Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. 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 Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants Ranitidine is Associated With Infections, Necrotizing Enterocolitis, and Fatal Outcome in Newborns Prevention of necrotizing enterocolitis in neonates at risk by oral administration of monomeric IgG. Mortality of necrotizing enterocolitis expressed by birth weight categories. The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial Impact of oral probiotics on neurodevelopmental outcomes in preterm infants Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. 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. Oral Probiotics Reduce the Incidence and Severity of Necrotizing Enterocolitis in Very Low Birth Weight Infants
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 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 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 IMPORTANCE NEC is a common and severe complication in premature neonates , particularly those with very-low-birth-weight ( VLBW , < 1500 g at birth ) .  Probiotics including lactobacillus rhamnosus GG ( LGG ) proved effective in preventing NEC in preterm infants in several RCTs . OBJECTIVE Lactoferrin , a mammalian milk glycoprotein involved in innate immune host defences , can reduce the incidence of NEC in animal models , and its action is enhanced by LGG . We tried to assess whether bovine lactoferrin ( BLF ) , alone or with the probiotic LGG , has a similar effect in human infants , something that has not yet been studied . DESIGN An international , multicenter , r and omized , double-blind , placebo-controlled trial conducted from October 1st , 2007 through July 31st , 2010 . SETTING Thirteen Italian and New Zeal and tertiary neonatal intensive care units . PARTICIPANTS 743 VLBW neonates were assessed until discharge for development of NEC . INTERVENTION Infants were r and omly assigned to receive orally either BLF ( 100 mg/day ) alone ( group LF ; n = 247 ) or with LGG ( at 6 × 10(9 ) CFU/day ; group BLF + LGG ; n = 238 ) , or placebo ( Control group ; n = 258 ) from birth until day 30 of life ( 45 for neonates < 1000 g at birth ) . MAIN OUTCOME MEASURES ≥ stage 2 NEC ; death- and /or-≥ stage 2 NEC prior to discharge . RESULTS Demographics , clinical and management characteristics of the 3 groups were similar , including type of feeding and maternal milk intakes . NEC incidence was significantly lower in groups BLF and BLF + LGG [ 5/247 ( 2.0 % ) ] and 0/238 ( 0 % ) , respectively ] than in controls [ 14/258 ( 5.4 % ) ] ( RR = 0.37 ; 95 % CI : 0.136 - 1.005 ; p = 0.055 for BLF vs. control ; RR = 0.00 ; p < 0.001 for BLF + LGG vs. control ) . The incidence of death- and /or-NEC was significantly lower in both treatment groups ( 4.0 % and 3.8 % in BLF and BLF + LGG vs. 10.1 % in control ; RR = 0.39 ; 95 % CI : 0.19 - 0.80 ; p = 0.008 . RR = 0.37 ; 95 % CI : 0.18 - 0.77 ; p = 0.006 , respectively ) . No adverse effects or intolerances to treatment occurred . CONCLUSIONS AND RELEVANCE Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death- and /or ≥ stage 2 NEC in VLBW neonates . BLF might be a promising strategy to prevent NEC in NICU setting s. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical setting s. TRIAL REGISTRATION IS RCT N53107700-http://www.controlled-_trials.com/IS RCT N53107700 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 Background : Necrotizing enterocolitis ( NEC ) is a costly morbidity in very low birth weight ( VLBW ; < 1,500 g birth weight ) infants that increases hospital length of stay and requires expensive treatments . Objectives : To evaluate the cost of NEC as a function of dose and exposure period of human milk ( HM ) feedings received by VLBW infants during the neonatal intensive care unit ( NICU ) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC . Methods : This study included 291 VLBW infants enrolled in an NIH-funded prospect i ve observational cohort study between February 2008 and July 2012 . We examined the incidence of NEC , NICU hospitalization cost , and cost of individual re sources used during the NICU hospitalization . Results : Twenty-nine ( 10.0 % ) infants developed NEC . The average total NICU hospitalization cost ( in 2012 USD ) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC ( p = 0.024 ) . NEC was associated with a marginal increase in costs of USD 43,818 , after controlling for demographic characteristics , risk of NEC , and average daily dose of HM during days 1 - 14 ( p < 0.001 ) . Each additional ml/kg/day of HM during days 1 - 14 decreased non-NEC-related NICU costs by USD 534 ( p < 0.001 ) . Conclusions : Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and result ing NICU costs in VLBW infants . Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs Background And Objective : Gastric acidity is a major nonimmune defense mechanism against infections . The objective of this study was to investigate whether ranitidine treatment in very low birth weight ( VLBW ) infants is associated with an increased risk of infections , necrotizing enterocolitis ( NEC ) , and fatal outcome . Methods : Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks , consecutively observed in neonatal intensive care units , were enrolled in a multicenter prospect i ve observational study . The rates of infectious diseases , NEC , and death in enrolled subjects exposed or not to ranitidine were recorded . Results : We evaluated 274 VLBW infants : 91 had taken ranitidine and 183 had not . The main clinical and demographic characteristics did not differ between the 2 groups . Thirty-four ( 37.4 % ) of the 91 children exposed to ranitidine and 18 ( 9.8 % ) of the 183 not exposed to ranitidine had contracted infections ( odds ratio 5.5 , 95 % confidence interval 2.9–10.4 , P < .001 ) . The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants ( 95 % confidence interval 1.7–25.0 , P = .003 ) than in control subjects . Mortality rate was significantly higher in newborns receiving ranitidine ( 9.9 % vs 1.6 % , P = .003 ) . Conclusions : Ranitidine therapy is associated with an increased risk of infections , NEC , and fatal outcome  in VLBW infants . Caution is advocated in the use of this drug in neonatal age Necrotizing enterocolitis ( NEC ) represents one of the major causes of morbidity in low-birth-weight ( LBW ) preterm infants . This r and omized clinical trial evaluated the efficacy of an oral immunoglobulin preparation ( containing monomeric IgG in a concentration of 90 % ) in reducing the incidence of NEC in infants of LBW for whom maternal breast milk was not available . One hundred and thirty-two formula-fed newborns with a birth weight less than or equal to 1,500 g or a gestational age less than or equal to 34 weeks were r and omly studied . Five hundred mg of IgG pro die , subdivided into 5 doses , were given orally to the test group of 65 neonates during the first 2 weeks of life . Although the number of infants included in this group is limited , the results of this study are encouraging : during the first 15 days after birth , none of the subjects developed NEC , while 4 cases were confirmed in the untreated control group . It , therefore , seems possible that oral monomeric IgG administration may prevent the development of NEC in LBW infants PURPOSE Low birth weight is the most important risk factor for developing necrotizing enterocolitis ( NEC ) . We aim ed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC . METHODS Five hundred eleven centers belonging to the Vermont Oxford Network prospect ively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006 . The primary outcome variable was in-hospital mortality . RESULTS Birth weight was divided into 4 categories by 250-g increments . The NEC risk ( P < .001 ) and mortality ( P < .001 ) decreased with higher birth weight category . Necrotizing enterocolitis was associated with a significant odds ratio for death for each category ( P < .001 ) . Across groups , the odds ratio for NEC mortality increased with higher birth weight category ( category 1 = 1.6 vs category 4 = 9.9 ; P < .001 ) . CONCLUSION The in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category . Although the risk and absolute mortality of NEC decrease with higher birth weight , the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight . These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers 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 OBJECTIVE This is a repeat cohort study in which we sought to determine whether an association of necrotizing enterocolitis ( NEC ) < 48 hours of a packed red blood cells ( PRBC ) transfusion was a prior sampling artifact . STUDY DESIGN All very low birth weight neonates with NEC Stage ≥ IIB admitted over an 18-month period were categorized for NEC : ( 1 ) < 48 hours after a PRBC transfusion ; ( 2 ) unrelated to the timing of PRBCs ; and ( 3 ) never transfused . RESULTS Eight hundred eighty-three admissions over 18 months were review ed ; 256 were very low birth weight that result ed in 36 NEC cases and 25 % were associated with PRBC ( n = 9 ) . PRBC-associated cases had lower birth weight , hematocrit , and rapid onset of signs ( < 5 hours ) . The timing of association of  PRBC transfusion and NEC differed from r and om , showing a distribution that was not uniform over time ( χ(2 ) = 170.7 , df = 40 ; P < .000001 ) consistent with the possibility of a causative relationship in certain cases of NEC . Current weight at onset of NEC did not differ ; however , the more immature the neonate the later the onset of NEC creating a curious centering of occurrence at a median of 31 weeks postconceptual age . CONCLUSIONS We conclude that PRBC-related NEC exists . Transfusion-related acute gut injury is an acronym we propose to characterize a severe neonatal gastrointestinal reaction proximal to a transfusion of PRBCs for anemia . The convergence at 31 weeks postconceptual age approximates the age of presentation of other O(2 ) delivery and neovascularization syndromes , suggesting a link to a generalized systemic maturational mechanism 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 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 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 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 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 a frequent cause of mortality and morbidity in very low birth weight ( VLBW ) infants .  Human milk ( HM ) feeding has been associated with lower risk of NEC . However , mothers of VLBW infants often experience insufficient milk production , result ing in mixed feedings of HM and formula . Moreover , medical complications often limit the volume of feeding they can be given . Objective : To determine if high proportions of ( 50 % or greater ) HM enteral feeding within the first 14 days of life are protective against NEC . Method : This was a prospect i ve cohort study of VLBW infants who were grouped according to the HM proportion of enteral feeding in the first 14 days : < 50 % ( low human milk , LHM , n=46 ) and ⩾50 % ( high human milk , HHM , n=156 ) . The outcome of interest was development of NEC ( Bell stage 2 or 3 ) . Logistic regression was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) and to assess potential confounding due to perinatal risk factors . Result : Two hundred and two infants were studied . Confirmed NEC occurred in 5/46 ( 10.6 % ) of the LHM group , as compared with 5/156 ( 3.2 % ) of the HHM . Gestational age was the only perinatal factor associated with risk of NEC . After adjustment for gestational age , HHM was associated with a lower risk of NEC ( ( OR=0.17 , 95 % CI : 0.04 to 0.68 ) , P=0.01 ) . Conclusion : Enteral feeding containing at least 50 % HM in the first 14 days of life was associated with a sixfold decrease in the odds of NEC 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 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 OBJECTIVES To determine the mortality and morbidity for infants weighing 401 to 1500 g ( very low birth weight [ VLBW ] ) at birth by gestational age , birth weight , and gender . STUDY DESIGN Perinatal data were collected prospect ively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports . Sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death were evaluated . RESULTS Eighty four percent of 4438 infants weighing 501 to 1500 g at birth  survived until discharge to home or to a long-term care facility ( compared with 80 % in 1991 and 74 % in 1988 ) . Survival to discharge was 54 % for infants 501 to 750 g at birth , 86 % for those 751 to 1000 g , 94 % for those 1001 to 1250 g , and 97 % for those 1251 to 1500 g . The incidence of chronic lung disease ( CLD ; defined as receiving supplemental oxygen at 36 weeks ' postmenstrual age ; 23 % ) , proven necrotizing enterocolitis ( NEC ; 7 % ) , and severe intracranial hemorrhage ( ICH ; grade III or IV ; 11 % ) remained unchanged between 1991 and 1996 . Furthermore , 97 % of all VLBW infants and 99 % of infants weighing < 1000 g at birth had weights less than the 10th percentile at 36 weeks ' postmenstrual age . Mortality for 195 infants weighing 401 to 500 g was 89 % , with nearly all survivors developing CLD . Mortality in infants weighing 501 to 600 g was 71 % ; among survivors , 62 % had CLD , 35 % had severe ICH , and 15 % had proven NEC . CONCLUSIONS Survival for infants between 501 and 1500 g at birth continued to improve , particularly for infants weighing < 1000 g at birth . This improvement in survival was not associated with an increase in major morbidities , because the incidence of CLD , proven NEC , and severe ICH did not change . However , poor postnatal growth remains a major concern , occurring in 99 % of infants weighing < 1000 g at birth . Mortality and major morbidity ( CLD , severe ICH , and NEC ) remain high for the smallest infants , particularly those weighing < 600 g at birth 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 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
Current evidence from systematic review and meta- analysis revealed that probiotics are the most promising intervention in reduction of the incidence of NEC in VLBW neonates .
As per the evidence , prebiotics modulate the composition of human intestine microflora to the benefit of the host by suppression of colonization of harmful microorganism and /or the stimulation of bifidobacterial growth , decreased stool viscosity , reduced gastrointestinal transit time , and better feed tolerance .
Necrotizing enterocolitis ( NEC ) is one of the most serious gastrointestinal emergencies in very low birth weight ( VLBW ) preterm neonates , affecting 7 - 14 % of these neonates .
Due to the seriousness of the disease , prevention of NEC is the most important goal .