Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial Synbiotics-supplemented amino acid-based formula supports adequate growth in cow's milk allergic infants. 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. A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. Effects of probiotic and prebiotic on gastrointestinal motility in newborns. 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. 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 Physiological and Bifidogenic Effects of Prebiotic Supplements in Infant Formulae Tolerance and Safety Evaluation in a Large Cohort of Healthy Infants Fed an Innovative Prebiotic Formula: A Randomized Controlled Trial Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial.
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 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 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 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 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 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 . Probiotics 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 probiotics in the prevention of allergy . Methods We identified the most relevant clinical questions and performed a systematic review of r and omized controlled trials of probiotics for the prevention of allergy . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . We search ed for and review ed the evidence about health effects , patient values and preferences , and re source use ( up to November 2014 ) . We followed the GRADE evidence -to-decision framework to develop recommendations . Results Currently available evidence does not indicate that probiotic supplementation  reduces the risk of developing allergy in children . However , considering all critical outcomes in this context , the WAO guideline panel determined that there is a likely net benefit from using probiotics result ing primarily from prevention of eczema . The WAO guideline panel suggests : a ) using probiotics in pregnant women at high risk for having an allergic child ; b ) using probiotics in women who breastfeed infants at high risk of developing allergy ; and c ) using probiotics in infants at high risk of developing allergy . All recommendations are conditional and supported by very low quality evidence . Conclusions WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding , and whether to give them to infants 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 BACKGROUND & AIM The addition of prebiotics to infant formula modifies the composition of intestinal microflora . Aim of the study was to test the hypothesis that prebiotics reduce the incidence of intestinal and respiratory infections in healthy infants . METHODS A prospect i ve , r and omized , placebo-controlled , open trial was performed . Healthy infants were enrolled and r and omized to a formula additioned with a mixture of galacto- and fructo-oligosaccharides or to a control formula . The incidence of intestinal and respiratory tract infections and the anthropometric measures were monitored for 12 months . RESULTS Three hundred and forty two infants ( mean age 53.7+/-32.1 days ) were enrolled . The incidence of gastroenteritis was lower in the supplemented group than in the controls ( 0.12+/-0.04 vs. 0.29+/-0.05 episodes/child/12 months ; p=0.015 ) . The number of children with more than 3 episodes tended to be lower in prebiotic group ( 17/60 vs. 29/65 ; p=0.06 ) . The number of children with multiple antibiotic courses/year was lower in children receiving prebiotics ( 24/60 vs. 43/65 ; p=0.004 ) . A transient increase in body weight was observed in children on prebiotics compared to controls during the first 6 months of follow-up . CONCLUSIONS Prebiotic administration reduce intestinal and , possibly , respiratory infections in healthy infants during the first year of age 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 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 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 Objectives : This r and omized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides ( GOS ) , oligofructose , and long-chain inulin ( fructooligosaccharides , FOS ) in formula . Methods : Subjects were r and omized to Orafti Synergy1 ( 50 oligofructose:50 FOS ) 0.4 g/dL or 0.8 g/dL , GOS : FOS ( 90:10 ) 0.8 g/dL , or a st and ard formula according to Good Clinical Practice guidelines . A breast-fed group was included for comparison . Outcome parameters were weight , length , intake , stool characteristics , crying , regurgitation , vomiting , adverse events , and fecal bacterial population counts . Statistical analyses used nonparametric tests . Results : During the first month of life , weight , length , intake , and crying increased significantly in all of the groups . Regurgitation and vomiting scores were low and similar . Stool frequency decreased significantly and similarly in all of the formula groups but was lower than in the breast-fed group . All of the prebiotic groups maintained soft stools , only slightly harder than those of breast-fed infants . The st and ard group had significantly harder stools at weeks 2 and 4 compared with 1 ( P < 0.001 and P = 0.0279 ) . The total number of fecal bacteria increased in all of the prebiotic groups ( 9.82 , 9.73 , and 9.91 to 10.34 , 10.38 , and 10.37 , respectively , log10 cells/g feces , P = 0.2298 ) and more closely resembled the breast-fed pattern . Numbers of lactic acid bacteria , bacteroides , and clostridia were comparable . In the SYN1 0.8 g/dL and GOS : FOS groups , Bifidobacterium counts were significantly higher at D14 and 28 compared with D3 and were comparable with the breast-fed group . Tolerance and growth were normal . Conclusions : Stool consistency and bacterial composition of infants taking SYN1 0.8 g/dL or GOS : FOS – supplemented formula were closer to the breast-fed pattern . There was no risk of dehydration 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 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 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 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 & AIMS The sterile newborn digestive tract is rapidly colonized after birth and feeding type could influence this process . Infant formulas try to mimic the bifidogenic effect of human milk using prebiotic supplementation . The aim of this study was to demonstrate the efficacy , safety and tolerance of a 0.8 g/dL Orafti( ® )Synergy1 ( oligofructose-enriched inulin ) supplemented infant formula during the first 4 months of life . METHODS In a double-blind , r and omized , placebo-controlled and parallel trial , formula fed healthy term newborns were r and omized to receive a control ( controls ) or SYN1 supplemented infant formula ( SYN1 ) . Breastfed newborns ( BF ) were also followed for comparison . Anthropometry , water balance , blood parameters , adverse events , stool frequency and characteristics and faecal microbiota were assessed . RESULTS A total of 252 formula fed infants were r and omized at birth ( n = 124 controls , n = 128 SYN1 ) and 131 BF infants were recruited ; after 4 months 68 controls , 63 SYN1 and 57 BF completed the study . SYN1 infants showed a microbiota composition closer to that of BF infants , with a trend towards higher Bifidobacterium cell counts , softer stools and a higher deposition frequency compared to controls . There were no differences between formulas in anthropometry and relevant adverse events , water balance or blood parameters . CONCLUSION A 0.8 g/dL SYN1-supplemented infant formula during the first 4 months of life is safe and effective , promoting a gut microbiota closer to that of breastfeeding . This clinical trial was registered at Clinical trials.gov as Study on Fermentable Carbohydrates in Healthy Infants ( number NCT00808756 )
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 .