Oral Probiotics Prevent Necrotizing Enterocolitis in Very Low Birth Weight Preterm Infants: A Multicenter, Randomized, Controlled Trial Oral Probiotics Reduce the Incidence and Severity of Necrotizing Enterocolitis in Very Low Birth Weight Infants Synbiotics for decreasing incidence of necrotizing enterocolitis among preterm neonates – a randomized controlled trial Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Necrotizing enterocolitis - classification and two initial steps towards prevention. Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. 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 Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Fecal Microbiota in Premature Infants Prior to Necrotizing Enterocolitis Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates.
OBJECTIVE . The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants . METHODS . A prospect i ve , blinded , r and omized , multicenter controlled trial was conducted at 7 NICUs in Taiwan , to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants ( birth weight : < 1500 g ) . Very low birth weight infants who survived to start enteral feeding were eligible and were assigned r and omly to 2 groups after parental informed consent was obtained . Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus , added to breast milk or mixed feeding ( breast milk and formula ) , twice daily for 6 weeks . Infants in the control group were fed with breast milk or mixed feeding . The clinicians caring for the infants were blinded to the group assignment . The primary outcome measurement was death or necrotizing enterocolitis ( Bell 's stage ≥2 ) . RESULTS . Four hundred thirty-four infants were enrolled , 217 in the study group and 217 in the control group . The incidence of death or necrotizing enterocolitis ( stage ≥2 ) was significantly lower in the study group ( 4 of 217 infants vs 20 of 217 infants ) . The incidence of necrotizing enterocolitis ( stage ≥2 ) was lower in the study group , compared with the control group ( 4 of 217 infants vs 14 of 217 infants ) . No adverse effect , such as sepsis , flatulence , or diarrhea , was noted . CONCLUSION . Probiotics , in the form of Bifidobacterium and Lactobacillus , fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis Objective . We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . Patients and Methods . A prospect i ve , masked , r and omized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW ( < 1500 g ) infants . VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial . They were r and omized into 2 groups after parental informed consents were obtained . The infants in the study group were fed with Infloran ( Lactobacillus acidophilus and Bifidobacterium infantis ) with breast milk twice daily until discharged . Infants in the control group were fed with breast milk alone . The clinicians caring for the infants were blinded to the group assignment . The primary outcome was death or NEC ( ≥ stage 2 ) . Results . Three hundred sixty-seven infants were enrolled : 180 in the study group and 187 in the control group . The demographic and clinical variables were similar in both groups . The incidence of death or NEC ( ≥ stage 2 ) was significantly lower in the study group ( 9 of 180 vs 24 of 187 ) . The incidence of NEC ( ≥ stage 2 ) was also significantly lower in the study when compared with the control group ( 2 of 180 vs 10 of 187 ) . There were 6 cases of severe NEC ( Bell stage 3 ) in the control group and none in the study group . None of the positive blood culture grew Lactobacillus or Bifidobacterium species . Conclusion . Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants Abstract Objective : To study the effect of synbiotics in reducing incidence and severity of necrotizing enterocolitis ( NEC ) among preterm neonates . Methods : This r and omized controlled trial conducted in a tertiary care teaching hospital , south India , included 220 enterally fed preterm neonates who were r and omized to receive either synbiotics or no intervention .  The synbiotic contained Lactobacillus , Bifidobacterium and fructo-oligosaccharide . The demographic parameters , risk factors for NEC and outcome including incidence of NEC , its severity , sepsis and mortality were evaluated . Results : Multiple pregnancies , preeclampsia and prolonged rupture of membranes were important maternal characteristics . The average birth weight and gestational age of the preterm neonates was 1.4 kg and 31 weeks , respectively . There was a 50 % reduction in the incidence of NEC of all stages in preterm infants who received synbiotics compared to the non-intervention group ( 7.4 % versus 14.5 % ) . Administration of synbiotics did not reduce the severity of NEC , sepsis or mortality . Conclusion : Enteral supplementation of synbiotics along with breastmilk results in a tendancy to decrease the incidence of NEC among preterm neonates OBJECTIVE To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense , thereby reducing both the incidence and severity of  necrotizing enterocolitis ( NEC ) in preterm neonates . STUDY DESIGN Neonates < or = 1500 g birth weight were r and omized to either receive a daily feeding supplementation with a probiotic mixture ( Bifidobacteria infantis , Streptococcus thermophilus , and Bifidobacteria bifidus ; Solgar , Israel ) of 10(9 ) colony forming units (CFU)/day or to not receive feed supplements .  NEC was grade d according to Bell 's criteria . RESULTS For 72 study and 73 control infants , respectively , birth weight ( 1152 + /- 262 g vs 1111 + /- 278 g ) , gestational age ( 30 + /- 3 weeks vs 29 + /- 4 weeks ) , and time to reach full feeds  ( 14.6 + /- 8.7 days vs 17.5 + /- 13.6 days ) were not different . The incidence of NEC was reduced in the study group ( 4 % vs 16.4 % ; P=.03 ) . NEC was less severe in the probiotic-supplemented infants ( Bell 's criteria 2.3 + /- 0.5 vs 1.3 + /- 0.5 ; P=.005 ) . Three of 15 babies who developed NEC died , and all NEC-related deaths occurred in control infants . CONCLUSION Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population BACKGROUND Necrotizing enterocolitis ( NEC ) is the most serious gastrointestinal problem in very low birth weight preterm infants . Multiple risk factors activate the inflammatory cascade leading to high expressions of pro-inflammatory mediators causing bowel injury in NEC . The anti-inflammatory effect of probiotics is due to the inhibition and reduction of inflammatory signal in intestinal epithelium . OBJECTIVE To evaluate the efficacy of probiotics supplementation in the prevention of NEC among very low birth weight preterm infants . STUDY DESIGN A prospect i ve r and omized controlled trial . MATERIAL AND METHOD All preterm infants with gestational age less than or equal to 34 weeks and birth weight less than or equal to 1,500 grams admitted in neonatal care unit , Queen Sirikit National Institute of Child Health during June 1st , 2012 and January 31th , 2013 were enrolled in this study . They were r and omized into two groups , study and control group . Infants in the study group were fed Infloran ( Lactobacillus acidophilus 1 x 10(9 ) and Bifidobacterium bifidum 1 x 10(9 ) organisms ) dose 125 mg/kg/dose twice a day with breast milk or premature formula from the start of feeding until 6 weeks or discharge . Infants in the control group were fed with either breast milk or premature formula alone . The primary outcome was NEC stage ≥ 2 . RESULTS Sixty infants completed the study , 31 infants in the study group and 29 infants in the control group . The baseline characteristic data of infants were similar except for more males in the present study group . Incidence of NEC stage ≥ 2 were similar in both the groups , 3.2 vs. 3.4 % ( p = 0.74 ) . There were no deaths during the study period . Days to reach full feeding , 150 ml/kg/day , were no differences between the two groups , 12.03 ± 5.49 days vs. 13.76 ± 8.25 days ( p = 0.31 ) . No adverse effects such as sepsis , flatulence or diarrhea were noted . CONCLUSION In this study , there was no difference in incidence of NEC stage ≥ 2 between the two groups . No adverse effects of probiotics supplementation were observed OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P < .001 ) . The times to reach full enteral feeding were faster ( P < .001 ) , the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants  , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC Background : 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 The premature infant suffers from immaturity of all organ systems , one of them being the gastrointestinal tract . When the infant is born , the immature gastrointestinal tract is exposed to milk and simultaneously colonized by high densities of bacteria . The combination of milk , microbiota and an immature gut , leaves the infant vulnerable to developing the dreaded intestinal emergency necrotizing enterocolitis ( NEC ) . NEC is often very aggressive and no cure exists , which means that prevention is an utmost important topic to research ers , physicians , parents - and infants . Despite immense research during the last decades , no specific test to determine if an infant suffers from NEC exists . Most neonatal units use Bell 's staging criteria , which are based on clinical and radiographic findings , as a diagnostic tool ; however the diagnosis given according to Bell 's stages has not been vali date d. In study I , we aim ed to determine the validity of the NEC diagnosis given at discharge . An expert panel consisting of a neonatologist , a paediatric surgeon and a paediatric radiologist served as the golden st and ard . We found that the diagnosis given at discharge had a poor validity which significantly affected the reported incidence of NEC in the neonatal department at Rigshospitalet , Denmark . The validity of the NEC diagnosis was worse than the validity of most other paediatric diagnoses that had been investigated . In studies II and III , we aim ed to explore possible means of NEC prevention . The role of nutrition in NEC development is well established with mother 's milk as the best option to avoid NEC in the preterm infant . Maternal milk is , however , most often not available in sufficient amounts during the first days of life , and preterm infant formula or human donor milk is used in its absence . Studies in preterm piglets showed that bovine colostrum equally to human donor milk protected against NEC compared to infant formula . Furthermore , bovine colostrum was superior to human donor milk in stimulating gut immunity and digestive functions . Hence , in study II we aim ed to design a pilot study of bovine colostrum used as a supplement to maternal milk in the first days of life and to determine if the study was feasible . In the paper , we present the protocol and the results of the first two phases of the Precolos study in which 12 infants were included and received pasteurized , spray-dried and reconstituted bovine colostrum during the first days of life as the first infants in the world . We found that the infants tolerated bovine colostrum without clinical adverse effects , but we also observed a transient hypertyrosinemia on day seven of life in five infants . The results were evaluated by a safety management board which encouraged us to continue the pilot study with the last phase , which was a r and omized controlled trial of 20 + 20 infants comparing supplementation with bovine colostrum to supplementation with st and ard nutrition . The r and omized trial has just finished recruitment . At last , we wanted to shed light on a possible microbiological angle of NEC prevention . Dysbiosis and bacterial translocation are believed to play a crucial role in the development of NEC as intestinal pneumatosis , which occurs when bacteria produce gas inside the intestinal wall , is a pathognomonic radiographic finding . In a quality improvement study from the US published in 2014 , NEC incidence was significantly reduced after the implementation of several quality improvement interventions . St and ardized weekly exchange of nasogastric feeding tubes was suggested as one of the potential NEC-reducing interventions . In the neonatal unit at Rigshospitalet , Denmark , preterm infants are fed 8 - 12 times daily through a resident nasogastric feeding tube which is exposed to body temperature , contains milk residuals from the last meal and is h and led by both parents and personnel . Since bacterial pollution of milk given through the nasogastric feeding tube might be NEC-inducing , we aim ed in study III to determine the bacterial load given to the infants when feeding them through a tube . We collected 92 used nasogastric feeding tubes and flushed them with one ml saline each to imitate a meal given through them . Eighty-nine percent of the tubes contaminated the meals with more than 1000 colony-forming units of bacteria and fifty-five percent contaminated the meals with the possible pathogens Enterobacteriaceae or Staphylococcus aureus . The concentration of bacteria in the saline flushed through the tubes was as high as 109 colony-forming units per ml ; however , neither the risk of contamination nor the concentration of bacteria in the flush was associated with the duration of use . Implementation of st and ardized weekly exchange of feeding tubes would therefore not prevent the contamination of meals . In conclusion , the studies included in this thesis serve as a base for future studies investigating the prevention of NEC . We found a poor validity of the NEC diagnosis given at discharge . This should be kept in mind when conducting epidemiological studies of NEC and especially when conducting interventional trials with NEC as an outcome . If the findings of the r and omized part of the Precolos study indicate a positive effect of bovine colostrum and do not give rise to concerns regarding feasibility , safety or tolerability , a large-scale r and omized controlled study with NEC as the primary outcome will be planned . Based on the high concentrations of bacteria found in the nasogastric feeding tubes , a r and omized controlled trial investigating whether the frequency of feeding tube exchange affects the early colonization has been commenced in the neonatal department at Rigshospitalet . Hopefully , the results of these studies will bring us closer to preventing NEC in the future 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 BACKGROUND Preterm infants remain at high risk of adverse outcomes following necrotizing enterocolitis  ( NEC ) and late onset sepsis ( LOS ) . Meta- analysis of r and omized trials has indicated a reduction in severe NEC following use of probiotics and bovine lactoferrin ( LF ) . Overall , however , uncertainty remains over which probiotic , or combination to use . The aim of this study was to compare the incidence of severe NEC and LOS before and after routine supplementation with Lactobacillus GG ( LGG ) and LF . METHODS In this retrospective cohort study , infants < 32 weeks or < 1500 g routinely received LGG and 100 mg lactoferrin daily from 2011 -2015 were compared with similar infants born from 2004 - 2008 . Cases of NEC were Bell stage 2 or greater and LOS was blood or spinal fluid culture positive after 48 hrs of age . RESULTS We noted a marked decline in the incidence of NEC from 3 % to 1 % with a RR of 0.29 ( CI 0.1 - 0.9 ) and a number needed to benefit of 50 . The cost of preventing one case of NEC was estimated to be NZ $ 2800 , considerably lower than the cost of treatment . LOS rates were not significantly different . There was a decrease in retinopathy treatment rates . During the period there was one case of LGG sepsis in a 23 week gestation infant with abdominal pathology and one infant developed NEC after stopping prophylaxis . CONCLUSION The rates of severe NEC was markedly reduced following prophylaxis . The case of LGG sepsis indicates caution is required in extremely preterm infants 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 OBJECTIVE To evaluate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis ( NEC ) in preterm very low birth weight ( VLBW ) infants . STUDY DESIGN Ar and omized double blind controlled trial . PLACE AND DURATION OF STUDY The Paediatrics Department of Sylhet M.A.G. Osmani Medical College Hospital , Sylhet Bangladesh , from July 2012 to June 2015 . METHODOLOGY Preterm ( 28 - 33 weeks gestation ) VLBW ( birth weight 1000 - 1499 g ) neonates were enrolled . The study group was fed with probiotics once daily with breast milk from first feeding , and the control group with only breast milk without the addition of probiotics . Both the groups received other st and ard care . The primary outcome was the development of NEC ( stage II and III ) , categorized by modified Bell 's classification . RESULTS In 108 neonates , development of NEC was significantly lower in the study group than that of control group [ 1 ( 1.9 % ) vs. 6 ( 11.5 % ) ; p=0.044 ] . Age of achievement of full oral feeding was significantly earlier in the study group than that in the control group ( 14.88 ±3.15 and 18.80 ±4.32 days ; p < 0.001 ) . Duration of hospital stay was significantly short in the study group compared to the control group ( 15.82 ±2.94 days vs. 19.57 ±4.26 days ; p < 0.001 ) . CONCLUSION Probiotic supplementation reduces the frequency of necrotising enterocolitis in preterm neonates with very low birth weight . It is also associated with faster achievement of full oral feeding and short duration of hospital stay Necrotizing enterocolitis ( NEC ) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone . Various combinations of inadequate tissue oxygenation , bacterial overgrowth , and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis . Presently , there is not a way to predict the onset of the disease or to prevent its occurrence . As part of risk-benefit assessment , we compared disease in hospitalized preterm infants fed a commercial ( control ) preterm formula or an experimental formula with egg phospholipids  for a r and omized , double-masked , clinical study of diet and infant neurodevelopment . Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula ( 2.9 versus 17.6 % , p < 0.05 ) , but had similar rates of bronchopulmonary dysplasia ( 23.4 versus 23.5 % ) , septicemia ( 26 versus 31 % ) , and retinopathy of prematurity ( 38 versus 40 % ) . Compared with the control formula , the experimental formula provided 7-fold more esterified choline , arachidonic acid ( AA , 0.4 % of total fatty acids ) , and docosahexaenoic acid ( 0.13 % ) . Phospholipids are constituents of mucosal membranes and intestinal surfactant , and their components , AA and choline , are substrates for intestinal vasodilatory and cytoprotective eicosanoids ( AA ) and the vasodilatory neurotransmitter , acetylcholine ( choline ) , respectively . One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study . Regardless of the potential mechanism , a larger r and omized trial design ed to test the effect of this egg phospholipid-containing formula on NEC seems warranted 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 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 Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis ( NEC ) , a common disease in preterm infants . Microbiota development , a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota , can now be studied in preterm infants using powerful molecular tools . Starting with the first stool and continuing until discharge , weekly stool specimens were collected prospect ively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g.  High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls . After removal of short and low quality reads we retained a total of 110,021 sequences . Microbiota composition differed in the matched sample s collected 1 week but not < 72 hours prior to NEC diagnosis . We detected a bloom ( 34 % increase ) of Proteobacteria and a decrease ( 32 % ) in Firmicutes in NEC cases between the 1 week and < 72 hour sample s. No significant change was identified in the controls . At both time points , molecular signatures were identified that were increased in NEC cases . One of the bacterial signatures detected more frequently in NEC cases ( p<0.01 ) matched closest to γ-Proteobacteria . Although this sequence grouped to the well-studied Enterobacteriaceae family , it did not match any sequence in Genbank by more than 97 % . Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC UNLABELLED The aim of the study is to compare the role of killed ( KP ) Lactobacillus acidophilus with living ( LP ) in reducing incidence of sepsis ( NS ) and necrotizing enterocolitis ( NEC ) in neonates . R and omized double blind placebo study , included 150 neonates admitted to NICU at day 1 , sixty received oral ( LP ) and 60 received ( KP ) and 30 received placebo .  One gram of stools was collected on admission , at day 7 , at end of the study , as well as on suspected NEC or NS and was sent for culture . RESULTS LP and KP were preventive factors for NEC with absolute risk reduction ( AAR ) 16 , 15 % , respectively and 18 % for NS compared to placebo .  Incidence of NEC and NS did not differ significantly between neonates supplemented with LP and those with KP . Preterm neonates supplemented with KP showed significantly lower incidence of NEC compared to placebo , while incidence of NS showed no significant difference between both groups . There is significant reduction in NS and NEC among neonates with positive Lactobacillus colonization of gut compared to those none colonized at day 7 ( 27.9 vs. 85.9 % , 0 vs. 7.8 % ) and at day 14 ( 48.7 vs. 91.7 % for NS and 0 vs. 20.8 % for NEC ) . Overall comparison between the three groups showed statistical significant reduction in the incidence of NEC . Present conclusions are that early gut colonization with beneficial bacteria lowers the incidence of NEC and NS . KP retained similar benefits to live bacteria
Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants .
There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth
BACKGROUND Necrotizing enterocolitis ( NEC ) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants .
Through prevention of bacterial migration across the mucosa , competitive exclusion of pathogenic bacteria , and enhancing the immune responses of the host , prophylactic enteral probiotics ( live microbial supplements ) may play a role in reducing NEC and the associated morbidity .
OBJECTIVES To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis , or both , in preterm infants .
PLAIN LANGUAGE SUMMARY Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis ( NEC ) is a serious disease that affects the bowel of premature infants in the first few weeks of life .
Although the cause of NEC is not entirely known , milk feeding and bacterial growth play a role .
Probiotics ( dietary supplements containing potentially beneficial bacteria or yeast ) have been used to prevent NEC .