Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial Early enteral feeding and nosocomial sepsis in very low birthweight infants Early versus delayed minimal enteral feeding and risk for necrotizing enterocolitis in preterm growth-restricted infants with abnormal antenatal Doppler results. Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583] The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A 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). Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial. Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case–control study Very early feeding in stable small for gestational age preterm infants: a randomized clinical trial. Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study Early versus Late Enteral Feeding in Preterm Intrauterine Growth Restricted Neonates with Antenatal Doppler Abnormalities: An Open-Label Randomized Trial Slow versus rapid enteral feed in preterm neonates with antenatal absent end diastolic flow Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g. [Necrotizing enterocolitis among preterm newborns with early feeding]. Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. A Randomized Controlled Trial of Enteral Glutamine Supplementation in Very Low Birth Weight Infants: Plasma Amino Acid Concentrations Growth, Efficacy, and Safety of Feeding an Iron-Fortified Human Milk Fortifier Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Hydrolyzed protein accelerates feeding advancement in very low birth weight infants. Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants
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 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 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 : 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 / 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 Background Enteral feeding of very low birth weight ( VLBW ) infants is a challenge , since metabolic dem and s are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract . The amino acid glutamine plays an important role in maintaining functional integrity of the gut . In addition , glutamine is utilised at a high rate by cells of the immune system . In critically ill patients , glutamine is considered a conditionally essential amino acid . VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth . Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression . This double-blind r and omised controlled trial is design ed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance , infectious morbidity and short-term outcome in VLBW infants . Furthermore , an attempt is made to eluci date the role of glutamine in postnatal adaptation of the gut and modulation of the immune response . Methods VLBW infants ( gestational age < 32 weeks and /or birth weight < 1500 g ) are r and omly allocated to receive enteral glutamine supplementation ( 0.3 g/kg/day ) or isonitrogenous placebo supplementation between day 3 and 30 of life . Primary outcome is time to full enteral feeding ( defined as a feeding volume ≥ 120 mL/kg/day ) . Furthermore , incidence of serious infections and short-term outcome are evaluated . The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora . The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation 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 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 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 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 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 Background Prevention of serious infections in preterm infants is a challenge , since prematurity and low birth weight often requires many interventions and high utility of devices . Furthermore , the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system . In combination with delayed intestinal bacterial colonisation compared with term infants , this may increase the risk for serious infections . Acidic and neutral oligosaccharides play an important role in the development of the immune system , intestinal bacterial colonisation and functional integrity of the gut . This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity ( primary outcome ) , immune response to immunizations , feeding tolerance and short-term and long-term outcome in preterm infants . In addition , an attempt is made to eluci date the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut . Methods / Design In a double-blind placebo controlled r and omised trial , 120 preterm infants ( gestational age < 32 weeks and /or birth weight < 1500 gram ) are r and omly allocated to receive enteral acidic and neutral oligosaccharides supplementation ( 20%/80 % ) or placebo supplementation ( maltodextrin ) between day 3 and 30 of life . Primary outcome is infectious morbidity ( defined as the incidence of serious infections ) . The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations , plasma cytokine concentrations , faecal Calprotectin and IL-8 . The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance , intestinal permeability , intestinal viscosity , and determining intestinal microflora . Furthermore , short-term and long-term outcome are evaluated . Discussion Especially preterm infants , who are at increased risk for serious infections , may benefit from supplementation of prebiotics . Most studies with prebiotics only focus on the colonisation of the intestinal microflora . However , the pathways how prebiotics may influence the immune system are not yet fully understood . Study ing the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants . The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system . Increased insight in the effects of prebiotics on the developing immune system may help to decrease the ( infectious ) morbidity and mortality in preterm infants . Trial registration Current Controlled Trials IS RCT N16211826 Background of the study Enteral feeding in preterm neonates with intrauterine growth restriction ( IUGR ) and absent or reversed end diastolic flow ( AREDF ) on umbilical artery ( UA ) Doppler is delayed owing to an increased risk of necrotizing enterocolitis ( NEC ) . Delaying enteral feeding with longer duration of parenteral nutrition ( PN ) carries an increased risk of sepsis . Objectives To study early versus late feeding in preterm IUGR neonates for time required to attain sufficient feed volume to discontinue PN and increased risk of NEC or feed intolerance ( FI ) . Design Open-label r and omized controlled trial . Setting Tertiary care neonatal unit and fetal-maternal medicine unit in India . Participants Preterm intrauterine growth restricted neonates ' ≤32 weeks with AREDF on UA Doppler enrolled from 1 January 2014 to 31 July 2015 . Intervention R and omized to receive early or late feeding using mothers own or donor breast milk as per a feed initiation and advancement protocol . Primary outcome Time in days required to attain sufficient feed volume allowing discontinuation of PN and incidence of NEC in neonates fed early versus late . Results There were 77 eligible neonates . Sixty-two neonates were included and stratified as extreme preterm ( 27 - 29 weeks ) ( n = 20 ) and very preterm ( 30 - 32 weeks ) ( n = 42 ) . Ten extreme preterm and 21 very preterm neonates were r and omized to each early feeding and late feeding arm . There was a significantly faster attainment of sufficient feeds in the early feeding arm of both the stratified groups [ extreme preterm : median 14 days ( Interquartile range IQR : 12 - 15 ) compared with 18 days ( IQR : 18 - 20 ) , hazard ratio ( HR ) : 1.59 , 95 % CI : 0.626 - 4.078 ; very preterm : 12 days ( IQR : 10 - 14 ) as compared with 16 days ( IQR 15 - 17 ) , HR : 1.89 , 95 % CI : 1.011 - 3.555 ] . There was no difference in the incidence of NEC , FI and combined outcome of NEC and FI . Conclusion Early feeding in preterm IUGR neonates with AREDF on antenatal UA Doppler allowed earlier discontinuation of PN , allowing birth weight to be regained earlier and did not increase the incidence of NEC and FI 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 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 INTRODUCTION The development of necrotizing enterocolitis is a common and serious risk to newborns . It is caused by splanchnic bed vasoconstriction that can produce intestinal necrosis . The role of onset time , type and , speed enhancements of The factors of enteral feeding related with necrotizing enterocolitis genesis such as feeding onset , type and frequency are not well understood . OBJECTIVE The incidence of necrotizing enterocolitis and mortality among infants will be compared in infants whose enteral feeding was initiated 48 hours after birth to those whose feeding began on day 5 postpartum . MATERIAL S AND METHODS A controlled clinical trial was conducted among 239 newborns weighing between 750 - 1,500 g and a gestation age of 27 - 32 weeks of gestational age . The infants were r and omly assigned to two groups--135 to an early feeding regime and 104 to delayed feeding . Breast milk or formula milk was used . Feeding was begun with one ml every six hours , progressing to three hour intervals and 20 ml/kg daily . This was increased to 150 ml/kg-d if the infant condition remained stable and it manifested no oral intolerance . RESULTS In the early feeding group , 14 ( 10;4 % ) necrotizing enterocolitis cases occurred , and in the late feeding group , 9 ( 8.7 % ) occurred ( RR= 1.22 , 95 % CI 0.49 - 3.20 , p= 0.65 ) . Five children died in early feeding group ( 3.7 % , 95 % CI 1.4 - 8.9 ) and eight in late feeding group ( 7.7 % , 95 % CI 3.6 - 15.0 , RR=0.46 , 95 % CI 0.12 - 1,60 , p= 0.18 ) . CONCLUSION Early enteral feeding in preterm newborns does not increase the risk of necrotizing enterocolitis or mortality among them ; however it represents nutritional advantages for these infants OBJECTIVE To evaluate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis ( NEC ) in preterm very low birth weight ( VLBW ) infants . STUDY DESIGN Ar and omized double blind controlled trial . PLACE AND DURATION OF STUDY The Paediatrics Department of Sylhet M.A.G. Osmani Medical College Hospital , Sylhet Bangladesh , from July 2012 to June 2015 . METHODOLOGY Preterm ( 28 - 33 weeks gestation ) VLBW ( birth weight 1000 - 1499 g ) neonates were enrolled . The study group was fed with probiotics once daily with breast milk from first feeding , and the control group with only breast milk without the addition of probiotics . Both the groups received other st and ard care . The primary outcome was the development of NEC ( stage II and III ) , categorized by modified Bell 's classification . RESULTS In 108 neonates , development of NEC was significantly lower in the study group than that of control group [ 1 ( 1.9 % ) vs. 6 ( 11.5 % ) ; p=0.044 ] . Age of achievement of full oral feeding was significantly earlier in the study group than that in the control group ( 14.88 ±3.15 and 18.80 ±4.32 days ; p < 0.001 ) . Duration of hospital stay was significantly short in the study group compared to the control group ( 15.82 ±2.94 days vs. 19.57 ±4.26 days ; p < 0.001 ) . CONCLUSION Probiotic supplementation reduces the frequency of necrotising enterocolitis in preterm neonates with very low birth weight . It is also associated with faster achievement of full oral feeding and short duration of hospital stay Objective : 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 , as enteral nutrition is limited in the first weeks of life . Enteral glutamine supplementation may have a positive effect on feeding tolerance , infectious morbidity and short-term outcome . The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations , reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants . Methods : In a double-blind placebo-controlled r and omized controlled trial , VLBW infants ( gestational age < 32 weeks or birth weight < 1500 g ) received enteral glutamine supplementation ( 0.3 g/kg per day ) or isonitrogenous placebo supplementation ( alanine ) between day 3 and day 30 of life . Supplementation was added to breast milk or to preterm formula . Plasma amino acid concentrations were measured at four time points : before the start of the study and at days 7 , 14 and 30 of life . Results : Baseline patient and nutritional characteristics were not different in glutamine ( n = 52 ) and control ( n = 50 ) groups . Plasma concentrations of most essential and non-essential amino acids increased throughout the study period . There was no effect of enteral glutamine supplementation . In particular , the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups ( P = 0.49 and P = 0.34 respectively , day 30 ) . Conclusions : Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine , glutamate or other amino acids . Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants 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 BACKGROUND Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly . Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer . AIM The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis ( NEC ) or sepsis in very low birth weight infants . STUDY DESIGN AND SUBJECTS A prospect i ve , double blind , placebo controlled trial was conducted in preterm infants ( ≤ 32 GWs , ≤ 1500 g birth weight ) . They were r and omized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo , starting with the first feed until discharged . OUTCOME MEASURES Necrotizing enterocolitis ( NEC ) or sepsis and NEC or death . RESULTS Birth weight and gestational age of the study ( n = 104 ) and the control ( n = 104 ) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks , respectively . Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group ( 9.6 % vs 7.7 % , p = 0.62 ; 28.8 % vs 23 % , p = 0.34 ) . Time to reach 100 mL/kg/day of enteral feeding ( 11.9 ± 7 vs 12.6 ± 7 days , p = 0.37 ) was not different between the groups . CONCLUSIONS Saccharomyces boulardii did not decrease the incidence of NEC or sepsis BACKGROUND Feeding intolerance is common in very low birth weight ( VLBW ; < 1500 g ) infants .  Hydrolyzed protein preterm infant formula ( HPF ) has been shown to accelerate the gastrointestinal transit of formula . The aim of this study was to investigate whether HPF improves early feeding tolerance compared with st and ard preterm infant formula ( SPF ) . We hypothesized that HPF would accelerate early enteral feeding advancement . METHODS Primary outcome was the time from initiation of milk feeds until full feeds ( 150 mL/kg birth weight/d ) were achieved in infants who received < 10 % human milk ( HM ) to exclude HM as a confounder . Because the availability of HM was not predictable at the time of enrollment , all eligible VLBW infants ( n = 129 ) were r and omly assigned in a r and omized , controlled trial to receive HPF or SPF if HM was not available . Infants who received > 10 % HM ( n = 42 ) were excluded . Milk bolus feeding every 2 to 3 hours was started at the discretion of the attending physician and advanced by 16 mL/kg/d . Prepr and ial gastric residuals were tolerated up to 5 mL/kg ; otherwise , feedings were reduced or withheld . Data are shown as median ( 5th and 95th percentile ) . RESULTS Forty-six and 41 ( HPF vs SPF ) infants received < 10 % HM . There was no significant difference with regard to birth weight , gestational age , and onset of milk feeds ( day 3 [ 1 - 8 ] vs 4 [ 2 - 6 ] ) . The time from initiation of milk feeds to full feeds was significantly shorter with HPF feeding ( 10 [ 9 - 27 ] vs 12 [ 9 - 28 ] days ) . CONCLUSION HPF improved the feeding tolerance and enabled a more rapid establishment of full enteral feeding in VLBW infants compared with SPF OBJECTIVE Approximately 90 % of infants who develop necrotizing enterocolitis (  NEC ) do so after being fed . Previous prospect i ve studies have shown that infants given small enteral feedings  for the first 7 to 10 days of feeding do not have an increased risk for NEC compared with those given no feedings . Although neonatologists now commonly increase feeding volumes , no study has compared the risk for NEC between infants fed these small volumes and those fed volumes that are increased slowly . The purpose of this study was to compare the risks and benefits of small and increasing feeding volume . METHODS In a r and omized , controlled trial , we r and omly assigned 141 preterm infants in the newborn intensive care unit to be fed 10 days using 1 of 2 schedules . One group was fed 20 mL/kg/d for the first 10 study days ( minimal ) . The other group ( advancing ) was fed 20 mL/kg/d on study day 1 ; feeding volume was increased by 20 mL/kg/d up to 140 mL/kg/d , which was maintained until study day 10 . The main outcome measure was incidence of NEC ; secondary outcomes were maturation of intestinal motor patterns , time to reach full enteral feedings , and incidence of late sepsis . RESULTS The study was closed early because 7 infants who were assigned to advancing feeding volumes developed NEC , whereas only 1 infant fed minimal feeding volumes did , or 10 % versus 1.4 % . Although infants who were fed minimal volumes established full enteral feeding volumes later than infants who were fed advancing volumes , maturation of intestinal motor patterns and the incidence of late sepsis and feeding intolerance was similar in the 2 groups . CONCLUSION Given that advancing feeding volumes increase the risk of NEC without providing benefits for motor function or feeding tolerance , neonatologists should consider using minimal feeding volumes until future trials assess the safety of advancing feeding volumes Background : Necrotizing enterocolitis ( NEC ) is 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
The evidence available from r and omised controlled trials suggested that delaying the introduction of progressive enteral feeds beyond four days after birth did not reduce the risk of developing NEC in very preterm or VLBW infants , including growth-restricted infants .
Delaying the introduction of progressive enteral feeds result ed in a few days ' delay in establishing full enteral feeds but the clinical importance of this effect was unclear .
BACKGROUND The introduction of enteral feeds for very preterm ( less than 32 weeks ' gestation ) or very low birth weight ( VLBW ; less than 1500 g ) infants is often delayed for several days or longer after birth due to concern that early introduction may not be tolerated and may increase the risk of necrotising enterocolitis ( NEC ) .
However , delaying enteral feeding could diminish the functional adaptation of the gastrointestinal tract and prolong the need for parenteral nutrition with its attendant infectious and metabolic risks .
OBJECTIVES To determine the effect of delayed introduction of progressive enteral feeds on the incidence of NEC , mortality and other morbidities in very preterm or VLBW infants .