Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics Prebiotic‐supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high‐risk infants: a randomized controlled trial A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Oligofructose-supplemented infant cereal: 2 randomized, blinded, community-based trials in Peruvian infants. 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Bifidogenic Effects of Solid Weaning Foods With Added Prebiotic Oligosaccharides: A Randomised Controlled Clinical Trial Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition [Randomised placebo controlled double blind study on the effect of prebiotic oligosaccharides on intestinal flora in healthy infants]. Colon Microflora in Infants Fed Formula with Galacto- and Fructo-Oligosaccharides: More Like Breast-Fed Infants Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Influence of maternal food antigen avoidance during pregnancy and lactation on incidence of atopic eczema in infants 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 Specific Prebiotic Mixture Added to Starting Infant Formula Has Long-Lasting Bifidogenic Effects123 The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants. Probiotics: a novel approach in the management of food allergy. Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial. A study of fructo oligosaccharides in the prevention of travellers’ diarrhoea Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial Consumption of organic foods and risk of atopic disease during the first 2 years of life in the Netherlands. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomised controlled trial Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. [Effects of feeding intervention on development of eczema in atopy high-risk infants: an 18-month follow-up study]. The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial 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. Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial. The effect of a prebiotic supplemented formula on growth and stool microbiology of term infants. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Prebiotic Effect Of Fructo-Oligosaccharide Supplemented Term Infant Formula at Two Concentrations Compared with Unsupplemented Formula and Human Milk Prebiotic Effect of an Infant Formula Supplemented with Galacto-Oligosaccharides: Randomized Multicenter Trial Probiotics in the prevention of eczema: a randomised controlled trial Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Prebiotics Improve Gastric Motility and Gastric Electrical Activity in Preterm Newborns Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial Postnatal Fish Oil Supplementation in High-Risk Infants to Prevent Allergy: Randomized Controlled Trial Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double‐blind placebo‐controlled trial Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast-fed 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 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 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 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 Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months , but evidence is mixed . Adding specific oligosaccharides may improve outcomes Background : Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora . Aims : To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis ( AD ) during the first six months of life in formula fed infants at high risk of atopy . Methods : Prospect i ve , double-blind , r and omised , placebo controlled trial ; 259 infants at risk for atopy were enrolled . A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study . If bottle feeding was started , the infant was r and omly assigned to one of two hydrolysed protein formula groups ( 0.8 g/100 ml prebiotics or maltodextrine as placebo ) . All infants were examined for clinical evidence of atopic dermatitis . In a subgroup of 98 infants , faecal flora was analysed . Results : Ten infants ( 9.8 % ; 95 CI 5.4–17.1 % ) in the intervention group and 24 infants ( 23.1 % ; 95 CI 16.0–32.1 % ) in the control group developed AD . The severity of the dermatitis was not affected by diet . Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts . Conclusion : Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants . Although the mechanism of this effect requires further investigation , it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy 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 Prebiotics are nondigestible food ingredients that stimulate the growth of Bifidobacterium and other bacteria in the gastrointestinal tract . Improved gastrointestinal and other health effects have been attributed to them . OBJECTIVE The objective of this study was to evaluate the effects of dietary supplementation with the prebiotic oligofructose with and without zinc on the prevalence of diarrhea in a community with a high burden of gastrointestinal and other infections . DESIGN Two consecutive r and omized , blinded , controlled clinical trials were performed in a shantytown community near Lima , Peru . The first trial compared an infant cereal supplemented with oligofructose ( 0.55 g/15 g cereal ) with nonsupplemented cereal . During the second trial , zinc ( 1 mg/15 g cereal ) was added to both oligofructose-supplemented and control cereals . RESULTS We enrolled 282 infants in the first trial and 349 in the second . In the first trial , mean ( + /- SD ) days of diarrhea were 10.3 + /- 9.6 in the nonsupplemented cereal group and 9.8 + /- 11.0 in the prebiotic-supplemented cereal group ( P = 0.66 ) . In the second trial , mean days of diarrhea were 10.3 + /- 8.9 in the group consuming cereal fortified only with zinc and 9.5 + /- 8.9 in the group consuming cereal containing both zinc and prebiotics ( P = 0.35 ) . Postimmunization titers of antibody to Haemophilus influenzae type B were similar in all groups , as were gains in height , visits to clinic , hospitalizations , and use of antibiotics . CONCLUSIONS Cereal supplemented with prebiotics was not associated with any change in diarrhea prevalence , use of health care re sources , or response to H. influenzae type B immunization .  Infants and young children who continue to breast-feed may not benefit from prebiotic supplementation Background Prevention of serious infections in preterm infants is a challenge , since prematurity and low birth weight often requires many interventions and high utility of devices . Furthermore , the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system . In combination with delayed intestinal bacterial colonisation compared with term infants , this may increase the risk for serious infections . Acidic and neutral oligosaccharides play an important role in the development of the immune system , intestinal bacterial colonisation and functional integrity of the gut . This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity ( primary outcome ) , immune response to immunizations , feeding tolerance and short-term and long-term outcome in preterm infants . In addition , an attempt is made to eluci date the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut . Methods / Design In a double-blind placebo controlled r and omised trial , 120 preterm infants ( gestational age < 32 weeks and /or birth weight < 1500 gram ) are r and omly allocated to receive enteral acidic and neutral oligosaccharides supplementation ( 20%/80 % ) or placebo supplementation ( maltodextrin ) between day 3 and 30 of life . Primary outcome is infectious morbidity ( defined as the incidence of serious infections ) . The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations , plasma cytokine concentrations , faecal Calprotectin and IL-8 . The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance , intestinal permeability , intestinal viscosity , and determining intestinal microflora . Furthermore , short-term and long-term outcome are evaluated . Discussion Especially preterm infants , who are at increased risk for serious infections , may benefit from supplementation of prebiotics . Most studies with prebiotics only focus on the colonisation of the intestinal microflora . However , the pathways how prebiotics may influence the immune system are not yet fully understood . Study ing the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants . The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system . Increased insight in the effects of prebiotics on the developing immune system may help to decrease the ( infectious ) morbidity and mortality in preterm infants . Trial registration Current Controlled Trials IS RCT N16211826 Antibiotics exert deleterious effects on the intestinal microbiota , favoring the emergence of opportunistic bacteria and diarrhea . Prebiotics are nondigestible food components that stimulate the growth of bifidobacteria . Our aim was to evaluate the effects on the intestinal microbiota of a prebiotic-supplemented milk formula after an antibiotic treatment . A r and omized , double-blind , controlled clinical trial was carried out in 140 infants 1–2 y of age distributed into two groups after a 1-wk amoxicillin treatment ( 50 mg/kg/d ) for acute bronchitis . The children received for 3 wk > 500 mL/d of a formula with prebiotics ( 4.5 g/L ) or a control without prebiotics . Fecal sample s were obtained on d –7 ( at the beginning of the antibiotic treatment ) , on d 0 ( end of the treatment and before formula administration ) , and on d 7 and 21 ( during formula administration ) . Counts of Bifidobacterium , Lactobacillus-Enterococcus , Clostridium lituseburiense cluster , Clostridium histolyticum cluster , Escherichia coli , and Bacteroides-Prevotella were evaluated by fluorescent in situ hybridization ( FISH ) and flow cytometry . Tolerance and gastrointestinal symptoms were recorded daily . Amoxicillin decreased total fecal bacteria and increased E. coli . The prebiotic significantly increased bifidobacteria from 8.17 ± 1.46 on d 0 to 8.54 ± 1.20 on d 7 compared with the control 8.22 ± 1.24 on d 0 versus 7.95 ± 1.54 on d 7 . The Lactobacillus population showed a similar tendency while the other bacteria were unaffected . No gastrointestinal symptoms were detected during the prebiotic administration . Prebiotics in a milk formula increase fecal bifidobacteria early after amoxicillin treatment without inducing gastrointestinal symptoms Background : Recent data have outlined a relationship between the composition of the intestinal microflora and  allergic inflammation  , and demonstrated the competence of probiotics in downregulation of such inflammation . Aims : Our aims were to characterise the relationship between gut microbes and the extent of allergic sensitisation and to assess whether the efficacy of bifidobacterial supplementation in the treatment of allergy could relate to modulation of the intestinal microbiota . Methods : This r and omised study included 21 infants with early onset atopic eczema of whom eight were intolerant ( highly sensitised group ( HSG ) ) and 13 tolerant ( sensitised group ( SG ) ) to extensively hydrolysed whey formula ( EHF ) .  In the SG , six were weaned to EHF without ( placebo group ( PG ) ) and seven to EHF with Bifidobacterium lactis Bb-12 supplementation ( bifidobacteria treated group ( BbG ) ) . The faecal microflora of infants in the HSG was analysed only before weaning whereas in the SG the faecal microflora was analysed both before and after weaning . Results : Infants in the HSG had greater numbers of lactobacilli/enterococci than those in the SG . Serum total IgE concentration correlated directly with Escherichia coli counts in all infants and with bacteroides counts in the HSG , indicating that the presence of these bacteria is associated with the extent of atopic sensitisation . The effect of supplementation was characterised as a decrease in the numbers of Escherichia coli and protection against an increase in bacteroides numbers during weaning . Conclusions : These data indicate that bifidobacterial supplementation appears to modify the gut microbiota in a manner that may alleviate allergic inflammation . Further studies are needed to confirm this conclusion Prebiotics are nondigestible food ingredients that encourage proliferation of selected groups of the colonic microflora , thereby altering the composition toward a more beneficial community . In the present study , the prebiotic potential of a novel galactooligosaccharide ( GOS ) mixture , produced by the activity of galactosyltransferases from Bifidobacterium bifidum 41171 on lactose , was assessed in vitro and in a parallel continuous r and omized pig trial .  In situ fluorescent hybridization with 16S rRNA-targeted probes was used to investigate changes in total bacteria , bifidobacteria , lactobacilli , bacteroides , and Clostridium histolyticum group in response to supplementing the novel GOS mixture . In a 3-stage continuous culture system , the bifidobacterial numbers for the first 2 vessels , which represented the proximal and traverse colon , increased ( P < 0.05 ) after the addition of the oligosaccharide mixture . In addition , the oligosaccharide mixture strongly inhibited the attachment of enterohepatic Escherichia coli ( P < 0.01 ) and Salmonella enterica serotype Typhimurium ( P < 0.01 ) to HT29 cells . Addition of the novel mixture at 4 % ( wt : wt ) to a commercial diet increased the density of bifidobacteria ( P < 0.001 ) and the acetate concentration ( P < 0.001 ) , and decreased the pH ( P < 0.001 ) compared with the control diet and the control diet supplemented with inulin , suggesting a great prebiotic potential for the novel oligosaccharide mixture Development of oral tolerance and its stimulation by probiotics are still incomprehensible . Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA , which participates in antigen elimination . In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo  we studied intestinal IgA and inflammation in the development of eczema , food allergy , asthma , and rhinitis ( allergic diseases ) . We performed a nested unmatched case-control study of 237 infants participating in a r and omized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth . We measured faecal IgA , alpha1-antitrypsin ( alpha1-AT ) , tumour necrosis factor-alpha ( TNF-alpha ) , and calprotectin  at the age of 3 and 6 months . By age 2 yr , 124 infants had developed allergic disease or IgE-sensitization  ( cases ) and 113 had not ( controls ) . In infants with high faecal IgA concentration at the age of 6 months , the risk of having any allergic disease before the age of 2 yr tended to reduce [ odds ratio ( OR : 0.52 ) ] and the risk for any IgE-associated ( atopic ) disease reduced significantly ( OR : 0.49 ) . High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr ( OR : 0.49 ) . All faecal inflammation markers ( alpha1-AT , TNF-alpha , and calprotectin ) correlated positively with faecal IgA ( p < 0.001 ) . Probiotics tended to augment faecal IgA ( p = 0.085 ) and significantly increased faecal alpha1-AT ( p = 0.001 ) . High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases Prebiotic oligosaccharides influence the intestinal microbiota and can positively modulate the infant 's immune system . It was demonstrated that a special prebiotic mixture ( Immunofortis ( ® ) ) of short-chain galacto-oligosaccharides ( scGOS ) and long-chain fructo-oligosaccharides ( lcFOS ) can reduce the cumulative incidence of atopic dermatitis ( AD ) in infants at risk for allergy as determined using the AD symptom score ( SCORAD ) . Additionally , it was shown very recently that immunoglobulin free light-chain ( Ig-fLC ) might be involved in the pathophysiology of allergic disease . Increased Ig-fLC concentrations were found in patients suffering from AD , cow 's milk allergy , allergic rhinitis , or asthma . In this study , the effect of supplementation of scGOS/lcFOS on the Ig-fLC plasma concentrations in infants at risk for allergy was assessed . The plasma kappa and lambda Ig-fLC concentrations were measured in a double-blind , placebo-controlled , r and omized trial , in which infants at risk for developing allergic disease received a  hypoallergenic whey formula containing 8 g/l of the scGOS/lcFOS mixture ( n = 34 ) or maltodextrin as a placebo ( n=40 ) for 6 months . After intervention , plasma sample s were collected , and total plasma concentrations of lambda and kappa Ig-fLC were analyzed using ELISA . Total kappa and lambda Ig-fLC plasma concentrations were higher in infants suffering from AD when compared to infants without any sign of AD . In infants receiving the prebiotic mixture  , the Ig-fLC levels were significantly lower compared to the placebo-fed infants ( p<0.001 ) . Interestingly , lambda Ig-fLC concentrations were positively correlated with total IgE ( p<0.05 ) . These data demonstrate for the first time that the specific scGOS/lcFOS mixture lowered kappa and lambda Ig-fLC plasma concentrations in infants at high risk for allergies when compared to infants receiving placebo formula . Because Ig-fLC concentrations were increased in infants suffering from AD , this may have contributed , at least in part , to the reduced incidence in AD as described previously . This suggests a possible role for Ig-fLC in the pathophysiology of AD in infants at risk for allergy development Objectives : Breast-fed infants have relatively high proportions of faecal bifidobacteria . This bifidogenic microbiota is at least partly explained by the high levels of prebiotic oligosaccharides in human milk . The present study aim ed at testing the effect of solid foods with added prebiotic galacto- and fructo-oligosaccharides ( GOS/FOS ) on the composition of the intestinal microbiota of fully formula-fed infants during the weaning period . Methods : The study was a double-blind , r and omised trial with an intervention period of 6 weeks . Infants aged 4 to 6 months who were about to start consuming solid foods were r and omised to receive either weaning products with a mixture of GOS/FOS or control weaning products with maltodextrin . After an adjustment period , the presented daily dose of GOS/FOS was 4.5 g. Total numbers of bacteria and bifidobacteria in faecal sample s were analysed with fluorescent in situ hybridization . Results : Thirty-five infants were included in the study , and 20 infants were included in a per- protocol analysis . In the GOS/FOS group , the faecal percentage of bifidobacteria significantly increased from 43 % to 57 % ( P = 0.031 ) from week 0 to week 6 , but did not significantly change in the control group ( 36 % and 32 % , respectively ; P = 0.387 ) . The change in the percentage of bifidobacteria between week 0 and week 6 in the GOS/FOS was significantly different from this change in the control group ( P = 0.026 ) . Conclusions : We conclude that addition of GOS/FOS to solid foods induces an increase in the faecal proportion of bifidobacteria in the intestinal microbiota of fully formula-fed infants with an established , mixed-type microbiota in the weaning period A mixture of neutral short-chain galactooligosaccharides ( scGOS ) and long-chain fructooligosaccharides ( lcFOS ) has been shown to reduce the incidence of atopic dermatitis ( AD ) and infectious episodes during the first 6 mo of life . This dual protection occurred through the intervention period . The present study evaluated if these protective effects were lasting beyond the intervention period . In a prospect i ve , r and omized , double-blind , placebo-controlled design , healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . Following this intervention period , blind follow-up continued until 2 y of life . Primary endpoints were cumulative incidence of allergic manifestations . Secondary endpoints were number of infectious episodes and growth .  Of 152 participants , 134 infants ( 68 in placebo , 66 in intervention group ) completed the follow-up . During this period , infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations . Cumulative incidences for AD , recurrent wheezing , and allergic urticaria were higher in the placebo group , ( 27.9 , 20.6 , and 10.3 % , respectively ) than in the intervention group ( 13.6 , 7.6 , and 1.5 % ) ( P < 0.05 ) . Infants in the scGOS/lcFOS group had fewer episodes of physician-diagnosed overall and upper respiratory tract infections ( P < 0.01 ) , fever episodes ( P < 0.00001 ) , and fewer antibiotic prescriptions ( P < 0.05 ) . Growth was normal and similar in both groups . Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections . The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action 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 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 AIM Effects of supplementing prebiotic oligosaccharides to formula for healthy infants were studied in this placebo controlled , r and omised , double blind study . METHODS Ninety-seven infants were included into the study ; among them 42 breast-fed infants , 14 infants fed formula supplemented with 0.4 g/100ml oligosaccharides ( 9 to 1 mixture of galacto- and fructooligosaccharides ) and 13 infants fed control formula  were followed-up throughout the 12-week-long study period . The groups receiving formula were compared with statistical methods , whereas data of breast-fed infants served as reference values . RESULTS Infants fed the two formulae did not differ in nutrient intakes , growth , occurrence rate of feeding difficulties and atopic manifestations , or in calcium excretion . The intestinal flora did not differ between the two formula fed groups at the beginning of the study . In contrast , numbers of Bifidobacteriae were significantly higher in infants receiving the formula supplemented with prebiotic oligosaccharides both at the 14th day ( 9 x 1011 versus 5 x 1010 , colony forming units/g faeces , median , p < 0.05 ) and 28th day ( 9 x 1012 versus 5 x 1010 , p < 0.05 ) of the study . CONCLUSION In this study , supplementation of infant formula with prebiotic oligosaccharides result ed in ameliorating the difference in intestinal flora between formula fed and breast-fed healthy infants Objectives : The intestinal flora of breast-fed infants is generally dominated by Bifidobacteria . We aim ed to investigate whether an infant formula supplemented with galacto-oligosaccharides and fructo-oligosaccharides ( GOS/FOS ) is able to establish a bifido-dominant microflora , not only in numbers but also with respect to the metabolic activity in the colon . Methods : Two groups of infants fed infant formula with 0.8 g/100 ml GOS/FOS in a ratio of 9:1 ( OSF group ) , or control formula ( SF group ) were evaluated in a r and omised , double blind , placebo controlled intervention study . A breast-fed group was studied in parallel . At study onset and after 4 and 6 weeks , faecal sample s were examined for the number of bifidobacteria , pH , short chain fatty acids and lactate . Results : After 6 weeks , the mean proportion of bifidobacteria was significantly higher in the OSF group ( 59.6 % versus 49.5 % in the SF group ; P < 0.05 ) . Compared with controls , infants in the OSF group had a lower stool mean pH and an increased proportion of acetate and a decreased proportion of propionate . The mean pH in the OSF and SF groups were 5.7 and 6.3 , respectively ( P < 0.001 ) . Conclusions : The addition of the prebiotic GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora . The changes in short chain fatty acids , lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula Necrotizing enterocolitis ( NEC ) continues to be a major cause of morbidity and mortality in premature infants . Although the pathogenesis of NEC remains unclear , abnormal bacterial colonization has been postulated as playing a central role . Various factors impact bacterial colonization following delivery . Compared to term infants , the bacterial colonization pattern in prematurely born infants is markedly different , with a greater predilection for colonization with pathogenic bacteria . Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment , favoring the growth of commensal bacteria . Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC . These preliminary studies support the need for a large , r and omized , controlled trial to further investigate the role of probiotics in the prevention of NEC AIM The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various components of breast milk , including prebiotic substances . This prospect i ve double-blind study compared the numbers of bifidobacteria in the stool flora of bottle-fed preterm infants r and omized to receive for 14 days either a formula with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same formula with maltodextrin as a placebo . METHODS Within 0 - 14 days after birth , 56 healthy bottle-fed infants were enrolled to receive either the prebiotic or placebo . Faecal sample s were taken at inclusion day and at study day 7 . The number of bifidobacteria in the stools , stool characteristics and somatic growth were recorded during the study . RESULTS In the group fed fructo-oligosaccharides , both the numbers of bifidobacteria in the stools and the proportion of infants colonized with them were significantly higher as compared to the placebo group ( p=0.032 and p=0.030 respectively ) . There was also a higher number of bacteroids in the fructo-oligosaccharide group as compared to the placebo ( p=0.029 ) . At the same time , reduction was noted in the numbers of Escherichia coli and enterococci . ( p=0.029 , and p=0.025 , respectively ) . Supplementation had also significant influence on stool frequency per day ( p=0.0080 ) . CONCLUSION An infant formula containing a small quantity of prebiotic oligosaccharides is well accepted and leads to rapid growth of bifidobacteria in the gut of bottle-fed preterm infants while decreasing the numbers of pathogenic microorganisms BACKGROUND Alterations in intestinal microflora have been linked to the development of allergic disease . Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains . OBJECTIVES We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life . METHODS Fecal sample s were collected 1 wk after birth from 98 infants at high risk of allergic disease , who were followed prospect ively to age 12 months .  Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism ( T-RFLP ) using restriction enzymes Sau96I and AluI , with a greater number of peaks representing greater diversity of bacterial communities . RESULTS Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema ( AluI mean number of peaks 13.1 vs. 15.5 , p = 0.003 , 95 % CI for difference in means -3.9 , -0.8 ; Sau96I 14.7 vs. 17.2 , p = 0.03 , 95 % CI -4.9 , -0.3 ) . No differences were observed for atopic compared to non-atopic infants , or infants with two allergic parents compared to those with one or no allergic parent . CONCLUSIONS A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease . Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants Abstract . One hundred and twenty‐one women with history of a previous child with atopic disease were r and omly allocated during the next pregnancy to antigen avoidance or control groups . Dietary advice consisted of almost complete exclusion of milk and dairy products , egg , fish , beef and peanut throughout pregnancy and lactation . A total of 109 completed the study . Maternal antigen avoidance was associated with reduced occurrence of atopic eczema and the skin involvement was less extensive and milder . The beneficial effect was observed mainly in the breast‐fed group . Among the fifty‐five who completed the trial of antigen avoidance , seventeen infants developed atopic eczema , five out of thirty‐five who were breast‐fed and twelve out of twenty who were formula‐fed . Among the offspring of fifty‐four control mothers given no dietary restriction , eczema was observed in twenty‐four infants , eleven out of thirty‐six breast‐fed and thirteen of eighteen formula‐fed . Avoidance of common dietary allergens during pregnancy and lactation enhanced the preventive beneficial effect of exclusive breast feeding on the incidence of atopic eczema among infants at high risk 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 There is some evidence that early colonization of the intestine affects the composition of the intestinal microbiota after weaning . In the present study , the effect of prebiotics administered from the first day of life on fecal counts of bifidobacteria and lactobacilli were studied during and after the administration of the prebiotics . In this double-blind , r and omized , placebo-controlled , explorative study , 20 newborns of hepatitis C virus-infected mothers who decided not to breast feed due to their concerns regarding their plasma viral load were r and omly assigned to either a formula with 8 g/L of a specific prebiotic mixture ( short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides , ratio 9:1 ) or a formula containing the same amount of maltodextrin ( placebo ) .  Clinical examination including anthropometric measurements , microbiological analysis of fecal sample s , and blood leukocyte population analysis were performed at birth and 3 , 6 , and 12 mo age . At the age of 12 mo , hepatitis B vaccine-specific IgG serum titers ( Hepatitis B virus surface antibodies ) were also measured . Prebiotic supplementation result ed in more fecal bifidobacteria ( P < 0.0001 ) and lactobacilli ( P = 0.0044 ) compared with the placebo group . These differences between the groups were maintained during the second half of the first year without any prebiotic supplementation . There was no influence of the different diets on anthropometric data or the measured immunological variables . The data from this small explorative study indicate that early colonization of the intestine might have long-lasting effects on the composition of the intestinal microbiota Preterm infants have an impaired gut barrier function . We aim ed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides ( LCFOS ) ) and acidic oligosaccharides ( AOS ) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life . Furthermore , we determined host- and treatment-related factors associated with intestinal permeability . In a r and omised controlled trial , preterm infants with a gestational age < 32 weeks and /or birth weight ( BW ) < 1500 g received enteral supplementation of SCGOS/LCFOS/AOS or placebo ( maltodextrin ) between days 3 and 30 of life . Intestinal permeability , reflected by the urinary lactulose/mannitol ( L/M ) ratio after oral ingestion of lactulose and mannitol , was assessed at three time points : before the start of the study ( t = 0 ) , at day 4 ( t = 1 ) and at day 7 ( t = 2 ) of life . Data were analysed by generalised estimating equations . In total , 113 infants were included . Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS ( n 55 ) and the placebo groups ( n 58 ) . SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2 . In both the groups , the L/M ratio decreased from t = 0 to t = 2 ( P < 0·001 ) . Low BW increased the L/M ratio ( P = 0·002 ) . Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio ( P < 0·001 and P < 0·05 , respectively ) . In conclusion , enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy BACKGROUND Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence -based guidelines , it is often justified by the belief in a subgroup effect in individuals developing atopic disease . We aim ed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction , atopic eczema , or allergic sensitisation . METHODS In the r and omised , double-blind , multicentre Bronchiolitis ALL trial , 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay . R and omisation was done central ly , and the two study medications ( 20 mg/mL racemic epinephrine or 0.9 % saline ) were prepared in identical bottles . The dose given depended on the infant 's weight : 0.10 mL , less than 5 kg ; 0.15 mL , 5 - 6.9 kg ; 0.2 mL , 7 - 9.9 kg ; and 0.25 mL , 10 kg or more ; all dissolved in 2 mL of 0.9 % saline before nebulisation . The primary outcome was the length of hospital stay . In this follow-up study , 294 children were reinvestigated at 2 years of age with an interview , a clinical examination , and a skin prick test for 17 allergens , determining bronchial obstruction , atopic eczema , and allergic sensitisation , on which subgroup analyses were done . Analyses were done by intention to treat . The trial has been completed and is registered at Clinical Trials.gov ( number NCT00817466 ) and EUDRACT ( number 2009 - 012667 - 34 ) . FINDINGS Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years ( 143 [ 48.6 % ] of 294 patients ; p(interaction)=0.40 ) . However , the presence of atopic eczema or allergic sensitisation by the age of 2 years ( n=77 ) significantly interacted with the treatment effect of inhaled epinephrine ( p(interaction)=0.02 ) ; the length of stay ( mean 80.3 h , 95 % CI 72.8 - 87.9 ) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years ( -19.9 h , -33.1 to -6.3 ; p=0.003 ) . No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years ( + 16.2 h , -11.0 to 43.3 ; p=0.24 ) . INTERPRETATION Contrary to our hypothesis , hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema , allergic sensitisation , or recurrent bronchial obstruction . The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases . FUNDING Medicines for Children Network , Norway : Prebiotic carbohydrates selectively stimulate the growth of bifidobacteria and lactobacilli in the human colon . These bacteria form part of the gut ’s inherent defence against invading pathogens BACKGROUND Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies . In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life . Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora . We assessed the effect on atopic disease of Lactobacillus GG ( which is safe at an early age and effective in treatment of allergic inflammation and food allergy ) . METHODS In a double-blind , r and omised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative ( or partner ) with atopic eczema , allergic rhinitis , or asthma , and postnatally for 6 months to their infants .  Chronic recurring atopic eczema , which is the main sign of atopic disease in the first years of life , was the primary endpoint . FINDINGS  Atopic eczema was diagnosed in 46 of 132 ( 35 % ) children aged 2 years . Asthma  was diagnosed in six of these children and allergic rhinitis in one . The frequency of atopic eczema in the probiotic group was half that of the placebo group ( 15/64 [ 23 % ] vs 31/68 [ 46 % ] ; relative risk 0.51 [ 95 % CI 0.32 - 0.84 ] ) . The number needed to treat was 4.5 ( 95 % CI 2.6 - 15.6 ) . INTERPRETATIONS Lactobacillus GG was effective in prevention of  early atopic disease in children at high risk . Thus , gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics , for prevention of atopic disease We prospect ively investigated whether organic food consumption by infants was associated with developing atopic manifestations in the first 2 years of life . The KOALA Birth Cohort Study in the Netherl and s ( n 2764 ) measured organic food consumption ,  eczema and wheeze in infants until age 2 years using repeated question naires . Diet was defined as conventional ( 90 % organic ) . Venous blood sample s taken from 815 infants at 2 years of age were analysed for total and specific IgE. Multivariate logistic regression models were fitted to control for potential confounding factors . Eczema was present in 32 % of infants , recurrent wheeze in 11 % and prolonged wheezing in 5 % . At 2 years of age , 27 % of children were sensitised against at least one allergen . Of all the children , 10 % had consumed a moderately organic diet and 6 % a strictly organic diet . Consumption of organic dairy products was associated with lower eczema risk ( OR 0.64 ( 95 % CI 0.44 , 0.93 ) ) , but there was no association of organic meat , fruit , vegetables or eggs , or the proportion of organic products within the total diet with the development of eczema , wheeze or atopic sensitisation . Further studies to substantiate these results are warranted Objective To determine whether dietary n-3 long chain polyunsaturated fatty acid ( LCPUFA ) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age . Design Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome ( DOMInO ) r and omised controlled trial . Setting Adelaide , South Australia . Participants 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial . Interventions The intervention group ( n=368 ) was r and omly allocated to receive fish oil capsules ( providing 900 mg of n-3 LCPUFA daily ) from 21 weeks ’ gestation until birth ; the control group ( n=338 ) received matched vegetable oil capsules without n-3 LCPUFA . Main outcome measure Immunoglobulin E associated allergic disease ( eczema or food allergy with sensitisation ) at 1 year of age . Results No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups ( 32/368 ( 9 % ) v 43/338 ( 13 % ) ; unadjusted relative risk 0.68 , 95 % confidence interval 0.43 to 1.05 , P=0.08 ; adjusted relative risk 0.70 , 0.45 to 1.09 , P=0.12 ) , although the percentage of infants diagnosed as having atopic eczema ( that is , eczema with associated sensitisation ) was lower in the n-3 LCPUFA group ( 26/368 ( 7 % ) v 39/338 ( 12 % ) ; unadjusted relative risk 0.61 , 0.38 to 0.98 , P=0.04 ; adjusted relative risk 0.64 , 0.40 to 1.02 , P=0.06 ) . Fewer infants were sensitised to egg in the n-3 LCPUFA group ( 34/368 ( 9 % ) v 52/338 ( 15 % ) ; unadjusted relative risk 0.61 , 0.40 to 0.91 , P=0.02 ; adjusted relative risk 0.62 , 0.41 to 0.93 , P=0.02 ) , but no difference between groups in immunoglobulin E associated food allergy was seen . Conclusion n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life , although atopic eczema and egg sensitisation were lower . Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12610000735055 ( DOMInO trial : ACTRN12605000569606 ) Background : The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant . Objective : To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants . Study design : To resemble the effect of human milk , an oligosaccharide mixture consisting of 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides was used to supplement a st and ard preterm formula at a concentration of 10 g/l . This supplemented formula was studied in 15 preterm infants , and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo .  A group fed fortified mother 's milk  was investigated as a reference group ( n = 12 ) . On four days during a 28 day feeding period ( 1 , 7 , 14 , and 28 ) , the faecal flora was investigated , and stool characteristics , growth , and possible side effects were recorded . Results : During the study period , the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group . The difference between the supplemented and non-supplemented groups was highly significant ( p = 0.0008 ) . The stool characteristics were also influenced by the supplement : the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group ( p = 0.0079 ) and the reference group ( p < 0.0001 ) . Over the study period , the stool consistency in the control group became harder , but remained fairly stable in the other two groups . There was no effect of the different diets on the incidence of side effects ( crying , regurgitation , vomiting ) or on weight gain or length gain . Conclusion : Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk . Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants BACKGROUND A mixture of neutral prebiotic oligosaccharides has been shown to reduce the incidence of atopic dermatitis ( AD ) and allergy associated symptoms during the first 2 years of life . OBJECTIVE To evaluate if this protective effect against allergy lasted beyond the intervention period until 5 y of age . METHODS In a prospect i ve , double blind , placebo-controlled fashion , healthy term infants at risk of atopy were fed either a prebiotic-supplemented ( 0.8 g/100 ml scGOS/lcFOS ) or placebo-supplemented ( 0.8 g/100 ml maltodextrin ) hypoallergenic formula during the first 6 mo of life . Following this intervention period , follow-up continued until 5 y of life . The present study evaluated ( i ) the cumulative incidence of allergic manifestations during 5 y , and ( ii ) the prevalence of allergic and persistent allergic manifestations at 5 y. Monitored allergic manifestations were AD , recurrent wheezing , allergic rhinoconjunctivitis and urticaria . RESULTS Ninety-two children ( 50 in placebo group , 42 in intervention group ) completed the 5-y follow-up . The 5-y cumulative incidences of any allergic manifestation and atopic dermatitis were significantly lower in the scGOS/lcFOS group ( 30.9 , 19.1 % , respectively ) compared to placebo group ( 66 , 38 % , respectively ) ( p < 0.01 and < 0.05 ) . Children in the scGOS/lcFOS group tended to have a lower incidence of allergic rhinoconjunctivitis , and allergic urticaria ( 4.8 vs 16 % for both manifestations , p=0.08 ) . There was no difference in the cumulative incidence of recurrent wheezing . With regard to the prevalences at 5 y , intervention group had significantly lower prevalence of any persistent allergic manifestation and rhinoconjunctivitis ( 4.8 , 2.4 % , respectively ) compared to placebo ( 26 , 14 % , respectively ) ( p < 0.01 and = 0.05 ) . Prevalence of persistent AD tended to be lower in the intervention group ( 2.4 vs 12 % , p= 0.09 ) . Although intervention group had 75 % reduction in the prevalence of persistent wheezing ( 4.8 vs 14 % ) , no significance was shown . CONCLUSION Oligosaccharide prebiotics ( scGOS/lcFOS ) , when started early in life have a protective effect against allergic manifestations in high risk infants . The protection lasts beyond infancy until 5 y of life , for AD and allergic rhinoconjunctivitis . Long-term follow-up studies in larger population s are warranted to evaluate the potential preventive effect of this mixture on asthma BACKGROUND An altered microbial exposure may underlie the increase of allergic diseases in affluent societies .  Probiotics may alleviate and even prevent eczema in infants . OBJECTIVE To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri . METHODS Double-blind , r and omized , placebo-controlled trial , which comprised 232 families with allergic disease , of whom 188 completed the study . The mothers received L reuteri ATCC 55730 ( 1 x 10(8 ) colony forming units ) daily from gestational week 36 until delivery . Their babies then continued with the same product from birth until 12 months of age and were followed up for another year . Primary outcome was allergic disease , with or without positive skin prick test or circulating IgE to food allergens . RESULTS The cumulative incidence of eczema was similar , 36 % in the treated versus 34 % in the placebo group . The L reuteri group had less IgE-associated eczema during the second year , 8 % versus 20 % ( P = .02 ) , however . Skin prick test reactivity was also less common in the treated than in the placebo group , significantly so for infants with mothers with allergies , 14 % versus 31 % ( P = .02 ) . Wheeze and other potentially allergic diseases were not affected . CONCLUSION Although a preventive effect of probiotics on infant eczema was not confirmed , the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease . CLINICAL IMPLICATION Probiotics may reduce the incidence of IgE-associated eczema in infancy OBJECTIVE To assess the preventive effects of different dietary regimens on development of eczema and food allergy in infants at high-risk for allergy . METHODS Forty-six infants whose parents were atopic and umbilical cord IgE > 0.35 kU/L were enrolled in the study . The infants were r and omly assigned at birth to one of 2 dietary regimen protocol s : those in intervention group ( 23 cases ) were breast fed till more than 4 months of age , then followed by feeding with partially hydrolyzed formula ( pHF ) , combined solid foods avoidance until 4-month of age , egg , fish , shrimp avoidance until 12-month of age . The other 23 cases in non-intervention group were breast fed for less than 4 months , or bottle fed with cow 's milk-based formula , egg yolk was introduced at 4-month of age , and egg white at 6-month of age , besides , no any other dietary avoidance was applied . All the infants were followed-up for 18 months . The primary end point was the presence of atopic eczema . Food allergy was detected by fresh food prick-to-prick tests or in vitro sIgE or Fx5E . RESULTS At 6 months , 12 months and 18 months , the incidence of eczema in intervention group was 4.3 % ( 1/23 ) , 8.7 % ( 2/23 ) , and 17.4 % ( 4/23 ) , respectively , which was significantly reduced as compared to that of the non-intervention group , which was 26.1 % ( 6/23 ) , 34.8 % ( 8/23 ) , and 39.1 % ( 9/23 ) , respectively . Food allergy was found in 13.0 % ( 3/23 ) of intervention group and 34.8 % ( 9/23 ) of non-intervention group by skin prick tests or sIgE. Egg white was the most common offending food . CONCLUSION Early life dietary interventions which included breastfeeding , delayed solid food introducing , pHF feeding , and high risk food avoidance could reduce the risk of atopic eczema and food allergy development , and was probably an effective primary intervention method for infants at high risk for atopy Background : Necrotizing enterocolitis ( NEC ) is one of the most destructive diseases associated with conditions of neonatal prematurity . Supplementation with enteral prebiotics may reduce the incidence of NEC , especially in infants who fed exclusively with breast-milk . Therefore , we compared the efficacy and safety of enteral supplementation of a prebiotic mixture ( short chain galacto-oligosaccharides/long chain fructo-oligosaccharides [ SCGOS/LCFOS ] ) versus no intervention on incidence of NEC in preterm infants . Methods : In a single-center r and omized control trial 75 preterm infants ( birth weight [ BW ] ≤1500 g , gestational age ≤34 weeks and were not fed with formula ) on 30 ml/kg/day volume of breast-milk were r and omly allocated to have enteral supplementation with a prebiotic mixture ( SCGOS/LCFOS ; 9:1 ) or not receive any prebiotic . The incidence of suspected NEC , feeding intolerance , time to full enteral feeds , duration of hospitalization were investigated . Results : Differences in demographic characteristics were not statistically important . SCGOS/LCFOS mixture significantly reduced the incidence of suspected NEC , ( 1 [ 4.0 % ] vs. 11 [ 22.0 % ] ; hazard ratio : 0.49 [ 95 % confidence interval : 0.29 - 0.84 ] ; P = 0.002 ) , and time to full enteral feeds ( 11 [ 7 - 21 ] vs. 14 [ 8 - 36 ] days ; P - 0.02 ] . Also duration of hospitalization was meaningfully shorter in the prebiotic group ( 16 [ 9 - 45 ] vs. 25 [ 11 - 80 ] ; P - 0.004 ] . Prebiotic oligosaccharides were well tolerated by very low BW ( VLBW ) infants . Conclusions : Enteral supplementation with prebiotic significantly reduced the incidence of NEC in VLBW infants who were fed exclusively breast-milk . This finding suggests that it might have been the complete removal of formula which caused a synergistic effect between nonhuman neutral oligosaccharides ( prebiotic ) and human oligosaccharides 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 The objective of the present study was to assess the effect of adding specific prebiotics to st and ard formula feeding on the number of fever episodes  in the first year of life . In the present r and omised , double-blind , placebo-controlled trial in seven centres in five West European countries , 830 healthy term infants , without a first-degree family history of allergic disease , of mothers who indicated to give only formula feeding were r and omised either to receive a st and ard non-hydrolysed cows ' milk-based formula to which a mixture of specific oligosaccharides was added ( prebiotics group ( PG ) ) , or to receive a similar formula without oligosaccharides ( control group ( CG ) ) . A separate reference group consisted of 300 breast-fed infants . The primary outcome was the number of fever episodes prospect ively documented by the parents . There was no difference in the number of fever episodes between the PG ( median value 1·19 ; 25th-75th percentile 0·09 - 2·34 ) and CG ( 1·16 ; 25th-75th percentile 0·06 - 2·38 ) . The median number of fever episodes in the separate breast-feeding reference group was 1·24 ( 25th-75th percentile 0·51 - 3·45 ) . There was no effect of adding specific prebiotics to st and ard formula feeding in reducing the number of fever episodes in the present study BACKGROUND 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 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 Controversy exists regarding the preventive effect of probiotics on the development of  eczema or atopic dermatitis .  We investigated whether supplementation of probiotics prevents the development of  eczema in infants at high risk . In a r and omized , double-blind , placebo-controlled trial , 112 pregnant women with a family history of allergic diseases received a once-daily supplement , either a mixture of Bifidobacterium bifidum BGN4 , B. lactis AD011 , and Lactobacillus acidophilus AD031 , or placebo , starting at 4 - 8 wks before delivery and continuing until 6 months after delivery . Infants were exclusively breast-fed during the first 3 months , and were subsequently fed with breastmilk or cow 's milk formula from 4 to 6 months of age . Clinical symptoms of the infants were monitored until 1 yr of age , when the total and specific IgE against common food allergens were measured . A total of 68 infants completed the study . The prevalence of eczema at 1 yr in the probiotic group was significantly lower than in the placebo group ( 18.2 % vs. 40.0 % , p=0.048 ) . The cumulative incidence of eczema during the first 12 months was reduced significantly in probiotic group ( 36.4 % vs. 62.9 % , p=0.029 ) ; however , there was no difference in serum total IgE level or the sensitization against food allergens between the two groups . Prenatal and postnatal supplementation with a mixture of B. bifidum BGN4 , B. lactis AD011 , and L. acidophilus AD031 is an effective approach in preventing the development of eczema in infants at high risk of allergy during the first year of life BACKGROUND Some breastfed infants with atopic eczema benefit from elimination of cow milk , egg , or other antigens from their mother 's diet . Maternal dietary antigens are also known to cross the placenta . OBJECTIVES To assess the effects of prescribing an antigen avoidance diet during pregnancy or lactation , or both , on maternal and infant nutrition and on the prevention or treatment of atopic disease in the child . SEARCH METHODS We search ed the Cochrane Pregnancy and Childbirth Group 's Trials Register ( 6 July 2012 ) . SELECTION CRITERIA All r and omized or quasi-r and omized comparisons of maternal dietary antigen avoidance prescribed to pregnant or lactating women . We excluded trials of multimodal interventions that included manipulation of the infant 's diet other than breast milk or of non-dietary aspects of the infant 's environment . DATA COLLECTION AND ANALYSIS We extracted data from published reports , supplemented by additional information received from the trialists we contacted . MAIN RESULTS The evidence from five trials , involving 952 participants , does not suggest a protective effect of maternal dietary antigen avoidance during pregnancy on the incidence of atopic eczema during the first 18 months of life . Data on allergic rhinitis or conjunctivitis , or both , and urticaria are limited to a single trial each and are insufficient to draw meaningful inferences . Longer-term atopic outcomes have not been reported . The restricted diet during pregnancy was associated with a slightly but statistically significantly lower mean gestational weight gain , a non-significantly higher risk of preterm birth , and a non-significant reduction in mean birthweight . The evidence from two trials , involving 523 participants , did not observe a significant protective effect of maternal antigen avoidance during lactation on the incidence of atopic eczema during the first 18 months or on positive skin-prick tests to cow milk , egg , or peanut antigen at one , two , or seven years . One crossover trial involving 17 lactating mothers of infants with established atopic eczema found that maternal dietary antigen avoidance was associated with a non-significant reduction in eczema severity . AUTHORS ' CONCLUSIONS Prescription of an antigen avoidance diet to a high-risk woman during pregnancy is unlikely to reduce substantially her child 's risk of atopic diseases , and such a diet may adversely affect maternal or fetal nutrition , or both . Prescription of an antigen avoidance diet to a high-risk woman during lactation may reduce her child 's risk of developing atopic eczema , but better trials are needed . Dietary antigen avoidance by lactating mothers of infants with atopic eczema may reduce the severity of the eczema , but larger trials are needed Background : Human milk components , including oligosaccharides , affect the gastrointestinal flora of infants . Previous studies in adults have demonstrated that fructo-oligosaccharides increase potentially beneficial fecal bacteria , including bifidobacteria . The purpose of this study was to determine the prebiotic effect of infant formula supplemented with fructo-oligosaccharides .  Methods : Healthy term infants 2 to 6 weeks of age were enrolled in a 5-week , prospect i ve , r and omized , crossover , single-site study with a nonr and omized human milk comparator group . Washout weeks preceded and followed a week of feeding with fructo-oligosaccharide-supplemented formula ( 1.5 or 3.0 g/L ) . Stool specimens were quantitatively cultured weekly for bacteroides , lactobacilli , bifidobacteria , clostridia and enterococci and were tested for Clostridium difficile toxin . Results : Seventy-two of 87 infants completed the trial ; 58 were formula fed and 14 were human milk fed .  Mean counts of bifidobacteria and lactobacilli were similar in all groups at entry and no group experienced a significant change in counts with fructo-oligosaccharide supplementation . After 7 days of fructo-oligosaccharide supplementation the bifidobacteria counts were greater in the 1.5 g/L fructo-oligosaccharide formula group than in the human milk fed or 3.0 g/L fructo-oligosaccharide formula groups . Formula-fed infants had higher counts of enterococci and bacteroides before fructo-oligosaccharide supplementation , and these counts did not change after supplementation . Clostridium counts increased 7 days after supplementation in the 1.5 g/L fructo-oligosaccharide formula group ( P = 0.0356 ) . No human milk fed infants had C. difficile toxin in stools .  Fructo-oligosaccharide ( 3.0 g/L ) supplementation result ed in more frequent and significantly softer stools . Conclusions : Infant formula supplemented with 1.5 or 3.0 g/L fructo-oligosaccharides was safe but had minimal effect on fecal flora and C. difficile toxin 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 Objective To evaluate a multistrain , high-dose probiotic in the prevention of  eczema .  Design A r and omised , double-blind , placebo-controlled , parallel group trial . Setting s Antenatal clinics , research clinic , children at home . Patients Pregnant women and their infants . Interventions Women from 36 weeks gestation and their infants to age 6 months received daily either the probiotic ( Lactobacillus salivarius CUL61 , Lactobacillus paracasei CUL08 , Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20 ; total of 1010 organisms/day ) or matching placebo . Main outcome measure Diagnosed eczema at age 2 years . Infants were followed up by question naire . Clinical examination and skin prick tests to common allergens were done at 6 months and 2 years . Results The cumulative frequency of diagnosed eczema at 2 years was similar in the probiotic ( 73/214 , 34.1 % ) and placebo arms ( 72/222 , 32.4 % ; OR 1.07 , 95 % CI 0.72 to 1.6 ) . Among the secondary outcomes , the cumulative frequency of skin prick sensitivity at 2 years was reduced in the probiotic ( 18/171 ; 10.5 % ) compared with the placebo arm ( 32/173 ; 18.5 % ; OR 0.52 , 95 % CI 0.28 to 0.98 ) . The statistically significant differences between the arms were mainly in sensitisation to cow 's milk and hen 's egg proteins at 6 months . Atopic eczema occurred in 9/171 ( 5.3 % ) children in the probiotic arm and 21/173 ( 12.1 % ) in the placebo arm ( OR 0.40 , 95 % CI 0.18 to 0.91 ) . Conclusions The study did not provide evidence that the probiotic either prevented eczema during the study or reduced its severity . However , the probiotic seemed to prevent atopic sensitisation to common food allergens and so reduce the incidence of atopic eczema in early childhood . Trial registration Number IS RCT N26287422 Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome ( AEDS ) and food allergy . In such infants we investigated effects of probiotic bacteria on faecal IgA , and on the intestinal inflammation markers tumour necrosis factor-alpha ( TNF-alpha ) , alpha1-antitrypsin ( AT ) , and eosinophil cationic protein ( ECP ) . A total of 230 infants with AEDS and suspected cow 's milk allergy ( CMA ) received in a r and omized double-blinded manner , concomitant with elimination diet , Lactobacillus GG ( LGG ) , a mixture of four probiotic strains ( MIX ) , or placebo for 4 wk . Four weeks after treatment , CMA was diagnosed with a double-blind placebo-controlled milk challenge . Faecal sample s of 102 infants , r and omly chosen for analysis , were collected before treatment , after 4-wk treatment , and on the first day of milk challenge . After treatment , IgA levels tended to be higher in probiotic groups than in the placebo group ( LGG vs. placebo , p=0.064 ; MIX vs. placebo , p=0.064 ) , and AT decreased in the LGG group , but not in other treatment groups . After challenge in IgE-associated CMA infants , faecal IgA was higher for LGG than for placebo ( p=0.014 ) , and TNF-alpha was lower for LGG than for placebo , but non-significantly ( p=0.111 ) . In conclusion , 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA The aim of this double-blind , r and omized , placebo-controlled study was to evaluate the effect of a prebiotic mixture on gastric motility in preterm newborns . After a feeding period of 15 days , gastric electrical activity was measured by electrogastrography , and the gastric emptying time was studied by ultrasound technique . No difference was seen in the daily increase of body weight , and no adverse events have been reported . The percentage of time in which propagation was detected in the electrogastrography signal was twice in newborns receiving formula with prebiotics  with respect to placebo , and the gastric half-emptying time was 30 % faster in the prebiotic group than the placebo group . Prebiotic oligosaccharides can modulate the electrical activity and the gastric emptying and may improve the intestinal tolerance of enteral feeding in preterm infants Purpose Currently , there is no consensus concerning the possible beneficial colonic and systemic effects of prebiotic-containing infant formula . This study assesses whether the feeding of a galactooligosaccharides (GOS)-containing infant formula ( 0.44 g/dl of GOS ) and the subsequent feeding of a GOS-containing follow-on formula ( 0.50 g/dl of GOS ) have a prebiotic effect on intestinal microbiota that helps to decrease infections and allergy manifestations in healthy infants during the first year of life . Methods A multicentre , r and omised , double-blind and placebo-controlled trial was carried out on 365 healthy term infants enrolled before 8 weeks of age and r and omly assigned to a formula with or without GOS , until 12 months of age . The incidence of infections and allergy manifestations , the antibiotics prescribed and faecal characteristics were recorded up to 12 months of age , while faecal sample s were collected up to 4 months for the measurement of secretory immunoglobulin A , short-chain fatty acids and microbiota . Results A prebiotic effect on the faecal analysis was observed at 4 months of life . The GOS group showed a lower faecal pH ( P = 0.019 ) , a lower decreasing trend in secretory immunoglobulin A ( P = 0.078 ) , lower butyric acid concentration ( P = 0.040 ) and an increase in Bifidobacterium counts ( P = 0.010 ) . Changes in faecal characteristics involved greater frequency ( P < 0.001 ) and softer consistency ( P < 0.05 ) . The incidence of infections or allergic manifestations during the first year of life was similar in both groups , with no statistical differences ( P > 0.05 ) . Conclusions The feeding of GOS-containing infant formula produced a definite prebiotic effect consisting of changes in faecal composition and microbiota , and in faecal consistency and the frequency of defaecation . No changes in the incidence of infection or allergic manifestation during the first year of life were observed BACKGROUND AND OBJECTIVE : Relative deficiency of dietary omega 3 polyunsaturated fatty acids ( n-3 PUFA ) has been implicated in the rising allergy prevalence in Westernized countries . Fish oil supplementation may provide an intervention strategy for primary allergy prevention . The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease . METHODS : In a double-blind r and omized controlled trial , 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control ( olive oil ) , from birth to age 6 months . PUFA levels were measured in 6-month-old infants ’ erythrocytes and plasma and their mothers ’ breast milk . Eczema , food allergy , asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age . RESULTS : At 6 months of age , infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher ( both P < .05 ) and erythrocyte arachidonic acid levels were lower ( P = .003 ) in the fish oil group . Although n-3 PUFA levels at 6 months were associated with lower risk of eczema ( P = .033 ) and recurrent wheeze ( P = .027 ) , the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes . Specifically , between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization , eczema , asthma , or food allergy . CONCLUSIONS : Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease Background : Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome ( AEDS ) in food‐allergic infants . We aim ed to investigate whether probiotic bacteria have any beneficial effect on AEDS 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
Differences were potentially attributable to differences in infant risk , prebiotic formulation or measurement of eczema .
There is insufficient evidence to determine the role of prebiotic supplementation of infant formula for prevention of allergic disease and food hypersensitivity .
Further trials are needed to determine whether this finding persists over a longer period of time , applies to other manifestations of allergic disease , is associated with reductions in allergen sensitisation , and is reproducible
BACKGROUND The composition of the intestinal microflora may be different in individuals with atopic eczema from those without this condition , and such differences may precede the development of eczema .
Prebiotics are nondigestible food components that benefit the host by selectively stimulating the growth or activity of non-pathogenic bacteria in the colon .
Prebiotics ( commonly oligosaccharides ) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens .
OBJECTIVES To determine the effect of prebiotics given to infants for the prevention of allergic disease or food hypersensitivity .