title: Effect of a whey-predominant starter formula containing LCPUFAs and oligosaccharides (FOS/GOS) on gastrointestinal comfort in infants. Effect of Neutral and Acidic Oligosaccharides on Fecal IL-8 and Fecal Calprotectin in Preterm Infants Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial. Quantitative Real-Time PCR Assays To Identify and Quantify Fecal Bifidobacterium Species in Infants Receiving a Prebiotic Infant Formula The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants. Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study. Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial. Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. 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. Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial. New Prebiotic Blend of Polydextrose and Galacto-oligosaccharides Has a Bifidogenic Effect in Young Infants “Minor” feeding problems during the first months of life: effect of a partially hydrolysed milk formula containing fructo‐ and galacto‐oligosaccharides Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial. The clinical effect of a new infant formula in term infants with constipation: a double-blind, randomized cross-over trial A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age Tolerance and Safety Evaluation in a Large Cohort of Healthy Infants Fed an Innovative Prebiotic Formula: A Randomized Controlled Trial Dosage-Related Bifidogenic Effects of Galacto- and Fructooligosaccharides in Formula-Fed Term Infants Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with IgE sensitization. Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study Acidic Oligosaccharides from Pectin Hydrolysate as New Component for Infant Formulae: Effect on Intestinal Flora, Stool Characteristics, and pH A Specific Prebiotic Mixture Added to Starting Infant Formula Has Long-Lasting Bifidogenic Effects123 Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583] Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. Prebiotic Effect Of Fructo-Oligosaccharide Supplemented Term Infant Formula at Two Concentrations Compared with Unsupplemented Formula and Human Milk Colon Microflora in Infants Fed Formula with Galacto- and Fructo-Oligosaccharides: More Like Breast-Fed Infants Prediction of allergy from family history and cord blood IgE levels. A follow-up at the age of 5 years. Cord blood IgE. IV. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. Allergy development and the intestinal microflora during the first year of life. Cytokine Responses in Very Low Birth Weight Infants Receiving Glutamine-enriched Enteral Nutrition The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Non-digestible oligosaccharides reduce immunoglobulin free light-chain concentrations in infants at risk for allergy. Pro- and Prebiotic Supplementation Induces a Transient Reduction in Hemoglobin Concentration in Infants Effects of probiotic and prebiotic on gastrointestinal motility in newborns. A Randomized, Double-Blind, Controlled Trial of the Effect of Prebiotic Oligosaccharides on Enteral Tolerance in Preterm Infants (ISRCTN77444690) Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Effect of probiotics on vaccine antibody responses in infancy--a randomized placebo-controlled double-blind trial. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. [Randomised placebo controlled double blind study on the effect of prebiotic oligosaccharides on intestinal flora in healthy infants]. Reduction of crying episodes owing to infantile colic: a randomized controlled study on the efficacy of a new infant formula Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Randomized Double-Blind Study of the Nutritional Efficacy and Bifidogenicity of a New Infant Formula Containing Partially Hydrolyzed Protein, a High &bgr;-Palmitic Acid Level, and Nondigestible Oligosaccharides Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics. Physiological and Bifidogenic Effects of Prebiotic Supplements in Infant Formulae Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Galacto-oligosaccharides Are Bifidogenic and Safe at Weaning: A Double-blind Randomized Multicenter Study High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Dietary Nucleotides and Early Growth in Formula-Fed Infants: A Randomized Controlled Trial Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. The effect of a prebiotic supplemented formula on growth and stool microbiology of term infants. Bifidogenic Effects of Solid Weaning Foods With Added Prebiotic Oligosaccharides: A Randomised Controlled Clinical Trial Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition Exploration of basal immune parameters in healthy infants receiving an infant milk formula supplemented with prebiotics. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: a randomized controlled trial. Prebiotics Improve Gastric Motility and Gastric Electrical Activity in Preterm Newborns Effects of a new mixture of prebiotics on faecal flora and stools in term infants Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast-fed Infants Oligosaccharides might stimulate calcium absorption in formula‐fed preterm infants Long-term Colonization of a Lactobacillus plantarum Synbiotic Preparation in the Neonatal Gut Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. A Randomized Placebo-controlled Comparison of 2 Prebiotic/Probiotic Combinations in Preterm Infants: Impact on Weight Gain, Intestinal Microbiota, and Fecal Short-chain Fatty Acids Effects on Faecal Microbiota of Dietary and Acidic Oligosaccharides in Children During Partial Formula Feeding A Randomized Controlled Trial of Enteral Glutamine Supplementation in Very Low Birth Weight Infants: Plasma Amino Acid Concentrations Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial The effect of glutamine-enriched enteral nutrition on intestinal microflora in very low birth weight infants: a randomized controlled trial. Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age. The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study. Effect of prebiotic galacto-oligosaccharide, long-chain fructo-oligosaccharide infant formula on serum cholesterol and triacylglycerol levels. 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.
abstract: Development of new infant formulas aims to replicate the benefits of breast milk . One benefit of breast milk over infant formulas is greater gastrointestinal comfort . We compared indicators of gastrointestinal comfort in infants fed a whey-predominant formula containing long-chain polyunsaturated fatty acids , galacto-oligo-saccharides and fructo-oligosaccharides , and infants fed a control casein-predominant formula without additional ingredients . The single-centre , prospect i ve , double-blind , controlled trial r and omly assigned healthy , full-term infants ( n=144 ) to receive exclusively either experimental or control formula from 30 days to 4 months of age . A group of exclusively breast-fed infants served as reference ( n=80 ) . At 1 , 2 , 3 , and 4 months , infants ' growth parameters were measured and their health assessed . Parents recorded frequency and physical characteristics of infants ' stool , frequency of regurgitation , vomiting , crying and colic . At 2-months , gastric emptying ( ultrasound ) and intestinal transit time ( H2 breath test ) were measured , and stool sample s collected for bacterial analysis . Compared to the control ( n=69 ) , fewer of the experimental group ( n=67 ) had hard stools ( 0.7 vs 7.5 % , p<0.001 ) and more had soft stools ( 90.8 vs 82.3 % , p<0.05 ) . Also compared to the control , the experimental group 's stool microbiota composition ( mean % bifidobacteria : 78.1 ( experimental , n=17 ) , 63.7 ( control , n=16 ) , 74.3 ( breast-fed , n=20 ) , gastric transit times ( 59.6 ( experimental , n=53 ) , 61.4 ( control , n=62 ) , 55.9 ( breast-fed , n=67 ) minutes ) and intestinal transit times ( data not shown ) were closer to that of the breast-fed group . Growth parameter values were similar for all groups . The data suggest that , in infants , the prebiotic-containing whey-based formula provides superior gastrointestinal comfort than a control formula The gastrointestinal inflammatory response may play a role in the susceptibility of preterm infants for infections . We previously reported a trend toward lower endogenous infection morbidity after enteral supplementation of neutral and acidic oligosaccharides ( SCGOS/LCFOS/AOS ) . We hypothesize that enteral supplementation of prebiotics may decrease infectious morbidity by reducing intestinal inflammation . Therefore , we aim ed to determine the effect of enteral supplementation of prebiotics on intestinal inflammation , as measured by fecal IL-8 ( f-IL-8 ) and calprotectin ( f-calprotectin ) , in preterm infants . In a r and omized controlled trial , infants with a GA < 32 wk and /or birth weight < 1,500 g received enteral supplementation of prebiotics or placebo ( maltodextrin ) between d 3 and 30 of life . F-IL-8 and f-calprotectin was assessed at baseline , d 7 , 14 , and 30 of life . In total , 113 infants were included . Baseline patient and nutritional characteristics were not different in the SCGOS/LCFOS/AOS ( n = 55 ) and the placebo group ( n = 58 ) . Enteral supplementation of prebiotics had no effect on f-IL-8 and f-calprotectin . F-IL-8 and f-calprotectin were strongly correlated at all time points ( p < 0.001 ) . In conclusion , enteral supplementation of prebiotics ( SCGOS/LCFOS/AOS ) does not affect f-IL-8 and f-calprotectin levels in preterm infants The addition of probiotics to infant formula has been shown to be an efficient way to increase the number of beneficial bacteria in the intestine in order to promote a gut flora resembling that of breast-fed infants . The objective of the present study was to evaluate the safety and tolerance of a combination of two probiotic strains in early infancy . A group of 126 newborns were r and omised to receive a prebiotic-containing starter formula supplemented with Lactobacillus paracasei ssp . paracasei and Bifidobacterium animalis ssp . lactis or the same formula without probiotics for the first 3 months of life . A total of eighty infants continued the study until they were aged 6 months .  Growth measurements were taken monthly at healthy baby clinics . Diaries were used to monitor behaviour , infections , use of antibiotics , as well as stool characteristics . Normal growth occurred in all infants and no statistically significant differences were detected between the probiotics group and the control group for gain in weight , length and head circumference . Infants in the probiotics group produced softer and more frequent stools during the first 3 months of life . No differences were found in crying and sleeping hours , number of parent-diagnosed infections , antibiotic use , visits to the general practitioner and number of adverse events . The use of a prebiotic-containing starter formula supplemented with L. paracasei ssp . paracasei and B. animalis ssp . lactis in early infancy is safe , well tolerated and has no adverse effects on growth and infant behaviour ABSTRACT A healthy intestinal microbiota is considered to be important for priming of the infants ' mucosal and systemic immunity . Breast-fed infants typically have an intestinal microbiota dominated by different Bifidobacterium species . It has been described that allergic infants have different levels of specific Bifidobacterium species than healthy infants . For the accurate quantification of Bifidobacterium adolescentis , Bifidobacterium angulatum , Bifidobacterium bifidum , Bifidobacterium breve , Bifidobacterium catenulatum , Bifidobacterium dentium , Bifidobacterium infantis , and Bifidobacterium longum in fecal sample s , duplex 5′ nuclease assays were developed . The assays , targeting rRNA gene intergenic spacer regions , were vali date d and compared with conventional PCR and fluorescent in situ hybridization methods . The 5′ nuclease assays were subsequently used to determine the relative amounts of different Bifidobacterium species in fecal sample s from infants receiving a st and ard formula or a st and ard formula supplemented with galacto- and fructo-oligosaccharides ( OSF ) . A breast-fed group was studied in parallel as a reference . The results showed a significant increase in the total amount of fecal bifidobacteria ( 54.8 % ± 9.8 % to 73.4 % ± 4.0 % ) in infants receiving the prebiotic formula ( OSF ) , with a diversity of Bifidobacterium species similar to breast-fed infants . The intestinal microbiota of infants who received a st and ard formula seems to resemble a more adult-like distribution of bifidobacteria and contains relatively more B. catenulatum and B. adolescentis ( 2.71 % ± 1.92 % and 8.11 % ± 4.12 % , respectively , versus 0.15 % ± 0.11 % and 1.38 % ± 0.98 % for the OSF group ) . In conclusion , the specific prebiotic infant formula used induces a fecal microbiota that closely resembles the microbiota of breast-fed infants also at the level of the different Bifidobacterium species 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 Galactooligosaccharides ( GOS ) and long-chain fructooligosaccharides ( lcFOS ) proliferate bifidobacteria in infant gut microbiota . However , it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring . OBJECTIVES We aim ed to test how supplementation with GOS and lcFOS ( GOS/lcFOS ) in the last trimester of pregnancy affects maternal and neonatal gut microbiota . Variables of fetal immunity were assessed as a secondary outcome . DESIGN In a r and omized , double-blind , placebo-controlled pilot study , 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS ( at a ratio of 9:1 ) or maltodextrin ( placebo ) from week 25 of gestation until delivery . Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal ( days 5 , 20 , and approximately 182 ) stool sample s. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis . RESULTS The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group ( 21.0 % and 12.4 % , respectively ; P = 0.026 ) ; the proportion of lactobacilli did not differ between the groups . In neonates , bifidobacteria and lactobacilli percentages , diversity and similarity indexes , and fetal immune parameters did not differ significantly between the 2 groups . Mother-neonate similarity indexes of bifidobacteria decreased over time . CONCLUSIONS GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates . The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables BACKGROUND Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression .  Very-low-birth-weight ( VLBW ) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life . OBJECTIVE The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance , infectious morbidity , and short-term outcome in VLBW infants . DESIGN In a double-blind r and omized controlled trial , VLBW infants ( gestational age < 32 wk or birth weight < 1500 g ) were allocated to receive enteral glutamine supplementation ( 0.3 g . kg(-1 ) . d(-1 ) ) or isonitrogenous control supplementation ( alanine ) between days 3 and 30 of life . The supplementations were added to breast milk or to preterm formula . The primary endpoint for the study was time to full enteral feeding . Secondary endpoints were other variables of feeding tolerance , infectious morbidity , and short-term outcome . RESULTS Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented ( n = 52 ) and the control ( n = 50 ) groups . The median time to full enteral feeding was 13 d ( range : 7 - 31 d ) in the glutamine-supplemented group and 13 d ( range : 6 - 35 d ) in the control group ( hazard ratio : 1.19 ; 95 % CI : 0.79 , 1.79 ; P = 0.40 ) . In the glutamine-supplemented group , 26 of 52 infants ( 50 % ) had > /=1 serious infection compared with 38 of 50 ( 76 % ) in the control group ( odds ratio : 0.32 ; 95 % CI : 0.14 , 0.74 ; P = 0.008 ) . Other variables of feeding tolerance and short-term outcome were not significantly different between groups . CONCLUSIONS Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants . However , infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition In this double-blind , r and omized , placebo-controlled study , we investigated the effect of an infant milk formula with 6 g/L short-chain galacto- and long-chain fructo-oligosaccharides [ ( scGOS/lcFOS ) ratio 9:1 ] on the development of the fecal secretory immunoglobulin A ( sIgA ) response and on the composition of the intestinal microbiota in 215 healthy infants during the first 26 wk of life . The infants received breast milk or were r and omized to receive an infant milk formula with or without scGOS/lcFOS . Stool sample s were collected after 8 and 26 wk of intervention . The concentration of fecal sIgA was determined by ELISA , and the composition of the intestinal microbiota was determined by quantitative fluorescent in situ hybridization . The scGOS/lcFOS group and the control group were compared in the statistical analysis . A breast fed group was included as a reference . In total , 187 infants completed the study . After 26 wk of intervention , in infants that were exclusively formula fed , the concentration of sIgA was higher ( P < 0.001 ) in the scGOS/lcFOS group ( 719 microg/g ) than in the control group ( 263 microg/g ) . In addition , the percentages of bifidobacteria were higher in the scGOS/lcFOS group ( 60.4 % ) than in the control group ( 52.6 % , P = 0.04 ) . The percentages of Clostridium spp . were 0.0 and 3.27 % , respectively ( P = 0.006 ) . In conclusion , an infant milk formula with 6 g/L scGOS/lcFOS results in higher concentrations of fecal sIgA , suggesting a positive effect on mucosal immunity BACKGROUND Dietary nucleotides are nonprotein nitrogenous compounds that are thought to be important for growth , repair , and differentiation of the gastrointestinal tract . A higher nucleotide intake may also have favorable effects on the fecal microbial composition and incidence of diarrhea in infancy . However , few studies have tested this hypothesis with an experimental study design . OBJECTIVE We tested the hypothesis that nucleotide supplementation of infant formula has beneficial effects on fecal bacteriology . DESIGN Oligonucleotide probes were used to measure bacterial genus-specific 16S ribosomal RNA in stools of a subset of infants ( mean age : 20.4 wk ) who were r and omly assigned to nucleotide-supplemented ( 31 mg/L ; n = 35 ) or control formula ( n = 37 ) from birth until age 20 wk or were breastfed ( reference group ; n = 44 ) . The microbial pattern was assessed as the ratio of Bacteroides-Porphyromonas-Prevotella group ( BPP ) to Bifidobacterium species . RESULTS The ratio of BPP to Bifidobacterium spp . rRNA in infants r and omly assigned to the nucleotide-supplemented formula was lower than in infants receiving the control formula ( mean difference : -118 % ; 95 % CI : -203 % , -34 % ; P = 0.007 ) , but it did not differ in infants who were breastfed . The difference between r and omized formula-fed groups was independent of potential confounding factors ( P = 0.003 ) . CONCLUSIONS Our data support the hypothesis that nucleotide supplementation improves the composition of the gut microbiota in formula-fed infants . Because this effect could contribute to previously described benefits of nucleotide supplementation for gastrointestinal tract and immune function , these findings have important implication s for optimizing the diet of formula-fed infants A mixture of neutral short chain galactooligosaccharides and long chain fructo-oligosaccharides ( scGOS/lcFOS ) has been shown to have prebiotic and immunomodulatory effects comparable to human milk oligosaccharides . This can be translated into clinical practice as a potential to prevent infections and allergy . The hypothesis of this study was that this specific prebiotic mixture could have a preventive effect against infections during the first 6 mo of life . In a prospect i ve , r and omized , double-blind , placebo-controlled trial , healthy term infants with a parental history of atopy were fed either prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . The primary outcome measures were infectious episodes , number of infections requiring antibiotics , and incidence of infections . During the study period , infants in the scGOS/lcFOS group had fewer episodes of all types of infections combined ( P = 0.01 ) . They also tended to have fewer upper respiratory tract infection episodes ( P = 0.07 ) and fewer infections requiring antibiotic treatment ( P = 0.10 ) . Similarly , the cumulative incidence of recurring infections was significantly lower in the scGOS/lcFOS group . The cumulative incidence of any recurring infection and recurring respiratory infections was 3.9 and 2.9 % in the scGOS/lcFOS group and 13.5 and 9.6 % in the placebo group , respectively ( P < 0.05 ) . Oligosaccharide prebiotics reduced the number of infectious episodes and the incidence of recurring , particularly respiratory , infections during the first 6 mo of life . Although the exact mechanism of action is under investigation , it is very likely that the immune modulating effect of this prebiotic mixture through intestinal flora modification is the principal mechanism for the observed infection prevention early in life BACKGROUND Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants . OBJECTIVE The objective was to evaluate infant formulas containing probiotics and synbiotics ( combinations of probiotics and prebiotics ) for safety and tolerance . DESIGN In a prospect i ve , controlled , double-blind , r and omized trial , healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 ( BL999 ) + Lactobacillus rhamnosus LPR ( LPR ) , BL999 + LPR + 4 g/L of 90 % galactooligosaccharide/10 % short-chain fructooligosaccharide ( GOS/SCFOS ) , or BL999 + Lactobacillus paracasei ST11 ( ST11 ) + 4 g/L GOS/SCFOS from < or = 2 to 16 wk of age ( treatment period ) . Safety and tolerance were assessed based on weight gain during the treatment period ( primary outcome ) as well as recumbent length , head circumference , digestive tolerance , and adverse events ( secondary outcomes ) , which were evaluated at 2 , 4 , 8 , 12 , 16 , and 52 wk of age . RESULTS Two hundred eighty-four infants were enrolled . During the treatment period , difference in mean weight gain between control and study formula groups in both the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d , indicating equivalent weight gain . Secondary outcomes did not show significant differences between groups during the treatment period . CONCLUSION Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well A 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 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 BACKGROUND Serious infectious morbidity is high in preterm infants .  Enteral supplementation of prebiotics may reduce the incidence of serious infections , especially infections related to the gastrointestinal tract . OBJECTIVE The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( (SC)GOS/(LC)FOS ) and acidic oligosaccharides ( AOS ) on serious infectious morbidity in preterm infants . DESIGN In a r and omized controlled trial , preterm infants ( gestational age < 32 wk and /or birth weight < 1500 g ) received enteral supplementation of 80 % (SC)GOS/(LC)FOS and 20 % AOS ( 1.5 g . kg(-1 ) . d(-1 ) ) or placebo ( maltodextrin ) between days 3 and 30 of life . Serious infectious morbidity was defined as a culture positive for sepsis , meningitis , pyelonephritis , or pneumonia . The analysis was performed by intention-to-treat and per- protocol , defined as > or = 50 % supplementation dose during the study period . RESULTS In total , 113 preterm infants were included . Baseline and nutritional characteristics were not different between groups . In the intention-to-treat analysis , the incidence of > or = 1 serious infection , > or = 1 serious endogenous infection , or > or = 2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups . In the per- protocol analysis , there was a trend toward a lower incidence of > or = 1 serious endogenous infection and > or = 2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group ( P = 0.09 and P = 0.07 , respectively ) . CONCLUSIONS Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants . However , there was a trend toward a lower incidence of serious infectious morbidity , especially for infections with endogenous bacteria . This finding suggests a possible beneficial effect that should be evaluated in a larger study . This trial was registered at is rct n.org as IS RCT N16211826 Objective : The aim of the study was to evaluate the effect of infant formula with polydextrose ( PDX ) and galacto-oligosaccharides ( GOS )  on fecal microbiota and secretory IgA ( sIgA ) . Material s and Methods : In the present double-blind , r and omized study , term infants received control ( Enfamil Lipil ) or the same formula with PDX/GOS ( 4 g/L , 1:1 ratio ; PDX/GOS ) for 60 days ; a reference breast-fed group was included . Formula intake , tolerance , and stool characteristics were collected via electronic diary and analyzed by repeated measures analysis of variance . Anthropometric measurements and stool sample s were obtained at baseline and after 30 and 60 days of feeding . Fecal sIgA was measured by enzyme-linked immunosorbent assay and fecal bacteria by fluorescent in situ hybridization and quantitative real-time polymerase chain reaction ( qPCR ) ; both were analyzed by Wilcoxon rank sum test . Results : Two hundred thirty infants completed the study . Infants consuming PDX/GOS had softer stools than control at all times ( P < 0.001 ) . Using qPCR , counts in PDX/GOS were closer to the breast-fed group , tended to be higher than control for total bifidobacteria ( P = 0.069 ) and Bifidobacterium longum ( P = 0.057 ) at 30 days , and were significantly higher for total bifidobacteria and B longum at 60 days and B infantis at 30 days ( P = 0.002 ) . No significant differences were detected between PDX/GOS and control in changes from baseline to 30 or 60 days for sIgA or total bifidobacteria by fluorescent in situ hybridization or qPCR ; however , significantly higher changes from baseline were detected between PDX/GOS and control for B infantis at 30 days and B longum at 60 days ( P ⩽ 0.035 ) . Conclusions : Infant formula with PDX/GOS produces soft stools and a bifidogenic effect closer to breast milk than formula without PDX/GOS Background : Colic , regurgitation and constipation are common feeding problems in formula‐fed infants that might benefit from dietary treatment . A formula containing fructo‐ and galacto‐oligosaccharides , partially hydrolysed proteins , low levels of lactose and palmitic acid in the β position and higher density has been tested to reduce the occurrence of these symptoms . The aim of this prospect i ve study was to describe the effects of such a formula in infants with minor gastrointestinal disorders . Methods : An observational prospect i ve trial involving practising Italian paediatricians was performed .  Formula fed‐infants up to 90 d of age with minor gastrointestinal problems such as infantile colics and /or regurgitation and /or constipation were enrolled in the study from January 2001 to May 2001 . The study was completed within 14 d of treatment . On days 1 , 7 and 14 the infants were visited by the paediatricians . Parents were given a structured diary to record daily episodes of colic , regurgitation and type and number of stools . Results : Of the 932 infants enrolled , 604 completed the study . Of the 214 infants with colic , 169 ( 79 % ) demonstrated a reduction in frequency of colic from 4.1 ± 2.0 per day at the beginning of the study to 2.0 ± 1.8 at the end of the study ( I.C. 95 % : 1.72–2.39 ; p < 0.005 ) . A reduction in the number of episodes of colic of 1.8 per day at the beginning of the study ( I.C. 95 % : 1.49–2.11 ; p < 0.05 ) was recorded between day 1 and day 7 , and of 0.26 ( I.C. 95 % : 0.15–0.37 ; p < 0.05 ) between day 7 and day 14 . Of the 201 infants with regurgitation problems , 141 ( 70 % ) demonstrated a reduction of frequency of the symptoms from 4.2 ± 2.0 per day at the beginningof the study to 2.1 ± 2.2 at the end of the study ( I.C. 95 % : 1.75–2.35 ; p < 0.005 ) . A reduction of 1.87 in the number of regurgitation episodes was reported between day 1 and day 7 ( I.C. 95 % : 1.57–2.16 ; p < 0.05 ) and of 0.18 ( I.C. 95 % : 0.06–0.31 ; p < 0.05 ) between day 7 and day 14 . Of the 232 infants with constipation , 147 ( 63 % ) demonstrated an increase in the daily number of stools of 0.42 ( I.C. 95 % : 0.5–0.3 ; p < 0.005 ) . An increase in stool frequency of 0.41 ( I.C. 95 % : 0.51–0.23 ; p < 0.05 ) was reported between day 1 and day 7 , and of 0.04 ( I.C. 95 % : 0.22–0.14 ; p= ns ) between day 7 and day 14 . Parents’evaluation of the formula was 7.9 ± 1.8 ( score 0–10 ) ; 550 parents ( 91 % ) gave a positive judgement ( score > 6 ) . The evaluation by the paediatricians of the improvement in symptoms after the treatment was 8.2 ± 1.5 ; 574 ( 95 % ) a positive effect ( score > 6 ) 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 Nutrilon Omneo ( new formula ; NF ) contains high concentration of sn-2 palmitic acid , a mixture of prebiotic oligosaccharides and partially hydrolyzed whey protein . It is hypothesized that NF positively affects stool characteristics in constipated infants . Methods Thirty-eight constipated infants , aged 3–20 weeks , were included and r and omized to NF ( n = 20 ) or a st and ard formula ( SF ; n = 18 ) in period 1 and crossed-over after 3 weeks to treatment period 2 . Constipation was defined by at least one of the following symptoms : 1 ) defecation frequency < 3/week ; 2 ) painful defecation ; 3 ) abdominal or rectal palpable mass . Results Period 1 was completed by 35 infants . A significant increase in defecation frequency ( NF : 3.5 pre versus 5.6/week post treatment ; SF 3.6 pre versus 4.9/week post treatment ) was found in both groups , but was not significantly different between the two formulas ( p = 0.36 ) . Improvement of hard stool consistency to soft stool consistency was found more often with NF than SF , but did not reach statistical significance ( 90 % versus 50 % ; RR , 1.8 ; 95 % CI , 0.9–3.5 ; p = 0.14 ) . No difference was found in painful defecation or the presence of an abdominal or rectal mass between the two groups . Twenty-four infants completed period 2 . Only stool consistency was significantly different between the two formulas ( 17 % had soft stools on NF and hard stools on SF ; no infants had soft stools on SF and hard stools on NF , McNemar test p = 0.046 ) . Conclusion The addition of a high concentration sn-2 palmitic acid , prebiotic oligosaccharides and partially hydrolyzed whey protein result ed in a strong tendency of softer stools in constipated infants , but not in a difference in defecation frequency . Formula transition to NF may be considered as treatment in constipated infants with hard stools 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 the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk . The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy . Methodology /Principal Findings this study was performed as a multi-center , r and omized , double-blind , placebo-controlled trial including healthy term infants . Infants were recruited before the age of 8 weeks , either having started with formula feeding or being fully breast-fed ( breastfeeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . Growth , tolerance and adverse events were assessed at 8 , 16 , 24 and 52 weeks of age . The prebiotic and control groups showed similar mean weight , length and head circumference , skin fold thicknesses , arm circumference gains and stool frequency at each study point . As far as the anthropometric parameters are concerned , the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point . The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants , whereas at 52 weeks were strikingly smaller . The stool consistency in the prebiotic group was softer than in the control group at 8 , 16 and 24 weeks ( p<0.001 ) and closer to that of the breastfeeding group . There was no difference in the incidence of adverse events between the two formula groups . Conclusions our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants . Trial Registration : drks-neu.uniklinik-freiburg.de DRKS Background Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine . In this study , the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low-molecular-weight galactooligosaccharides and high-molecular-weight fructooligosaccharides was analyzed in 90 term infants . Methods Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides . In the control formula , maltodextrin was used as placebo . At study day 1 and study day 28 , the fecal species , colony forming units ( cfu ) and pH were measured and stool characteristics , growth , and side effects were recorded . Results At study day 1 , the median number of Bifidobacteria did not differ among the groups ( 0.4 g/dL group , mean [ interquartile range ] 8.5 [ 1.9 ] cfu/g ; 0.8 g/dL group , 7.7 [ 6.1 ] cfu/g ; and the placebo group , 8.8 [ 6.1 ] cfu/g ) ( figures in square brackets are interquartile range ) . At the end of the 28-day feeding period , the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas ( the 0.4 g/dL group , 9.3 [ 4.9 ] cfu/g ; the 0.8 g/dL group , 9.7 [ 0.8 ] cfu/g ) versus the placebo group ( 7.2 [ 4.9 ] cfu/g , P < 0.001 ) . This effect was dose dependent ( 0.4 g/dL versus 0.8 g/dL , P < 0.01 ) . The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas ( versus placebo , P < 0.001 ) , but there was no statistically significant difference between the group fed formula with 0.4 g/dL oligosaccharides and the group fed formula with 0.8 g/dL oligosaccharides . The dosage of supplement significantly influenced the change in fecal pH ( P < 0.05 ) ( placebo , pH 5.5–6.1 ; 0.4 g/dL formula , pH 5.48–5.44 ; 0.8 g/dL formula , pH 5.54–5.19 ) . Slight changes in the stool frequency result ed in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 ( P < 0.01 ) . Supplementation had a significant dose-dependent influence on stool consistency ( 0.8 g/dL versus placebo , P < 0.0001 ; 0.8 g/dL versus 0.4 g/dL , P < 0.01 ) . Supplementation had no influence on the incidence of side effects ( crying , regurgitation , vomiting ) or growth . Conclusions These data indicate that supplementation of a term infant 's formula with a mixture of galacto- and fructooligosaccharides has a dose-dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation CONTEXT Sepsis is a common and severe complication in premature neonates , particularly those with very low birth weight ( VLBW ) ( < 1500 g ) . Whether lactoferrin , a mammalian milk glycoprotein involved in innate immune host defenses , can reduce the incidence of sepsis is unknown . In animal models , the probiotic Lactobacillus rhamnosus GG ( LGG ) enhances the activity of lactoferrin but has not been studied in human infants . OBJECTIVE To establish whether bovine lactoferrin ( BLF ) , alone or in combination with LGG , reduces the incidence of late-onset sepsis in VLBW neonates . DESIGN , SETTING , AND PATIENTS Prospect i ve , multicenter , double-blind , placebo-controlled , r and omized trial conducted in 11 Italian tertiary neonatal intensive care units . Patients were 472 VLBW infants enrolled from October 1 , 2007 , through July 31 , 2008 , and assessed until discharge for development of sepsis . INTERVENTION Infants were r and omly assigned to receive orally administered BLF ( 100 mg/d ) alone ( n = 153 ) , BLF plus LGG ( 6 x 10(9 ) colony-forming units/d ) ( n = 151 ) , or placebo ( n = 168 ) from birth until day 30 of life ( day 45 for neonates < 1000 g at birth ) . MAIN OUTCOME MEASURE First episode of late-onset sepsis , ie , sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid . RESULTS Demographic , clinical , and management characteristics of the 3 groups were similar , including type of feeding and intake of maternal milk . Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups ( 9/153 [ 5.9 % ] and 7/151 [ 4.6 % ] , respectively ) than in the control group receiving placebo ( 29/168 [ 17.3 % ] ) ( risk ratio , 0.34 ; 95 % confidence interval , 0.17 - 0.70 ; P = .002 for BLF vs control and risk ratio , 0.27 ; 95 % confidence interval , 0.12 - 0.60 ; P < .001 for BLF plus LGG vs control ) . The decrease occurred for both bacterial and fungal sepsis . No adverse effects or intolerances to treatment occurred . CONCLUSION Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53107700 Risk of allergic diseases has been linked to abnormal patterns of fetal immune development , suggesting that priming of the immune system may occur in utero . The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells ( C BMC ) shows association with allergic diseases and IgE sensitization at 2 yr of age , and to study the effect of maternal probiotic supplementation on C BMC immune responses . C BMC were isolated from 98 neonates in a r and omized double-blinded intervention study . C BMC were stimulated with beta-lactoglobulin , and phytohemaglutinin ( PHA ) .  Secretion of interferon-gamma ( IFN-gamma ) , interleukin-5 ( IL-5 ) , and IL-13 was measured by an ELISA ; IL-2 , IL-4 , and IL-10 by a cytokine bead assay . T-cell polarization-associated IL-4 receptor and IL-12R expressions , and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR . The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age , and with the maternal probiotic or placebo supplementation .  PHA-stimulated GATA-3 expression and IL-2 secretion in C BMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized , non-allergic children ( p = 0.03 and 0.026 ) . PHA-induced expression of GATA-3 correlated with IL-5 ( p = 0.003 , r = 0.300 ) and IL-13 ( p = 0.007 , r = 0.278 ) secretion of C BMC , and IL-5 secretion of beta-lactoglobulin-stimulated C BMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized , non-allergic children ( p = 0.013 ) . Probiotic  bacteria had no effect on C BMC immune responses . In C BMC -enhanced induction of GATA-3 , which activates several Th2 cytokines genes , was a risk factor for IgE sensitization . The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens 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 Objectives : To come even closer to the functional composition of human milk , acidic oligosaccharides ( AOS ) from pectin were added to well known neutral prebiotics ( galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( FOS ) ) . The effect of AOS and GOS/FOS/AOS on intestinal flora , stool characteristics as well as acceptance and tolerance was investigated . Methods : Human milk contains 75 % to 85 % neutral and 15 % to 25 % acidic oligosaccharides . In this prospect i ve , r and omized , double blind study , a mixture of 80 % neutral oligosaccharides ( from long-chain galacto- and long-chain fructo-oligosaccharides ) with 20 % acidic oligosaccharides derived from pectin hydrolysis was investigated . Forty-six term infants were fed a st and ard formula supplemented with either maltodextrin as control ( n = 15 ) , or with 0.2 g acidic oligosaccharides ( n = 16 ) , or with the latter plus 0.6 g neutral oligosaccharides ( mixture of galacto- and fructo-oligosaccharides ; n = 15 ) . Fecal flora using plating technique and pH were measured . Stool characteristics and possible side effects ( crying , vomiting , and regurgitation ) were recorded . Results : There was no difference in the bifidobacteria counts between the control and the group supplemented with acidic oligosaccharides alone ( 8.75 ± 0.50 vs. 8.58 ± 0.94 log colony forming units [CFU]/g stool ) . In infants fed the combination of acidic and neutral oligosaccharides , bifidobacteria were increased ( 9.61 ± 0.70 log CFU/g stool ; P < 0.01 ) . The same pattern was observed with lactobacilli . Stool consistency was softest in infants fed the complete oligosaccharide mixture , but also in those fed formula supplemented with acidic oligosaccharides alone , the stool consistency was significantly softer compared with the control group . Fecal pH increased in the controls , remained constant in acidic oligosaccharides alone , and decreased in the complete mixture of oligosaccharides group . Conclusion : There was no difference in growth , crying , vomiting , and regurgitation patterns between the groups . In summary , acidic oligosaccharides from pectin hydrolysate are well tolerated as ingredient in infant formulae but do not affect intestinal microecology 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 Background To ensure the suitability of an infant formula as the sole source of nutrition or provide benefits similar to outcomes in breastfed infants , advancements in formula composition are warranted as more research detailing the nutrient composition of human milk becomes available . This study was design ed to evaluate growth and tolerance in healthy infants who received one of two investigational cow ’s milk-based formulas with adjustments in carbohydrate , fat , and calcium content and supplemented with a prebiotic blend of polydextrose ( PDX ) and galactooligosaccharides ( GOS ) or GOS alone . Methods In this multi-center , double-blind , parallel- design ed , gender-stratified prospect i ve study 419 infants were r and omized and consumed either a marketed routine cow ’s milk-based infant formula ( Control ; Enfamil ® LIPIL ® , Mead Johnson Nutrition , Evansville , IN ) ( n = 142 ) or one of two investigational formulas from 14 to 120 days of age . Investigational formulas were supplemented with 4 g/L ( 1:1 ratio ) of a prebiotic blend of PDX and GOS ( PDX/GOS ; n = 139 ) or 4 g/L of GOS alone ( GOS ; n = 138 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age . Daily recall of formula intake , tolerance , and stool characteristics was collected during study weeks 1 and 2 and 24-h recall was collected at 60 , 90 , and 120 days of age . Medically-confirmed adverse events were recorded throughout the study . Results There were no group differences in growth rate from 14 to 120 days of age . Discontinuation rates were not significantly different among study groups . No differences in formula intake or infant fussiness or gassiness were observed . During study weeks 1 and 2 and at 60 days of age stool consistency ratings were higher ( i.e. softer stools ) for infants in the PDX/GOS and GOS groups versus Control and remained higher at 120 days for the PDX/GOS group ( all P < 0.05 ) . The overall incidence of medically-confirmed adverse events was similar among groups . Conclusions Investigational routine infant formulas supplemented with 4 g/L of either a prebiotic blend of PDX and GOS or GOS alone were well-tolerated and supported normal growth . Compared to infants who received the unsupplemented control formula , infants who received prebiotic supplementation experienced a softer stooling pattern similar to that reported in breastfed infants . Trial registration Clinical Trials.gov Identifier : Background Enteral feeding of very low birth weight ( VLBW ) infants is a challenge , since metabolic dem and s are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract . The amino acid glutamine plays an important role in maintaining functional integrity of the gut . In addition , glutamine is utilised at a high rate by cells of the immune system . In critically ill patients , glutamine is considered a conditionally essential amino acid . VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth . Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression . This double-blind r and omised controlled trial is design ed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance , infectious morbidity and short-term outcome in VLBW infants . Furthermore , an attempt is made to eluci date the role of glutamine in postnatal adaptation of the gut and modulation of the immune response . Methods VLBW infants ( gestational age < 32 weeks and /or birth weight < 1500 g ) are r and omly allocated to receive enteral glutamine supplementation ( 0.3 g/kg/day ) or isonitrogenous placebo supplementation between day 3 and 30 of life . Primary outcome is time to full enteral feeding ( defined as a feeding volume ≥ 120 mL/kg/day ) . Furthermore , incidence of serious infections and short-term outcome are evaluated . The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora . The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation 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 AIM To investigate the effect of a new infant formula supplemented with a low level ( 0.24 g/100 mL ) of galacto-oligosaccharide ( GOS ) on intestinal micro-flora ( Bifidobacteria , Lactobacilli and E. coli ) and fermentation characteristics in term infants , compared with human milk and a st and ard infant formula without GOS . METHODS Term infants ( n = 371 ) were approached in this study in three hospitals of China . All infants started breast-feeding . Those who changed to formula-feeding within 4 wk after birth were r and omly assigned to one of the two formula groups . Growth and stool characteristics , and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period . Fecal sample s were collected from a sub population of recruited infants for analysis of intestinal bacteria ( culture technique ) , acetic acid ( gas chromatography ) and pH ( indicator strip ) . RESULTS After 3 mo , the intestinal Bifidobacteria , Lactobacilli , acetic acid and stool frequency were significantly increased , and fecal pH was decreased in infants fed with the GOS-formula or human milk , compared with those fed with the formula without GOS . No significant differences were observed between the GOS formula and human milk groups . Supplementation with GOS did not influence the incidence of crying , regurgitation and vomiting . CONCLUSION A low level of GOS ( 0.24 g/100 mL ) in infant formula can improve stool frequency , decrease fecal pH , and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk 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 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 Screening of total IgE in 1189 cord blood sample s was conducted by Phadebas IgE PRIST  in a one-year birth cohort 1983 - 1984 in Viborg , Denmark . 113 children with cord blood IgE levels > or = 0.5 kU/l and 138 children chosen at r and om among those with cord blood IgE levels < 0.5 kU/l were seen at a follow-up at 5 years of age . Based upon history and physical examination a diagnosis of definite atopy or no atopy was established . Allergy ( IgE mediated ) was defined as atopic disease combined with increased total IgE levels at 5 years of age . The cumulative prevalence of atopic disease was not influenced by cord blood IgE levels or atopic predisposition . Cord blood IgE levels had a low sensitivity as a predictor of atopic disease . A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found ( p < 0.001 ) , and a significantly greater number of children with elevated cord blood IgE levels developed allergic disease before 5 years of age ( p < 0.01 ) . A cut-off limit of 0.3 kU/l was superior to the originally suggested limit of 0.5 kU/l . A total IgE level > 63 kU/l ( geometric mean + 1 SD ) at the age of 5 years can be regarded as being an elevated level . A cord blood IgE level > or = 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease , especially allergic bronchial asthma . With regard to allergic disease , the positive predictive value was 26 % , the sensitivity 33 % and the rate ratio for development of allergic disease 4 . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Prebiotic-containing infant formula may beneficially affect gastrointestinal tolerance and commensal microbiota composition . OBJECTIVE Assess gastrointestinal tolerance and fecal microbiota , pH , and short-chain fatty acid ( SCFA ) concentrations of infants consuming formula with or without prebiotics .  DESIGN Full-term formula-fed infants were studied to a breastfed comparison group ( BF ) . Formula-fed infants ( FF ) were r and omized to consume a partially hydrolyzed whey formula with ( PRE ) or without ( CON ) 4 g/L of galacto-oligosaccharides and fructo-oligosaccharides ( 9:1 ) . Fecal bacteria , pH , and SCFA were assessed at baseline , 3 weeks , and 6 weeks . Caregivers of patients recorded stool characteristics and behavior for 2 days before the 3- and 6-week visits . RESULTS Feces from infants fed PRE had a higher absolute number ( P = .0083 ) and proportion ( P = .0219 ) of bifidobacteria than CON-fed infants and did not differ from BF . BF had a higher proportion of bifidobacteria than CON ( P = .0219 ) and lower number of Clostridium difficile than FF ( P = .0087 ) . Feces from formula-fed infants had higher concentrations of acetate ( P < .001 ) , butyrate ( P < .001 ) , propionate ( P < .001 ) , and total SCFAs ( P = .0230 ) than BF ; however , fecal pH was lower ( P = .0161 ) in PRE and BF than CON . Prebiotic supplementation did not alter stool patterns , tolerance , or growth . BF had more frequent stools that were yellow ( P < .0001 ) and more often liquid than FF ( P < .0001 ) . CONCLUSIONS Infant formula containing the studied oligosaccharides was well tolerated , increased abundance and proportion of bifidobacteria , and reduced fecal pH in healthy infants BACKGROUND The intestinal microflora is a likely source for the induction of immune deviation  in infancy . OBJECTIVE The purpose of this study was to prospect ively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases . METHODS Newborn infants were followed prospect ively through the first 2 years of life in Estonia ( n = 24 ) and Sweden ( n = 20 ) . By that age , 9 Estonian and 9 Swedish infants had developed atopic dermatitis and /or positive skin prick test results .  Stool sample s were obtained at 5 to 6 days and at 1 , 3 , 6 , and 12 months , and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of st and ard methods . RESULTS In comparison with healthy infants , babies who developed allergy were less often colonized with enterococci during the first month of life ( 72 % vs 96 % ; P < .05 ) and with bifidobacteria during the first year of life ( 17 % to 39 % vs 42 % to 69 % ; P < .05 ) . Furthermore , allergic infants had higher counts of clostridia at 3 months ( median value , 10.3 vs 7.2 log(10 ) ; P < .05 ) . The prevalence of colonization with Staphylococcus aureus was also higher at 6 months ( 61 % vs 23 % ; P < .05 ) , whereas the counts of Bacteroides were lower at 12 months ( 9.9 vs 10.6 log(10 ) ; P < .05 ) . CONCLUSION Differences in the composition of the gut flora between infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy . Because the observations were made in 2 countries with different st and ards of living , we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy Objective : Very low birth weight ( VLBW ) infants receiving glutamine-enriched enteral nutrition  may present with a lower infection rate , which may result from enhanced antimicrobial innate or Th1 cytokine responses . We investigated whether glutamine-enriched enteral nutrition in VLBW infants increased these cytokine responses following in vitro stimulation of whole blood cells . Methods : In a double-blind , placebo-controlled , r and omized controlled trial , VLBW infants ( gestational age < 32 weeks and /or birth weight < 1500 g )  received enteral glutamine supplementation ( 0.3 g · kg−1 · day−1 ) or isonitrogenous placebo supplementation ( alanine ) between days 3 and 30 of life . Cytokine responses following in vitro whole blood cell stimulation with anti-(α)CD3/αCD28 or lipopolysaccharide were analyzed by cytometric bead array at 3 time points : before the start of the study , at day 7 of life , and at day 14 of life . Results : Baseline patient and nutritional characteristics were not different between groups . At least 2 blood sample s were analyzed in 25 of 52 ( 48 % ) and 38 of 50 ( 76 % ) infants in the glutamine-supplemented and control groups , respectively . Glutamine-enriched enteral nutrition was not associated with significant alterations in cytokine responses ( interferon-γ , tumor necrosis factor-α , interleukin [IL]-2 , IL-4 , IL-5 , and IL-10 ) of peripheral blood cells upon stimulation with either anti-αCD3/αCD28 or lipopolysaccharide . Conclusions : We hypothesize that glutamine-enriched enteral nutrition decreases the infection rate in VLBW infants by influencing the mucosal and not the systemic immune system 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 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 : Regarding safety , we investigated the effect of prenatal probiotic and 6 months of pro- and prebiotic supplementation of infants on their hematologic values at 6 months and 2 years and factors affecting these values . Patients and Methods : In a prospect i ve r and omized controlled probiotic intervention trial in infants at high risk for allergy , we obtained blood sample s consecutively from 98 infants at 6 months and from 658 children at 2 years to measure hematologic values . We collected fecal sample s at 3 and 6 months to measure immunologic development by calprotectin , α-1-antitrypsin , tumor necrosis factor-α , and immunoglobulin A. Results : At 6 months , infants in the probiotic group had significantly lower hemoglobin ( Hb ) values than did the placebo group , mean ( SD ) : 119.8 g/L ( 6.3 ) versus 123.3 g/L ( 8.4 ) , P = 0.025 . Adjustment for factors that might affect Hb values ( breast-feeding duration , solid-food introduction , and sex ) , revealed no need for adjustment . A significant negative correlation emerged between Hb values at 6 months and fecal calprotectin at age 3 months r = −0.301 , P = 0.009 , which was affected neither by breast-feeding , sex , nor study group . At 2 years , hematologic values in both groups became similar . Conclusions : Probiotics cause a gut mucosal inflammation with decreased Hb values during intervention , corrected after halting the supplementation To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk . The aim of this study was to evaluate the effects of prebiotic , probiotic added to a st and ard formula on gastrointestinal motility respect to placebo-formula .  Cutaneous electrogastrography ( EGG ) and ultrasound gastric emptying ( GE ) were performed in 49 preterm newborns . 17 newborns were exclusively breast-fed ; 32 were r and omly assigned to receive prebiotic-added formula ( 0.8 g/dl of a mixture from scGOS and lcFOS , ratio 9:1 ) ( 10 ) , a probiotic-added formula ( L. reuteri at dose of 1x10(8 ) colony forming units ( CFU ) per day ) ( 10 ) , a formula with placebo ( 12 ) for 30 days . No difference was seen in the nutritional parameters and no adverse events were reported . After the intervention period , the prebiotic , probiotic , and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group ( ANOVAon ranks p<0.001 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 ; and ANOVA on ranks p=0.005 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 , respectively ) . Feeding preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk Breast milk prebiotic oligosaccharides are believed to promote enteral tolerance . Many mothers delivering preterm are unable to provide sufficient milk . We conducted a multicenter , r and omized , controlled trial comparing preterm formula containing 0.8 g/100 mL short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in a 9:1 ratio and an otherwise identical formula , using formula only to augment insufficient maternal milk volume . Infants were r and omized within 24 h of birth . The primary outcome ( PO ) was time to establish a total milk intake of 150 mL/kg/d PO and the principal secondary outcome ( PSO ) was proportion of time between birth and 28 d/discharge that a total milk intake of ≥150 mL/kg/d was tolerated . Other secondary outcomes included growth , fecal characteristics , gastrointestinal signs , necrotizing enterocolitis , and bloodstream infection . Outcomes were compared adjusted for prespecified covariates . We recruited 160 infants appropriately grown for GA <33 wk . There were no significant differences in PO or PSOs . After covariate adjustment , we showed significant benefit from trial formula in PSO with increasing infant immaturity ( 2.9 % improved tolerance for a baby born at 28-wk gestation and 9.9 % at 26-wk gestation ; p < 0.001 ) but decreased or no benefit in babies > 31-wk gestation . Prebiotic supplementation appears safe and may benefit enteral tolerance in the most immature infants AIM To investigate whether a mixture of prebiotic non-digestible oligosaccharides ( GosFos ; referring to galacto- and fructo-oligosaccharides ) would improve feeding tolerance in preterm infants on full enteral formula feeding . We hypothesized that GosFos would : ( 1 ) reduce stool viscosity and ( 2 ) accelerate gastrointestinal transport . METHODS In a placebo-controlled double-blind trial 20 preterm infants on full enteral nutrition ( gestational age 27 ( 24 - 31 ) weeks , postnatal age 42 ( 11 - 84 ) days , and weight at study entry 1570 ( 1080 - 2300 ) g were r and omly allocated to have their feedings supplemented with either GosFos ( 1 g/100 mL ) or placebo for 14 days . Stool viscosity was measured by high-pressure capillary rheometry . Gastrointestinal transport time was assessed as the time from feeding carmine red to its appearance in the diaper . The hypotheses were tested as a priori ordered hypotheses . Data are shown as median ( range ) . RESULTS Birth weight , gestational age , postnatal age , and weight at study entry did not differ between groups . GosFos significantly reduced both stool viscosity , as measured by extrusion force ( 32 ( 2 - 67 ) versus 158 ( 24 - 314 ) N ) , and gastrointestinal transit time ( 12 ( 4 - 33 ) versus 26 ( 5 - 52 ) h ) . No adverse effects were observed . CONCLUSION Formula supplementation with GosFos reduced stool viscosity and accelerated gastrointestinal transport . Further trials are required to investigate whether GosFos facilitates enteral feeding advancement and early enteral nutrition thereby eventually reducing the incidence of catheter-related nosocomial infections and improving long-term outcome Probiotics are immunomodulatory and may thus affect vaccine antibody responses . With the accumulating evidence of their health-promoting effects , probiotics are increasingly administered in allergy-prone infants . Therefore , we studied the effect of probiotics on antibody responses to diphtheria , tetanus and Haemophilus influenzae type b ( Hib ) vaccines in 6-month-old infants participating in a r and omized placebo-controlled double-blind allergy-prevention trial . Mothers of unborn children at increased risk for atopy used a combination of four probiotic strains , or a placebo , for 4 wk before delivery . During 6 months from birth , their infants received the same probiotics and galacto-oligosaccharides , or a placebo . The infants were immunized with a DTwP ( diphtheria , tetanus and whole cell pertussis ) at ages 3 , 4 , and 5 months , and with a Hib polysaccharide conjugate at 4 months . Serum diphtheria , tetanus , and Hib IgG antibodies were measured at 6 months . In the probiotic group , protective Hib antibody concentrations ( > /=1 microg/ml ) occurred more frequently , 16 of 32 ( 50 % ) vs. six of 29 ( 21 % ) ( p = 0.020 ) , and the geometric mean ( inter-quartile range ) Hib IgG concentration tended to be higher 0.75 ( 0.15 - 2.71 ) microg/ml than in the placebo group 0.40 ( 0.15 - 0.92 ) microg/ml ( p = 0.064 ) . In these respective groups , diphtheria , 0.38 ( 0.14 - 0.78 ) vs. 0.47 ( 0.19 - 1.40 ) IU/ml ( p = 0.449 ) , and tetanus , 1.01(0.47 - 1.49 ) vs. 0.81 ( 0.56 - 1.39 ) IU/ml ( p = 0.310 ) , IgG titers were comparable . In conclusion , in allergy-prone infants probiotics seem not to impair antibody responses to diphtheria , tetanus , or Hib , but may improve response to Hib immunization 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 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 aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins , prebiotic oligosaccharides ( OS ) , with a high β-palmitic acid content . Design : Prospect i ve r and omized controlled study . Setting : Italy . Subjects : Two hundred and sixty-seven formula-fed infants , aged less than 4 months , with infantile colic , were r and omized to receive either the new infant formula ( study treatment ( ST ) ) or a st and ard formula and simethicone ( 6 mg/kg twice a day ) ( control treatment ( CT ) ) . A question naire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time . Results : Out of the 199 infants who completed the study , 96 were treated with the new formula and 103 were not treated . Infants receiving the new formula had a significant decrease in colic episodes after 1 week ( 2.47±1.94 at day 7 vs 5.99±1.84 at the study entry ) compared to infants receiving the CT ( 3.72±1.98 at day 7 vs 5.41±1.88 at the study entry ) ( P<0.0001 ) . Also at day 14 , the crying episodes were significantly different between the two groups of infants ( 1.76±1.60 in ST vs 3.32±2.06 in CT ) ( P<0.0001 ) . Conclusions : The use of a partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a st and ard formula and simethicone . Sponsorship : The study was supported by funds from Numico , Italy 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 Objectives The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics of a new infant formula containing partially hydrolyzed whey protein , modified vegetable oil with a high & bgr;-palmitic acid content , prebiotic oligosaccharides , and starch . Methods In a double-blind study , healthy formula-fed term infants aged younger than 2 weeks were r and omized to receive either the new infant formula ( NF ) or a st and ard formula ( SF )  until the age of 12 weeks .  Anthropometric measurements were taken at enrollment , 6 weeks , and 12 weeks . In a sub sample of infants , blood sample s were taken at 6 weeks and stool sample s were taken at enrollment and 6 weeks . Blood sample s were analyzed for biochemical measures of protein status and amino acids , and stools were analyzed for total bacteria and bifidobacteria . Mothers completed a feeding diary and question naire at 6 and 10 weeks . Results One hundred fifty-four infants were enrolled in the study ; 102 completed the trial . The growth of infants in both formula groups was in line with published growth curves . During the first 6 weeks , NF girls gained more weight and head circumference than the SF girls . These velocity differences were not maintained throughout the 12-week study period . The NF stools had a higher proportion of bifidobacteria at 6 weeks compared with the SF stools , and they were softer . There were no clinical ly significant differences in the blood biochemical and amino acid values between groups . Both formulas were well tolerated by the infants . Conclusions When compared with a st and ard infant formula , the new formula supported satisfactory growth , led to higher counts of bifidobacteria in the feces , produced blood bio-chemical values typical of formula-fed infants , and was well tolerated OBJECTIVES The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants . We assessed the safety and tolerability of an experimental formula containing 2 x 10(7 ) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides . METHODS A 7-mo prospect i ve , r and omized , reference-controlled , double-blinded trial was performed in infants who were not breast fed after the 14th day of birth . One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old .  Mean weight gain ( primary outcome ) and recumbent length , head circumference , tolerability ( gastrointestinal symptoms ) , and overall morbidity ( secondary outcomes ) were measured at 14 , 28 , 56 , 84 , and 112 d of age . RESULTS Equivalence in mean weight gain between the two groups was shown . The treatment difference in the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d . No statistically significant difference in recumbent length , head circumference , or incidence of adverse events was found between the two groups . Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well . Furthermore , these infants showed a trend toward fewer respiratory tract infections . CONCLUSIONS The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated Objectives : This r and omized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides ( GOS ) , oligofructose , and long-chain inulin ( fructooligosaccharides , FOS ) in formula . Methods : Subjects were r and omized to Orafti Synergy1 ( 50 oligofructose:50 FOS ) 0.4 g/dL or 0.8 g/dL , GOS : FOS ( 90:10 ) 0.8 g/dL , or a st and ard formula according to Good Clinical Practice guidelines . A breast-fed group was included for comparison . Outcome parameters were weight , length , intake , stool characteristics , crying , regurgitation , vomiting , adverse events , and fecal bacterial population counts . Statistical analyses used nonparametric tests . Results : During the first month of life , weight , length , intake , and crying increased significantly in all of the groups . Regurgitation and vomiting scores were low and similar . Stool frequency decreased significantly and similarly in all of the formula groups but was lower than in the breast-fed group . All of the prebiotic groups maintained soft stools , only slightly harder than those of breast-fed infants . The st and ard group had significantly harder stools at weeks 2 and 4 compared with 1 ( P < 0.001 and P = 0.0279 ) . The total number of fecal bacteria increased in all of the prebiotic groups ( 9.82 , 9.73 , and 9.91 to 10.34 , 10.38 , and 10.37 , respectively , log10 cells/g feces , P = 0.2298 ) and more closely resembled the breast-fed pattern . Numbers of lactic acid bacteria , bacteroides , and clostridia were comparable . In the SYN1 0.8 g/dL and GOS : FOS groups , Bifidobacterium counts were significantly higher at D14 and 28 compared with D3 and were comparable with the breast-fed group . Tolerance and growth were normal . Conclusions : Stool consistency and bacterial composition of infants taking SYN1 0.8 g/dL or GOS : FOS – supplemented formula were closer to the breast-fed pattern . There was no risk of dehydration The aim of the study was to evaluate whether supplementation of milk-formulas with prebiotic fructo-oligosaccharides or a probiotic , Lactobacillus johnsonii La1 ( La1 ) , could modulate the composition of the fecal microbiota of formula-fed infants , compared to breastfed ( BF ) infants . Ninety infants close to 4 months of age were r and omized into one of three groups to be blindly assigned to receive for 13 weeks : a ) an infant formula ( Control ) , b ) the same formula with fructo-oligosaccharides ( Prebio ) , or c ) with La1 ( Probio ) . At the end of this period , all infants received the control formula for 2 additional weeks . Twenty-six infants , breastfed throughout the study , were recruited to form group BF . Fecal sample s were obtained upon enrolment and after 7 and 15 weeks . Bacterial population s were assessed with classical culture techniques and fluorescent in situ hybridisation ( FISH ) . Seventy-six infants completed the study . On enrolment , higher counts of Bifidobacterium and Lactobacillus and lower counts of enterobacteria were observed in BF compared to the formula-fed infants ; these differences tended to disappear at weeks 7 and 15 . No major differences for Clostridium , Bacteroides or Enterococcus were observed between the groups or along the follow up . Probio increased fecal Lactobacillus counts ( p<0.001 ) ; 88 % of the infants in this group excreted live La1 in their stools at week 7 but only 17 % at week 15 . Increased Bifidobacterium counts were observed at week 7 in the 3 formula groups , similar to BF infants . These results confirm the presence of higher counts of bifidobacteria and lactobacilli in the microbiota of BF infants compared to formula-fed infants before dietary diversification , and that La1 survives in the infant digestive tract Objectives : The primary objective of this study was to determine the bifidogenic effect of galacto-oligosaccharides ( GOS ) in a follow-on formula and the effects on other intestinal bacteria . Secondary objectives were the effects on stool characteristics , growth , and general well-being . Participants and Methods : In a multicenter , double-blind study , 159 healthy infants , formula-fed at enrollment ( at 4–6 months ) , were r and omized to an experimental follow-on formula supplemented with 5 g/L ( GOS ) ( 77 infants ) , or to a st and ard follow-on formula ( control , 82 infants ) . Infants were evaluated at enrollment ( study day 1 = sd1 ) , after 6 weeks ( study day 2 = sd2 ) , and after an additional 12 weeks ( study day 3 = sd3 ) . At each study day , a fresh stool sample for the bacterial counts was collected , and the growth parameters were measured . At sd2 , urinary specimens were collected for the evaluation of urinary osmolarity . Results : At sd2 and sd3 , the GOS group had a higher median number ( colony-forming units per gram of stool ) of bifidobacteria than did the control group ( sd2 GOS 9.2 × 109 vs control 4.4 × 109 , P = 0.012 ) ; ( sd3 GOS 7.2 × 109 vs control 2.4 × 109 , P = 0.027 ) . Other bacteria did not show any significant differences between the 2 groups at all study days . The GOS produced softer stools but had no effect on stool frequency . The urinary osmolarity ( mOsm/L ) at sd2 was comparable in both groups . Supplementation had no influence on the incidence of gastrointestinal side effects or on the growth of the infants . Conclusions : These data indicate that the addition of GOS ( 5 g/L ) to a follow-on formula positively influences the bifidobacteria flora and the stool consistency in infants during the supplementation period at weaning . No local or systemic side effects were recorded 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 BACKGROUND : Dietary nucleotides are nonprotein nitrogenous compounds that are found in high concentrations in breast milk and are thought to be conditionally essential nutrients in infancy . A high nucleotide intake has been suggested to explain some of the benefits of breastfeeding compared with formula feeding and to promote infant growth . However , relatively few large-scale r and omized trials have tested this hypothesis in healthy infants . OBJECTIVE : We tested the hypothesis that nucleotide supplementation of formula benefits  early infant growth .  PATIENTS AND METHODS :  Occipitofrontal head circumference , weight , and length were assessed in infants who were r and omly assigned to groups fed nucleotide-supplemented ( 31 mg/L ; n = 100 ) or control formula without nucleotide supplementation ( n = 100 ) from birth to the age of 20 weeks , and in infants who were breastfed ( reference group ; n = 101 ) . RESULTS : Infants fed with nucleotide-supplemented formula had greater occipitofrontal head circumference at ages 8 , 16 , and 20 weeks than infants fed control formula ( mean difference in z scores at 8 weeks : 0.4 [ 95 % confidence interval : 0.1–0.7 ] ; P = .006 ) even after adjustment for potential confounding factors ( P = .002 ) . Weight at 8 weeks and the increase in both occipitofrontal head circumference and weight from birth to 8 weeks were also greater in infants fed nucleotide-supplemented formula than in those fed control formula . CONCLUSIONS : Our data support the hypothesis that nucleotide supplementation leads to increased weight gain and head growth in formula-fed infants . Therefore , nucleotides could be conditionally essential for optimal infant growth in some formula-fed population s. Additional research is needed to test the hypothesis that the benefits of nucleotide supplementation for early head growth , a critical period for brain growth , have advantages for long-term cognitive development BACKGROUND Oligosaccharides in human milk may protect infants by improving the intestinal micro-flora and fermentation . This study was to investigate effects of  infant formula milk consisting of galacto-oligosaccharide ( GOS ) on intestinal microbial population s and the fermentation characteristics in term infants in comparison with that of human milk . METHODS The test formula ( Frisolac H , Friesl and , Netherl and ) was supplemented with GOS at a concentration of 0.24 g/dl . Human milk and another formula without oligosaccharides ( Frisolac H , Friesl and , Netherl and ) were used as positive and negative control respectively . Growth , stool characteristics , and side effects of the recruited infants were recorded after 3 and 6 months ' follow-up , and the fecal species were collected for the analysis of intestinal micro-flora , short chain fatty acid ( SCFA ) and pH. RESULTS At the end of 3- and 6-month feeding period , intestinal Bifidobacteria and Lactobacilli were significantly increased in infants fed with GOS supplemented formula and human milk when compared with infants fed with negative control formula ; however , there was no statistically significant difference between GOS supplemented formula and human milk groups . Stool characteristics were influenced by the supplement and main fecal SCFA ( acetic ) , and stool frequency were significantly increased in infants fed with GOS supplemented formula and human milk , while the fecal pH was significantly decreased as compared with that of negative control ( P < 0.05 ) . Supplementation had no influence on incidence of side effects ( including crying , regurgitation and vomiting ) . CONCLUSIONS Supplementing infant formula with GOS at a concentration of 0.24 g/dl stimulates the growth of Bifidobacteria and Lactobacilli in the intestine and stool characteristics are similar to in term infants fed with human milk 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 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 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 This double-blind , r and omized , placebo-controlled study , aim ed to explore the effect of an infant milk formula ( IMF ) with 6 g/l short-chain galacto- and long-chain fructo-oligosaccharides ( scGOS/lcFOS , ratio 9:1 ) on basal immune parameters in 215 healthy , term infants during the first 26 wk of life . After birth , the infants  received breast milk or were r and omized to receive an IMF with or without scGOS/lcFOS .  Blood sample s were collected at the age of 8 wk and 26 wk for the analysis of serum immunoglobulins , lymphocyte sub population s , and cytokines . The scGOS/lcFOS group and the control group were compared in the statistical analysis . A breast fed group was included as a reference . In total , 187 Infants completed the study . No significant differences were observed between both formula groups in the different studied immune parameters at weeks 8 and 26 . This explorative study indicates that supplementation of infant formula with a mixture of prebiotic oligosaccharides did not change the basal level of the measured parameters of the developing immune system in healthy infants with a balanced immune system during the first 6 months of life in comparison to feeding a st and ard infant formula and in comparison to exclusive breastfeeding BACKGROUND Very-low-birth-weight ( VLBW ) infants are susceptible to glutamine depletion . Glutamine depletion has negative effects on intestinal integrity . The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition  may originate from improved intestinal integrity , as reflected by decreased intestinal permeability . The aim of our study was to investigate whether glutamine-enriched enteral nutrition in VLBW infants enhances the normal decrease in intestinal permeability , as measured by the sugar absorption test ( SAT ) . METHODS In a double-blind , r and omized , placebo-controlled trial , VLBW infants ( gestational age < 32 weeks or birth weight < 1,500 g ) received enteral glutamine supplementation ( 0.3 g/kg/d ) or an isonitrogenous placebo supplementation ( alanine ) between days 3 and 30 of life . Intestinal permeability , determined from the urinary lactulose/mannitol ( L/M ) ratio after an oral dose of lactulose and mannitol , was assessed at 4 time points : before the start of the study , and at days 7 , 14 , and 30 of life . RESULTS At least 2 SATs were performed in 45/52 ( 86 % ) and 45/50 ( 90 % ) infants in the glutamine-supplemented and control groups , respectively . Baseline patient and nutrition characteristics were not different between the groups . There was no effect of glutamine-enriched enteral nutrition on the decrease of the L/M ratio between the start and end of the study ( p = .78 ) . In both treatment groups , median urinary lactulose concentrations decreased ( p < .001 ) , whereas median urinary mannitol concentrations increased ( p = .003 ) . CONCLUSIONS Glutamine-enriched enteral nutrition does not enhance the postnatal decrease in intestinal permeability in VLBW infants . Any beneficial effect of glutamine may involve other aspects of intestinal integrity ; for example , modulation of the intestinal inflammatory response 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 A double‐blind , r and omized , controlled study was performed in 90 full term infants to evaluate dose‐related bifidogenic effects of a new synergistic mixture of galacto‐oligosaccharides ( GOS ) and fructo‐oligosacharides ( FOS ) . The GOS/FOS mixture showed a dose‐dependent stimulatory effect on the intestinal growth of bifidobacteria . Also stool consistency and faecal pH were positively affected 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 Among other components of human milk , oligosaccharides might contribute to the high efficiency of calcium absorption of breastfed infants . In adults , it can be shown that dietary oligosaccharides can improve calcium absorption . The present analysis was performed to evaluate a possible influence of dietary oligosaccharides on parameters of calcium metabolism in preterm infants .  The concentrations of calcium and phosphorus in plasma and in spot urine sample s as well as the plasma activity of the alkaline phosphatase were measured in preterm infants fed either a st and ard formula ( n= 15 ) or a formula supplemented with dietary oligosaccharides ( n= 15 ) at the end of a 4‐wk feeding period Background : Probiotic , prebiotic , and synbiotic ( a combination of pro- and prebiotic ) supplements increasingly are being used to prevent and treat a variety of health conditions . Although colonization is considered a key element in the success of such treatments , few clinical studies have addressed colonizing ability . Studies are even more limited in neonates and infants , who may benefit most from such treatment . The present study was conducted to determine the colonizing ability , tolerance , and impact on the stool flora of 7 days of administration of a synbiotic supplement to a neonatal cohort , in preparation for a larger hospital-based trial . Patients and Methods : In this r and omized , double-masked , controlled trial , healthy inborn newborns > 35 weeks of gestational age and > 1800 g birth weight were r and omized between 1 and 3 days after birth to receive an oral synbiotic preparation ( Lactobacillus plantarum and fructooligosaccharides ) or a dextrose saline placebo .  Two babies were treated with the synbiotic preparation for every 1 baby treated with the placebo . Duration of therapy was 7 days . Comprehensive stool cultures were done at baseline and on days 3 , 7 , 14 , 21 , and 28 . Results : Nineteen infants received the active study supplement and 12 infants received the placebo for 7 days . L plantarum was cultured from the stools of 84 % of the treated infants after 3 days of treatment , and from 95 % of infants on day 28 after birth . Of the infants , 100 % , 94 % , 88 % , 56 % , and 32 % remained colonized at months 2 , 3 , 4 , 5 , and 6 , respectively . In both groups , the total mean number of species and the mean log colony counts increased over time . The number of bacterial species was significantly higher on days 21 and 28 in the synbiotic preparation group compared with placebo ( P = 0.002 and 0.03 , respectively ) . There was a linear increase in the mean log gram-negative colony counts in the placebo group during the 4-week period that was significantly higher than that in the Lactobacillus group on days 14 , 21 , and 28 ( P < 0.001 for each ) . In contrast , the supplement group had significantly higher gram-positive colony counts on days 14 ( P = 0.002 ) and 28 ( P = 0.04 ) . Only 1 infant in the placebo group was colonized with L fermentum during the first 28 days of life . No difference was found in the percent increase in weight between baseline and day 7 , but on day 28 and months 2 , 3 , and 6 , the percent increase from baseline was higher in the probiotic-treated group ( P ≤ 0.05 ) . The supplement was tolerated well . Conclusions : The synbiotic preparation colonized quickly after 3 days of administration and the infants stayed colonized for several months after therapy was stopped . There was an increase in bacterial diversity and gram-positive organisms and a reduction of gram-negative bacterial load in the treatment group . Because a combination preparation was used , it is difficult to specifically attribute the colonization to either the probiotic or prebiotic component in this study . Larger efficacy trials are warranted to examine the mechanism of action and precise effects of these supplements Secretory immunoglobulin A ( SIgA ) plays an important role in the defence of the gastrointestinal tract . The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses . Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aim ed at study ing the effects of st and ard , prebiotic and probiotic infant formulas on the faecal SIgA levels . At birth , infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a r and omized , double-blind fashion . Nineteen infants received st and ard infant formula ; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 x 10(9 ) cfu Bifidobacterium animalis/100 ml formula . Faecal sample s were taken on postnatal day 5 , day 10 , wk 4 and every 4 wk thereafter until wk 32 . SIgA in faeces was determined by an enzyme-linked immunosorbent assay . During the intervention , infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the st and ard formula-fed infants reaching statistical significance at the age of 16 wk . In contrast , infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the st and ard formula group . Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion . Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend Objective : To compare the effect of 2 prebiotic/probiotic products on weight gain , stool microbiota , and stool short-chain fatty acid ( SCFA ) content of premature infants . Patients and Methods : This r and omized , blinded , placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides ( CUL , Culturelle , ConAgra , Omaha , NE ) , a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides ( PBP  , ProBioPlus DDS , UAS Laboratories , Eden Prairie , MN ) , or placebo ( a dilute preparation of Pregestamil formula ) twice daily for 28 days or until discharge if earlier . The primary outcome was weight gain . Secondary outcomes were stool bacterial analysis by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA content measured by high performance liquid chromatography . Results : Both prebiotic/probiotic combinations contained more bacterial species than noted on the label . No significant effect on infant growth of either prebiotic/probiotic supplement was observed . By cultures , 64 % of infants receiving PBP became colonized with bifidobacteria , compared with 18 % of infants receiving CUL and 27 % of infants receiving placebo ( chi-square , P = 0.064 ) . No differences were noted between groups in colonization rates for lactobacilli , Gram-negative enteric bacteria , or staphylococci . By 16S rDNA polymerase chain reaction analysis , the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo ( Kruskal-Wallis , P = 0.011 ) . No significant differences in stool SCFA content were detected between groups . No adverse reactions were noted . Conclusions : Infants receiving PBP were more likely to become colonized with bifidobacteria . No significant differences in weight gain or stool SCFA content were detected Objective : To test the safety and effect on faecal microbiota of a formula with prebiotic oligosaccharides alone or in combination with acidic oligosaccharides in infants at the age of partial formula feeding . Patients and Methods : The study was a double-blind , placebo-controlled , r and omised intervention trial in which 82 healthy , full-term , partially breast-fed children , from 1 week to 3 months old , were given 1 of the following formulae : whey-based formula ( control group ) , whey-based formula with galacto- and long-chain fructo-oligosaccharides ( scGOS/lcFOS group ) , or whey-based formula with galacto- and long-chain fructo-oligosaccharides added with pectin-derived acidic oligosaccharides ( scGOS/lcFOS/pAOS group ) . Children were studied for the duration of the partial formula feeding period and every 2 weeks for 2 months after breast-feeding cessation . The total bacteria count and the proportion of 7 bacterial families were determined using in situ hybridisation coupled to flow cytometry . Results : The total bacterial count did not alter with time or type of feeding ( 9.9 ± 0.1 log10 cells per gram wet weight ) . Compared with the control group , there was an increase of the Bifidobacterium genus ( P = 0.0001 ) , and a decrease of proportions for the Bacteroides group ( P = 0.02 ) and the Clostridium coccoides group ( P = 0.01 ) in both oligosaccharide groups . The proportion of bifidobacteria was significantly higher in the scGOS/lcFOS/pAOS compared with the scGOS/lcFOS group ( P < 0.01 ) . Conclusions : Infant formulae appear to be clinical ly safe and effective on infant microbiota . They minimize the alteration of faecal microbiota after cessation of breast-feeding and promote bifidobacteria proportions , with a stronger effect when acidic oligosaccharides are present Objective : Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression .  Very low birth weight ( VLBW ) infants are susceptible to glutamine depletion , as enteral nutrition is limited in the first weeks of life . Enteral glutamine supplementation may have a positive effect on feeding tolerance , infectious morbidity and short-term outcome . The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations , reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants . Methods : In a double-blind placebo-controlled r and omized controlled trial , VLBW infants ( gestational age < 32 weeks or birth weight < 1500 g ) received enteral glutamine supplementation ( 0.3 g/kg per day ) or isonitrogenous placebo supplementation ( alanine ) between day 3 and day 30 of life . Supplementation was added to breast milk or to preterm formula . Plasma amino acid concentrations were measured at four time points : before the start of the study and at days 7 , 14 and 30 of life . Results : Baseline patient and nutritional characteristics were not different in glutamine ( n = 52 ) and control ( n = 50 ) groups . Plasma concentrations of most essential and non-essential amino acids increased throughout the study period . There was no effect of enteral glutamine supplementation . In particular , the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups ( P = 0.49 and P = 0.34 respectively , day 30 ) . Conclusions : Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine , glutamate or other amino acids . Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants OBJECTIVE . Live probiotic bacteria and dietary prebiotic oligosaccharides ( together termed synbiotics ) increasingly are being used in infancy , but evidence of long-term safety is lacking . In a r and omized , placebo-controlled , double-blind trial , we studied the safety and long-term effects of feeding synbiotics to newborn infants . METHODS . Between November 2000 and March 2003 , pregnant mothers carrying infants at high risk for allergy were r and omly assigned to receive a mixture of 4 probiotic species ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve Bb99 , and Propionibacterium freudenreichii ssp shermanii ) or a placebo for 4 weeks before delivery . Their infants received the same probiotics with 0.8 g of galactooligosaccharides , or a placebo , daily for 6 months after birth . Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3 , 6 , and 24 months and from question naires at ages 3 , 6 , 12 , and 24 months . Growth data were collected at each time point . RESULTS . Of the 1018 eligible infants , 925 completed the 2-year follow-up assessment . Infants in both groups grew normally . We observed no difference in neonatal morbidity , feeding-related behaviors ( such as infantile colic ) , or serious adverse events between the study groups . During the 6-month intervention , antibiotics were prescribed less often in the synbiotic group than in the placebo group ( 23 % vs 28 % ) . Throughout the follow-up period , respiratory infections occurred less frequently in the synbiotic group ( geometric mean : 3.7 vs 4.2 infections ) . CONCLUSION . Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life BACKGROUND & AIMS In a previous study , we have found that glutamine supplementation decreased the infection rate in very low birth weight ( VLBW ) infants . In this study , we investigated whether this beneficial effect originated from increased number of bifidobacteria and lactobacilli in the intestinal microflora of these infants . METHODS In a r and omized controlled trial , VLBW infants ( gestational age < 32 weeks and /or birth weight < 1500 g ) received enteral glutamine supplementation ( 0.3g/kg/day ) or isonitrogenous placebo supplementation between d3 and d30 of life . Faecal microflora was determined by fluorescent in situ hybridization < 48h , at d7 , d14 and d30 of life . RESULTS In 43/52 (  glutamine group ) and 43/50 ( control group ) infants , > or = 2 sample s were analyzed . Baseline characteristics were not different between groups . The prevalence of bifidobacteria , lactobacilli , Escheria coIi , streptococci and clostridia was not different between groups ( p>0.05 ) . In both groups , colonization with bifidobacteria was delayed , whereas potentially pathogenic bacteria such as E. coli , appeared rapidly after birth . Antibiotic treatment decreased the prevalence of all faecal bacteria ( p<0.05 ) . CONCLUSIONS Decreased infectious morbidity in VLBW infants that received glutamine supplementation was not associated with alterations in the prevalence of bifidobacteria , lactobacilli , E. coIi , streptococci and clostridia . In general , colonization with health-promoting bacteria was delayed , whereas potentially pathogenic bacteria appeared rapidly after birth . Antibiotic treatment delayed the bacterial colonization STUDY OBJECTIVES We sought to identify early life factors ( ie , first 4 years ) associated with  wheeze , asthma , and bronchial hyperresponsiveness ( BHR ) at age 10 years , comparing their relative influence for these conditions . METHODS Children were seen at birth , and at 1 , 2 , 4 , and 10 years of age in a whole- population birth cohort study ( 1,456 subjects ) . Information was collected prospect ively on genetic and environmental risk factors .  Skin-prick testing  was performed at 4 years of age . Current wheeze ( in the last 12 months ) and currently diagnosed asthma ( CDA ) [ ie , current wheeze and ever-diagnosed asthmatic subject ] were recorded at 10 years of age when BHR was measured at bronchial challenge . Independent significant risk factors for these outcomes were identified by logistic regression . RESULTS Independent significance for current wheeze occurred with maternal asthma ( odds ratio [ OR ] , 2.08 ; 95 % confidence interval [ CI ] , 1.27 to 3.41 ) and paternal asthma ( OR , 2.12 ; 95 % CI 1.29 to 3.51 ) , recurrent chest infections at 2 years ( OR , 3.98 ; 95 % CI , 2.36 to 6.70 ) , atopy at 4 years of age ( OR , 3.69 ; 95 % CI , 2.36 to 5.76 ) , eczema at 4 years of age ( OR , 2.15 ; 95 % CI , 1.24 to 3.73 ) , and parental smoking at 4 years of age ( OR , 2.18 ; 95 % CI , 1.25 to 3.81 ) . For CDA , significant factors were maternal asthma ( OR , 2.26 ; 95 % CI , 1.24 to 3.73 ) , paternal asthma ( OR , 2.30 ; 95 % CI , 1.17 to 4.52 ) , and sibling asthma ( OR , 2.00 ; 95 % CI , 1.16 to 3.43 ) , recurrent chest infections at 1 year of age ( OR , 2.67 ; 95 % CI , 1.12 to 6.40 ) and 2 years of age ( OR , 4.11 ; 95 % CI , 2.06 to 8.18 ) , atopy at 4 years of age ( OR , 7.22 ; 95 % CI , 4.13 to 12.62 ) , parental smoking at 1 year of age ( OR , 1.99 ; 95 % CI , 1.15 to 3.45 ) , and male gender ( OR , 1.72 ; 95 % CI , 1.01 to 2.95 ) . For BHR , atopy at 4 years of age ( OR , 5.38 ; 95 % CI , 3.06 to 9.47 ) and high social class at birth ( OR , 2.03 ; 95 % CI , 1.16 to 3.53 ) proved to be significant . CONCLUSIONS Asthmatic heredity , predisposition to early life atopy , plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age . BHR at 10 years of age has a narrower risk profile , suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR OBJECTIVE To assess the safety and prebiotic effects of lactulose in preterm infants . STUDY DESIGN This was a prospect i ve , double-blinded , placebo-controlled , single-center study in 23- to 34-weeks premature infants . The study group received 1 % lactulose , and control infants received 1 % dextrose in all feeds ( human milk or formula ) . RESULTS Twenty-eight infants participated ( 15 lactulose , 13 placebo ) . Small doses of lactulose appeared to be safe and did not cause diarrhea .  Premature infants on lactulose had more Lactobacilli-positive stool cultures that appeared earlier with larger number of colonies . The lactulose group tended to have less intolerance to enteral feedings , to reach full oral feeds earlier , and to be discharged home earlier . They also tended to have fewer episodes of late-onset sepsis , lower Bell stage necrotizing enterocolitis , and their nutritional laboratory indices were better , especially calcium and total protein . CONCLUSIONS This pilot study supports the safety of supplementing preterm infants ' feeds with low doses of lactulose . It also demonstrated trends that may suggest positive prebiotic effects OBJECTIVE Cholesterol is a nutrient of essential importance in infant feeding because it is necessary in membrane development . In adults with high lipid levels , high doses of inulin ( oligofructose ) inconsistently decreased levels of serum cholesterol . The aim of the present study was to evaluate cholesterol and triacylglycerol levels in infants receiving a formula with a specific mixture of 0.6 g/100 mL of galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( lcFOS ) in a ratio of 9/1 , a  control formula , or  breast milk .  Because the level of lcFOS in the infant milk is low , we hypothesized that there would be no differences between the formula groups . METHODS Two hundred fifteen infants were included in a prospect i ve , r and omized , double-blinded , placebo-controlled trial during the first 6 mo of life . Formula-fed infants were r and omized to receive a st and ard infant formula with a specific mixture of 0.6 g/100 mL of GOS/lcFOS , in a ratio of 9/1 , or a control formula .  Breast-fed infants were r and omized to receive one of these two formulas after the mother had decided to discontinue breastfeeding . Serum levels of cholesterol , high-density lipoprotein , low-density lipoprotein ( LDL ) , and triacylglycerol were determined at 8 and 26 wk of age and were provided for infants who received the GOS/lcFOS formula or control formula from birth or after cessation of breastfeeding and for the subgroups that were fully fed with breast milk and formula . RESULTS One hundred eighty-seven infants completed the study .  Total cholesterol and LDL levels at 8 and 26 wk were significantly lower in the formula-fed groups than in the breast-fed infants . There were no significant differences between the formula-fed groups . Levels of triacylglycerols and high-density lipoprotein did not differ between groups . CONCLUSION Our study demonstrated no differences in total cholesterol and LDL cholesterol in infants receiving an infant formula with GOS/lcFOS from infants receiving a control infant formula . Furthermore , total cholesterol and LDL cholesterol levels were higher in breast-fed infants than in formula-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
target: No statistically significant subgroup differences were found according to infant risk of allergy or type of infant feed .
  There is some evidence that a prebiotic supplement added to infant feeds may prevent eczema .
  It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk population s ; or whether it may have an effect on other allergic diseases including asthma
background: BACKGROUND Prebiotics ( commonly oligosaccharides ) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens .
  OBJECTIVES To determine the effect of prebiotic given to infants for the prevention of allergy .