Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis 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. Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. Synbiotics for decreasing incidence of necrotizing enterocolitis among preterm neonates – a randomized controlled trial Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. The politics of probiotics: probiotics, necrotizing enterocolitis and the ethics of neonatal research Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: 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. 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. Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less. Impact of oral probiotics on neurodevelopmental outcomes in preterm infants The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. Prophylactic Probiotics to Prevent Death and Nosocomial Infection in Preterm Infants Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? Necrotizing enterocolitis - classification and two initial steps towards prevention. Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. 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 Oral Probiotics Reduce the Incidence and Severity of Necrotizing Enterocolitis in Very Low Birth Weight Infants Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial Early enteral feeding and nosocomial sepsis in very low birthweight infants Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: a randomised controlled trial Bacillus clausii for Prevention of Late-onset Sepsis in Preterm Infants: A Randomized Controlled Trial. Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight 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 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 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 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 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 OBJECTIVE Lactoferrin ( LF ) is effective in the prevention of sepsis in very low birth weight ( VLBW ) neonates .  T-regulatory cells ( Tregs ) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis . The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis ( NEC ) in premature infants and to evaluate the possible effects of LF on Treg levels . STUDY DESIGN In this prospect i ve , placebo-controlled , double-blind , r and omized trial , infants either VLBW or born before 32 weeks were assigned to receive either placebo ( n = 25 ) , or 200 mg LF ( n = 25 ) daily throughout hospitalization . Episodes of culture proven nosocomial sepsis and NEC were recorded . The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge . A third comparison was made with healthy term neonates ( n = 16 ) . RESULTS Fewer sepsis episodes were observed in LF-treated infants ( 4.4 vs. 17.3/1,000 patient days , p = 0.007 ) with none developing NEC , without statistical significance . Treg levels at birth and discharge were similar , while preterm infants showed significantly lower levels than term controls . However , individual increases in Treg levels were higher in the LF group . CONCLUSION LF prophylaxis reduced nosocomial sepsis episodes . Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed . Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis 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 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 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 ) 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 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 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 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 The incidence of culture-proven neonatal sepsis and necrotizing enterocolitis ( NEC ) in preterm infants maintained at pharmacologic ( mean 5.1 mg/dL + /- 1.45 SD ) serum vitamin E levels for long periods was prospect ively studied as part of a double-masked clinical trial of the effect of prophylactic vitamin E v placebo treatment on the development and course of retinopathy of prematurity ( ROP ) . Within a few days of birth , 914 preterm infants were enrolled in the study ; 545 ( 275 placebo-treated infants , 270 vitamin E-treated infants had birth weight of 1,500 g or less . A significant difference in incidence of neonatal sepsis ( 17 placebo-treated infants , 37 vitamin E-treated infants ) and NEC ( 18 placebo-treated infants , 32 vitamin E-treated infants ) was observed among infants who had been treated for eight or more days and who had developed neither sepsis nor NEC before that time . The association of vitamin E treatment with increased incidence of disease was much higher with sepsis than with NEC . The most likely reason for these observations is a pharmacologic serum vitamin E-related decrease in oxygen-dependent intracellular killing ability which results in a decreased resistance to infection in preterm infants . The data suggest that , if this occurs , it is clinical ly significant only in the more immature infants . In view of the known variability of absorption of oral vitamin E and the association between high serum vitamin E levels and increased incidence of sepsis and late-onset NEC reported here , it can be concluded that serum vitamin E levels must be monitored when supplemental vitamin E is administered to premature infants , especially those with birth weight 1,500 g or less . The risk-benefit ratio of long-term treatment using vitamin E at high serum levels should be clearly assessed Abstract Objective : The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . Methods : A prospect i ve follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Cognitive and neuromotor developments 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 18–24 months ’ corrected age . Results : A total of 400 infants completed the trial protocol . Of the 370 infants eligible for follow-up , 249 infants ( 124 in the probiotics group and 125 in the control group ) were evaluated . There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups . Conclusion : Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor , neurosensory and cognitive outcomes at 18–24 months ’ corrected age 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 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 OBJECTIVE To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants . STUDY DESIGN Infants fed their own mothers ' milk were r and omized to 1 of 3 study groups . Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d , respectively , and both groups received pasteurized donor human milk if no mother 's milk was available . Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother 's milk was available . Outcomes included duration of parenteral nutrition , morbidity , and growth . RESULTS The 3 groups ( total n = 207 infants ) had similar baseline demographic variables , duration of parenteral nutrition , rates of late-onset sepsis , and growth . The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis ( NEC ; P = .02 ) and NEC requiring surgical intervention ( P = .007 ) . CONCLUSIONS For extremely premature infants , an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother 's milk-based diet that also includes bovine milk-based products 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 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 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 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 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 . 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 compare the effect of fortified pasteurized donor human milk ( PDHM ) versus unfortified PDHM on the incidence of necrotizing enterocolitis ( NEC ) and immediate outcome among preterm neonates . Methods : This r and omized controlled trial ( RCT ) conducted in a tertiary care teaching hospital , south India included 80 healthy preterm neonates r and omized to two groups ( Group A and B ) . Neonates in Group A and B were fed with fortified PDHM and unfortified PDHM , respectively . Neonates in both groups were managed uniformly as per st and ard NICU protocol . The primary outcome was the incidence of NEC and the secondary outcomes included severity of NEC , incidence of sepsis , mortality , duration of hospital stay , number of days to reach full enteral feeds and weight gain . Neonates were followed up for 28 days or discharge whichever was earlier . Results : The baseline maternal and neonatal characteristics in both groups were comparable . There was no increase in incidence of NEC in fortified PDHM group compared to unfortified PDHM group ( 2.5 versus 7.5 % , p = .31 ) . Severity of NEC , incidence of sepsis , mortality , duration of hospital stay , number of days to reach full enteral feeds and weight gain were also similar in both groups . Conclusions : St and ard fortification of PDHM does not increase the incidence of NEC among preterm neonates Background : The interrelations between early enteral feeding , necrotising enterocolitis ( NEC ) , and nosocomial sepsis ( NS ) remain unclear . Objective : To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight ( VLBW < 1500 g ) infants . Methods : Data were collected on the pattern of enteral feeding  and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995–2001 .  Enteral feeding was compared between infants with and without NS and /or NEC . Results : The study sample included 385 infants . Of these , 163 ( 42 % ) developed NS and 35 ( 9 % ) developed NEC .  Enteral feeding was started at a significantly earlier mean ( SD ) age in infants who did not develop nosocomial sepsis ( 2.8 ( 2.6 ) v 4.8 ( 3.7 ) days , p = 0.0001 ) . Enteral feeding was introduced at the same age in babies who did or did not develop NEC ( 3.1 ( 2 ) v 3.7 ( 3 ) days , p = 0.28 ) . Over the study period , the mean annual age at the start of enteral feeding fell consistently , and this correlated with the mean annual incidence of NS ( r2 = 0.891 , p = 0.007 ) . Multiple logistic regression analysis showed age at start of enteral feeding , respiratory distress syndrome , and birth weight to be the most significant predictors of risk of NS ( p = 0.0005 , p = 0.024 , p = 0.011 ) . Conclusions : Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC  in VLBW infants . These findings support the use of early enteral feeding in this high risk population , but this needs to be confirmed in a large r and omised controlled trial 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 OF THE STUDY Preterm infants are managed with antibiotics for sepsis , including suspected or probable sepsis . This leads to a delayed and abnormal colonization of the gut with potentially pathogenic organisms and a microbiome , which lacks biodiversity and increases the risk for late-onset sepsis ( LOS ) . Probiotics have been proven to reduce the risk for necrotizing enterocolitis , but evidence for prevention of LOS is inconclusive . Probiotic effect depends also on the strain used , dose and indication for use . This study evaluated Bacillus clausii probiotic administered prophylactically to preterm neonates for prevention of LOS . OBJECTIVES To study B.clausii given prophylactically to preterm neonates for prevention of LOS . DESIGN Double-blinded , placebo-controlled , r and omized trial . SETTING S Tertiary care neonatal unit in India . PARTICIPANTS Consecutive preterm neonates < 34 weeks , admitted from 1 March 2012 to 28 February 2014 were stratified as extreme preterm and very preterm . INTERVENTION R and omized to receive either probiotic or placebo for 6 weeks , discharge from hospital , death or occurrence of sepsis , whichever was earlier . PRIMARY OUTCOME Incidence of definite and probable LOS in probiotic group compared with placebo . RESULTS Of 326 eligible preterm infants , 244 were enrolled and 82 were excluded . Of these , 120 were stratified as extreme preterm and r and omized to receive placebo ( n = 59 ) and probiotic ( n = 61 ) . Of 124 babies stratified as very preterm , an equal number was r and omized to receive placebo ( n = 62 ) and probiotic ( n = 62 ) . There was no significant difference in the incidence of LOS between the two arms in the extreme preterm group [ 29 % vs. 23 % ; relative risk ( RR ) 1.27 ; 95 % confidence interval ( CI ) 0.88 - 1.66 ; p = 0.36 ] and the very preterm group ( 13 % vs. 10 % ; RR 1.33 ; 95 % CI 0.96 - 1.70 ; p = 0.32 ) . Full feeds were achieved significantly faster in the probiotic group in both the extreme preterm ( RR 0.82 ; 95 % CI 0.74 - 0.88 ) and the very preterm ( RR 0.67 ; 95 % 0.32 - 0.77 ) . CONCLUSIONS Prophylactic administration of B.clausii to preterm neonates did not result in a significant difference in the incidence of LOS as compared with placebo OBJECTIVE To evaluate growth and neurodevelopmental outcomes in preterm very low birth weight ( PVLBW ) infants treated with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . STUDY DESIGN A prospect i ve follow-up study was performed in a cohort of PVLBW infants enrolled in a single center with a masked r and omized control trial to evaluate the efficacy of oral probiotics in preventing NEC . Growth measures included weight , length , and head circumference . Neurologic and sensory performance was evaluated with st and ard techniques . Psychometric parameters were measured used the Bayley Scales of Infant Development II ( BSID-II ) . The studies were performed at 3 years corrected age . The primary outcome was death or neurodevelopmental impairment . RESULTS Of the 367 subjects enrolled in trial , 301 ( 89.9 % ) were evaluated ( 153 in the probiotics group and 148 in the control group ) . There were no significant differences in growth or in any of the neurodevelopmental and sensory outcomes between the 2 groups . CONCLUSIONS Oral probiotics given to PVLBW infants at 1 week after birth to reduce the incidence of NEC did not affect growth and neurodevelopmental and sensory outcomes at 3 years corrected age
Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants .
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 .