Oral Probiotics Prevent Necrotizing Enterocolitis in Very Low Birth Weight Preterm Infants: A Multicenter, Randomized, Controlled Trial Synbiotics for decreasing incidence of necrotizing enterocolitis among preterm neonates – a randomized controlled trial Early enteral feeding does not affect the incidence of necrotizing enterocolitis. ORACLE—antibiotics for preterm prelabour rupture of the membranes: short‐term and long‐term outcomes A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. Using a Count of Neonatal Morbidities to Predict Poor Outcome in Extremely Low Birth Weight Infants: Added Role of Neonatal Infection The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. A prospective controlled trial of oral kanamycin in the prevention of neonatal necrotizing enterocolitis. [Necrotizing enterocolitis among preterm newborns with early feeding]. The politics of probiotics: probiotics, necrotizing enterocolitis and the ethics of neonatal research Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. Early versus delayed minimal enteral feeding and risk for necrotizing enterocolitis in preterm growth-restricted infants with abnormal antenatal Doppler results. Prevention of necrotizing enterocolitis in neonates at risk by oral administration of monomeric IgG. Slow versus rapid enteral feed in preterm neonates with antenatal absent end diastolic flow Enteral granulocyte-colony stimulating factor and erythropoietin early in life improves feeding tolerance in preterm infants: a randomized controlled trial. Alterations in stool flora resulting from oral kanamycin prophylaxis of necrotizing enterocolitis. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less. Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial. Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants.
OBJECTIVE . The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants . METHODS . A prospect i ve , blinded , r and omized , multicenter controlled trial was conducted at 7 NICUs in Taiwan , to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants ( birth weight : < 1500 g ) . Very low birth weight infants who survived to start enteral feeding were eligible and were assigned r and omly to 2 groups after parental informed consent was obtained . Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus , added to breast milk or mixed feeding ( breast milk and formula ) , twice daily for 6 weeks . Infants in the control group were fed with breast milk or mixed feeding . The clinicians caring for the infants were blinded to the group assignment . The primary outcome measurement was death or necrotizing enterocolitis ( Bell 's stage ≥2 ) . RESULTS . Four hundred thirty-four infants were enrolled , 217 in the study group and 217 in the control group . The incidence of death or necrotizing enterocolitis ( stage ≥2 ) was significantly lower in the study group ( 4 of 217 infants vs 20 of 217 infants ) . The incidence of necrotizing enterocolitis ( stage ≥2 ) was lower in the study group , compared with the control group ( 4 of 217 infants vs 14 of 217 infants ) . No adverse effect , such as sepsis , flatulence , or diarrhea , was noted . CONCLUSION . Probiotics , in the form of Bifidobacterium and Lactobacillus , fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis Abstract Objective : To study the effect of synbiotics in reducing incidence and severity of necrotizing enterocolitis ( NEC ) among preterm neonates . Methods : This r and omized controlled trial conducted in a tertiary care teaching hospital , south India , included 220 enterally fed preterm neonates who were r and omized to receive either synbiotics or no intervention .  The synbiotic contained Lactobacillus , Bifidobacterium and fructo-oligosaccharide . The demographic parameters , risk factors for NEC and outcome including incidence of NEC , its severity , sepsis and mortality were evaluated . Results : Multiple pregnancies , preeclampsia and prolonged rupture of membranes were important maternal characteristics . The average birth weight and gestational age of the preterm neonates was 1.4 kg and 31 weeks , respectively . There was a 50 % reduction in the incidence of NEC of all stages in preterm infants who received synbiotics compared to the non-intervention group ( 7.4 % versus 14.5 % ) . Administration of synbiotics did not reduce the severity of NEC , sepsis or mortality . Conclusion : Enteral supplementation of synbiotics along with breastmilk results in a tendancy to decrease the incidence of NEC among preterm neonates To begin to determine the optimal time for initiating enteral feedings , 34 sick , very low birth weight infants were prospect ively selected from all neonates of less than 1,500 g ( N = 116 ) and r and omly divided into two groups . Infants were fed either on day 1 ( early ) or 7 ( late ) of life , according to a feeding protocol which included parenteral nutrition and a scheduled progression from sterile water to 2.5 % dextrose , half-strength , and finally full-strength formula over seven days . The incidence of necrotizing enterocolitis and subsequent hospital course were compared . Initiating enteral feedings on day 1 did not significantly increase the incidence of necrotizing enterocolitis , produce a clustering of cases , or induce an earlier onset of necrotizing enterocolitis . The overall incidence of necrotizing enterocolitis in sick , very low birth weight neonates was 29 % ( 5/17 ) and 35 % ( 6/17 ) in the early and late groups , respectively , compared with 4.2 % ( 2/47 ) in minimally sick , very low birth weight neonates . No significant differences between groups were seen in obstetrical complications , birth weight , gestational age , Apgar scores , presence of patent ductus arteriosus or intraventricular hemorrhage , use of umbilical catheterization , and respiratory or oxygen requirements . Infants fed enterally from day 1 did show a significantly higher energy and protein intake during the second week of life . These data show that providing dilute , early enteral calories does not adversely affect the incidence of necrotizing enterocolitis Preterm prelabour rupture of the foetal membranes ( pPROM ) is the most common antecedent of preterm birth and can lead to death , neonatal disease and long‐term disability . Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate , but the results were inconclusive . A large , r and omized , multicentre trial was undertaken to try to resolve this issue . In total , 4826 women with pPROM were r and omized to one of four treatments : 325 mg co‐amoxiclav plus 250 mg erythromycin , co‐amoxiclav plus erythromycin placebo , erythromycin plus co‐amoxiclav placebo , or coamoxiclav placebo plus erythromycin placebo , four times daily for 10 d or until delivery . The primary outcome measure was a composite of neonatal death , chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital . The analysis was undertaken by intention to treat . Indications of short‐term respiratory function , chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin . In contrast , the use of co‐amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis OBJECTIVE The use of probiotics is increasingly popular in preterm neonates , as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance . There is only limited literature on Saccharomyces boulardii CNCM I-745 ( S. boulardii ) in preterm infants . METHOD A prospect i ve , r and omized , case-controlled trial with the probiotic S. boulardii ( 50mg/kg twice daily ) was conducted in newborns with a gestational age of 30 - 37 weeks and a birth weight between 1500 and 2500 g . RESULTS 125 neonates were enrolled ; 63 in the treatment and 62 in the control group . Weight gain ( 16.14±1.96 vs. 10.73±1.77g/kg/day , p<0.05 ) and formula intake at maximal enteral feeding ( 128.4±6.7 vs. 112.3±7.2mL/kg/day , p<0.05 ) were significantly higher in the intervention group . Once enteral feeding was started , the time needed to reach full enteral feeding was significantly shorter in the probiotic group ( 0.4±0.1 vs. 1.7±0.5 days , p<0.05 ) . There was no significant difference in sepsis . Necrotizing enterocolitis did not occur . No adverse effects related to S. boulardii were observed . CONCLUSION Prophylactic supplementation of S. boulardii at a dose of 50mg/kg twice a day improved weight gain , improved feeding tolerance , and had no adverse effects in preterm infants > 30 weeks old OBJECTIVE Lactoferrin ( LF ) is effective in the prevention of sepsis in very low birth weight ( VLBW ) neonates .  T-regulatory cells ( Tregs ) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis . The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis ( NEC ) in premature infants and to evaluate the possible effects of LF on Treg levels . STUDY DESIGN In this prospect i ve , placebo-controlled , double-blind , r and omized trial , infants either VLBW or born before 32 weeks were assigned to receive either placebo ( n = 25 ) , or 200 mg LF ( n = 25 ) daily throughout hospitalization . Episodes of culture proven nosocomial sepsis and NEC were recorded . The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge . A third comparison was made with healthy term neonates ( n = 16 ) . RESULTS Fewer sepsis episodes were observed in LF-treated infants ( 4.4 vs. 17.3/1,000 patient days , p = 0.007 ) with none developing NEC , without statistical significance . Treg levels at birth and discharge were similar , while preterm infants showed significantly lower levels than term controls . However , individual increases in Treg levels were higher in the LF group . CONCLUSION LF prophylaxis reduced nosocomial sepsis episodes . Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed . Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis OBJECTIVE . A count of 3 neonatal morbidities ( bronchopulmonary dysplasia , brain injury , and severe retinopathy of prematurity ) strongly predict the risk of death or neurosensory impairment in extremely low birth weight infants who survive to 36 weeks ' postmenstrual age . Neonatal infection has also been linked with later impairment . We examined whether the addition of infection to the count of 3 neonatal morbidities further improves the prediction of poor outcome . METHODS . We studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in Preterms and survived to 36 weeks ' postmenstrual age .  Culture-proven sepsis , meningitis , and stage II or III necrotizing enterocolitis were recorded prospect ively . We investigated the incremental prognostic importance of neonatal infection by adding terms for the different types of infection to a logistic model that already contained terms for the count of bronchopulmonary dysplasia , brain injury , and severe retinopathy . Poor outcome at 18 months of age was death or survival with 1 or more of the following : cerebral palsy , cognitive delay , severe hearing loss , and bilateral blindness . RESULTS . There were 414 ( 44 % ) infants with at least 1 episode of infection or necrotizing enterocolitis . Meningitis and the presence of any type of infection added independent prognostic information to the morbidity-count model . The odds ratio associated with infection or necrotizing enterocolitis in this model was 50 % smaller than the odds ratio associated with each count of the other 3 neonatal morbidities . Meningitis was rare and occurred in 22 ( 2.3 % ) of 944 infants . CONCLUSIONS . In this cohort of extremely low birth weight infants who survived to 36 weeks ' postmenstrual age , neonatal infection increased the risk of a late death or survival with neurosensory impairment . However , infection was a weaker predictor of poor outcome than bronchopulmonary dysplasia , brain injury , and severe retinopathy 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 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 Alimentary kanamycin , 15 mg/kg/day , was given as prophylaxis for  neonatal necrotizing enterocolitis  in a prospect i ve study . Newborn infants of less than 1,500 gm birth weight who survived until initiation of alimentary nutrition at the University of Florida Neonatal Intensive Care Unit were admitted to a control or study group based on the last digit of the hospital number .  Alimentary kanamycin was not absorbed ; all blood levels determined were less than 0.5 μg/ml . The two groups had similar gestational ages , birth weights , severity of neonatal illness , and frequency of therapeutic procedures . In the study group of 35 infants , none developed neonatal necrotizing enterocolitis , whereas five cases occurred in the 40 control infants ( p=0.038 ) 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 There have been over twenty prospect i ve , r and omized trials of the use of probiotics to prevent  necrotizing enterocolitis ( NEC ) in premature babies . A Cochrane meta- analysis of 16 of the studies ( 1 ) including 2842 preterm infants , reported that ‘ enteral probiotics supplementation significantly reduced the incidence of severe NEC ( stage II or more ) ( typical RR , 0.35 ; 95 % CI , 0.24–0.52 ) and mortality ( typical RR , 0.40 ; 95 % CI , 0.27–0.60 ) with no evidence of harm . They concluded , ‘ Enteral supplementation of probiotics prevents severe NEC and all-cause mortality in preterm infants ’ . In a sensitivity analysis , including only the 4 highest quality studies , the results and conclusions were unchanged . For neonates born at < 32 weeks of gestation , the number needed to treat in order to prevent one NEC or one death is twenty . The risks of probiotics are minimal . A more recently published systematic review included several additional r and omized controlled trials , mostly published in the Chinese literature , and analysed a total of 20 publications and over 3800 preterm infants ; it came to similar conclusions as the Cochrane meta- analysis ( 2 ) . Probiotics are used in many European units but only rarely in North-America . In spite of the evidence , this safe and effective treatment for one of the most serious complications of prematurity has never been studied in the United States and perhaps never will . Probiotics will probably never be approved by the U.S. Food and Drug Administration ( FDA ) . Instead , they will remain in regulatory purgatory , neither approved nor unapproved , an evidence -based treatment that can not become the st and ard of care , a safe and effective treatment that is not on hospital formularies in the United States . Probiotics fall into a peculiar lacuna of the regulatory system . Most innovative treatments are either drugs or devices , and the regulatory pathways for evaluating and approving them are fairly well defined by federal law . The FDA has jurisdiction over both drugs and devices . Probiotics are neither drugs nor devices , and they are made by companies that generally market health products to the general public . In contrast , in Canada , probiotics are under the jurisdiction of the Natural Health Products Directorate ( NHPD ) which has rigorous requirements for quality control and detailed labelling . But the NHPD does not evaluate overtly medical cl aims made about a product . It has little experience dealing with either a product that could actually decrease major complications or save lives in a particularly fragile population where mortality is rather common . Probiotics are quite inexpensive to manufacture . People can even make them at home . They are in most yogurts . For pennies , some parents buy them for their preterm infants in health food stores . Some mothers have started adding probiotics to their breast milk . In these cases , the medical team can either be unaware a preterm infant is in fact receiving probiotics or tacitly not interfere with these parental initiatives . Given the low cost of probiotics and Articles in the series A Different View are edited by William Meadow ( wlm1@uchicago.edu ) . We encourage you to offer your own different view either in response to A Different View you do not fully agree with , or on an unrelated topic . Send your article to Dr. Meadow ( wlm1@uchicago.edu ) 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 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 Necrotizing enterocolitis ( NEC ) represents one of the major causes of morbidity in low-birth-weight ( LBW ) preterm infants . This r and omized clinical trial evaluated the efficacy of an oral immunoglobulin preparation ( containing monomeric IgG in a concentration of 90 % ) in reducing the incidence of NEC in infants of LBW for whom maternal breast milk was not available . One hundred and thirty-two formula-fed newborns with a birth weight less than or equal to 1,500 g or a gestational age less than or equal to 34 weeks were r and omly studied . Five hundred mg of IgG pro die , subdivided into 5 doses , were given orally to the test group of 65 neonates during the first 2 weeks of life . Although the number of infants included in this group is limited , the results of this study are encouraging : during the first 15 days after birth , none of the subjects developed NEC , while 4 cases were confirmed in the untreated control group . It , therefore , seems possible that oral monomeric IgG administration may prevent the development of NEC in LBW infants 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 efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor ( rhG-CSF ) and recombinant human erythropoietin ( rhEPO ) in preventing feeding intolerance . STUDY DESIGN An interventional r and omized control trial was conducted in 90 preterm infants born at ≤33 weeks gestational age . The neonates were assigned to 4 groups ; 20 received rhG-CSF , 20 received rhEPO , 20 received both , and 30 received distilled water ( placebo control ) . The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days , whichever came first . Feeding tolerance and adverse effects of treatment were assessed . Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment . RESULTS All neonates  tolerated the treatment without side effects . Neonates who received rhG-CSF and /or rhEPO had better feeding tolerance , as reflected by earlier achievement of 75 mL/kg/day , 100 mL/kg/day , and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay ( P < .05 ) . The risk of necrotizing enterocolitis was reduced from 10 % to 0 % in all treatment groups ( P < .05 ) . There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo ( P < .05 ) . Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups . CONCLUSIONS Enteral administration of rhG-CSF and /or rhEPO  improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates . The mechanism may involve the prevention of villous atrophy To evaluate the effects of oral kanamycin prophylaxis for  necrotizing enterocolitis  on stool flora , 99 high-risk infants were studied on a double-blind basis during the first month of life . Oral kanamycin prophylaxis result ed in a significant decrase in gram-negative enteric colonization on Days 3 to 5 , 10 , 17 , and 24 compared to control infants ( P P P = 0.2 ) . The data indicate that oral kanamycin prophylaxis significantly reduces the colonization rate and overgrowth of gram-negative enteric flora , but does not eliminate the occurrence of NEC in a high-risk group of infants 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 The incidence of culture-proven neonatal sepsis and necrotizing enterocolitis ( NEC ) in preterm infants maintained at pharmacologic ( mean 5.1 mg/dL + /- 1.45 SD ) serum vitamin E levels for long periods was prospect ively studied as part of a double-masked clinical trial of the effect of prophylactic vitamin E v placebo treatment on the development and course of retinopathy of prematurity ( ROP ) . Within a few days of birth , 914 preterm infants were enrolled in the study ; 545 ( 275 placebo-treated infants , 270 vitamin E-treated infants had birth weight of 1,500 g or less . A significant difference in incidence of neonatal sepsis ( 17 placebo-treated infants , 37 vitamin E-treated infants ) and NEC ( 18 placebo-treated infants , 32 vitamin E-treated infants ) was observed among infants who had been treated for eight or more days and who had developed neither sepsis nor NEC before that time . The association of vitamin E treatment with increased incidence of disease was much higher with sepsis than with NEC . The most likely reason for these observations is a pharmacologic serum vitamin E-related decrease in oxygen-dependent intracellular killing ability which results in a decreased resistance to infection in preterm infants . The data suggest that , if this occurs , it is clinical ly significant only in the more immature infants . In view of the known variability of absorption of oral vitamin E and the association between high serum vitamin E levels and increased incidence of sepsis and late-onset NEC reported here , it can be concluded that serum vitamin E levels must be monitored when supplemental vitamin E is administered to premature infants , especially those with birth weight 1,500 g or less . The risk-benefit ratio of long-term treatment using vitamin E at high serum levels should be clearly assessed 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 Abstract Objective : To compare the effect of fortified pasteurized donor human milk ( PDHM ) versus unfortified PDHM on the incidence of necrotizing enterocolitis ( NEC ) and immediate outcome among preterm neonates . Methods : This r and omized controlled trial ( RCT ) conducted in a tertiary care teaching hospital , south India included 80 healthy preterm neonates r and omized to two groups ( Group A and B ) . Neonates in Group A and B were fed with fortified PDHM and unfortified PDHM , respectively . Neonates in both groups were managed uniformly as per st and ard NICU protocol . The primary outcome was the incidence of NEC and the secondary outcomes included severity of NEC , incidence of sepsis , mortality , duration of hospital stay , number of days to reach full enteral feeds and weight gain . Neonates were followed up for 28 days or discharge whichever was earlier . Results : The baseline maternal and neonatal characteristics in both groups were comparable . There was no increase in incidence of NEC in fortified PDHM group compared to unfortified PDHM group ( 2.5 versus 7.5 % , p = .31 ) . Severity of NEC , incidence of sepsis , mortality , duration of hospital stay , number of days to reach full enteral feeds and weight gain were also similar in both groups . Conclusions : St and ard fortification of PDHM does not increase the incidence of NEC among preterm neonates BACKGROUND Necrotizing enterocolitis ( NEC ) is the most serious gastrointestinal problem in very low birth weight preterm infants . Multiple risk factors activate the inflammatory cascade leading to high expressions of pro-inflammatory mediators causing bowel injury in NEC . The anti-inflammatory effect of probiotics is due to the inhibition and reduction of inflammatory signal in intestinal epithelium . OBJECTIVE To evaluate the efficacy of probiotics supplementation in the prevention of NEC among very low birth weight preterm infants . STUDY DESIGN A prospect i ve r and omized controlled trial . MATERIAL AND METHOD All preterm infants with gestational age less than or equal to 34 weeks and birth weight less than or equal to 1,500 grams admitted in neonatal care unit , Queen Sirikit National Institute of Child Health during June 1st , 2012 and January 31th , 2013 were enrolled in this study . They were r and omized into two groups , study and control group . Infants in the study group were fed Infloran ( Lactobacillus acidophilus 1 x 10(9 ) and Bifidobacterium bifidum 1 x 10(9 ) organisms ) dose 125 mg/kg/dose twice a day with breast milk or premature formula from the start of feeding until 6 weeks or discharge . Infants in the control group were fed with either breast milk or premature formula alone . The primary outcome was NEC stage ≥ 2 . RESULTS Sixty infants completed the study , 31 infants in the study group and 29 infants in the control group . The baseline characteristic data of infants were similar except for more males in the present study group . Incidence of NEC stage ≥ 2 were similar in both the groups , 3.2 vs. 3.4 % ( p = 0.74 ) . There were no deaths during the study period . Days to reach full feeding , 150 ml/kg/day , were no differences between the two groups , 12.03 ± 5.49 days vs. 13.76 ± 8.25 days ( p = 0.31 ) . No adverse effects such as sepsis , flatulence or diarrhea were noted . CONCLUSION In this study , there was no difference in incidence of NEC stage ≥ 2 between the two groups . No adverse effects of probiotics supplementation were observed
REVIEW ER 'S CONCLUSIONS Evidence suggests that oral antibiotics reduce the incidence of NEC in low birth weight infants .
BACKGROUND Necrotizing enterocolitis continues to be a problem , particularly in preterm neonates .
There have been reports published suggesting that the use of enteral antibiotics may be effective as prophylaxis .
This systematic review was undertaken to clarify the issue .
OBJECTIVES To evaluate the benefits and harms of enteral antibiotic prophylaxis for  necrotizing enterocolitis in low birth weight and preterm infants .