title: Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal colonization and invasive fungal infection in premature infants Role of Enteric Supplementation of Probiotics on Late-onset Sepsis by Candida species in Preterm Low Birth Weight Neonates: A Randomized, Double Blind, Placebo-controlled Trial Efficacy of Bifidobacterium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birth-weight preterm infants: a double-blind, randomized, controlled trial. Early nutrition and leptin concentrations in later life. Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Effects of Bifidobacterium lactis Bb12 Supplementation on Intestinal Microbiota of Preterm Infants: a Double-Blind, Placebo-Controlled, Randomized Study Effects of bifidobacterium breve supplementation on intestinal flora of low birth weight infants. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome Prophylactic Probiotics to Prevent Death and Nosocomial Infection in Preterm Infants Effect of Bifidobacterium lactis on the Incidence of Nosocomial Infections in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial Cohort study of probiotics in a North American neonatal intensive care unit. Double-blind, randomised clinical assay to evaluate the efficacy of probiotics in preterm newborns weighing less than 1500 g in the prevention of necrotising enterocolitis Enteral feeding of premature infants with Saccharomyces boulardii. Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: a randomised controlled trial Safety and Tolerability of Lactobacillus reuteri DSM 17938 and Effects on Biomarkers in Healthy Adults: Results from a Randomized Masked Trial Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: A randomized, placebo-controlled trial Effect of Bifidobacterium breve M-16V Supplementation on Fecal Bifidobacteria in Preterm Neonates - A Randomised Double Blind Placebo Controlled Trial Enteral feeding of premature infants with Lactobacillus GG. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Lack of effect of Lactobacillus on gastrointestinal bacterial colonization in premature infants Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants Probiotics-supplemented feeding in extremely low-birth-weight infants Probiotics supplementation increases intestinal blood flow velocity in extremely low birth weight preterm infants Effects of probiotic and prebiotic on gastrointestinal motility in newborns. Low nutrient intake and early growth for later insulin resistance in adolescents born preterm Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial Effect of Bifidobacterium administration on very-low-birthweight infants. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial. The effects of probiotics on feeding tolerance, bowel habits, and gastrointestinal motility in preterm newborns.
abstract: Aim This study aims to compare the efficacy of orally administered Saccharomyces boulardii versus nystatin in prevention of fungal colonization and invasive fungal infections in very low birth weight infants . Method A prospect i ve , r and omized comparative study was conducted in preterm infants with a gestational age of ≤32 weeks and birth weight of ≤1,500 g. They were r and omized into two groups , to receive S. boulardii or nystatin .  Skin and stool cultures were performed for colonization and blood cultures for invasive infections , weekly . Results A total of 181 infants were enrolled ( S. boulardii group , n = 91 ; nystatin group , n = 90 ) . Fungal colonization of the skin ( 15.4 vs 18.9 % , p = 0.532 ) and the stool ( 32.2 vs 27 % , p = 0.441 ) were not different between the probiotic and nystatin groups . Two patients  had C and ida-positive blood culture in the nystatin group whereas none in the probiotic group . Feeding intolerance , clinical sepsis , and number of sepsis attacks were significantly lower in the probiotics group than in the nystatin group . Conclusion Prophylactic S. boulardii supplementation is as effective  as nystatin  in reducing fungal colonization and invasive fungal infection , more effective in reducing the incidence of clinical sepsis and number of sepsis attacks and has favorable effect on feeding intolerance Background : The increase in invasive fungal infections ( IFIs ) in neonatal intensive care unit ( NICU ) is jeopardizing the survival of preterm neonates . Probiotics modulating the intestinal microflora of preterm neonates may minimize enteral fungal colonization . Aims : This study was to examine whether probiotic supplementation in neonates reduced fungal septicemia . Material s and Methods : This prospect i ve , r and omized , double blind trial investigating the  supplementation of preterm infants with a probiotic  was done from May 2012 to April 2013 , with 112 subjects r and omized into two groups . Primary outcome : Decreased fungal colonization in gastrointestinal tract . Others : Incidence of late onset septicemia ; duration of the primary hospital admission ; number of days until full enteral feeds established . Results : Full feed establishment was earlier in probiotics group compared to placebo group ( P = 0.016 ) . The duration of hospitalization was less in the probiotic group ( P = 0.002 ) . Stool fungal colonization , an important outcome parameter was 3.03 ± 2.33 × 105 colony formation units ( CFU ) in the probiotics group compared to 3 ± 1.5 × 105 CFU in the placebo group ( P = 0.03 ) . Fungal infection is less in the study group ( P = 0.001 ) . Conclusion : The key features of our study were reduced enteral fungal colonization , reduce invasive fungal sepsis , earlier establishment of full enteral feeds , and reduced duration of hospital stay in the probiotics group BACKGROUND Probiotics are used for the prevention of necrotizing enterocolitis ( NEC ) because of their positive effects on intestinal motor function , modulation of inflammatory response , and mucosal barrier function . OBJECTIVE The objective was to assess whether the combined use of Lactobacillus casei and Bifidobacterium breve may prevent the occurrence of NEC stage ≥ 2 by the criteria of Bell in very-low-birth-weight preterm infants . DESIGN A double-blind , r and omized , controlled clinical trial was conducted in 231 preterm infants weighing from 750 to 1499 g at birth . The intervention group was composed of 119 infants who received human milk with probiotic supplementation ( B. breve and L. casei )  and a control group of 112 infants who received human milk containing no probiotics .  The primary outcome was the occurrence of NEC stage ≥ 2 as defined by Bell 's modified criteria . RESULTS Four confirmed cases of NEC stage ≥ 2 by Bell 's criteria occurred only in the control group . CONCLUSIONS Oral supplementation of B. breve and L. casei reduced the occurrence of NEC ( Bell 's stage ≥ 2 ) . It was considered that an improvement in intestinal motility might have contributed to this result . This trial was registered at www.is rct in.org as number 67165178 ( International St and ard R and omized Controlled Trial ) BACKGROUND Formula feeding or overweight in infancy may increase the later risk of obesity , but the mechanisms involved are uncertain . Because obesity is associated with high leptin concentrations relative to fat mass , programming of leptin concentrations may be one mechanism by which early nutrition influences later obesity . OBJECTIVE We tested the hypothesis that high nutrient intake or formula feeding in infancy programs greater leptin concentrations relative to fat mass in later life . DESIGN Serum leptin concentrations were measured by radioimmunoassay in 197 adolescents aged 13 - 16 y who were born preterm and r and omly assigned at birth to receive either a nutrient-enriched preterm formula or banked donated breast milk ( trial 1 ) or a preterm formula or a st and ard formula ( trial 2 ) . Fat mass was estimated with the use of bioelectrical impedance analysis . RESULTS After combining the results of trials 1 and 2 as planned , the ratio of leptin to fat mass was significantly greater in the children who received the preterm formula ( geometric : 0.84 microg x L(-1 ) x kg(-1 ) ) than in those who received st and ard formula or banked breast milk ( 0.62 microg x L(-1 ) x kg(-1 ) ; mean difference : 30.8 % ; 95 % CI for difference : 8.4 % , 53.2 % ; P = 0.007 ) . The difference between the diet groups remained significant after adjustment for age , sex , Tanner stage , social class , and fat mass . Human milk intake was significantly associated with lower leptin concentrations relative to fat mass in adolescence ( P = 0.023 ) , independent of potential confounding factors . CONCLUSION Programming of relative leptin concentrations by early diet may be one mechanism that links early nutrition with later obesity BACKGROUND Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly . Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer . AIM The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis ( NEC ) or sepsis in very low birth weight infants . STUDY DESIGN AND SUBJECTS A prospect i ve , double blind , placebo controlled trial was conducted in preterm infants ( ≤ 32 GWs , ≤ 1500 g birth weight ) . They were r and omized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo , starting with the first feed until discharged . OUTCOME MEASURES Necrotizing enterocolitis ( NEC ) or sepsis and NEC or death . RESULTS Birth weight and gestational age of the study ( n = 104 ) and the control ( n = 104 ) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks , respectively . Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group ( 9.6 % vs 7.7 % , p = 0.62 ; 28.8 % vs 23 % , p = 0.34 ) . Time to reach 100 mL/kg/day of enteral feeding ( 11.9 ± 7 vs 12.6 ± 7 days , p = 0.37 ) was not different between the groups . CONCLUSIONS Saccharomyces boulardii did not decrease the incidence of NEC or sepsis ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants . In particular , the colonization of preterm infants by bifidobacteria is delayed . A double-blind , placebo-controlled , r and omized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota . Both culture-dependent and culture-independent approaches were used to study the gut microbiota . Bifidobacterial numbers , determined by fluorescence in situ hybridization , were significantly higher in the probiotic than in the placebo group ( log10 values per g of fecal wet weight : probiotic , 8.18 + 0.54 [ st and ard error of the mean ] ; placebo , 4.82 + 0.51 ; P < 0.001 ) . A similar trend for bifidobacterial numbers was also obtained with the culture-dependent method . The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae ( log10 values of CFU per g of fecal wet weight : probiotic , 7.80 + 0.34 ; placebo , 9.03 + 0.35 ; P = 0.015 ) and Clostridium spp . ( probiotic , 4.89 + 0.30 ; placebo , 5.99 + 0.32 ; P = 0.014 ) than the infants in the placebo group . Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population . However , the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia BACKGROUND It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases . Because bacterial population s develop during the first day of life , the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants . METHODS The effects of oral administration of Bifidobacterium breve ( B. breve ) supplements were studied in a controlled trial with low birth weight infants ( average birth weight 1489 g ) . The infants were divided into three groups : Group A and B received a dose of 1.6 x 10(8 ) cells of B. breve supplement twice a day , commencing either from several hours after birth ( group A ) or 24 h after birth ( group B ) . Group C , the control group , received no supplement . RESULTS There were no significant differences in birth weight , treatment with antibiotics , and the starting time of breast-feeding among the three groups . A Bifidobacterium-predominant flora was formed at an average of 2 weeks after birth in group A and at an average of 4 weeks after birth in group B , while no Bifidobacterium was isolated in eight out of 10 infants in group C during the observation period of 7 weeks . In comparison between group A and B , Bifidobacterium was detected significantly earlier in group A , and the number of Enterobacteriaceae present in the infants at 2 weeks after birth was significantly lower in group A. CONCLUSION The results of the present study suggest that very early administration of B. breve to low birth weight infants is useful in promoting the colonization of the Bifidobacterium and the formation of a normal intestinal flora Objective : To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by C and ida species , of late-onset sepsis and neurological outcome in preterm newborns . Study Design : A prospect i ve study was conducted in 249 preterms who were subdivided into three groups :  one group ( n=83 ) was supplemented with Lactobacillus ( L. ) reuteri , one group with L. rhamnosus ( n=83 ) and the other with no supplementation ( n=83 ) . The fungal colonization in the gastrointestinal tract , the late onset of sepsis and clinical parameters were recorded . A neurological structured assessment was further performed at 1 year of age . Result : C and ida stool colonization was significantly higher ( P<0.01 ) in the control group than in the groups treated with probiotics . The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups . Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group . Conclusion : The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by C and ida , in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms BACKGROUND AND OBJECTIVE : It has been suggested that probiotics may decrease  infant mortality and nosocomial infections because of their ability to suppress colonization and translocation of bacterial pathogens in the gastrointestinal tract . We design ed a large double-blinded placebo-controlled trial using Lactobacillus reuteri to test this hypothesis in preterm infants . METHODS : Eligible infants were r and omly assigned during the first 48 hours of life to either daily probiotic administration or placebo .  Infants in the intervention group were administered enterally 5 drops of a probiotic preparation containing 108 colony-forming units of L reuteri DSM 17938 until death or discharge from the NICU . RESULTS : A total of 750 infants ≤2000 g were enrolled . The frequency of the primary outcome , death , or nosocomial infection , was similar in the probiotic and placebo groups ( relative risk 0.87 ; 95 % confidence interval : 0.63–1.19 ; P = .376 ) . There was a trend toward a lower rate of nosocomial pneumonia in the probiotic group ( 2.4 % vs 5.0 % ; P = .06 ) and a nonsignificant 40 % decrease in necrotizing enterocolitis ( 2.4 % vs 4.0 % ; P = .23 ) . Episodes of feeding intolerance and duration of hospitalization were lower in infants ≤ 1500 g ( 9.6 % vs 16.8 % [ P = .04 ] ; 32.5 days vs 37 days [ P = .03 ] ) . CONCLUSIONS : Although L reuteri did not appear to decrease the rate of the composite outcome , the trends suggest a protective role consistent with what has been observed in the literature . Feeding intolerance and duration of hospitalization were decreased in premature infants ≤1500 Background : Nosocomial infections endanger preterm infants . Objective : The aim of the present controlled r and omized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight ( VLBW ; < 1,500 g ) < 30 weeks of gestation . Patients and Methods : In a r and omized controlled trial , 183 VLBW infants < 30 weeks of gestation were stratified according to gestational age ( 23–26 and 27–29 weeks ) and early antibiotic therapy ( days 1–3 , yes or no ) and r and omly assigned to have their milk feedings supplemented with B. lactis ( 6 × 2.0 × 109 CFU/kg/day , 12 billion CFU/kg/day ) or placebo for the first 6 weeks of life . Primary outcome was the ‘ incidence density ’ of nosocomial infections defined as periods of elevated C-reactive protein ( > 10 mg/l ) from day 7 after initiation of milk feedings until the 42nd day of life ( number of nosocomial infections/total number of patient days ) . The main secondary outcome was necrotizing enterocolitis ( NEC ; ≧stage 2 ) . Results : There were 93 infants in the B. lactis group and 90 in the placebo group . There was no significant difference between the two groups with regard to the incidence density of nosocomial infections ( 0.021 vs. 0.016 ; p = 0.9 , χ2 test ) . There were 2 cases of NEC in the B. lactis group and 4 in the placebo group . None of the blood cultures grew B. lactis . Conclusion : In the present setting , B. lactis at a dosage of 6 × 2.0 × 109 CFU/kg/day ( 12 billion CFU/kg/day ) did not reduce the incidence density of nosocomial infections in VLBW infants . No adverse effect of B. lactis was observed BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset  sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing < 1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe OBJECTIVE To determine whether routine probiotic administration to very preterm infants would reduce the incidence of necrotizing enterocolitis ( NEC ) without adverse consequences . STUDY DESIGN Since the end of July 2011 , we have administered a probiotic mixture to all admitted infants of < 32 weeks ' gestation . We give 0.5 g of a mixture of 4 bifidobacteria ( Bifidobacterium breve , bifidum , infantis , and longum ) and Lactobacillus rhamnosus HA-111 [ corrected ] ( 2 × 10(9 ) colony-forming units ) per day , starting with the first feed , until the infant reaches 34 weeks . We compared complications among infants admitted during the first 17 months of routine use with those admitted during the previous 17 months . RESULTS Two hundred ninety-four infants received probiotics , and 317 infants formed the comparison group . Introduction of probiotics was associated with a reduction in NEC ( from 9.8 % to 5.4 % , P < .02 ) , a nonsignificant decrease in death ( 9.8 % to 6.8 % ) , and a significant reduction in the combined outcome of death or NEC ( from 17 % to 10.5 % , P < .05 ) . After adjustment for gestational age , intrauterine growth restriction , and sex , the improvements remained significant ( OR for NEC , 0.51 ; 95 % CI , 0.26 - 0.98 ; OR for death or NEC , 0.56 ; 95 % CI , 0.33 - 0.93 ) . There was no effect of probiotics on health care-associated infection . DISCUSSION A product that is readily available in North America , that has excellent quality control , and that contains strains similar to those that have been shown effective in r and omized controlled trials substantially reduced the frequency of NEC in our neonatal intensive care unit Background A r and omised , double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in the prevention of  necrotising enterocolitis ( NEC ) in newborns weighing < 1500 g. Methods We studied a group of 150 patients who were r and omised in two groups after parental consent was obtained , to receive either a daily feeding supplementation with a multispecies probiotic ( Lactobacillus acidophilus , Lactobacillus rhamnosus , Lactobacillus casei , Lactobacillus plantarum , Bifidobacteruim infantis , Streptococcus thermophillus ) 1 g per day plus their regular feedings or to receive their regular feedings with nothing added ( control group ) , over the period of January 2007 through June 2010 . Clinicians in care of the infants were blinded to the group assignment . Results The primary outcome was the development of NEC . Both groups were comparable , with no differences during hospitalisation , including the type of nutrition received . Blood cultures obtained from cases that developed sepsis did not reveal lactobacillus or Bifidobacteria growth . No differences were detected in terms of NEC risk reduction ( RR : 0.54 , 95 % CI 0.21 to 1.39 ) although we did observe a clear trend in the reduction of NEC frequency in the studied cases : 6 ( 8 % ) versus 12 ( 16 % ) in the control group . When the combined risk of NEC or death was calculated as a post hoc analysis , we found a significantly lower risk ( RR : 0.39 , 95 % CI 0.17 to 0.87 ) for the study group . Conclusions Probiotics may offer potential benefits for premature infants and are a promising strategy in the reduction of the risk of NEC in preterm newborns BACKGROUND Saccharomyces boulardii ( SB ) is a yeast that acts both as a probiotic and as a polyamine producer . Probiotics prevent the overgrowth of pathogens in the gut while polyamines enhance intestinal maturation . The aim of this r and omized study was to investigate the ability of SB to modify the gut microbial ecology and its function . METHODS A total of 87 healthy babies with gestational age 28 - 32 weeks were studied . They were r and omly assigned to receive a preterm formula to which SB or maltodextrins was added for 30 days . Evaluations were made on the following : SB tolerance and weight gain , faecal flora analysis , intestinal D-xylose absorption and faecal lipid excretion . RESULTS SB was well tolerated by the infants . There was no difference in weight gain between the two groups . Median log of colony forming units per gram of faeces for Escherichia coli and enterococci was significantly lower in the SB group [ E. coli : 2.67 ( 0.045 ) vs. 2.75 ( 0.058 ) , P<0.001 ; enterococci : 2.14 ( 0.359 ) vs. 2.19 ( 0.138 ) , P<0.05 ] . On the other h and , the number of bifidobacteria and staphylococci in the stools was significantly higher in the SB group [ bifidobacteria : 2.65 ( 0.083 ) vs. 2.27 ( 0.075 ) , P<0.001 ; staphylococci : 1.23 ( 0.869 ) vs. 0.6 ( 0.281 ) , P<0.001 ] . D-Xylose and lipid absorption was not improved by SB [ median blood D-xylose : 1.5 ( 0.4 ) mmol/l vs. 1.35 ( 0.3 ) mmol/l , P>0.1 ; median stool steatocrit : 64 % ( 3.05 % ) vs. 65 % ( 2.72 % ) P>0.5 ] . CONCLUSIONS An SB-supplemented formula is well tolerated by preterm infants , it has a beneficial effect on stool flora bringing it closer to that of breast fed babies but it does not improve D-xylose or lipid gut absorption Objective To evaluate the effect of oral Lactobacillus reuteri ( L reuteri ) first on the incidence and severity of Necrotising enterocolitis ( NEC ) and second on sepsis . Design Prospect i ve r and omised controlled study . Setting Tertiary neonatal intensive care unit . Patients and interventions Preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 g were included ( n=400 ) . Infants in the first group were given 100 million CFU/day ( 5 drops ) of lyophilised L reuteri ( DSM 17938 ) mixed in breast milk or formula , starting from first feeding until discharge . Participants in the control group were given a placebo . Main outcome measures To determine and compare the frequency of NEC and /or death after 7 days , frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Results There was no statistically significant difference between groups in terms of frequency of NEC stage ≥2 ( 4 % vs 5 % ; p=0.63 ) or overall NEC or mortality rates ( 10 % vs 13.5 % ; p=0.27 ) . Frequency of proven sepsis was significantly lower in the probiotic group compared to the control group ( 6.5 % vs 12.5 % ; p=0.041 ) . A significant difference was also observed with regard to rates of feeding intolerance ( 28 % vs 39.5 % ; p=0.015 ) and duration of hospital stay ( 38 ( 10–131 ) vs 46 ( 10–180 ) days ; p=0.022 ) . Conclusions Our results show that oral L reuteri does not seem to affect the overall rates of NEC and /or death in preterm infants followed up in the neonatal intensive care unit , and significant reductions were observed in the frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Trial registration number NCT01531179 Background There are few carefully- design ed studies investigating the safety of individual probiotics approved under Investigational New Drug policies . Objectives The primary aim of this prospect i ve , double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 ( LR )  for 2 months is safe and well-tolerated . Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages , expression of toll-like receptors (TLR)-2 and −4 on circulating peripheral blood mononuclear cells ( PMBCs ) , cytokine expression by stimulated P BMC , and intestinal inflammation as measured by fecal calprotectin . Methods Forty healthy adults were r and omized to a daily dose of 5 × 108 CFUs of LR ( n = 30 ) or placebo ( n = 10 ) for 2 months . Participants completed a daily diary card and had 7 clinic visits during treatment and observation . Results There were no severe adverse events ( SAEs ) and no significant differences in adverse events ( AEs ) . There were no differences in P BMC subclasses , TLRs , or cytokine expression after treatment . The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment : 50 µg/g ( IQR 24–127 µg/g ) vs. 17 µg/g ( IQR 11–26 µg/g ) , p = 0.03 , although values remained in the normal clinical range ( 0–162.9 µg/g ) . LR vials retained > 108 CFUs viable organisms/ml . Conclusions LR is safe and well tolerated in adults , without significant changes in immunologic markers . There was a small but significant increase in fecal calprotectin , perhaps indicating some element of immune recognition at the intestinal level . Trial Registration Clinical Trials.gov Background Simple and safe strategies for the prevention of viral respiratory tract infections ( RTIs )  are needed . Objective We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants . Methods In this r and omized , double-blind , placebo-controlled trial ( Clinical Trials.gov no. NCT00167700 ) , 94 preterm infants ( gestational age , ≥32 + 0 and ≤36 + 6 weeks ; birth weight , > 1500 g ) treated at Turku University Hospital , Turku , Finl and , were allocated to receive oral prebiotics ( galacto-oligosaccharide and polydextrose mixture , 1:1 ) , a probiotic ( Lactobacillus rhamnosus GG , ATCC 53103 ) , or placebo ( microcrystalline cellulose ) between days 3 and 60 of life . The primary outcome was the incidence of clinical ly defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing . Secondary outcomes were the severity and duration of RTIs . Results A significantly lower incidence of RTIs was detected in infants receiving prebiotics  ( rate ratio [ RR ] , 0.24 ; 95 % CI , 0.12 - 0.49 ; P < .001 ) or probiotics ( RR , 0.50 ; 95 % CI , 0.28 - 0.90 ; P = .022 ) compared with those receiving placebo . Also , the incidence of rhinovirus-induced episodes , which comprised 80 % of all RTI episodes , was found to be significantly lower in the prebiotic ( RR , 0.31 ; 95 % CI , 0.14 - 0.66 ; P = .003 ) and probiotic ( RR , 0.49 ; 95 % CI , 0.24 - 1.00 ; P = .051 ) groups compared with the placebo group . No differences emerged among the study groups in rhinovirus RNA load during infections , duration of rhinovirus RNA shedding , duration or severity of rhinovirus infections , or occurrence of rhinovirus RNA in asymptomatic infants . Conclusions Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections Background Probiotic supplementation significantly reduces the risk of necrotising enterocolitis ( NEC ) and all cause mortality  in preterm neonates . Independent quality assessment is important before introducing routine probiotic supplementation in this cohort . Aim To assess product quality , and confirm that Bifidobacterium breve ( B. breve ) M-16V supplementation will increase fecal B. breve counts without adverse effects . Methods and Participants Strain identity ( 16S rRNA gene sequencing ) , viability over 2 year shelf-life were confirmed , and microbial contamination of the product was ruled out . In a controlled trial preterm neonates ( Gestation <33 weeks ) ready to commence or on feeds for < 12 hours were r and omly allocated to either B. breve M-16V ( 3 × 109 cfu/day ) or placebo ( dextrin ) supplementation  until the corrected age 37 weeks . Stool sample s were collected before ( S1 ) and after 3 weeks of supplementation ( S2 ) for study ing fecal B. breve levels using quantitative PCR ( Primary outcome ) . Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II . Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests , and McNemar and Wilcoxon signed-rank tests for paired comparisons . Results A total of 159 neonates ( Probiotic : 79 , Placebo : 80 ) were enrolled . Maternal and neonatal demographic characteristics were comparable between the groups . The proportion of neonates with detectable B. breve increased significantly post intervention : Placebo : [ S1:2/66 ( 3 % ) , S2 : 25/66 ( 38 % ) , p<0.001 ] Probiotic : [ S1 : 29/74 ( 40 % ) , S2 : 67/74 ( 91 % ) , p<0.001 ] . Median S1 B. breve counts in both groups were below detection ( < 4.7 log cells.g−1 ) , increasing significantly in S2 for the probiotic group ( log 8.6 ) while remaining < 4.7 log in the control group ( p<0.001 ) . There were no adverse effects including probiotic sepsis and no deaths . NEC≥Stage II occurred in only 1 neonate ( placebo group ) . Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates . Trial Registration Australia New Zeal and Clinical Trial Registry ACTRN The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so , does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae , enterococci , yeasts or staphylococci , and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome . Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge . The infants were r and omised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks . The clinical features of the two groups of infants were similar . Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants . However , colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation .  Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms . Thirty premature infants were matched by birth weight and gestational age , r and omized and fed double blind either lactobacilli-containing formula or non-lactobacilli-containing formula within 72 hours of delivery . The two study groups were screened weekly by culture for stool lactobacilli , for gram-negative bacteria and for antibiotic resistance of these bacteria .  Lactobacilli  were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli ( P < 0.001 ) . Gram-negative enteric organisms were isolated during 40 of the 86 weeks ( 47 % ) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks ( 49 % ) for patients not receiving lactobacilli . There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates ( 4 of 40 vs. 0 of 28 ) . These results suggest that facultative gram-negative enteric bacterial colonization , with either total or aminoglycoside-resistant strains , is not decreased by oral feedings of Lactobacillus acidophilus in premature infants Background : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age <33 weeks or birthweight < 1,500 g were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration  of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population Objective : The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight ( ELBW ) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age ( PMA ) . Other important outcome measures , such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated . Study Design : We conducted a multicenter r and omized controlled double-blinded clinical study . The probiotics-supplementation ( PS ) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks ( PMA ) . The control ( C ) group received unsupplemented feedings .  Infant weight and feeding volumes were recorded daily during the first 28 days of study period . Weights were also recorded at 34 weeks PMA . Result : A total of 101 infants were enrolled ( PS 50 versus C 51 ) . There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA ( PS group 58 % versus C group 60 % , ( P value 0.83 ) ) or in the average volume of feeding during 28 days after study entry ( PS group 59 ml kg−1 versus C group 71 ml kg−1 , ( P value 0.11 ) ) . Calculated growth velocity was higher in the PS group compared with the C group ( 14.9 versus 12.6 g per day , ( P value 0.05 ) ) . Incidences of necrotizing enterocolitis ( NEC ) , as well as mortality were similar between the two groups . Conclusion : Although probiotic-supplemented feedings improve growth velocity in ELBW infants , there was no improvement in the percentage of infants with growth delay at 34 weeks PMA . There were no probiotic-related adverse events reported Objective : To determine whether probiotics supplementation affects intestinal blood flow velocity in extremely low birth weight neonates . Study Design : In this r and omized , double-blind , placebo-controlled study , probiotics were added to the first enteral feeding and continued until discharge or 34 weeks postmenstrual age . Pulsed Doppler was used to measure prepr and ial and postpr and ial ( at 30 and 60 min ) time-averaged mean velocity ( TAMV ) , peak systolic velocity ( PSV ) and end diastolic velocity ( EDV ) during the second week of life after ⩾7 days of probiotics supplementation . Result : A total of 31 infants were studied , 15 were r and omized to the probiotic and 16 to the placebo groups . There was a significant postpr and ial increase in TAMV for the probiotic vs the placebo group ( P=0.035 ) , with PSV and EDV showing a trend . Demographic and clinical variables were similar between the groups . Conclusion : Probiotics administration significantly increases postpr and ial intestinal blood flow in extremely low birth weight preterm neonates when compared with the placebo group To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk . The aim of this study was to evaluate the effects of prebiotic , probiotic added to a st and ard formula on gastrointestinal motility respect to placebo-formula .  Cutaneous electrogastrography ( EGG ) and ultrasound gastric emptying ( GE ) were performed in 49 preterm newborns . 17 newborns were exclusively breast-fed ; 32 were r and omly assigned to receive prebiotic-added formula ( 0.8 g/dl of a mixture from scGOS and lcFOS , ratio 9:1 ) ( 10 ) , a probiotic-added formula ( L. reuteri at dose of 1x10(8 ) colony forming units ( CFU ) per day ) ( 10 ) , a formula with placebo ( 12 ) for 30 days . No difference was seen in the nutritional parameters and no adverse events were reported . After the intervention period , the prebiotic , probiotic , and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group ( ANOVAon ranks p<0.001 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 ; and ANOVA on ranks p=0.005 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 , respectively ) . Feeding preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk BACKGROUND In animals , acceleration of neonatal growth is thought to increase the later propensity to insulin resistance and non-insulin-dependent diabetes , whereas slow growth as a consequence of undernutrition is thought to have a beneficial effect . To test this hypothesis in people , we measured fasting concentrations of 32 - 33 split proinsulin , a marker of insulin resistance , in adolescents born preterm who had participated in r and omised intervention trials of neonatal nutrition , and in adolescents born at term . METHODS We determined fasting 32 - 33 split proinsulin concentration in participants aged 13 - 16 years born preterm and r and omised to receive a nutrient-enriched or lower-nutrient diet ( n=216 ) or in a reference group born at term ( n=61 ) . FINDINGS Fasting 32 - 33 split proinsulin concentration was greater in children given a nutrient-enriched diet ( geometric mean 7.2 pmol/L , 95 % CI 6.4 - 8.1 ) than in those given the lower-nutrient diet ( 5.9 pmol/L [ 5.2 - 6.4 ] ; mean difference 20.6 % [ 5.0 - 36.3 ] ; p=0.01 ) . Healthy babies born at term had similar fasting 32 - 33 split proinsulin concentrations ( 6.9 pmol/L ; 6.0 - 8.2 ) to the nutrient-enriched group . In non-r and omised analyses , fasting 32 - 33 split proinsulin concentration was associated with greater weight gain the first 2 weeks of life ( 13.2 % [ 5.4 - 20.9 ] change per 100 g weight increase ; p=0.001 ) independent of birthweight , gestation , neonatal morbidity , and demographic , anthropometric , and socioeconomic factors . INTERPRETATION Our results suggest that relative undernutrition early in life in children born preterm may have beneficial effects on insulin resistance BACKGROUND Colonization by C and ida species is the most important predictor of the development of invasive fungal disease in preterm neonates , and the enteric reservoir is a major site of colonization . We evaluated the effectiveness of an orally supplemented probiotic ( Lactobacillus casei subspecies rhamnosus ; Dicoflor [ Dicofarm spa ] ; 6 x 10(9 ) cfu/day ) in the prevention of gastrointestinal colonization by C and ida species in preterm , very low birth weight ( i.e. , < 1500-g ) neonates during their stay in a neonatal intensive care unit . METHODS Over a 12-month period , a prospect i ve , r and omized , blind , clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit . During the first 3 days of life , the neonates were r and omly assigned to receive either an oral probiotic added to human ( maternal or pooled donors ' ) milk ( group A ) or human milk alone ( group B ) for 6 weeks or until discharge from the NICU , if the neonate was discharged before 6 weeks . On a weekly basis , specimens obtained from various sites ( i.e. , oropharyngeal , stool , gastric aspirate , and rectal specimens ) were collected from all patients for surveillance culture , to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract . RESULTS The incidence of fungal enteric colonization ( with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site ) was significantly lower in group A than in group B ( 23.1 % vs. 48.8 % ; relative risk , 0.315 [ 95 % confidence interval , 0.120 - 0.826 ] ; P = .01 ) . The numbers of fungal isolates obtained from each neonate ( P = .005 ) and from each colonized patient ( P = .005 ) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001 - 1500 g. There were no changes in the relative proportions of the different C and ida strains . No adverse effects potentially associated with the probiotic were recorded . CONCLUSIONS Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by C and ida species among very low birth weight neonates Background / Objective : The identification of probiotic species involved in gut homeostasis and their potential therapeutic benefits have led to an interest in their use for preventing necrotizing enterocolitis ( NEC ) . Although bifidobacterium and lactobacilli sp. have been used to reduce the incidence of NEC in clinical trials . Lactobacillus sporogenes has not been used in the prevention of NEC in very low-birth weight infants yet . The objective of this study was to evaluate the efficacy of orally administered L sporogenes in reducing the incidence and severity of NEC in very low-birth weight ( VLBW ) infants . Subjects/ Methods : A prospect i ve , blinded , r and omized controlled trial was conducted in preterm infants with a gestational age of <33 weeks or birth weight of < 1500 g. VLBW infants who survived to start enteral feeding were r and omized into two groups The infants in the study group were given L. sporogenes with a dose of 350 000 000 c.f.u . added to breast milk or formula , once a day , starting with the first feed until discharged . The infants in the control group were fed without L. sporogenes supplementation . The primary outcome measurement was death or NEC ( Bell 's stage ⩾2 ) . Results : A total of 221 infants were studied : 110 in the study group and 111 in the control group . There was no significant difference in the incidence of death or NEC between the groups . Feeding intolerance was significantly lower in the probiotics group than in the control group ( 44.5 % ( n : 49 ) vs 63.1 % ( n : 70 ) , respectively ; P=0.006 ) . Conclusions : L. sporogenes supplementation at the dose of 350 000 000 c.f.u/day is not effective in reducing the incidence of death or NEC in VLBW infants , however , it could improve the feeding tolerance BACKGROUND Despite data relating body size in early life to later cardiovascular outcomes , the hypothesis that nutrition affects such outcomes has not been established . Breastfeeding has been associated with lower blood pressure in later life , but previous studies have not controlled for possible confounding factors by using a r and omised design with prospect i ve follow-up . We undertook such a study to test the hypothesis that early diet programmes blood pressure in later life in children r and omly assigned different diets at birth . METHODS Blood pressure was measured at age 13 - 16 years in 216 ( 23 % ) of a cohort of 926 children who were born prematurely and had participated at birth in two parallel r and omised trials in five neonatal units in the UK . Dietary interventions were : donated banked breastmilk versus preterm formula and st and ard term formula versus preterm formula . FINDINGS Children followed up at age 13 - 16 years were similar to those not followed up in terms of social class and anthropometry at birth . Mean arterial blood pressure at age 13 - 16 years was lower in the 66 children assigned banked breastmilk ( alone or in addition to mother 's milk ) than in the 64 assigned preterm formula ( mean 81.9 [ SD 7.8 ] vs 86.1 [ 6.5 ] mm Hg ; 95 % CI for difference -6.6 to -1.6 ; p=0.001 ) . In non-r and omised analyses , the proportion of enteral intake as human milk in the neonatal period was inversely related to later mean arterial pressure ( beta=-0.3 mm Hg per 10 % increase [ 95 % CI -0.5 to -0.1 ] ; p=0.006 ) . No differences were found in the term formula ( n=44 ) versus preterm formula ( n=42 ) comparison . INTERPRETATION Breastmilk consumption was associated with lower later blood pressure in children born prematurely . Our data provide experimental evidence of programming of a cardiovascular risk factor by early diet and further support the long-term beneficial effects of breastmilk BACKGROUND Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG )  and 49 received placebo .  The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed < or = 1000 g , presumably because of more frequent suspensions of enteral feeding , more courses of antibiotic treatment , or both . CONCLUSIONS Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576 AIM To investigate the colonisation withBifidobacterium breve of the bowels of very low birthweight ( VLBW ) infants . METHODS The adverse effects of B breve were examined in 66 VLBW infants ( preliminary study ) . A prospect i ve r and omised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years . Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants . The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody . RESULTS In the preliminary study there were no side effects attributable to the bacteria . Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73 % at 2 weeks of age , but only 12 % in the control group . Early administration of B brevesignificantly decreased aspirated air volume from the stomach and improved weight gain . CONCLUSIONS B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants , probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules BACKGROUND The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 ( B. bifidum ) on accelerating enteral feeding and bacterial colonization in very-low-birthweight ( VLBW ) infants . METHODS We conducted a single-center prospect i ve pilot study . Thirty-six VLBW infants were r and omly divided into two groups : group E , wherein B. bifidum was supplemented within 48 h of birth , and group L , wherein it was supplemented more than 48 h after birth . RESULTS Group E and group L reached a total feeding volume of 100 mL/(kg/day ) after 10 [ 7 - 13 ] days and 11 [ 10 - 15 ] days , respectively ( median [ quartile ] ) . The daily bodyweight gain in group E was significantly higher ( 21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day , P < 0.02 ; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day , P < 0.04 ) . No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real-time polymerase chain reaction assay at 1 and 4 weeks of age . However , the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth . The incidence of morbidities between the groups was similar . CONCLUSION The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity . Furthermore , the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth BACKGROUND Nutrient intakes meeting recommended dietary intakes ( RDIs ) take time to establish and once established are rarely maintained throughout hospital stay in preterm infants . A nutrient deficit , therefore , accrues . RDI are based on needs for maintenance and growth , with no provision to replace this deficit . We , therefore , hypothesized that postnatal malnutrition and growth retardation were inevitable in infants fed current RDI . METHODOLOGY Dietary intakes were prospect ively collected , by a single observer ( N.P. ) , on a daily basis in a group of preterm infants ( n = 105 ; birth weight < /=1750 g ; gestational age < /=34 weeks ) admitted to neonatal intensive care unit over a 6-month period . Actual was subtracted from recommended energy ( 120 kcal/kg/day ) and protein ( 3 g/kg/day ) intakes and nutritional deficits calculated . Infants were weighed on admission and throughout hospital stay . The data were analyzed using a combination of repeated measures analysis of variance and stepwise regression analysis . RESULTS Nutrient intakes meeting current RDIs were rarely achieved during early life . By the end of the first week , cumulative energy and protein deficits were 406 + /- 92 and 335 + /- 86 kcal/kg and 14 + /- 3 and 12 + /- 4 g/kg in infants < /=30 and those at > /=31 weeks . By the end of the fifth week , cumulative energy and protein deficits were 813 + /- 542 and 382 + /- 263 kcal/kg and 23 + /- 12 and 13 + /- 15 g/kg and the z scores were -1.14 + /-.6 and -.82 + /-.5 for infants at < /=30 and > /=31 weeks . Stepwise regression analysis indicated that variation in dietary intake accounted for 45 % of the variation in changes in z score . CONCLUSIONS Preterm infants inevitably accumulate a significant nutrient deficit in the first few weeks of life that will not be replaced when current RDIs are fed . This deficit can be directly related to subsequent postnatal growth retardation.postnatal growth retardation , preterm infants BACKGROUND AND AIM Intestinal flora of preterms , dominantly presents with decreased amounts of physiological microbiota . This double blinded r and omized control trial compared the stool of bottle fed preterms , r and omized to receive lactobacillus rhamnosus GG ( LGG ) 6x109or placebo with formula feeding . STUDY DESIGN 46 enterally fed preterms were r and omized to receive probiotics or placebo within 0 - 3days after birth . All personnel were blinded to treatment assignment . Faecal sampling  was preformed at day 7 , 21 , 42 . Presence of LGG colonization , somatic growth and length of hospital stay were recorded . RESULTS 60 patients were initially identified and enrolled but after exclusion criteria were applied , 21 babies were analyzed in the probiotic group and 26 in the placebo group . The number of lactobacillus were significantly higher ( p=0.014 ) on day 7 , and 21 ( p=0.024 ) in the study group , and so was the number of enterobacteriaceae on all study days ( p=0.004 , p=0.000 , p=0.000 ) , and Enterococcus sp on day 21 ( p=0.000 ) . The amount of sample s positive for staphylococci was significantly higher in the study group , on days 7 and 42 ( p=0.001 and 0.011 ) . We did not show a significant difference in weight gain upon discharge between the groups p=0.567 , 95 % CI ( -168 ; 305 ) or mean of hospital stay p=0.421 95 % CI ( -13.43;5.71 ) . CONCLUSIONS A preterm infant formula with an addition of probiotics leads to a rapid growth of LGG in the gut of bottle fed infants , but does not decrease the amount of pathogenic organisms , nor increase weight gain during enteral feeding , or decrease length of hospital stay OBJECTIVE To investigate the effect of dietary supplementation with a probiotic on feeding tolerance and gastrointestinal motility in healthy formula-fed preterm infants . STUDY DESIGN Thirty preterm newborns were enrolled ; 10 were exclusively breast-fed , and the remaining 20 were r and omly assigned in a double-blind manner to receive either Lactobacillus reuteri ATCC 55730 ( at dose of 1 x 10(8 ) colony forming units a day ) or placebo for 30 days . Clinical symptoms of gastrointestinal function ( regurgitation , vomiting , inconsolable crying , and evacuation ) and physiological variables ( gastric electrical activity and emptying ) were recorded before and after the dietary intervention . RESULTS Body weight gains per day were similar for the 3 groups , and no adverse events were recorded . Newborns receiving probiotics showed a significant decrease in regurgitation and mean daily crying time and a larger number of stools compared with those given placebo .  Gastric emptying rate was significantly increased , and fasting antral area was significantly reduced in both the newborns receiving L. reuteri and breast-fed newborns compared with placebo . CONCLUSIONS Our results suggest a useful role for L. reuteri supplementation in improving feeding tolerance and gut function in formula-fed preterm newborns
target: Other benefits included fewer episodes of feed intolerance , better weight gain and growth velocity , decreased transition time from orogastric to breast feeds , and increased postpr and ial mesenteric flow .
  There were no adverse effects of probiotic supplementation .
  Probiotics reduced the time to full enteral feeds  in preterm neonates .
background: INTRODUCTION The optimization of enteral nutrition is a priority in preterm neonates worldwide .
  Probiotics are known to improve gut maturity and function in preterm neonates .
  To our knowledge , previous systematic review s have not adequately assessed the effects of probiotic supplementation on enteral nutrition in preterm neonates .
  OBJECTIVE We assessed the evidence on effects of probiotics on enteral nutrition in preterm neonates .