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
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
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 .