infants developing atopic dermatitis have a low risk for atopy . Primary prevention of atopic dermatitis is difficult . OBJECTIVE To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life . METHODS Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks , either having started with formula feeding or being on full breast-feeding ( breast-feeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . RESULTS A total of 414 infants were r and omized to the prebiotic group and 416 infants to the control group . A total of 300 infants were followed in the breast-feeding group . Up to the first birthday , atopic dermatitis occurred in significantly fewer infants from the prebiotic group ( 5.7 % ) than from the control group ( 9.7 % ; P = .04 ) . The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group ( 7.3 % ) . In a Cox regression model , the rate of atopic dermatitis was significantly lower by 44 % in the prebiotic group versus the control group ( P = .04 ) . The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants . CONCLUSION Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants Probiotics and long-chain PUFA ( LC-PUFA ) may be beneficial supplements for infants who are not breast-fed . The aim of the present study is to evaluate the safety of an infant formula containing the LC-PUFA DHA and arachidonic acid ( AA ) and the probiotic Bifidobacterium lactis by comparing the growth rate of infants fed the supplemented and unsupplemented formulas . One hundred and forty-two healthy , term infants were enrolled in a single-centre , r and omised , double-blind , controlled , parallel-group trial , and allocated to receive either st and ard or probiotic and LC-PUFA-containing experimental formulas . The infants were fed with their assigned formulas for 7 months . The primary outcome ( weight gain ) and the secondary outcomes ( length , head circumference and formula tolerance ) were measured throughout the study . LC-PUFA status was assessed at 4 months of age and immune response to childhood vaccines was measured at 7 months of age . There was no significant difference in growth between the two groups . The 90 % CI for the difference in mean weight gain was - 0.08 , 3.1 g in the intention-to-treat population and 0.1 - 3.8 g in the per protocol population , which lay within the predefined boundaries of equivalence , - 3.9 - 3.9 . There were no significant differences in mean length and head circumference . DHA and AA concentrations were higher in infants in the experimental formula group compared with the control formula group . No influence of the supplements on the response to vaccines was observed . Growth characteristics of term infants fed the starter formula containing a probiotic and LC-PUFA were similar to st and ard formula-fed infants Objective . To investigate the effect of 2 different species of probiotics in preventing infections in infants attending child care centers . Methods . A double-blind , placebo-controlled , r and omized trial was conducted from December 1 , 2000 , to September 30 , 2002 , at 14 child care centers in the Beer-Sheva area of Israel in healthy term infants 4 to 10 months old . Infants were assigned r and omly to formula supplemented with Bifidobacterium lactis ( BB-12 ) , Lactobacillus reuteri ( American Type Culture Collection 55730 ) , or no probiotics . Duration of feeding , including follow-up , for each participant was 12 weeks . All infants were fed only the assigned formula and were not breastfed due to parental decision before recruitment to the study . Probiotic or prebiotic food products or supplements were not allowed . Main outcome measures were number of days and number of episodes with fever ( > 38 ° C ) and number of days and number of episodes with diarrhea or respiratory illness . Results . Participants ( n = 201 ) were similar regarding gestational age , birth weight , gender , and previous breastfeeding . The controls ( n = 60 ) , compared with those fed B lactis ( n = 73 ) or L reuteri ( n = 68 ) , had significantly more febrile episodes ( mean [ 95 % confidence interval ] : 0.41 [ 0.28–0.54 ] vs 0.27 [ 0.17–0.37 ] vs 0.11 [ 0.04–0.18 ] , respectively ) . The controls also had more diarrhea episodes ( 0.31 [ 0.22–0.40 ] vs 0.13 [ 0.05–0.21 ] vs 0.02 [ 0.01–0.05 ] , respectively ) and episodes of longer duration ( 0.59 [ 0.34–0.84 ] vs 0.37 [ 0.08–0.66 ] vs 0.15 [ 0.12–0.18 ] days , respectively ) . The L reuteri group , compared with BB-12 or controls , had a significant decrease of number of days with fever , clinic visits , child care absences , and antibiotic prescriptions . Rate and duration of respiratory illnesses did not differ significantly between groups . Conclusions . Child care infants fed a formula supplemented with L reuteri or B lactis had fewer and shorter episodes of diarrhea , with no effect on respiratory illnesses . These effects were more prominent with L reuteri , which was also the only supplement to improve additional morbidity parameters Objectives : The present study was design ed to evaluate the effect of 2 different combinations of prebiotic ingredients , polydextrose ( PDX ) , galactooligosaccharides ( GOS ) , and lactulose ( LOS ) , at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age . Patients and Methods : Healthy , formula-fed , term infants ( n = 226 ) were r and omly assigned to 1 of 3 study formula groups : control group ( n = 76 ) , PG4 group ( control formula supplemented with 4 g/L of a prebiotic blend , n = 74 ) , or PGL8 group ( control formula supplemented with 8 g/L of a prebiotic blend , n = 76 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age , and 24-hour dietary recall and 24-hour tolerance recall were recorded at 30 , 60 , 90 , and 120 days of age . Adverse events were recorded throughout the study . Results : There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point . Significant differences in stool consistency were detected among the 3 formula groups at 30 , 60 , and 90 days of age ( P < 0.001 , P = 0.025 , P = 0.004 , respectively ) , with the supplemented formula groups having looser stools than the control group . The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age ( P = 0.021 and P = 0.017 , respectively ) , but all of the groups were similar at 60 , 90 , and 120 days of age . A statistical difference was detected among the formula groups in 3 categories of adverse events : diarrhea ( control vs PG4 , 4 % vs 18 % , P = 0.008 ) , eczema ( PG4 vs control , 18 % vs 7 % , P = 0.046 ; PG4 vs PGL8 , 18 % vs 4 % , P = 0.008 ) , and irritability ( control vs PGL8 , 4 % vs 16 % , P = 0.027 ) . Conclusions : Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula . A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics Necrotizing enterocolitis ( NEC ) continues to be a major cause of morbidity and mortality in premature infants . Although the pathogenesis of NEC remains unclear , abnormal bacterial colonization has been postulated as playing a central role . Various factors impact bacterial colonization following delivery . Compared to term infants , the bacterial colonization pattern in prematurely born infants is markedly different , with a greater predilection for colonization with pathogenic bacteria . Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment , favoring the growth of commensal bacteria . Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC . These preliminary studies support the need for a large , r and omized , controlled trial to further investigate the role of probiotics in the prevention of NEC The objective of the study was to evaluate the safety and tolerance of an infant formula supplemented with Lactobacillus fermentum CECT5716 , a probiotic strain isolated from breast milk , in infants of 1 - 6 months of age . A r and omized double blinded controlled study including healthy infants was conducted . One month aged infants received a prebiotic infant formula supplemented with L. fermentum ( experimental group ) or the same formula without the probiotic strain ( control group ) for 5 months . The primary outcome of the study was average daily weight gain between baseline and 4 months of age . Secondary outcomes were other anthropometric data ( length and head circumference ) , formula consumption , and tolerance . Incidence of infections was also recorded by pediatricians . No significant differences in weight gain were observed between both groups , neither at 4 months of age ( 29.0±7.8 vs 28.9±5.7g/day ) nor at 6 months ( 25.1±6.1 vs 24.7±5.2g/day ) . There were no statistically significant differences in the consumption of the formulae or symptoms related to the tolerance of the formula . The incidence rate of gastrointestinal infections in infants of the control group was 3 times higher than in the probiotic group ( p=0.018 ) . Therefore , consumption of a prebiotic infant formula enriched with the human milk probiotic strain L. fermentum CECT5716 from 1 to 6 months of life is well tolerated and safe . Furthermore , the consumption of this formula may improve the health of the infants by reducing the incidence of gastrointestinal infections BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit .  Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children Purpose Currently , there is no consensus concerning the possible beneficial colonic and systemic effects of prebiotic-containing infant formula . This study assesses whether the feeding of a galactooligosaccharides (GOS)-containing infant formula ( 0.44 g/dl of GOS ) and the subsequent feeding of a GOS-containing follow-on formula ( 0.50 g/dl of GOS ) have a prebiotic effect on intestinal microbiota that helps to decrease infections and allergy manifestations in healthy infants during the first year of life . Methods A multicentre , r and omised , double-blind and placebo-controlled trial was carried out on 365 healthy term infants enrolled before 8 weeks of age and r and omly assigned to a formula with or without GOS , until 12 months of age . The incidence of infections and allergy manifestations , the antibiotics prescribed and faecal characteristics were recorded up to 12 months of age , while faecal sample s were collected up to 4 months for the measurement of secretory immunoglobulin A , short-chain fatty acids and microbiota . Results A prebiotic effect on the faecal analysis was observed at 4 months of life . The GOS group showed a lower faecal pH ( P = 0.019 ) , a lower decreasing trend in secretory immunoglobulin A ( P = 0.078 ) , lower butyric acid concentration ( P = 0.040 ) and an increase in Bifidobacterium counts ( P = 0.010 ) . Changes in faecal characteristics involved greater frequency ( P < 0.001 ) and softer consistency ( P < 0.05 ) . The incidence of infections or allergic manifestations during the first year of life was similar in both groups , with no statistical differences ( P > 0.05 ) . Conclusions The feeding of GOS-containing infant formula produced a definite prebiotic effect consisting of changes in faecal composition and microbiota , and in faecal consistency and the frequency of defaecation . No changes in the incidence of infection or allergic manifestation during the first year of life were observed AIM The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various components of breast milk , including prebiotic substances . This prospect i ve double-blind study compared the numbers of bifidobacteria in the stool flora of bottle-fed preterm infants r and omized to receive for 14 days either a formula with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same formula with maltodextrin as a placebo . METHODS Within 0 - 14 days after birth , 56 healthy bottle-fed infants were enrolled to receive either the prebiotic or placebo . Faecal sample s were taken at inclusion day and at study day 7 . The number of bifidobacteria in the stools , stool characteristics and somatic growth were recorded during the study . RESULTS In the group fed fructo-oligosaccharides , both the numbers of bifidobacteria in the stools and the proportion of infants colonized with them were significantly higher as compared to the placebo group ( p=0.032 and p=0.030 respectively ) . There was also a higher number of bacteroids in the fructo-oligosaccharide group as compared to the placebo ( p=0.029 ) . At the same time , reduction was noted in the numbers of Escherichia coli and enterococci . ( p=0.029 , and p=0.025 , respectively ) . Supplementation had also significant influence on stool frequency per day ( p=0.0080 ) . CONCLUSION An infant formula containing a small quantity of prebiotic oligosaccharides is well accepted and leads to rapid growth of bifidobacteria in the gut of bottle-fed preterm infants while decreasing the numbers of pathogenic microorganisms AIM Effects of supplementing prebiotic oligosaccharides to formula for healthy infants were studied in this placebo controlled , r and omised , double blind study . METHODS Ninety-seven infants were included into the study ; among them 42 breast-fed infants , 14 infants fed formula supplemented with 0.4 g/100ml oligosaccharides ( 9 to 1 mixture of galacto- and fructooligosaccharides ) and 13 infants fed control formula  were followed-up throughout the 12-week-long study period . The groups receiving formula were compared with statistical methods , whereas data of breast-fed infants served as reference values . RESULTS Infants fed the two formulae did not differ in nutrient intakes , growth , occurrence rate of feeding difficulties and atopic manifestations , or in calcium excretion . The intestinal flora did not differ between the two formula fed groups at the beginning of the study . In contrast , numbers of Bifidobacteriae were significantly higher in infants receiving the formula supplemented with prebiotic oligosaccharides both at the 14th day ( 9 x 1011 versus 5 x 1010 , colony forming units/g faeces , median , p < 0.05 ) and 28th day ( 9 x 1012 versus 5 x 1010 , p < 0.05 ) of the study . CONCLUSION In this study , supplementation of infant formula with prebiotic oligosaccharides result ed in ameliorating the difference in intestinal flora between formula fed and breast-fed healthy infants Objective : The objective of the study was to investigate the effects of a galacto-oligosaccharides (GOS)-supplemented formula on the intestinal microbiota in healthy term infants , with a specific consideration for gastrointestinal symptoms as colic , stool frequency and consistency , regurgitation . Methods : This was a r and omized , double-blind , controlled , parallel-group clinical trial performed simultaneously by 6 centers in Italy . Three groups were considered : breastfed , formula-fed , and GOS-supplemented formula-fed infants . Formula-fed infants were r and omized to receive either the control or the study formula and consume the assigned formula exclusively until the introduction of complementary feeding . The nutritional composition of the 2 formulas were identical , apart from the supplemented GOS ( 0.4 g/100 mL ) in the study formula . Four different types of bacteria were evaluated in order to assess the efficacy of  GOS-supplemented formula on infants : Bifidobacterium , Lactobacillus , and Clostridium , Escherichia coli . Results : A total of 199 breastfed infants and 163 formula-fed infants were recruited . When considering stool frequency and consistency , GOS-supplemented formula presented normal and soft stools in the majority of episodes ( 89 % ) . In the supplemented group the incidence of colic was lower with respect to the control group . A significantly lower count of Clostridium and a higher count of Bifidobacterium were found when comparing study formula and control formula in infants with colic . In children with colic the ratio between Clostridium count and Bifidobacterium and Lactobacillus count was in favor of the latter two when considering the GOS-supplemented formula group with respect to the control one . Conclusions : The prebiotic-supplemented formula mimicked the effect of human milk in promoting Bifidobacterium and Lactobacillus growth and in inhibiting Clostridium growth , result ing in a significantly lower presence of colic Background . Lactobacillus reuteri has been studied for its safety and beneficial effects in infants . This study assessed growth of infants fed a partially hydrolyzed whey formula with L reuteri . Methods . Healthy term infants were r and omized to 1 of 2 formulas ( partially hydrolyzed whey formula with ( PRO ) or without ( CON ) L reuteri  from 14 to 112 days of age . Anthropometric measures were assessed at 14 , 28 , 56 , 84 , and 112 days of age . Tolerance records were completed 2 days prior to each visit . Results . A total of 122 subjects completed study per protocol ( 60 PRO , 62 CON ) . No differences were seen in daily weight gain , length , or head circumference . Overall , between groups , there were no significant differences in formula intake , stool frequency , color , consistency , flatulence , frequency of spit-up/vomiting , mood , sleep , or incidence of adverse events . Conclusion . Infants fed probiotic formula  had similar growth to infants fed control formula .  Both formulas were well tolerated This article by the ESPGHAN Committee on Nutrition summarizes available information on the effects of adding prebiotic oligosaccharides to infant and follow-on formulae . Currently there are only limited studies evaluating prebiotic substances in dietetic products for infants . Although administration of prebiotic oligosaccharides has the potential to increase the total number of bifidobacteria in feces and may also soften stools , there is no published evidence of clinical benefits of adding prebiotic oligosaccharides to dietetic products for infants . Data on oligosaccharide mixtures in infant formulae do not demonstrate adverse effects , but further evaluation is recommended . Combinations and dosages in addition to those so far studied need to be fully evaluated with respect to both safety and efficacy before their use in commercial infant food products . Well- design ed and carefully conducted r and omized controlled trials with relevant inclusion /exclusion criteria , adequate sample sizes and vali date d clinical outcome measures are needed both in preterm and term infants . Future trials should define optimal quantity and types of oligosaccharides with prebiotic function , optimal dosages and duration of intake , short and long term benefits and safety . At the present time , therefore , the Committee takes the view that no general recommendation on the use of oligosaccharide supplementation in infancy as a prophylactic or therapeutic measure can be made Objective Atopic dermatitis ( AD ) is the most common chronic relapsing skin disease seen in infancy and childhood . The intestinal microbiota play an important role in immune development and may play a role in the development of allergic disorders . Manipulation of the intestinal microbiota by synbiotics may therefore offer an approach to the prevention or treatment of AD and allergic diseases . We studied the clinical and immunologic effects of a new symbiotic ( a mixture of seven probiotic strains of bacteria and Fructooligosaccharide ) in infants and children with AD . Methods In a r and omized , double-blind , placebo-controlled study , 40 infants and children aged 3 months to 6 years with AD received either a synbiotic or placebo for 8 weeks . The Severity Scoring of Atopic Dermatitis ( SCORAD ) index was recorded at baseline and also at 4 and 8 weeks of treatment . Findings There was no significant difference between the probiotic and placebo group in baseline characteristics including sex , age , family history , corticosteroid usage and prick testing . Mean age was 23 months . The synbiotic group showed a significantly greater reduction in SCORAD than did the placebo group ( P=0.001 ) . No specific effect was demonstrated of the probiotics employed on cytokine profile ( P=0.4 , P=0.6 ) . Egg white was the most common ( 45 % ) allergen followed by peanut and cow 's milk . Conclusion This study provides evidence that a mixture of seven strains of probiotics and Fructooligosaccharide can clinical ly improve the severity of  AD in young children . Further studies are needed to investigate the effects on underlying immune responses and the potential long term benefits for patients with AD BACKGROUND Nonpathogenic live bacteria are consumed as food by many children , particularly in the form of yogurt . The tolerance and safety of long-term consumption of specific types and strains of probiotic bacteria are not well documented . OBJECTIVE The goal was to evaluate tolerance to formulas containing 2 levels of probiotic supplementation and effects on growth , general clinical status , and intestinal health in free-living healthy infants . DESIGN This was a prospect i ve , double-blind , r and omized , placebo-controlled study of healthy infants aged 3 - 24 mo . Infants were assigned to receive a st and ard milk-based formula containing 1 x 10(7 ) colony-forming units (CFU)/g each of Bifidobacterium lactis and Streptococcus thermophilus , formula containing 1 x 10(6 ) CFU/g each of B. lactis and S. thermophilus , or unsupplemented formula . Clinical outcomes included formula intake , gastrointestinal tolerance , anthropometric measures , daycare attendance , and history of illness . RESULTS One hundred eighteen infants aged ( + /- SD ) 7.0 + /- 2.9 mo at enrollment consumed formula for 210 + /- 127 d. There were no significant differences in age , sex , formula consumption , or length of study between groups . The supplemented formulas were well accepted and were associated with a lower frequency of reported colic or irritability ( P < 0.001 ) and a lower frequency of antibiotic use ( P < 0.001 ) than was the unsupplemented formula . There were no significant differences between groups in growth , health care attention seeking , daycare absenteeism , or other health variables . CONCLUSION Long-term consumption of formulas supplemented with B. lactis and S. thermophilus was well tolerated and safe and result ed in adequate growth , reduced reporting of colic or irritability , and a lower frequency of antibiotic use Prebiotic oligosaccharides influence the intestinal microbiota and can positively modulate the infant 's immune system . It was demonstrated that a special prebiotic mixture ( Immunofortis ( ® ) ) of short-chain galacto-oligosaccharides ( scGOS ) and long-chain fructo-oligosaccharides ( lcFOS ) can reduce the cumulative incidence of atopic dermatitis ( AD ) in infants at risk for allergy as determined using the AD symptom score ( SCORAD ) . Additionally , it was shown very recently that immunoglobulin free light-chain ( Ig-fLC ) might be involved in the pathophysiology of allergic disease . Increased Ig-fLC concentrations were found in patients suffering from AD , cow 's milk allergy , allergic rhinitis , or asthma . In this study , the effect of supplementation of scGOS/lcFOS on the Ig-fLC plasma concentrations in infants at risk for allergy was assessed . The plasma kappa and lambda Ig-fLC concentrations were measured in a double-blind , placebo-controlled , r and omized trial , in which infants at risk for developing allergic disease received a  hypoallergenic whey formula containing 8 g/l of the scGOS/lcFOS mixture ( n = 34 ) or maltodextrin as a placebo ( n=40 ) for 6 months . After intervention , plasma sample s were collected , and total plasma concentrations of lambda and kappa Ig-fLC were analyzed using ELISA . Total kappa and lambda Ig-fLC plasma concentrations were higher in infants suffering from AD when compared to infants without any sign of AD . In infants receiving the prebiotic mixture  , the Ig-fLC levels were significantly lower compared to the placebo-fed infants ( p<0.001 ) . Interestingly , lambda Ig-fLC concentrations were positively correlated with total IgE ( p<0.05 ) . These data demonstrate for the first time that the specific scGOS/lcFOS mixture lowered kappa and lambda Ig-fLC plasma concentrations in infants at high risk for allergies when compared to infants receiving placebo formula . Because Ig-fLC concentrations were increased in infants suffering from AD , this may have contributed , at least in part , to the reduced incidence in AD as described previously . This suggests a possible role for Ig-fLC in the pathophysiology of AD in infants at risk for allergy development Lactobacillus fermentum CECT5716 is a probiotic strain originally isolated from human breast milk . Previous clinical studies in infants showed that the early administration of a milk formula containing this probiotic strain was safe and may be useful for the prevention of community-acquired infections . This is a 3-year follow-up study aim ed at evaluating the long-term effects produced by the early consumption of an infant formula supplemented with L. fermentum CECT5716 ( experimental group , EG ) compared with a control formula without the probiotic ( control group , CG ) . The infants included in this follow-up study had previously completed a 5-month r and omized double-blind controlled trial ( from 1 to 6 months of age ) , where the safety and tolerance of the probiotic formula was evaluated . The main outcome of the follow-up study was the growth of the children . The secondary outcomes included the incidence of infectious and non-infectious diseases , parameters related with intestinal function and faecal microbiota . At 3 years , the mean values of weight , length and head circumference were similar in children of the EG compared with those of the CG . No differences were observed in the incidence of infectious and non-infectious diseases or disorders related with intestinal function . The pattern of faecal microbiota was also similar between both groups . In conclusion , this 3-year study shows that the early administration of the probiotic of L. fermentum CECT5716 in an infant formula is safe and it does not produce measurable differences in children compared with a control formula ABSTRACT A healthy intestinal microbiota is considered to be important for priming of the infants ' mucosal and systemic immunity . Breast-fed infants typically have an intestinal microbiota dominated by different Bifidobacterium species . It has been described that allergic infants have different levels of specific Bifidobacterium species than healthy infants . For the accurate quantification of Bifidobacterium adolescentis , Bifidobacterium angulatum , Bifidobacterium bifidum , Bifidobacterium breve , Bifidobacterium catenulatum , Bifidobacterium dentium , Bifidobacterium infantis , and Bifidobacterium longum in fecal sample s , duplex 5′ nuclease assays were developed . The assays , targeting rRNA gene intergenic spacer regions , were vali date d and compared with conventional PCR and fluorescent in situ hybridization methods . The 5′ nuclease assays were subsequently used to determine the relative amounts of different Bifidobacterium species in fecal sample s from infants receiving a st and ard formula or a st and ard formula supplemented with galacto- and fructo-oligosaccharides ( OSF ) . A breast-fed group was studied in parallel as a reference . The results showed a significant increase in the total amount of fecal bifidobacteria ( 54.8 % ± 9.8 % to 73.4 % ± 4.0 % ) in infants receiving the prebiotic formula ( OSF ) , with a diversity of Bifidobacterium species similar to breast-fed infants . The intestinal microbiota of infants who received a st and ard formula seems to resemble a more adult-like distribution of bifidobacteria and contains relatively more B. catenulatum and B. adolescentis ( 2.71 % ± 1.92 % and 8.11 % ± 4.12 % , respectively , versus 0.15 % ± 0.11 % and 1.38 % ± 0.98 % for the OSF group ) . In conclusion , the specific prebiotic infant formula used induces a fecal microbiota that closely resembles the microbiota of breast-fed infants also at the level of the different Bifidobacterium species The objective of the present study was to assess the effect of adding specific prebiotics to st and ard formula feeding on the number of fever episodes  in the first year of life . In the present r and omised , double-blind , placebo-controlled trial in seven centres in five West European countries , 830 healthy term infants , without a first-degree family history of allergic disease , of mothers who indicated to give only formula feeding were r and omised either to receive a st and ard non-hydrolysed cows ' milk-based formula to which a mixture of specific oligosaccharides was added ( prebiotics group ( PG ) ) , or to receive a similar formula without oligosaccharides ( control group ( CG ) ) . A separate reference group consisted of 300 breast-fed infants . The primary outcome was the number of fever episodes prospect ively documented by the parents . There was no difference in the number of fever episodes between the PG ( median value 1·19 ; 25th-75th percentile 0·09 - 2·34 ) and CG ( 1·16 ; 25th-75th percentile 0·06 - 2·38 ) . The median number of fever episodes in the separate breast-feeding reference group was 1·24 ( 25th-75th percentile 0·51 - 3·45 ) . There was no effect of adding specific prebiotics to st and ard formula feeding in reducing the number of fever episodes in the present study Background To ensure the suitability of an infant formula as the sole source of nutrition or provide benefits similar to outcomes in breastfed infants , advancements in formula composition are warranted as more research detailing the nutrient composition of human milk becomes available . This study was design ed to evaluate growth and tolerance in healthy infants who received one of two investigational cow ’s milk-based formulas with adjustments in carbohydrate , fat , and calcium content and supplemented with a prebiotic blend of polydextrose ( PDX ) and galactooligosaccharides ( GOS ) or GOS alone . Methods In this multi-center , double-blind , parallel- design ed , gender-stratified prospect i ve study 419 infants were r and omized and consumed either a marketed routine cow ’s milk-based infant formula ( Control ; Enfamil ® LIPIL ® , Mead Johnson Nutrition , Evansville , IN ) ( n = 142 ) or one of two investigational formulas from 14 to 120 days of age . Investigational formulas were supplemented with 4 g/L ( 1:1 ratio ) of a prebiotic blend of PDX and GOS ( PDX/GOS ; n = 139 ) or 4 g/L of GOS alone ( GOS ; n = 138 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age . Daily recall of formula intake , tolerance , and stool characteristics was collected during study weeks 1 and 2 and 24-h recall was collected at 60 , 90 , and 120 days of age . Medically-confirmed adverse events were recorded throughout the study . Results There were no group differences in growth rate from 14 to 120 days of age . Discontinuation rates were not significantly different among study groups . No differences in formula intake or infant fussiness or gassiness were observed . During study weeks 1 and 2 and at 60 days of age stool consistency ratings were higher ( i.e. softer stools ) for infants in the PDX/GOS and GOS groups versus Control and remained higher at 120 days for the PDX/GOS group ( all P < 0.05 ) . The overall incidence of medically-confirmed adverse events was similar among groups . Conclusions Investigational routine infant formulas supplemented with 4 g/L of either a prebiotic blend of PDX and GOS or GOS alone were well-tolerated and supported normal growth . Compared to infants who received the unsupplemented control formula , infants who received prebiotic supplementation experienced a softer stooling pattern similar to that reported in breastfed infants . Trial registration Clinical Trials.gov Identifier : Background : Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora . Aims : To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis ( AD ) during the first six months of life in formula fed infants at high risk of atopy . Methods : Prospect i ve , double-blind , r and omised , placebo controlled trial ; 259 infants at risk for atopy were enrolled . A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study . If bottle feeding was started , the infant was r and omly assigned to one of two hydrolysed protein formula groups ( 0.8 g/100 ml prebiotics or maltodextrine as placebo ) . All infants were examined for clinical evidence of atopic dermatitis . In a subgroup of 98 infants , faecal flora was analysed . Results : Ten infants ( 9.8 % ; 95 CI 5.4–17.1 % ) in the intervention group and 24 infants ( 23.1 % ; 95 CI 16.0–32.1 % ) in the control group developed AD . The severity of the dermatitis was not affected by diet . Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts . Conclusion : Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants . Although the mechanism of this effect requires further investigation , it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy
Synbiotics failed to significantly increase growth in boys and girls .
Use of synbiotics increased stool frequency , had no impact on stool consistency , colic , spitting up / regurgitation , crying , restlessness or vomiting .
Probiotics in formula also failed to have any significant effect on growth , stool frequency or consistency .
Probiotics did not lower the incidence of diarrhoea , colic , spitting up / regurgitation , crying , restlessness or vomiting .
Prebiotics in formula did increase weight gain but had no impact on length or head circumference gain .
Prebiotics increased stool frequency but had no impact on stool consistency , the incidence of colic , spitting up / regurgitation , crying , restlessness or vomiting .
There was no impact of prebiotics on the volume of formula tolerated , infections and gastrointestinal microflora .
Authors ’ conclusions There is not enough evidence to state that supplementation of term infant formula with synbiotics , probiotics or prebiotics does result in improved growth or clinical outcomes in term infants .
There is no data available to establish if synbiotics are superior to probiotics or prebiotics
Background Synbiotics , probiotics or prebiotics are being added to infant formula to promote growth and development in infants .
Previous review s ( 2007 to 2011 ) on term infants given probiotics or prebiotics focused on prevention of allergic disease and food hypersensitivity .
This review focused on growth and clinical outcomes in term infants fed only infant formula containing synbiotics , probiotics or prebiotics .