Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case–control study Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants Does the Enteral Feeding Advancement Affect Short-term Outcomes in Very Low Birth Weight Infants? Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g. ADEPT - Abnormal Doppler Enteral Prescription Trial Early enteral feeding and nosocomial sepsis in very low birthweight infants Parenteral nutrition compared with transpyloric feeding. Growth and morbidity of extremely preterm infants after early full enteral nutrition Slow versus fast enteral feed advancement in very low birth weight infants: a randomized control trial. Slow versus rapid enteral feed in preterm neonates with antenatal absent end diastolic flow Breast milk and neonatal necrotising enterocolitis Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Enteral human IgG for prevention of necrotising enterocolitis: a placebo-controlled, randomised trial Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial Feeding infants below 29 weeks’ gestation with abnormal antenatal Doppler: analysis from a randomised trial Two-hourly versus 3-hourly feeding for very low birthweight infants: a randomised controlled trial Early versus delayed minimal enteral feeding and risk for necrotizing enterocolitis in preterm growth-restricted infants with abnormal antenatal Doppler results. Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial. Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Very early feeding in stable small for gestational age preterm infants: a randomized clinical trial. Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants
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 AIMS To improve energy intake in sick very low birthweight ( VLBW ) infants ; to decrease growth problems , lessen pulmonary morbidity , shorten hospital stay , and avoid possible feeding related morbidity . Morbidity in VLBW infants thought to be associated with parenteral and enteral feeding includes bronchopulmonary dysplasia , necrotising enterocolitis , septicaemia , cholestasis and osteopenia of prematurity . METHODS A prospect i ve r and omised controlled trial ( RCT ) comparing two types of nutritional intervention was performed involving 125 sick VLBW infants in the setting of a regional neonatal intensive care unit . Babies were r and omly allocated to either an aggressive nutritional regimen ( group A ) or a control group ( group B ) . Babies in group B received a conservative nutritional regimen while group A received a package of more aggressive parenteral and enteral nutrition . Statistical analysis was done using Student’st test , the Mann-Whitney U test , the χ2 test and logistic regression . RESULTS There was an excess of sicker babies in group A , as measured by initial disease severity ( P < 0.01 ) , but mean total energy intakes were significantly higher ( P < 0.001 ) in group A at days 3 to 42 while receiving total or partial parenteral nutrition . Survival and the incidences of bronchopulmonary dysplasia , septicaemia , cholestasis , osteopenia and necrotising enterocolitis were similar in both groups . Growth in early life and at discharge from hospital was significantly better in babies in group A. There were no decreases in pulmonary morbidity or hospital stay . CONCLUSION Nutritional intake in sick VLBW infants can be improved without increasing the risk of adverse clinical or metabolic sequelae . Improved nutritional intake result ed in better growth , both in the early neonatal period and at hospital discharge , but did not decrease pulmonary morbidity or shorten hospital stay Background and Objectives : Controversy exists regarding the optimal enteral feeding regimen of very low birth weight infants ( VLBW ) . Rapid advancement of enteral feeding has been associated with an increased rate of necrotizing enterocolitis . In contrast , delaying enteral feeding may have unfavorable effects on nutrition , growth , and neurodevelopment . The aim is to compare the short-term outcomes of VLBW infants in tertiary care centers according to their enteral feeding advancement . Patients and Methods : We prospect ively studied the influence of center-specific enteral feeding advancement in 1430 VLBW infants recruited from 13 tertiary neonatal intensive care units in Germany on short-term outcome parameters . The centers were post hoc stratified to “ rapid advancement to full enteral feeds ” ( median duration of advancement to full enteral feeds ≤12.5 days ; 6 centers ) , that is , rapid advancement ( RA ) , or “ slow advancement to full enteral feeds ” ( median duration of advancement to full enteral feeds > 12.5 days ; 7 centers ) , that is , slow advancement ( SA ) . Results : VLBW infants born in centers with SA ( n = 713 ) had a significantly higher rate of sepsis compared with VLBW infants born in centers with RA ( n = 717 ) , which was particularly evident for late-onset sepsis ( 14.0 % vs 20.4 % ; P = 0.002 ) . Furthermore , more central venous lines ( 48.6 % vs 31.1 % , P < 0.001 ) and antibiotics ( 92.4 % vs 77.7 % , P < 0.001 ) were used in centers with SA . Conclusions : Center differences in enteral feeding advancement occur and may have a significant impact on short-term outcomes such as nosocomial sepsis . Large , multicenter , prospect i ve trials are required to further eluci date the optimal feeding strategy for VLBW infants OBJECTIVE To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750 - 1250 g birth weight . STUDY DESIGN A total of 92 stable neonates 750 - 1250 g and gestational age < 32 weeks were r and omly allocated to enteral feeding advancement of 20 mL/kg/d ( n = 46 ) or 30 mL/kg/d ( n = 46 ) . The primary outcome was days to reach full enteral feeding , defined as 180 mL/kg/d . Secondary outcomes included rates of necrotizing enterocolitis ( NEC ) and culture-proven sepsis , days of parenteral nutrition ( PN ) , length of hospital stay , and growth end points . RESULTS Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group . They received significantly fewer days of PN , exhibited a shorter time to regain birth weight , and had a shorter duration of hospital stay . The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups , whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement . Excluding infants who were small for gestational age at birth , the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge . CONCLUSION Rapid enteral feeding advancements in 750 - 1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration . Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants Background Pregnancies complicated by abnormal umbilical artery Doppler blood flow patterns often result in the baby being born both preterm and growth-restricted . These babies are at high risk of milk intolerance and necrotising enterocolitis , as well as post-natal growth failure , and there is no clinical consensus about how best to feed them . Policies of both early milk feeding and late milk feeding are widely used . This r and omised controlled trial aims to determine whether a policy of early initiation of milk feeds is beneficial compared with late initiation . Optimising neonatal feeding for this group of babies may have long-term health implication s and if either of these policies is shown to be beneficial it can be immediately adopted into clinical practice . Methods and Design Babies with gestational age below 35 weeks , and with birth weight below 10th centile for gestational age , will be r and omly allocated to an " early " or " late " enteral feeding regimen , commencing milk feeds on day 2 and day 6 after birth , respectively . Feeds will be gradually increased over 9 - 13 days ( depending on gestational age ) using a schedule derived from those used in hospitals in the Eastern and South Western Regions of Engl and , based on surveys of feeding practice . Primary outcome measures are time to establish full enteral feeding and necrotising enterocolitis ; secondary outcomes include sepsis and growth .  The target sample size is 400 babies . This sample size is large enough to detect a clinical ly meaningful difference of 3 days in time to establish full enteral feeds between the two feeding policies , with 90 % power and a 5 % 2-sided significance level . Initial recruitment period was 24 months , subsequently extended to 38 months . Discussion There is limited evidence from r and omised controlled trials on which to base decisions regarding feeding policy in high risk preterm infants . This multicentre trial will help to guide clinical practice and may also provide pointers for future research .Trial registration Current Controlled Trials IS RCT N : Background : The interrelations between early enteral feeding , necrotising enterocolitis ( NEC ) , and nosocomial sepsis ( NS ) remain unclear . Objective : To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight ( VLBW < 1500 g ) infants . Methods : Data were collected on the pattern of enteral feeding  and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995–2001 .  Enteral feeding was compared between infants with and without NS and /or NEC . Results : The study sample included 385 infants . Of these , 163 ( 42 % ) developed NS and 35 ( 9 % ) developed NEC .  Enteral feeding was started at a significantly earlier mean ( SD ) age in infants who did not develop nosocomial sepsis ( 2.8 ( 2.6 ) v 4.8 ( 3.7 ) days , p = 0.0001 ) . Enteral feeding was introduced at the same age in babies who did or did not develop NEC ( 3.1 ( 2 ) v 3.7 ( 3 ) days , p = 0.28 ) . Over the study period , the mean annual age at the start of enteral feeding fell consistently , and this correlated with the mean annual incidence of NS ( r2 = 0.891 , p = 0.007 ) . Multiple logistic regression analysis showed age at start of enteral feeding , respiratory distress syndrome , and birth weight to be the most significant predictors of risk of NS ( p = 0.0005 , p = 0.024 , p = 0.011 ) . Conclusions : Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC  in VLBW infants . These findings support the use of early enteral feeding in this high risk population , but this needs to be confirmed in a large r and omised controlled trial Fifty nine infants of birthweight less than 1500 g were allocated alternately to initial total parenteral nutrition or to transpyloric feeding .  Mortality was similar between the two groups . Ten of the 29 infants in the transpyloric group failed to establish full enteral nutrition during the first week of life . No beneficial effects on growth were shown in infants receiving parenteral nutrition . Acquired bacterial infection was higher in the parenteral group and associated with morbidity and mortality . Conjugated hyperbilirubinaemia occurred only in the parenterally fed infants . The incidence of necrotising enterocolitis was higher in the transpyloric group . Parenteral nutrition does not confer any appreciable benefit and because of greater complexity and higher risk of complications should be reserved for those infants in whom enteral feeding is impossible Objectives To evaluate feasibility and consequences of accelerated feeding advancement on short-term outcomes in extremely low gestational age neonates ( ELGANs ) who stayed in our institution for > 28 days . Methods Retrospective single-centre cohort analysis covering the years 2011–2013 . Data are presented as median ( IQR ) . Results Infants ' ( n=77 ) birth weight was 745 ( 640 to 960 ) g and gestational age at birth 26.7 ( 25.1 to 27.4 ) weeks .  Full enteral feeds were attained by postnatal day 7 ( 5 to 11 ) . Weight gain from birth to discharge was 14.3 ( 13.3 to 16.1 ) g/kg/day , change in SD score for weight −0.03 ( −0.55 to 0.46 ) and 0.09 ( −0.78 and 0.82 ) for head circumference . Rates of necrotising enterocolitis and spontaneous intestinal perforation in all ELGANs admitted during the study period were 3.1 % and 9.4 % , respectively . Conclusions This cohort of ELGANs showed good weight gain and head growth after early full enteral nutrition . The impact of this feeding practice on neonatal morbidity and long-term outcome remains to be tested in adequately powered r and omised trials OBJECTIVE To evaluate the tolerance of rapid advancement of enteral feeds in VLBW babies . SETTING Tertiary teaching hospital . DESIGN R and omized controlled trial . METHODS All stable neonates with birth weight less than 1250 grams were included in the study . The primary outcome variable was the time taken to achieve full enteral feeds ( defined as 180 ml/kg/day ) . The secondary outcome variables were incidence of Necrotizing enterocolitis ( NNEC ) and incidence of apnea . At 48 hours , the infants were r and omized into the slow advancement group ( enteral feeds advanced by increments of 15 ml/kg/day ) or fast advancement group ( enteral feeds advanced by increments of 30 ml/kg/day ) . The monitoring during feeding included daily weight record , two hourly abdominal girth charting , gastric aspirates , apnea , time taken to reach full enteral feedings and for NNEC . RESULTS There were 53 infants who were enrolled for the study ( 27 in the fast advancement group and 26 in the slow advancement group ) . In the fast advancement group , 20 percent completed the trial ; whereas 14 ( 53.8 percent ; ) in the slow advancement group completed the study . The two groups were comparable for birth weights , gestational age , sex , intrauterine growth status , Apgar and CRIB scores . The infants in the fast group reached full enteral intake of 180 ml/kg/day significantly earlier ( 10 + /- 1.8 days ) than in the slow group ( 14.8 + /- 1.5 days ) . The two groups were comparable for episodes of feed intolerance , apnea , NNEC . Infants in the fast group regained birth weight significantly earlier ( median 18 days ) than in the slow advancement group ( median 23 days ) . CONCLUSIONS Stable VLBW neonates can tolerate rapid advancements of enteral feeding without increased risk of adverse effects Abstract Objective : Incidence of feed intolerance ( FI ) and necrotizing enterocolitis ( NEC ) in preterm neonates with Doppler evidence of absent end diastolic flow ( AEDF ) velocities in the fetal umbilical artery when enteral feed volumes were started by 6–72 h and advanced either slowly or rapidly . Methods : Stable inborn neonates , 30–36 weeks gestation , weighing ≥1000 g and with antenatal evidence of AEDF were included in this pilot study . Infants ( stratified in < 1250 g and ≥1250 g birth weight categories ) were allocated under r and omized controlled trial , to receive either slow or rapid advancement of enteral feeding , while initiating the feeds after 6 h of birth if bowel sounds were present . Primary outcome measure was , FI and NEC till day 7 after reaching full feeds . Results : Of 159 eligible infants , 83 were r and omized : 53 infants in the ≥1250 g category ( 28 in rapid and 25 in slow group ) and 30 in the < 1250 g category ( 15 in each group ) . FI was present in 11 % versus 16 % in ≥1250 g ( p = 0.570 ) and 27 % versus 33 % in < 1250 g ( p = 0.690 ) , NEC developed in 8.4 % ( 3 versus 1 ) in ≥1250 g and ( 1 versus 2 ) in < 1250 g , in slow versus rapid feeding . Conclusion : This trial did not find increase in incidence of feed intolerance with very early introduction and rapid advancement of enteral feeds in stable preterm neonates with AEDF and birth weight ≥1250 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 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 Neonatal necrotising enterocolitis is a serious , commonly fatal disease in premature neonates . Although feeding with expressed breast milk and other good nursery practice s are partly protective , preventive measures are needed . Treating neonates enterally with a mixture of human IgA and IgG , prepared from donated blood , has been cl aim ed to protect against necrotising enterocolitis . However , no IgA preparation is available in Australia . Our aim , therefore , was to identify whether or not enteral IgG could prevent the disorder . METHODS We did a multicentre , double-blind , placebo- controlled trial . We r and omly assigned 768 infants to receive human IgG 1200 mg/kg daily , and 761 to receive placebo , for up to 28 days . Treatment began at the same time as enteral feeding . The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial , and any deaths that result ed from the disorder in the treatment and placebo groups . Analysis was on an intention-to-treat basis . FINDINGS 43 infants developed definite necrotising enterocolitis  in the IgG group , ten of whom died . In the placebo group , 41 infants contracted the disorder and six died ( p=0.47 ) . 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis ( p=0.14 ) . INTERPRETATION Supplementation of enteral feeds with human IgG does not reduce necrotising 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 BACKGROUND : Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis ( NEC ) and initiation of enteral feeding is frequently delayed . There is no evidence that this delay is beneficial and it might further compromise nutrition and growth . METHODS : Infants with gestation below 35 weeks , birth weight below the 10th centile , and abnormal antenatal umbilical artery Doppler waveforms were r and omly allocated to commence enteral feeds “ early , ” on day 2 after birth , or “ late , ” on day 6 . Gradual increase in feeds was guided by a “ feeding prescription ” with rate of increase the same for both groups . Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC . RESULTS : Four hundred four infants were r and omly assigned from 54 hospitals in the United Kingdom and Irel and ( 202 to each group ) . Median gestation was 31 weeks . Full , sustained , enteral feeding was achieved at an earlier age in the early group : median age was 18 days compared with 21 days ( hazard ratio : 1.36 [ 95 % confidence interval : 1.11–1.67 ] ) . There was no evidence of a difference in the incidence of NEC : 18 % in the early group and 15 % in the late group ( relative risk : 1.2 [ 95 % confidence interval : 0.77–1.87 ] ) . Early feeding result ed in shorter duration of parenteral nutrition and high-dependency care , lower incidence of cholestatic jaundice , and improved SD score for weight at discharge . CONCLUSIONS : Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC Objective To describe feeding and gastrointestinal outcomes in growth-restricted infants < 29 weeks ’ gestation and to determine the rate of feed advancement which they tolerate . Design Analysis of prospect ively collected data from a r and omised feeding trial , the Abnormal Doppler Enteral Prescription Trial ( ADEPT ) . Setting 54 neonatal units in the UK and Irel and . Participants 404 preterm , growth-restricted infants with abnormal antenatal Doppler studies from ADEPT . 83 infants < 29 weeks and 312 infants ≥29 weeks ’ gestation were included in this analysis . Interventions In ADEPT , infants were r and omised to start milk ‘ early ’ on day 2 after birth , or ‘ late ’ on day 6 . Subsequent feed advancement followed a regimen , which should have achieved full feeds by day 16 in the early and day 20 in the late group . Main outcome measures Full feeds were achieved later in infants < 29 weeks ; median age 28 days { IQR 22–40 } compared with 19 days { IQR 17–23 } in infants ≥29 weeks ( HR 0.35 , 95 % CI 0.3 to 0.5 ) . The incidence of necrotising enterocolitis was also higher in this group ; 32/83 ( 39 % ) compared to 32/312 ( 10 % ) in those ≥29 weeks ( RR 3.7 , 95 % CI 2.4 to 5.7 ) . Infants < 29 weeks tolerated very little milk for the first 10 days of life and reached full feeds 9 days later than predicted from the trial regimen . Conclusions Growth-restricted infants born < 29 weeks ’ gestation with abnormal antenatal Doppler failed to tolerate even the careful feeding regimen of ADEPT . A slower advancement of feeds may be required for these infants . Trial registration number IS RCT N87351483 Objective To determine whether feeding with 2-hourly or 3-hourly feeding interval reduces the time to achieve full enteral feeding and to compare their outcome in very low birthweight preterm infants . Design Parallel-group r and omised controlled trial with a 1:1 allocation ratio . Setting Two regional tertiary neonatal intensive care units . Patients 150 preterm infants less than 35 weeks gestation with birth weight between 1.0 and 1.5 kg were recruited . Interventions Infants were enrolled to either 2-hourly or 3-hourly interval feeding after r and omisation . Blinding was not possible due to the nature of the intervention . Main outcome measures The primary outcome was time to achieve full enteral feeding ( ≥100 mL/kg/day ) . Secondary outcomes include time to regain birth weight , episode of feeding intolerance , peak serum bilirubin levels , duration of phototherapy , episode of necrotising enterocolitis , nosocomial sepsis and gastro-oesophageal reflux . Results 72 infants were available for primary outcome analysis in each group as three were excluded due to death — three deaths in each group . The mean time to full enteral feeding was 11.3 days in the 3-hourly group and 10.2 days in the 2-hourly group ( mean difference 1.1 days ; 95 % CI −0.4 to 2.5 ; p=0.14 ) . The mean time to regain birth weight was shorter in 3-hourly group ( 12.9 vs 14.8 days , p=0.04 ) . Other subgroup analyses did not reveal additional significant results . No difference in adverse events was found between the groups . Conclusion 3-hourly feeding was comparable with 2-hourly feeding to achieve full enteral feeding without any evidence of increased adverse events . Trial registration number ACTRN12611000676910 , pre- result We studied the effect of early ( < or = 5 days ) versus delayed ( > or = 6 days ) initiation of minimal enteral feeding ( MEF ) on the incidence of necrotizing enterocolitis ( NEC ) and feeding intolerance in preterm infants with intrauterine growth restriction ( IUGR ) and abnormal antenatal Doppler results . We performed a r and omized , nonblinded pilot trial of infants receiving early or delayed MEF in addition to parenteral feeding within 48 hours of life .  Demographic data , maternal preeclampsia , antenatal steroid exposure , Doppler studies , as well as cases of NEC and feeding intolerance were all recorded . Of the 84 infants enrolled , 81 completed the study : 40 received early ( median age : 2 days , range : 1 to 5 days ) and 41 delayed ( median age : 7 days , range : 6 to 14 days ) MEF . The incidence of NEC and feeding intolerance was not significantly different between groups ( p = 0.353 and p = 0.533 , respectively ) . Birth weight was an independent risk factor for NEC in both groups . Early MEF of preterm infants with IUGR and abnormal antenatal Doppler results may not have a significant effect on the incidence of NEC or feeding intolerance . Furthermore , birth weight seems to be an independent risk factor for the development of NEC , irrespectively of the timing of MEF introduction BACKGROUND Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression .  Very-low-birth-weight ( VLBW ) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life . OBJECTIVE The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance , infectious morbidity , and short-term outcome in VLBW infants . DESIGN In a double-blind r and omized controlled trial , VLBW infants ( gestational age < 32 wk or birth weight < 1500 g ) were allocated to receive enteral glutamine supplementation ( 0.3 g . kg(-1 ) . d(-1 ) ) or isonitrogenous control supplementation ( alanine ) between days 3 and 30 of life . The supplementations were added to breast milk or to preterm formula . The primary endpoint for the study was time to full enteral feeding . Secondary endpoints were other variables of feeding tolerance , infectious morbidity , and short-term outcome . RESULTS Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented ( n = 52 ) and the control ( n = 50 ) groups . The median time to full enteral feeding was 13 d ( range : 7 - 31 d ) in the glutamine-supplemented group and 13 d ( range : 6 - 35 d ) in the control group ( hazard ratio : 1.19 ; 95 % CI : 0.79 , 1.79 ; P = 0.40 ) . In the glutamine-supplemented group , 26 of 52 infants ( 50 % ) had > /=1 serious infection compared with 38 of 50 ( 76 % ) in the control group ( odds ratio : 0.32 ; 95 % CI : 0.14 , 0.74 ; P = 0.008 ) . Other variables of feeding tolerance and short-term outcome were not significantly different between groups . CONCLUSIONS Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants . However , infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition OBJECTIVE To evaluate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis ( NEC ) in preterm very low birth weight ( VLBW ) infants . STUDY DESIGN Ar and omized double blind controlled trial . PLACE AND DURATION OF STUDY The Paediatrics Department of Sylhet M.A.G. Osmani Medical College Hospital , Sylhet Bangladesh , from July 2012 to June 2015 . METHODOLOGY Preterm ( 28 - 33 weeks gestation ) VLBW ( birth weight 1000 - 1499 g ) neonates were enrolled . The study group was fed with probiotics once daily with breast milk from first feeding , and the control group with only breast milk without the addition of probiotics . Both the groups received other st and ard care . The primary outcome was the development of NEC ( stage II and III ) , categorized by modified Bell 's classification . RESULTS In 108 neonates , development of NEC was significantly lower in the study group than that of control group [ 1 ( 1.9 % ) vs. 6 ( 11.5 % ) ; p=0.044 ] . Age of achievement of full oral feeding was significantly earlier in the study group than that in the control group ( 14.88 ±3.15 and 18.80 ±4.32 days ; p < 0.001 ) . Duration of hospital stay was significantly short in the study group compared to the control group ( 15.82 ±2.94 days vs. 19.57 ±4.26 days ; p < 0.001 ) . CONCLUSION Probiotic supplementation reduces the frequency of necrotising enterocolitis in preterm neonates with very low birth weight . It is also associated with faster achievement of full oral feeding and short duration of hospital stay Background : 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 examine the effect of initiating very early feeding on time-to-reach full feeding in stable , small for gestational age ( SGA ) preterm infants . METHOD Preterm infants with gestational age below 37 weeks and birth weight below the 10(th ) percentile were r and omly allocated to a  very early ( within 24 hours of birth ) feeding regimen or delayed ( after 24 hours of birth ) feeding .  All infants had in utero evidence of absent or reverse diastolic flow . Infants unable to start early feeding were excluded .  Time-to-reach full feeding , feeding progression , and related morbidity were compared .  Electrogastrography ( EGG )  was used to measure pre- and postpr and ial gastric motility on the second and seventh day after feeding initiation . RESULTS Sixty infants were included in the study , 30 in each group . Infants included in the very early feeding regimen achieved full enteral feeding sooner than controls ( 98±80 - 157 vs. 172±123 - 261 hours of age , respectively ; p= 0.004 ) and were discharged home earlier ( p=0.04 ) . No necrotizing enterocolitis ( NEC ) was documented in both study groups . Gastric motility was improved at day seven after feeding initiation in both study groups , with no difference between groups . CONCLUSIONS Stable SGA preterm infants on a very early feeding regimen achieved full enteral feeding and were discharged home significantly earlier than those on a delayed regimen , with no excess morbidity AIMS To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis  in preterm , very low birthweight infants . METHODS A prospect i ve , double blind , r and omised , placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit . The babies were r and omly allocated to receive oral vancomycin ( 15 mg/kg every 8 hours for 7 days ) or an equivalent volume of placebo solution . Prophylaxis was started 24 hours before the start of oral feeds . All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs . Necrotising enterocolitis was diagnosed and staged according to modified Bell ’s criteria . RESULTS Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis ( p=0.035 ) . Infants with necrotising enterocolitis were associated with a significant increase in mortality ( p=0.026 ) and longer duration of hospital stay ( p = 0.002 ) . CONCLUSIONS Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm , very low birthweight infants and was associated with a 50 % reduction in the incidence . However , widespread implementation of this preventive measure is not recommended , as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms . Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients
The available trial data suggest that advancing enteral feed volumes at daily increments of 30 ml/kg to 35 ml/kg does not increase the risk of necrotising enterocolitis in very preterm or VLBW infants .
Advancing the volume of enteral feeds at slow rates result ed in several days delay in regaining birth weight and establishing full enteral feeds .
The applicability of these findings to extremely preterm , extremely low birth weight , or growth-restricted infants is limited .
BACKGROUND Early enteral feeding practice s are potentially modifiable risk factors for necrotising enterocolitis  in very preterm or very low birth weight ( VLBW ) infants .
Observational studies suggest that conservative feeding regimens , including slowly advancing enteral feed volumes , reduce the risk of necrotising enterocolitis .
However , slow feed advancement may delay establishment of full enteral feeding and be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition .
OBJECTIVES To determine the effect of slow rates of enteral feed advancement on the incidence of necrotising enterocolitis , mortality , and other morbidities in very preterm or VLBW infants .