Breast milk and neonatal necrotising enterocolitis The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: a randomised controlled trial Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case–control study 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. Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial. Alimentazione del neonato pretermine IUGR: studio multicentrico ADEPT (Abnormal Doppler Enteral Prescription Trial). (Feeding the IUGR premature newborn infant: the multicenter ADEPT study). Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants
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 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 To evaluate the effect of oral Lactobacillus reuteri ( L reuteri ) first on the incidence and severity of Necrotising enterocolitis ( NEC ) and second on sepsis . Design Prospect i ve r and omised controlled study . Setting Tertiary neonatal intensive care unit . Patients and interventions Preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 g were included ( n=400 ) . Infants in the first group were given 100 million CFU/day ( 5 drops ) of lyophilised L reuteri ( DSM 17938 ) mixed in breast milk or formula , starting from first feeding until discharge . Participants in the control group were given a placebo . Main outcome measures To determine and compare the frequency of NEC and /or death after 7 days , frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Results There was no statistically significant difference between groups in terms of frequency of NEC stage ≥2 ( 4 % vs 5 % ; p=0.63 ) or overall NEC or mortality rates ( 10 % vs 13.5 % ; p=0.27 ) . Frequency of proven sepsis was significantly lower in the probiotic group compared to the control group ( 6.5 % vs 12.5 % ; p=0.041 ) . A significant difference was also observed with regard to rates of feeding intolerance ( 28 % vs 39.5 % ; p=0.015 ) and duration of hospital stay ( 38 ( 10–131 ) vs 46 ( 10–180 ) days ; p=0.022 ) . Conclusions Our results show that oral L reuteri does not seem to affect the overall rates of NEC and /or death in preterm infants followed up in the neonatal intensive care unit , and significant reductions were observed in the frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Trial registration number NCT01531179 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 : 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 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 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 AIM Pregnancies complicated by abnormal antenatal Doppler blood flow often result in the preterm delivery of a growth restricted baby . These babies have a high risk of milk intolerance and necrotising enterocolitis ( 1 ) , and introduction of milk feeds is frequently delayed . Our aim was to determine the effect of early or late introduction on success of achieving full milk feeds and on adverse outcomes including NEC . METHODS Eligible babies with birthweight below 10th centile and gestation below 34 + 6 weeks , born after abnormal antenatal Dopplers , were r and omised between 20 and 48 hours to either early ( 24 - 48 hours ) or late ( 120 - 144 hours ) introduction  of milk feeds .  Babies with major congenital anomaly , in-utero transfusion , multi-organ failure or need for inotropes were excluded . Feed volumes and rate of increase were st and ardised , and were the same for both groups . Daily feed logs were kept . RESULTS 404 babies were r and omised from 56 units in U.K. and Irel and ( 202 in each group ) . There were no important differences between groups at r and omisation . CONCLUSION growth restricted preterm infants born after absent or reversed end-diastolic flow in the umbilical artery who are fed from the second day after birth achieve full feeds faster than those commencing feeds on day six . No difference was been seen in the incidence of NEC , in preliminary analysis . Final data analysis is currently being completed and will be presented at the conference 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
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 .