Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial Necrotizing enterocolitis - classification and two initial steps towards prevention. Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial. Randomized Trial of Donor Human Milk Versus Preterm Formula as Substitutes for Mothers' Own Milk in the Feeding of Extremely Premature Infants 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. Oral Probiotics Prevent Necrotizing Enterocolitis in Very Low Birth Weight Preterm Infants: A Multicenter, Randomized, Controlled Trial Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants Breast milk and neonatal necrotising enterocolitis Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. An exclusively human milk diet reduces necrotizing enterocolitis. Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case–control study Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Oral Probiotics Reduce the Incidence and Severity of Necrotizing Enterocolitis in Very Low Birth Weight Infants Comparison of fast- and slow-feeding rate schedules to the development of necrotizing enterocolitis. Early enteral feeding does not affect the incidence of necrotizing enterocolitis.
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 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 IMPORTANCE Infections and necrotizing enterocolitis , major causes of mortality and morbidity in preterm infants , are reduced in infants fed their own mother 's milk when compared with formula . When own mother 's milk is not available , human donor milk is considered a good alternative , albeit an expensive one . However , most infants at modern neonatal intensive care units are predominantly fed with own mother 's milk . The benefits of add-on donor milk over formula are not clear . OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother 's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection , necrotizing enterocolitis , and mortality . DESIGN , SETTING S , AND PARTICIPANTS The Early Nutrition Study was a multicenter , double-blind r and omized clinical trial in very low-birth-weight infants ( birth weight < 1500 g ) admitted to 1 of 6 neonatal intensive care units in the Netherl and s from March 30 , 2012 , through August 17 , 2014 . Intent-to-treat analysis was performed . INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother 's milk was not ( sufficiently ) available . MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection ( sepsis or meningitis ) , necrotizing enterocolitis , or mortality during the first 60 days of life . RESULTS A total of 930 infants were screened for inclusion ; 557 were excluded , result ing in 373 infants ( 183 receiving donor milk and 190 receiving formula )  who were evaluated by intent-to-treat analysis ( median birth weight , 1066 g ; mean gestational age , 28.4 weeks ) . Own mother 's milk comprised 89.1 % and 84.5 % of total mean intake during the intervention period for the donor milk and formula groups , respectively . The incidence of the combined outcome was not different ( 85 [ 44.7 % ] [ formula ] vs 77 [ 42.1 % ] [ donor milk ] ; mean difference , 2.6 % ; 95 % CI , -12.7 % to 7.4 % ) . The adjusted hazard ratio was 0.87 ( 95 % CI , 0.63 - 1.19 ; P = .37 ) . CONCLUSIONS AND RELEVANCE In the current study , pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother 's milk availability was insufficient . Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary . TRIAL REGISTRATION trialregister.nl Identifier : NTR3225 Objective . Compared with preterm formula ( PF ) , mother 's milk ( MM ) is associated with lower rates of late-onset sepsis ( LOS ) and necrotizing enterocolitis ( NEC ) among premature infants . Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization , we reasoned that pasteurized donor human milk ( DM ) would be a suitable alternative . Methods . Extremely premature infants ( < 30 weeks of gestation ) whose mothers intended to breastfeed were assigned r and omly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study ( birth to 90 days of age or hospital discharge ) . Infection-related events ( LOS , NEC , meningitis , presumed sepsis , or urinary tract infection ) that occurred after the attainment of a milk intake of 50 mL/kg , dietary intake , growth , skin-to-skin contact , and duration of hospital stay were compared . The primary analysis compared groups DM and PF on an intent-to-treat basis . If no differences were noted , then these groups were combined and compared with the reference group , group MM . If differences were noted , then the subsequent analyses compared each group with group MM . Results . Of 243 infants , 70 ( 29 % ) received only MM ; group DM included 81 infants and group PF included 92 infants . Because of poor weight gain , 17 infants ( 21 % ) , all in group DM , were switched to PF . There were no differences in birth weight , gestational age , multiple births , and age at attainment of feeding of 50 mL/kg among groups . There were no differences between group DM and group PF in LOS and /or NEC , other infection-related events , hospital stay , or number of deaths . Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain , compared with group PF . Compared with groups DM and PF , group MM had fewer episodes of LOS and /or NEC and total infection-related events and a shorter duration of hospital stay . Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups . Conclusions . In this r and omized , blinded trial of feeding of extremely premature infants , we found that , as a substitute for MM , DM offered little observed short-term advantage over PF for feeding extremely premature infants . Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays 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 OBJECTIVE . The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants . METHODS . A prospect i ve , blinded , r and omized , multicenter controlled trial was conducted at 7 NICUs in Taiwan , to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants ( birth weight : < 1500 g ) . Very low birth weight infants who survived to start enteral feeding were eligible and were assigned r and omly to 2 groups after parental informed consent was obtained . Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus , added to breast milk or mixed feeding ( breast milk and formula ) , twice daily for 6 weeks . Infants in the control group were fed with breast milk or mixed feeding . The clinicians caring for the infants were blinded to the group assignment . The primary outcome measurement was death or necrotizing enterocolitis ( Bell 's stage ≥2 ) . RESULTS . Four hundred thirty-four infants were enrolled , 217 in the study group and 217 in the control group . The incidence of death or necrotizing enterocolitis ( stage ≥2 ) was significantly lower in the study group ( 4 of 217 infants vs 20 of 217 infants ) . The incidence of necrotizing enterocolitis ( stage ≥2 ) was lower in the study group , compared with the control group ( 4 of 217 infants vs 14 of 217 infants ) . No adverse effect , such as sepsis , flatulence , or diarrhea , was noted . CONCLUSION . Probiotics , in the form of Bifidobacterium and Lactobacillus , fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis 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 In a prospect i ve multicentre study on 926 preterm infants formally assigned to their early diet , necrotising enterocolitis developed in 51 ( 5.5 % ) .  Mortality was 26 % in stringently confirmed cases . In exclusively  formula-fed  babies confirmed disease was 6 - 10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk . Pasteurised donor milk seemed to be as protective as raw maternal milk . Among babies born at more than 30 weeks ' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk ; it was 20 times more common in those fed formula only . Other risk factors included very low  gestational age , respiratory disease , umbilical artery catheterisation , and polycythaemia . In formula-fed but not breast-milk-fed infants , delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis . With the fall in the use of breast milk in British neonatal units , exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year . About 100 of these infants would die OBJECTIVE To compare the duration of parenteral nutrition , growth , and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula ( BOV ) or donor human milk and human milk-based human milk fortifier ( HUM )  , in a r and omized trial of formula vs human milk . STUDY DESIGN Multicenter r and omized controlled trial . The authors studied extremely preterm infants whose mothers did not provide their milk . Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM . The major outcome was duration of parenteral nutrition . Secondary outcomes were growth , respiratory support , and necrotizing enterocolitis ( NEC ) . RESULTS Birth weight ( 983 vs 996 g ) and  gestational age ( 27.5 vs 27.7 wk ) , in BOV and HUM , respectively , were similar . There was a significant difference in median parenteral nutrition days : 36 vs 27 , in BOV vs HUM , respectively ( P = .04 ) . The incidence of NEC in BOV was 21 % ( 5 cases ) vs 3 % in HUM ( 1 case ) , P = .08 ; surgical NEC was significantly higher in BOV ( 4 cases ) than HUM ( 0 cases ) , P = .04 . CONCLUSIONS In extremely preterm infants given exclusive diets of preterm formula vs human milk , there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula . This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit OBJECTIVE This study tested the hypothesis that feeding an exclusively human milk ( EHM ) diet  to premature infants reduces the incidence of necrotizing enterocolitis ( NEC ) associated with enteral feeding . STUDY DESIGN An observational study for infants born at less than 33 weeks of gestational age was performed in a single neonatal intensive care unit . An EHM diet prospect ively eliminated bovine-based artificial milk , including bovine-based fortifier , through 33 weeks postmenstrual age ( PMA ) . The clinical data from a 2.5-year interval of the EHM diet were compared with data from the previous 6.5 years for similar infants who received bovine-based milk products  before 33 weeks PMA . RESULTS In the EHM diet cohort , 148 of 162 infants ( 91 % ) received EHM through 33 weeks PMA . In order to achieve an EHM diet , 140 of 162 infants ( 86 % ) received their own mother 's milk , and 98 of 162 infants ( 60 % ) received donor human milk . The EHM cohort was also fed a human milk-based fortifier to truly eliminate bovine products . The distribution of NEC onset in the EHM cohort was significantly different from that in the control cohort for the day of onset ( p=0.042 ) and the PMA at onset ( p=0.011 ) . In the control cohort , NEC onset after Day 7 of life occurred in 15 of 443 infants ( 3.4 % ) , significantly more than in the EHM cohort where NEC occurred in two of 199 infants ( 1 % ) ( p=0.009 ) . CONCLUSIONS Changing to an EHM milk diet through 33 weeks PMA reduced the incidence of NEC associated with enteral feeding Background : Most preterm infants who develop necrotising enterocolitis ( NEC )  have received enteral feeds . Uncertainty exists about which aspects of the feeding regimen affect the risk of NEC . Aim : To examine associations between various enteral feeding practice s and the development of  NEC  in preterm infants . Methods : Multicentre case – control study . 53 preterm infants with NEC were enrolled together with a gestational age frequency-matched control without NEC from a r and omly selected neonatal unit . Clinical and feeding data were extracted and compared between the groups . Results : Significantly fewer cases than controls had received human breast milk ( 75 % vs 91 % ; OR 0.32 , 95 % CI 0.11 to 0.98 ) . The day on which enteral feeding was started did not differ significantly ( mean ( SD ) days after birth : cases 2.9 ( 2.8 ) and controls 2.8 ( 1.8 ) ) . The mean ( SD ) duration of trophic feeding ( < 1 ml/kg/h ) was significantly shorter in the cases ( 3.3 ( 3.1 ) days ) than controls ( 6.2 ( 6.7 ) days ) ( mean difference ( MD ) −2.9 , 95 % CI −4.9 to −0.9 ) days . Cases were fully fed significantly earlier than controls ( mean ( SD ) days after birth : cases 9.9 ( 4.2 ) and controls 14.3 ( 9.8 ) ; MD −4.4 , 95 % CI −7.3 to −1.5 ) . Conclusions : These data suggest that the duration of trophic feeding and rate of advancement of feed volumes may be modifiable risk factors for NEC in preterm infants . Further r and omised controlled trials are warranted to assess the effect of different rates of feed advancement on the incidence of NEC , as well as other outcomes 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 Approximately 90 % of infants who develop necrotizing enterocolitis (  NEC ) do so after being fed . Previous prospect i ve studies have shown that infants given small enteral feedings  for the first 7 to 10 days of feeding do not have an increased risk for NEC compared with those given no feedings . Although neonatologists now commonly increase feeding volumes , no study has compared the risk for NEC between infants fed these small volumes and those fed volumes that are increased slowly . The purpose of this study was to compare the risks and benefits of small and increasing feeding volume . METHODS In a r and omized , controlled trial , we r and omly assigned 141 preterm infants in the newborn intensive care unit to be fed 10 days using 1 of 2 schedules . One group was fed 20 mL/kg/d for the first 10 study days ( minimal ) . The other group ( advancing ) was fed 20 mL/kg/d on study day 1 ; feeding volume was increased by 20 mL/kg/d up to 140 mL/kg/d , which was maintained until study day 10 . The main outcome measure was incidence of NEC ; secondary outcomes were maturation of intestinal motor patterns , time to reach full enteral feedings , and incidence of late sepsis . RESULTS The study was closed early because 7 infants who were assigned to advancing feeding volumes developed NEC , whereas only 1 infant fed minimal feeding volumes did , or 10 % versus 1.4 % . Although infants who were fed minimal volumes established full enteral feeding volumes later than infants who were fed advancing volumes , maturation of intestinal motor patterns and the incidence of late sepsis and feeding intolerance was similar in the 2 groups . CONCLUSION Given that advancing feeding volumes increase the risk of NEC without providing benefits for motor function or feeding tolerance , neonatologists should consider using minimal feeding volumes until future trials assess the safety of advancing feeding volumes Background : Necrotizing enterocolitis ( NEC ) is one of the most destructive diseases associated with conditions of neonatal prematurity . Supplementation with enteral prebiotics may reduce the incidence of NEC , especially in infants who fed exclusively with breast-milk . Therefore , we compared the efficacy and safety of enteral supplementation of a prebiotic mixture ( short chain galacto-oligosaccharides/long chain fructo-oligosaccharides [ SCGOS/LCFOS ] ) versus no intervention on incidence of NEC in preterm infants . Methods : In a single-center r and omized control trial 75 preterm infants ( birth weight [ BW ] ≤1500 g , gestational age ≤34 weeks and were not fed with formula ) on 30 ml/kg/day volume of breast-milk were r and omly allocated to have enteral supplementation with a prebiotic mixture ( SCGOS/LCFOS ; 9:1 ) or not receive any prebiotic . The incidence of suspected NEC , feeding intolerance , time to full enteral feeds , duration of hospitalization were investigated . Results : Differences in demographic characteristics were not statistically important . SCGOS/LCFOS mixture significantly reduced the incidence of suspected NEC , ( 1 [ 4.0 % ] vs. 11 [ 22.0 % ] ; hazard ratio : 0.49 [ 95 % confidence interval : 0.29 - 0.84 ] ; P = 0.002 ) , and time to full enteral feeds ( 11 [ 7 - 21 ] vs. 14 [ 8 - 36 ] days ; P - 0.02 ] . Also duration of hospitalization was meaningfully shorter in the prebiotic group ( 16 [ 9 - 45 ] vs. 25 [ 11 - 80 ] ; P - 0.004 ] . Prebiotic oligosaccharides were well tolerated by very low BW ( VLBW ) infants . Conclusions : Enteral supplementation with prebiotic significantly reduced the incidence of NEC in VLBW infants who were fed exclusively breast-milk . This finding suggests that it might have been the complete removal of formula which caused a synergistic effect between nonhuman neutral oligosaccharides ( prebiotic ) and human oligosaccharides Objective . 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 NECROTIZING ENTEROCOLITIS is a serious disorder of the newborn infant that rarely occurs before the institution of oral feedings . ' -3 Various feeding practice s have been shown to be important in the pathogenesis of the disease . Low-birth-weight infants fed a hyperosmolar , 650 mOsm/1 , elemental formula  have an increased incidence of NEC when compared to low-birth-weight infants fed a cow milk formula . 4 It has also been suggested that cow milk feedings themselves or the exclusion of breast milk from the diet of small newborn infants may be predisposing factors ? The quantity of feedings in the first weeks of life may also be important , and Krouskop and associates ~ have associated the development of NEC with early institution of oral feedings . In another retrospective study , however , there were no differences between the volume of formula offered NEC patients at the time symptoms developed and infants of similar size and age who did not develop NEC . 1 Conflicting opinions therefore exist regarding the relationship of oral feeding to the development of NEC ; there have been no r and omized , prospect i ve , clinical trials dealing with this issue . The purpose s of this paper are to report the relationship of different feeding practice s in the Intermountain Newborn Intensive Care Center to the incidence of NEC , and the results of a prospect i ve controlled investigation comparing two different feeding schedules in low-birth-weight infants To begin to determine the optimal time for initiating enteral feedings , 34 sick , very low birth weight infants were prospect ively selected from all neonates of less than 1,500 g ( N = 116 ) and r and omly divided into two groups . Infants were fed either on day 1 ( early ) or 7 ( late ) of life , according to a feeding protocol which included parenteral nutrition and a scheduled progression from sterile water to 2.5 % dextrose , half-strength , and finally full-strength formula over seven days . The incidence of necrotizing enterocolitis and subsequent hospital course were compared . Initiating enteral feedings on day 1 did not significantly increase the incidence of necrotizing enterocolitis , produce a clustering of cases , or induce an earlier onset of necrotizing enterocolitis . The overall incidence of necrotizing enterocolitis in sick , very low birth weight neonates was 29 % ( 5/17 ) and 35 % ( 6/17 ) in the early and late groups , respectively , compared with 4.2 % ( 2/47 ) in minimally sick , very low birth weight neonates . No significant differences between groups were seen in obstetrical complications , birth weight , gestational age , Apgar scores , presence of patent ductus arteriosus or intraventricular hemorrhage , use of umbilical catheterization , and respiratory or oxygen requirements . Infants fed enterally from day 1 did show a significantly higher energy and protein intake during the second week of life . These data show that providing dilute , early enteral calories does not adversely affect the incidence of necrotizing enterocolitis
None of the trials individually found any statistically significant difference in the incidence of NEC .
However , meta- analysis found that feeding with donor human milk was associated with a significantly reduced relative risk ( RR ) of NEC .
OBJECTIVES To determine if enteral feeding with donor human milk compared with formula milk reduces the incidence of necrotising enterocolitis ( NEC ) in preterm or low birthweight infants .