Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: A randomized, placebo-controlled trial Effects of probiotic and prebiotic on gastrointestinal motility in newborns. 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 Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. Probiotics and prebiotics in gastrointestinal disorders World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial. The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight 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. Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Effect of Neutral and Acidic Oligosaccharides on Fecal IL-8 and Fecal Calprotectin in Preterm Infants Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis The effect of early nutritional supplementation with a mixture of probiotic, prebiotic, fiber and micronutrients in infants with acute diarrhea in Indonesia. Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1-6 months of age: a randomized controlled trial. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study Pro- and Prebiotic Supplementation Induces a Transient Reduction in Hemoglobin Concentration in Infants The politics of probiotics: probiotics, necrotizing enterocolitis and the ethics of neonatal research
OBJECTIVE To evaluate the impact of early prebiotic and probiotic intervention on  preterm infants ' well-being , crying , growth , and microbiological programming . STUDY DESIGN Ninety-four preterm infants ( gestational age 32 - 36 weeks and birth weight > 1500 g ) r and omized to receive prebiotics ( mixture of galacto-oligosaccharide and polydextrose 1:1 ) , probiotics ( Lactobacillus rhamnosus GG ) , or placebo during the first 2 months of life were followed up for 1 year . Infants were categorized based on the extent of crying and irritability during the first 2 months of life , and their gut microbiota was investigated by fluorescence in situ hybridization ( n = 66 ) and quantitative polymerase chain reaction ( n = 63 ) . RESULTS A total of 27 of 94 infants ( 29 % ) infants were classified as excessive criers , significantly less frequently in the prebiotic and the probiotic groups than in the placebo group ( 19 % vs 19 % vs 47 % , respectively ; P = .02 ) . The placebo group had a higher percentage of Clostridium histolyticum group bacteria in their stools than did the probiotic group ( 13.9 % vs 8.9 % , respectively ; P = .05 ) . There were no adverse events related to either supplementation . CONCLUSIONS Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants . This original finding may offer new therapeutic and preventive measures for this common disturbance in early life 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 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 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 BACKGROUND : Eczema is the most common inflammatory skin disease of childhood , characterized by an itchy red rash that usually involves the face and skin folds . There is currently no curative treatment for eczema , so the reduction of eczema incidence through disease prevention is a desirable goal . Potential interventions for preventing eczema include exclusive breastfeeding , hydrolysed protein formulas and soy formulas when bottle feeding , maternal antigen avoidance , omega oil supplementation , prebiotics and probiotics . OBJECTIVES : This overview of review s aims to present the current body of data from Cochrane and non-Cochrane review s to provide the most up-to- date evidence on the efficacy and safety of interventions to prevent eczema in infants and children at different risk levels for developing allergic disease . METHODS : Our pool of Cochrane and non-Cochrane review s came from the 2010 United Kingdom National Health Service ( NHS ) Evidence Skin Disorders Annual Evidence Up date s Mapping Exercise on Atopic Eczema . This group used a comprehensive search strategy last conducted in August 2010 to identify all systematic review s on eczema prevention . We identified all review s that met our pre-specified inclusion criteria , and data were extracted , analysed , compiled into tables and synthesized using quantitative and qualitative methods . MAIN RESULTS : Seven systematic review s containing 39 relevant trials with 11 897 participants were included in this overview . Overall , there was no clear evidence that any of the main interventions review ed reduced eczema incidence . In subgroup analyses of infants at high risk of allergic disease , an observational study found that exclusive breastfeeding for at least six months compared with introduction of solids at three to six months decreased the incidence of eczema by 60 % ( risk ratio ( RR ) : 0.40 ; 95 % confidence interval ( CI ) : 0.21 , 0.78 ) , and a r and omized controlled trial found that prebiotics compared with no prebiotics  decreased incidence by 58 % ( RR : 0.42 ; 95 % CI : 0.21 , 0.84 ) . However , each of these findings was based on the results of a single small trial , and no intervention reduced eczema incidence beyond the first two years of life . Although we pre-specified incidence of atopic eczema ( i.e. eczema associated with immunoglobulin E ( IgE ) sensitization ) as a primary outcome , data on whether participants diagnosed with eczema were truly atopic were largely lacking from systematic review s. Similarly , data on atopy , measured using skin prick tests or specific IgE tests to allergens , were not reported in many review s. No interventions were found to decrease atopy when reported . Adverse events data were generally lacking , but data from a trial of probiotics versus no probiotics showed significantly more spitting up in the first one ( RR : 1.88 ; 95 % CI : 1.03 , 3.45 ) and two ( RR : 1.69 ; 95 % CI : 1.02 , 2.80 ) months of life , but no overall increase in risk of gastrointestinal symptoms in the first year . AUTHORS # ENTITYSTARTX02019 ; CONCLUSIONS : Although there is currently no clear evidence showing that any of the interventions examined in this overview prevent eczema in participants not selected for risk of allergic disease , there is some evidence that exclusive breastfeeding for at least six months and prebiotics might reduce eczema incidence in high-risk participants . However , these conclusions are based on limited evidence with method ological shortcomings . Future research on prevention of eczema is needed and should examine different types of hydrolysed formulas , prebiotics and probiotics , as well as enhancement of the skin barrier and other novel approaches in infants at different risk levels for developing allergic disease Purpose of review This review summarizes the clinical efficacy of probiotics and prebiotics in gastrointestinal disorders and examines the mechanisms of action related to their therapeutic effect . Recent findings The demonstration that immune and epithelial cells can discriminate between different microbial species has extended the known mechanism(s ) of action of probiotics beyond simple barrier and antimicrobial effects . It has also confirmed that probiotic bacteria modulate mucosal and systemic immune activity and epithelial function . The progressive unraveling of these mechanisms of action has led to new credence for the use of probiotics and prebiotics in clinical medicine . Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhea in children , recurrent Clostridium difficile – induced infections and postoperative pouchitis . Level II evidence is emerging for the use of probiotics in other gastrointestinal infections , prevention of postoperative bacterial translocation , irritable bowel syndrome , and in both ulcerative colitis and Crohn disease . Nevertheless , one consistent feature has emerged over the past year : Not all probiotic bacteria have similar therapeutic effects . Future clinical trials will need to incorporate this fact into trial planning and design . Summary The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the “ mainstream . ” Mechanisms of action explain the therapeutic effects and r and omized ; controlled trials provide the necessary evidence for their incorporation into the therapeutic armamentarium Background The prevalence of allergic diseases in infants , whose parents and siblings do not have allergy , is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative . Intestinal microbiota may modulate immunologic and inflammatory systemic responses and , thus , influence development of sensitization and allergy . Prebiotics – non-digestible oligosaccharides that stimulate growth of probiotic bacteria – have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations about the use of prebiotics in the prevention of allergy . Methods The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy . We performed a systematic review of r and omized controlled trials of prebiotics , and review ed the evidence about patient values and preferences , and re source requirements ( up to January 2015 , with an up date on July 29 , 2015 ) . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . Results Based on GRADE evidence to decision frameworks , the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants . Both recommendations are conditional and based on very low certainty of the evidence . We found no experimental or observational study of prebiotic supplementation  in pregnant women or in breastfeeding mothers . Thus , the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding , at this time . Conclusions WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy , term infants BACKGROUND 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 OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P < .001 ) . The times to reach full enteral feeding were faster ( P < .001 ) , the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants  , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC 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 This article by the ESPGHAN Committee on Nutrition summarizes available information on the effects of adding prebiotic oligosaccharides to infant and follow-on formulae . Currently there are only limited studies evaluating prebiotic substances in dietetic products for infants . Although administration of prebiotic oligosaccharides has the potential to increase the total number of bifidobacteria in feces and may also soften stools , there is no published evidence of clinical benefits of adding prebiotic oligosaccharides to dietetic products for infants . Data on oligosaccharide mixtures in infant formulae do not demonstrate adverse effects , but further evaluation is recommended . Combinations and dosages in addition to those so far studied need to be fully evaluated with respect to both safety and efficacy before their use in commercial infant food products . Well- design ed and carefully conducted r and omized controlled trials with relevant inclusion /exclusion criteria , adequate sample sizes and vali date d clinical outcome measures are needed both in preterm and term infants . Future trials should define optimal quantity and types of oligosaccharides with prebiotic function , optimal dosages and duration of intake , short and long term benefits and safety . At the present time , therefore , the Committee takes the view that no general recommendation on the use of oligosaccharide supplementation in infancy as a prophylactic or therapeutic measure can be made Background : Necrotizing enterocolitis ( NEC ) is one of the most destructive diseases associated with conditions of neonatal prematurity . Supplementation with enteral prebiotics may reduce the incidence of NEC , especially in infants who fed exclusively with breast-milk . Therefore , we compared the efficacy and safety of enteral supplementation of a prebiotic mixture ( short chain galacto-oligosaccharides/long chain fructo-oligosaccharides [ SCGOS/LCFOS ] ) versus no intervention on incidence of NEC in preterm infants . Methods : In a single-center r and omized control trial 75 preterm infants ( birth weight [ BW ] ≤1500 g , gestational age ≤34 weeks and were not fed with formula ) on 30 ml/kg/day volume of breast-milk were r and omly allocated to have enteral supplementation with a prebiotic mixture ( SCGOS/LCFOS ; 9:1 ) or not receive any prebiotic . The incidence of suspected NEC , feeding intolerance , time to full enteral feeds , duration of hospitalization were investigated . Results : Differences in demographic characteristics were not statistically important . SCGOS/LCFOS mixture significantly reduced the incidence of suspected NEC , ( 1 [ 4.0 % ] vs. 11 [ 22.0 % ] ; hazard ratio : 0.49 [ 95 % confidence interval : 0.29 - 0.84 ] ; P = 0.002 ) , and time to full enteral feeds ( 11 [ 7 - 21 ] vs. 14 [ 8 - 36 ] days ; P - 0.02 ] . Also duration of hospitalization was meaningfully shorter in the prebiotic group ( 16 [ 9 - 45 ] vs. 25 [ 11 - 80 ] ; P - 0.004 ] . Prebiotic oligosaccharides were well tolerated by very low BW ( VLBW ) infants . Conclusions : Enteral supplementation with prebiotic significantly reduced the incidence of NEC in VLBW infants who were fed exclusively breast-milk . This finding suggests that it might have been the complete removal of formula which caused a synergistic effect between nonhuman neutral oligosaccharides ( prebiotic ) and human oligosaccharides OBJECTIVE . 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 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 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 Necrotizing enterocolitis ( NEC ) continues to be a major cause of morbidity and mortality in premature infants . Although the pathogenesis of NEC remains unclear , abnormal bacterial colonization has been postulated as playing a central role . Various factors impact bacterial colonization following delivery . Compared to term infants , the bacterial colonization pattern in prematurely born infants is markedly different , with a greater predilection for colonization with pathogenic bacteria . Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment , favoring the growth of commensal bacteria . Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC . These preliminary studies support the need for a large , r and omized , controlled trial to further investigate the role of probiotics in the prevention of NEC A r and omized double blind clinical trial was conducted to assess the efficacy of a special infant formula containing Lactobacillus rhamnosus LMG P-22799 ( probiotic : 5 x 10(8 ) CFU/100mL ) , inulin ( prebiotic : 0.15 g/100mL ) , dietary fiber ( soy polysaccharides : 0.2 g/100mL ) and increased amounts of zinc+iron ( + 0.4 and + 0.6 mg/100mL , respectively ) as active ingredients for the early dietary management of 58 Indonesian well-nourished male infants aged 3 - 12 months suffering from acute diarrhea with moderate dehydration . After adequate oral rehydration , the patients were r and omly assigned to receive either a low lactose infant formula supplemented with added precooked rice ( 1.5 g/100mL ) with the above active ingredients ( study group ) or a low lactose infant formula with added precooked rice without the above active ingredient supplement ( control group ) . No antibiotic , anti-secretory drug or antiemetic was given at all . Both study and control groups showed similar outcomes for weight gain and stool weight . The duration of diarrhea was significantly shorter in the study group than in the control group ( 1.63 versus 2.45 days ; p<0.05 ; for the study and control group respectively ) . No treatment failure or other side effects were observed during the course of the study . The present study supports the evidence for the efficacy of a special anti-diarrhea infant formula containing probiotic , prebiotic , fiber and iron+zinc after oral rehydration by shortening the duration of infantile diarrhea in developing countries . However , from the results of our study we can not discern the individual contribution of the active ingredients and also not whether they may act independent from each other or in a synergistic way The objective of the study was to evaluate the safety and tolerance of an infant formula supplemented with Lactobacillus fermentum CECT5716 , a probiotic strain isolated from breast milk , in infants of 1 - 6 months of age . A r and omized double blinded controlled study including healthy infants was conducted . One month aged infants received a prebiotic infant formula supplemented with L. fermentum ( experimental group ) or the same formula without the probiotic strain ( control group ) for 5 months . The primary outcome of the study was average daily weight gain between baseline and 4 months of age . Secondary outcomes were other anthropometric data ( length and head circumference ) , formula consumption , and tolerance . Incidence of infections was also recorded by pediatricians . No significant differences in weight gain were observed between both groups , neither at 4 months of age ( 29.0±7.8 vs 28.9±5.7g/day ) nor at 6 months ( 25.1±6.1 vs 24.7±5.2g/day ) . There were no statistically significant differences in the consumption of the formulae or symptoms related to the tolerance of the formula . The incidence rate of gastrointestinal infections in infants of the control group was 3 times higher than in the probiotic group ( p=0.018 ) . Therefore , consumption of a prebiotic infant formula enriched with the human milk probiotic strain L. fermentum CECT5716 from 1 to 6 months of life is well tolerated and safe . Furthermore , the consumption of this formula may improve the health of the infants by reducing the incidence of gastrointestinal infections 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 OBJECTIVE To evaluate the growth and neurodevelopment outcomes of very low-birth-weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . STUDY DESIGN This prospect i ve follow-up study was conducted in a cohort of VLBW preterm infants enrolled in a r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Growth outcomes included weight , length , and head circumference . Cognitive and neuromotor development were assessed by using the Bayley Scales of Infant Development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18 to 22 months ' corrected age . RESULTS A total of 221 infants completed the trial protocol . Of the 208 infants eligible for follow-up , 174 infants ( 86 in the probiotics group and 88 in the control group ) were evaluated . There was no significant difference in growth and neurodevelopmental outcomes between the two groups . CONCLUSION Oral probiotic administered to VLBW infants to reduce the incidence and severity of NEC started with the first feed did not affect growth , neuromotor , neurosensory , and cognitive outcomes at 18 to 22 months ' corrected age 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 : 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 There have been over twenty prospect i ve , r and omized trials of the use of probiotics to prevent  necrotizing enterocolitis ( NEC ) in premature babies . A Cochrane meta- analysis of 16 of the studies ( 1 ) including 2842 preterm infants , reported that ‘ enteral probiotics supplementation significantly reduced the incidence of severe NEC ( stage II or more ) ( typical RR , 0.35 ; 95 % CI , 0.24–0.52 ) and mortality ( typical RR , 0.40 ; 95 % CI , 0.27–0.60 ) with no evidence of harm . They concluded , ‘ Enteral supplementation of probiotics prevents severe NEC and all-cause mortality in preterm infants ’ . In a sensitivity analysis , including only the 4 highest quality studies , the results and conclusions were unchanged . For neonates born at < 32 weeks of gestation , the number needed to treat in order to prevent one NEC or one death is twenty . The risks of probiotics are minimal . A more recently published systematic review included several additional r and omized controlled trials , mostly published in the Chinese literature , and analysed a total of 20 publications and over 3800 preterm infants ; it came to similar conclusions as the Cochrane meta- analysis ( 2 ) . Probiotics are used in many European units but only rarely in North-America . In spite of the evidence , this safe and effective treatment for one of the most serious complications of prematurity has never been studied in the United States and perhaps never will . Probiotics will probably never be approved by the U.S. Food and Drug Administration ( FDA ) . Instead , they will remain in regulatory purgatory , neither approved nor unapproved , an evidence -based treatment that can not become the st and ard of care , a safe and effective treatment that is not on hospital formularies in the United States . Probiotics fall into a peculiar lacuna of the regulatory system . Most innovative treatments are either drugs or devices , and the regulatory pathways for evaluating and approving them are fairly well defined by federal law . The FDA has jurisdiction over both drugs and devices . Probiotics are neither drugs nor devices , and they are made by companies that generally market health products to the general public . In contrast , in Canada , probiotics are under the jurisdiction of the Natural Health Products Directorate ( NHPD ) which has rigorous requirements for quality control and detailed labelling . But the NHPD does not evaluate overtly medical cl aims made about a product . It has little experience dealing with either a product that could actually decrease major complications or save lives in a particularly fragile population where mortality is rather common . Probiotics are quite inexpensive to manufacture . People can even make them at home . They are in most yogurts . For pennies , some parents buy them for their preterm infants in health food stores . Some mothers have started adding probiotics to their breast milk . In these cases , the medical team can either be unaware a preterm infant is in fact receiving probiotics or tacitly not interfere with these parental initiatives . Given the low cost of probiotics and Articles in the series A Different View are edited by William Meadow ( wlm1@uchicago.edu ) . We encourage you to offer your own different view either in response to A Different View you do not fully agree with , or on an unrelated topic . Send your article to Dr. Meadow ( wlm1@uchicago.edu )
The 2 meta-analyses also demonstrated that probiotics reduce the risk of death due to all causes , but do not have an effect on the risk of sepsis or death due to NEC .
Because of the limited data regarding synbiotics , the relationship between their use and clinical outcomes in preterm infants remains unclear .
The findings from the 2 meta-analyses of the effects of probiotic administration on the prevention of NEC show potential for such dietary supplementation .
BACKGROUND Uncertainty exists regarding the efficacy and safety of using probiotics and prebiotics in preterm infants .
AIM To review the evidence on the effects of administering probiotics and /or prebiotics to preterm infants .