Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition 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 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. 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. Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1-6 months of age: a randomized controlled trial. Early Low Volume Oral Synbiotic/Prebiotic Supplemented Enteral Stimulation of the Gut in Patients with Severe Acute Pancreatitis: A Prospective Feasibility Study The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. Synbiotics-supplemented amino acid-based formula supports adequate growth in cow's milk allergic infants. Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast-fed Infants Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised 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. Prebiotic Effect of an Infant Formula Supplemented with Galacto-Oligosaccharides: Randomized Multicenter Trial Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Long-term Colonization of a Lactobacillus plantarum Synbiotic Preparation in the Neonatal Gut World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics
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 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 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 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 : 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 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 Abstract Background : Experience with administration of synbiotics ( prebiotics/probiotics ) in patients with severe acute pancreatitis ( SAP ) has demonstrated immunomodulatory capacity . The aim of this trial was evaluation of the feasibility and perspective of early clinical application of oral synbiotic/prebiotic supplements in patients with SAP . Methods : 90 SAP patients were enrolled during the period from 2005–2008 . Patients were stratified according to the feeding mode . CONTROL ( n = 32 ) group received st and ard whole protein feeding formula . SYNBIO ( n = 30 ) and FIBRE groups ( n = 28 ) received early ( within first 24–48 hours ) synbiotic or prebiotic supplements . Oral administration of synbiotics or prebiotics was commenced when patients were able to sip water . Results : Daily provided average volume and calories of synbiotic/prebiotic blends were smaller compared to the CONTROL , p = 0.001 . Oral administration of synbiotic/prebiotic supplements was associated with lower infection rate ( pancreatic and peripancreatic necrosis ) compared to the CONTROL , ( p = 0.03 ; p = 0.001 ) , lower rate of surgical interventions , p = 0.005 , shorter ICU ( p = 0.05 ) and hospital stay ( p = 0.03 ) . Synbiotic supplemented enteral stimulation of the gut result ed in reduced mortality rate compared to the CONTROL , p = 0.02 . Conclusion : Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut seems to be a potentially valuable complement to the routine treatment protocol of SAP 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 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 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 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 OBJECTIVE This study was conducted to develop evidence -based clinical practice guidelines for nutrition support ( ie , enteral and parenteral nutrition ) in mechanically ventilated critically ill adults . OPTIONS The following interventions were systematic ally review ed for inclusion in the guidelines : enteral nutrition ( EN ) versus parenteral nutrition ( PN ) , early versus late EN , dose of EN , composition of EN ( protein , carbohydrates , lipids , immune-enhancing additives ) , strategies to optimize delivery of EN and minimize risks ( ie , rate of advancement , checking residuals , use of bedside algorithms , motility agents , small bowel versus gastric feedings , elevation of the head of the bed , closed delivery systems , probiotics , bolus administration ) , enteral nutrition in combination with supplemental PN , use of PN versus st and ard care in patients with an intact gastrointestinal tract , dose of PN and composition of PN ( protein , carbohydrates , IV lipids , additives , vitamins , trace elements , immune enhancing substances ) , and the use of intensive insulin therapy . OUTCOMES The outcomes considered were mortality ( intensive care unit [ ICU ] , hospital , and long-term ) , length of stay ( ICU and hospital ) , quality of life , and specific complications . EVIDENCE We systematic ally search ed MEDLINE and CINAHL ( cumulative index to nursing and allied health ) , EMBASE , and the Cochrane Library for r and omized controlled trials and meta-analyses of r and omized controlled trials that evaluated any form of nutrition support in critically ill adults . We also search ed reference lists and personal files , considering all articles published or unpublished available by August 2002 . Each included study was critically appraised in duplicate using a st and ard scoring system . VALUES For each intervention , we considered the validity of the r and omized trials or meta-analyses , the effect size and its associated confidence intervals , the homogeneity of trial results , safety , feasibility , and the economic consequences . The context for discussion was mechanically ventilated patients in Canadian ICUs .  BENEFITS , HARMS , AND COSTS The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients ( reduced mortality and ICU stay ) . Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions . SUMMARIES OF EVIDENCE AND RECOMMENDATIONS : When considering nutrition support in critically ill patients , we strongly recommend that EN be used in preference to PN . We recommend the use of a st and ard , polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU , that patients be cared for in the semirecumbent position , and that arginine-containing enteral products not be used . Strategies to optimize delivery of EN ( starting at the target rate , use of a feeding protocol using a higher threshold of gastric residuals volumes , use of motility agents , and use of small bowel feeding ) and minimize the risks of EN ( elevation of the head of the bed ) should be considered . Use of products with fish oils , borage oils , and antioxidants should be considered for patients with acute respiratory distress syndrome . A glutamine-enriched formula should be considered for patients with severe burns and trauma . When initiating EN , we strongly recommend that PN not be used in combination with EN . When PN is used , we recommend that it be supplemented with glutamine , where available . Strategies that maximize the benefit and minimize the risks of PN ( hypocaloric dose , withholding lipids , and the use of intensive insulin therapy to achieve tight glycemic control ) should be considered . There are insufficient data to generate recommendations in the following areas : use of indirect calorimetry ; optimal pH of EN  ; supplementation with trace elements , antioxidants , or fiber ; optimal mix of fats and carbohydrates ; use of closed feeding systems ; continuous versus bolus feedings ; use of probiotics ; type of lipids ; and mode of lipid delivery . VALIDATION This guideline was peer- review ed and endorsed by official representatives of the Canadian Critical Care Society , Canadian Critical Care Trials Group , Dietitians of Canada , Canadian Association of Critical Care Nurses , and the Canadian Society for Clinical Nutrition . SPONSORS This guideline is a joint venture of the Canadian Critical Care Society , the Canadian Critical Trials Group , the Canadian Society for Clinical Nutrition , and Dietitians of Canada . The Canadian Critical Care Society and the Institute of Nutrition , Metabolism , and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline 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 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 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 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 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 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 : 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 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 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 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
On the basis of this review , available scientific data suggest that the administration of currently evaluated probiotic- and /or prebiotic-supplemented formula to healthy infants does not raise safety concerns with regard to growth and adverse effects .
Infant formulae are increasingly supplemented with probiotics , prebiotics , or synbiotics despite uncertainties regarding their efficacy .
The present article , developed by the Committee on Nutrition of the European Society for Paediatric Gastroenterology , Hepatology , and Nutrition , systematic ally review s published evidence related to the safety and health effects of the administration of formulae supplemented with probiotics and /or prebiotics compared with unsupplemented formulae .