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
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
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 .