Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight 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. Randomized Trial of Donor Human Milk Versus Preterm Formula as Substitutes for Mothers' Own Milk in the Feeding of Extremely Premature Infants Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants 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. Comparison of fast- and slow-feeding rate schedules to the development of necrotizing enterocolitis. An exclusively human milk diet reduces necrotizing enterocolitis. The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. The Speed of Increasing milk Feeds: a randomised controlled trial Prevention of necrotizing enterocolitis in neonates at risk by oral administration of monomeric IgG. 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. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial Breast milk and neonatal necrotising enterocolitis Oral Probiotics Reduce the Incidence and Severity of Necrotizing Enterocolitis in Very Low Birth Weight Infants Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. Rotavirus-associated necrotizing enterocolitis: an insight into a potentially preventable disease? Growth, Efficacy, and Safety of Feeding an Iron-Fortified Human Milk Fortifier A randomised multicentre study of human milk versus formula and later development in preterm infants.
OBJECTIVE This study evaluated the cost-effectiveness of a 100 % human milk-based diet composed of mother 's milk fortified with a donor human milk-based human milk fortifier ( HMF ) versus mother 's milk fortified with bovine milk-based HMF to initiate enteral nutrition among extremely premature infants in the neonatal intensive care unit ( NICU ) . METHODS A net expected costs calculator was developed to compare the total NICU costs among extremely premature infants who were fed either a bovine milk-based HMF-fortified diet or a 100 % human milk-based diet  , based on the previously observed risks of overall necrotizing enterocolitis ( NEC ) and surgical NEC in a r and omized controlled study that compared outcomes of these two feeding strategies among 207 very low birth weight infants . The average NICU costs for an extremely premature infant without NEC and the incremental costs due to medical and surgical NEC were derived from a separate analysis of hospital discharges in the state of California in 2007 . The sensitivity of cost-effectiveness results to the risks and costs of NEC and to prices of milk supplements was studied . RESULTS The adjusted incremental costs of medical NEC and surgical NEC over and above the average costs incurred for extremely premature infants without NEC , in 2011 US$ , were $ 74,004 ( 95 % confidence interval , $ 47,051-$100,957 ) and $ 198,040 ( 95 % confidence interval , $ 159,261-$236,819 ) per infant , respectively . Extremely premature infants fed with 100 % human-milk based products had lower expected NICU length of stay and total expected costs of hospitalization , result ing in net direct savings of 3.9 NICU days and $ 8,167.17 ( 95 % confidence interval , $ 4,405-$11,930 ) per extremely premature infant ( p < 0.0001 ) . Costs savings from the donor HMF strategy were sensitive to price and quantity of donor HMF , percentage reduction in risk of overall NEC and surgical NEC achieved , and incremental costs of surgical NEC . CONCLUSIONS Compared with feeding extremely premature infants with mother 's milk fortified with bovine milk-based supplements , a 100 % human milk-based diet that includes mother 's milk fortified with donor human milk-based HMF may result in potential net savings on medical care re sources by preventing NEC 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 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 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 . 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 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 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 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 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 : 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 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 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 In the UK , 1–2 % of infants are born very preterm ( < 32 weeks of gestation ) or have very low birth weight ( < 1500 g ) . Very preterm infants are initially unable to be fed nutritional volumes of milk and therefore require intravenous nutrition . Milk feeding strategies influence several long and short term health outcomes including growth , survival , infection ( associated with intravenous nutrition ) and necrotising enterocolitis ( NEC ) ; with both infection and NEC being key predictive factors of long term disability . Currently there is no consistent strategy for feeding preterm infants across the UK . The SIFT trial will test two speeds of increasing milk feeds with the primary aim of determining effects on survival without moderate or severe neurodevelopmental disability at 24 months of age , corrected for prematurity . The trial will also examine many secondary outcomes including infection , NEC , time taken to reach full feeds and growth . Methods / design Two thous and eight hundred very preterm or very low birth weight infants will be recruited from approximately 30 hospitals across the UK to a r and omised controlled trial . Infants with severe congenital anomaly or no realistic chance of survival will be excluded . Infants will be r and omly allocated to either a faster ( 30 ml/kg/day ) or slower ( 18 ml/kg/day ) rate of increase in milk feeds . Data will be collected during the neonatal hospital stay on weight , infection rates , episodes of NEC , length of stay and time to reach full milk feeds . Long term health outcomes comprising vision , hearing , motor and cognitive impairment will be assessed at 24 months of age ( corrected for prematurity ) using a parent report question naire . Discussion Extensive search es have found no active or proposed studies investigating the rate of increasing milk feeds . The results of this trial will have importance for optimising incremental milk feeding for very preterm and /or very low birth weight infants . No additional re sources will be required to implement an optimal feeding strategy , and therefore if successful , the trial results could rapidly be adopted across the NHS at low cost . Trial registration IS RCT N Registry ; IS RCT N76463425 on 5 March , 2013 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 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 / 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 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 . 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 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 PURPOSE The aim of this study was to test the hypothesis that rotavirus-associated necrotizing enterocolitis ( NEC + RV ) differs from NEC associated with other organisms ( NEC-RV ) . METHODS Neonates with modified Bell stage II or higher NEC were identified . Demographic , clinical , and outcome information was collected prospect ively . Fecal specimens from all infants were tested for confirmation of rotavirus infection ( RVI ) by immunoelectron microscopy ( IEM ) . RESULTS Of 2,444 admissions in the neonatal intensive care unit ( NICU ) , 129 ( 5.3 % ) had NEC . Thirty-eight ( 29 % ) were rotavirus positive . The 2 groups did not differ in maternal or neonatal characteristics . Stage III or higher NEC was more common in the NEC-RV infants ( 62 % v. 39 % ; P = .032 ) , whereas recurrence was more common in NEC + RV group ( P < .0001 ) . The predominant distribution of nondiffuse pneumatosis ( n = 52 ) was right sided in NEC-RV group and left sided in NEC + RV group ( P < .0001 ) . Surgical intervention ( SI ) did not differ between the 2 groups . The complications and mortality rates also were similar . Severe pneumatosis ( P = .009 ) and severe thrombocytopenia ( Platelet count < 50,000/mm3 ; P < .0001 ) increased , while human milk feedings decreased ( P = .022 ) the odds for surgery . The annual distribution of NEC + RV paralleled RVI in the community . CONCLUSIONS Generally , NEC + RV is a less severe disease than NEC - RV as classified by modified Bell staging . However , it can reach advanced stages obscuring distinction from NEC - RV . Indications for surgery should not be altered by identification of RVI in these infants . Monitoring RVI in the community , adhering to infection control measures , human milk feedings , and improving neonatal immunity against RVI may reduce the incidence of NEC + RV Objective . Survival rates for preterm infants who weigh between 501 and 1500 g at birth have continued to improve over time . In response to this continuing decrease in birth weight of surviving preterm infants , Enfamil Human Milk Fortifier has recently been reformulated to meet the nutritional requirements of these smaller , more rapidly growing infants . It now provides an increased protein level of 1.1 g/58 kJ , a decreased carbohydrate level of 0.2 g/58 kJ , and a combined linoleic and α-linolenic fatty acid content of 157 mg/58 kJ. As these very small preterm infants have an increased requirement for dietary iron , the fortifier has been supplemented with 1.44 mg/58 kJ of iron , an amount of iron similar to that provided in a typical iron-fortified term infant formula . An iron-fortified product obviates the need for administration of an iron supplement , a hyperosmolar-inducing intervention . The purpose of this prospect i ve , double-blind , r and omized , controlled study was to evaluate growth , safety , and efficacy in a population of very low birth weight ( VLBW ) preterm infants who received human milk fortified with either the reformulated iron-fortified powdered human milk fortifier test product ( HMF-T ) or a powdered commercially available human milk fortifier control product ( HMF-C ) .  Methods . Infants who weighed ≤1500 g , had a gestational age ≤33 weeks postmenstrual age , and had an enteral intake of at least 100 mL/kg per day of unfortified human milk were stratified by gender and birth weight and r and omized to receive HMF-T or HMF-C product from study day 1 to study day 28 , hospital discharge , or the termination of human milk feedings , whichever came first . Unless medically indicated , investigators were not to administer iron supplements from study days 1 to 14 . Infants were assessed serially for growth ; enteral and parenteral intake ; serum chemistry and hematologic values ; clinical histories , including the administration of blood transfusions ; feeding tolerance ; respiratory outcomes ; and morbidities , including adverse events . Results . Of the 181 participating infants in this study , 96 received HMF-T and 85 received HMF-C. At r and omization , there were no significant differences in infant characteristics between the fortifier groups . The percentage of participants who remained in the study for 28 days was similar between fortifier groups ( 57 % HMF-T , 46 % HMF-C ) . For both fortifier groups , the most frequent reasons for discontinuing the study before study day 28 were unavailability of human milk and hospital discharge . Rate of weight gain was similar between the fortifier groups ( 17.5 ± 0.53 g/kg per day for HMF-T and 17.3 ± 0.59 g/kg per day for HMF-C  ) . Mean achieved weight , length , and head circumference were comparable between groups across the 28-day study period . Total protein intake from enteral and parenteral nutrition was significantly greater for the HMF-T fortifier group ; however , this difference did not result in any difference in growth between the 2 fortifier groups . An analysis of the growth and energy intake data of a subset of the intent-to-treat population who adhered more strictly to the study feeding protocol yielded results similar to those seen for the intent-to-treat population . There were no clinical ly significant differences in the results of laboratory studies between the groups at study days 0 , 14 , and 28 . Anemia of prematurity was prevalent in both study groups ; by study day 28 , median hematocrit levels were 27.0 % ( interquartile range [ IQR ] : 24.0%–29.6 % ) for the HMF-T group and 26.0 % ( IQR : 24.0%–31.0 % ) for the HMF-C group . Median ferritin levels were 77.0 ng/mL ( IQR : 37 - 155 ng/ml ) for HMF-T and 92.0 ng/mL ( IQR : 33 - 110 ng/mL ) for HMF-C. There were no significant differences between the study fortifier groups in regard to the receipt of medically indicated iron supplements on or before study day 14 or in the administration of blood transfusions before study day 0 or from study days 0 through 14 . However , from study day 15 to study day 28 , fewer HMF-T infants ( n = 12 ) required a blood transfusion than did HMF-C infants ( n = 20 ) . Although the higher levels of iron in the HMF-T fortifier ( 1.44 mg vs 0.35 mg for HMF-C per 4 packets of powdered fortifier ) did not prevent anemia per se , it did reduce the frequency of one of the most serious outcomes of anemia : the need for a blood transfusion . There was no statistically significant difference between fortifier groups in regard to feeding tolerance . Rates of suspected sepsis ( 26 % HMF-T vs 31 % HMF-C ) and confirmed sepsis ( 5 % HMF-T , 7 % HMF-C ) were low as were the rates of suspected necrotizing enterocolitis ( NEC ; 6 % HMF-T and 5 % HMF-C ) and confirmed Bell 's stage 2 or more NEC ( 1 % HMF-T and 1 % HMF-C ) . There were no statistically significant differences between the study fortifier groups in regard to the incidence of confirmed and suspected sepsis and NEC . Conclusion . Both human milk fortifiers studied are safe , are well tolerated , and facilitate comparable good growth ; however , using the iron-fortified product may reduce the need for blood transfusions in VLBW infants . The similar low rates of suspected and confirmed NEC and sepsis seen in both fortifier groups in this study refutes the premise that the inclusion of iron in fortifiers will increase the incidence of sepsis and NEC . Indeed , the incidence for NEC and sepsis for both groups in this study was lower than is reported for VLBW infants and similar to that seen for infants who are fed human milk Whether breast milk influences later neurodevelopment  has been explored in non-r and omised studies , potentially confounded by social and demographic differences between feed groups . Here in a strictly r and omised prospect i ve multicentre trial , Bayley psychomotor and mental development indices ( PDI and MDI ) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive , during their early weeks , mature donor breast milk or a preterm formula .  These diets were compared as sole enteral feeds or as supplements to the mother 's expressed breast milk . No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants . These results contrast with those reported from our parallel two centre study that compared infants r and omly assigned a st and ard term formula or the preterm formula during their early weeks ; those fed st and ard formula , now regarded as nutritionally insufficient for preterm infants , were substantially disadvantaged in PDI and MDI at 18 months post-term . It is shown here that infants from that study fed solely on st and ard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study ; yet the st and ard formula had a higher nutrient content than the donor milk . Thus , donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants . As these outcome advantages were not confounded by the social and educational biases usually associated with mothers ' choice to breast feed , our data add significant support to the view that breast milk promotes neurodevelopment
It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC .
BACKGROUND Necrotizing enterocolitis ( NEC ) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality .
Mother 's own milk is protective against NEC but is not always available .
In such cases , donor human milk has also been shown to be protective ( although to a lesser extent ) compared with formula milk , but it is more expensive .
This systematic review aim ed at evaluating the cost of donor milk , the cost of treating NEC , and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC .