Bacillus clausii for Prevention of Late-onset Sepsis in Preterm Infants: A Randomized Controlled Trial. Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial Influence of a combination of probiotics on bacterial infections in very low birthweight newborns Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials. Detection of Sepsis in Preterm Infants by Fecal Volatile Organic Compounds Analysis: A Proof of Principle Study Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO study. Pasteurization of Mother’s Own Milk for Preterm Infants Does Not Reduce the Incidence of Late-Onset Sepsis The politics of probiotics: probiotics, necrotizing enterocolitis and the ethics of neonatal research Role of Enteric Supplementation of Probiotics on Late-onset Sepsis by Candida species in Preterm Low Birth Weight Neonates: A Randomized, Double Blind, Placebo-controlled Trial Hand hygiene with alcohol hand rub and gloves reduces the incidence of late onset sepsis in preterm neonates Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants Elimination of admission hypothermia in preterm very low-birth-weight infants by standardization of delivery room management. [Effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria in preterm infants]. Delayed Cord Clamping in Very Preterm Infants Reduces the Incidence of Intraventricular Hemorrhage and Late-Onset Sepsis: A Randomized, Controlled Trial Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. Effects of Probiotics on Enteric Flora and Feeding Tolerance in Preterm Infants Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT. Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis
BACKGROUND OF THE STUDY Preterm infants are managed with antibiotics for sepsis , including suspected or probable sepsis . This leads to a delayed and abnormal colonization of the gut with potentially pathogenic organisms and a microbiome , which lacks biodiversity and increases the risk for late-onset sepsis ( LOS ) . Probiotics have been proven to reduce the risk for necrotizing enterocolitis , but evidence for prevention of LOS is inconclusive . Probiotic effect depends also on the strain used , dose and indication for use . This study evaluated Bacillus clausii probiotic administered prophylactically to preterm neonates for prevention of LOS . OBJECTIVES To study B.clausii given prophylactically to preterm neonates for prevention of LOS . DESIGN Double-blinded , placebo-controlled , r and omized trial . SETTING S Tertiary care neonatal unit in India . PARTICIPANTS Consecutive preterm neonates < 34 weeks , admitted from 1 March 2012 to 28 February 2014 were stratified as extreme preterm and very preterm . INTERVENTION R and omized to receive either probiotic or placebo for 6 weeks , discharge from hospital , death or occurrence of sepsis , whichever was earlier . PRIMARY OUTCOME Incidence of definite and probable LOS in probiotic group compared with placebo . RESULTS Of 326 eligible preterm infants , 244 were enrolled and 82 were excluded . Of these , 120 were stratified as extreme preterm and r and omized to receive placebo ( n = 59 ) and probiotic ( n = 61 ) . Of 124 babies stratified as very preterm , an equal number was r and omized to receive placebo ( n = 62 ) and probiotic ( n = 62 ) . There was no significant difference in the incidence of LOS between the two arms in the extreme preterm group [ 29 % vs. 23 % ; relative risk ( RR ) 1.27 ; 95 % confidence interval ( CI ) 0.88 - 1.66 ; p = 0.36 ] and the very preterm group ( 13 % vs. 10 % ; RR 1.33 ; 95 % CI 0.96 - 1.70 ; p = 0.32 ) . Full feeds were achieved significantly faster in the probiotic group in both the extreme preterm ( RR 0.82 ; 95 % CI 0.74 - 0.88 ) and the very preterm ( RR 0.67 ; 95 % 0.32 - 0.77 ) . CONCLUSIONS Prophylactic administration of B.clausii to preterm neonates did not result in a significant difference in the incidence of LOS as compared with placebo BACKGROUND Preterm infants remain at high risk of adverse outcomes following necrotizing enterocolitis  ( NEC ) and late onset sepsis ( LOS ) . Meta- analysis of r and omized trials has indicated a reduction in severe NEC following use of probiotics and bovine lactoferrin ( LF ) . Overall , however , uncertainty remains over which probiotic , or combination to use . The aim of this study was to compare the incidence of severe NEC and LOS before and after routine supplementation with Lactobacillus GG ( LGG ) and LF . METHODS In this retrospective cohort study , infants < 32 weeks or < 1500 g routinely received LGG and 100 mg lactoferrin daily from 2011 -2015 were compared with similar infants born from 2004 - 2008 . Cases of NEC were Bell stage 2 or greater and LOS was blood or spinal fluid culture positive after 48 hrs of age . RESULTS We noted a marked decline in the incidence of NEC from 3 % to 1 % with a RR of 0.29 ( CI 0.1 - 0.9 ) and a number needed to benefit of 50 . The cost of preventing one case of NEC was estimated to be NZ $ 2800 , considerably lower than the cost of treatment . LOS rates were not significantly different . There was a decrease in retinopathy treatment rates . During the period there was one case of LGG sepsis in a 23 week gestation infant with abdominal pathology and one infant developed NEC after stopping prophylaxis . CONCLUSION The rates of severe NEC was markedly reduced following prophylaxis . The case of LGG sepsis indicates caution is required in extremely preterm infants BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset  sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing < 1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe Summary Background Late-onset infections are an important cause of morbidity and mortality in preterm infants . The purpose of our prospect i ve r and omised study was to establish whether a combination of probiotics ( Lactobacillus acidophilus , Enterococcus faecium and Bifidobacterium infantum ) affects the incidence of late-onset sepsis and other infections in very low birthweight infants ( birthweight under 1500 g , gestational age under 33 weeks ) . Methods From 80 included infants , one half received probiotics ( L. acidophilus , E. faecium and B. infantum ) in the ratio 1.5:1:1.5 , at a dose of 0.6 × 107 colony-forming units twice daily , given with the first portions of milk until discharge , whereas the other half did not . Results In the group receiving probiotics , 16 children had late-onset sepsis compared with 29 in the group without probiotics ; p = 0.006 . The number of late-onset septic events was lower ( 30 ) in the group receiving probiotics than in the group that did not receive probiotics ( 69 ) ; p = 0.003 . Furthermore , fewer children had at least one late-onset infection ( 20 infants in the group receiving probiotics compared with 32 in the group without them ; p = 0.009 ) . There were less episodes of late-onset infections in the group receiving probiotics ( 35 ) than in the group without probiotics ( 79 ) ; p = 0.002 . Conclusions A combination of probiotics at a low dose ( 1.2 × 107 colony-forming units ) decreased the frequency of late-onset sepsis and other infections , as described in previous studies . In addition , children were discharged at a lower postmenstrual age . There were no side effects of probiotics reported Objective : To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by C and ida species , of late-onset sepsis and neurological outcome in preterm newborns . Study Design : A prospect i ve study was conducted in 249 preterms who were subdivided into three groups :  one group ( n=83 ) was supplemented with Lactobacillus ( L. ) reuteri , one group with L. rhamnosus ( n=83 ) and the other with no supplementation ( n=83 ) . The fungal colonization in the gastrointestinal tract , the late onset of sepsis and clinical parameters were recorded . A neurological structured assessment was further performed at 1 year of age . Result : C and ida stool colonization was significantly higher ( P<0.01 ) in the control group than in the groups treated with probiotics . The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups . Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group . Conclusion : The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by C and ida , in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms BACKGROUND Probiotics may reduce  necrotising enterocolitis and late-onset sepsis after preterm birth . However , there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely . We aim ed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis , late-onset sepsis , and death in preterm infants . METHODS In this multicentre , r and omised controlled phase 3 study ( the PiPS trial ) , we recruited infants born between 23 and 30 weeks ' gestational age within 48 h of birth from 24 hospitals in southeast Engl and . Infants were r and omly assigned ( 1:1 ) to probiotic or placebo via a minimisation algorithm r and omisation programme . The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU ; the placebo was dilute infant formula alone . Clinicians and families were masked to allocation . The primary outcomes were necrotising enterocolitis ( Bell stage 2 or 3 ) , blood culture positive sepsis more than 72 h after birth ; and death before discharge from hospital . All primary analyses were by intention to treat . This trial is registered with IS RCT N , number 05511098 and EudraCT , number 2006 - 003445 - 17 . FINDINGS Between July 1 , 2010 , and July 31 , 2013 , 1315 infants were recruited ; of whom 654 were allocated to probiotic and 661 to placebo . Five infants had consent withdrawn after r and omisation , thus 650 were analysed in the probiotic group and 660 in the placebo group . Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups . 61 infants ( 9 % ) in the probiotic group had necrotising enterocolitis compared with 66 ( 10 % ) in the placebo group ( adjusted risk ratio 0·93 ( 95 % CI 0·68 - 1·27 ) ; 73 ( 11 % ) infants in the probiotics group had sepsis compared with 77 ( 12 % ) in the placebo group ( 0·97 ( 0·73 - 1·29 ) ; and 54 ( 8 % ) deaths occurred before discharge home in the probiotic group compared with 56 ( 9 % ) in the placebo group ( 0·93 [ 0·67 - 1·30 ] ) . No probiotic-associated adverse events were reported . INTERPRETATION There is no evidence of benefit for this intervention in this population ; this result does not support the routine use of B breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepis in very preterm infants . FUNDING UK National Institute for Health Research Health Technology Assessment programme BACKGROUND Lactoferrin is the major antimicrobial protein in human milk . In our r and omized controlled trial ( RCT ) of bovine lactoferrin ( BLF ) supplementation in preterm neonates , BLF reduced  late-onset sepsis ( LOS ) .  Mother 's own milk ( MM ) contains higher concentrations of lactoferrin than donor milk or formula , but whether BLF is more effective in infants who receive formula or donor milk is uncertain . AIM To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and /or donor milk . STUDY DESIGN This is a ( A ) post hoc subgroup analysis , in our RCT of BLF , of its effects in preterm infants fed MM , with or without formula , versus those fed formula and /or donor milk ( no-MM ) and ( B ) post hoc meta- analysis , in our RCT of BLF and in the ELFIN ( Enteral Lactoferrin in Neonates ) RCT , of the effect of BLF in subgroups not exclusively fed MM . RESULTS ( A ) Of 472 infants in our RCT , 168 were r and omized to placebo and 304 were r and omized to BLF . Among MM infants , LOS occurred in 22/133 ( 16.5 % ) infants r and omized to placebo and in 14/250 ( 5.6 % ) r and omized to BLF ( relative risk or risk ratio ( RR ) : 0.34 ; relative risk reduction ( RRR ) : 0.66 ; 95 % confidence interval ( 95 % CI ) for RR : 0.18 - 0.64 ; p < 0.0008 ) . Among no-MM infants , LOS occurred in 7/35 ( 20.0 % ) r and omized to placebo and in 2/54 ( 3.7 % ) r and omized to BLF ( RR : 0.19 ; RRR : 0.81 ; 95 % CI for RR : 0.16 - 0.96 ; p = 0.026 ) . In multivariable logistic regression analysis , there was no interaction between BLF treatment effect and type of feeding ( p = 0.628 ) . ( B ) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT , BLF reduced the RR of LOS by 18 % ( RR : 0.82 ; 95 % CI : 0.71 - 0.96 ; p = 0.01 ) . CONCLUSION Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM . Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS Objectives : Several studies associated altered gut microbiota composition in preterm infants with late-onset sepsis ( LOS ) , up to days before clinical onset of sepsis . Microbiota analysis as early diagnostic biomarker is , however , in clinical practice currently not feasible because of logistic aspects and high costs . Therefore , we hypothesized that analysis of  fecal volatile organic compounds ( VOCs ) may serve as noninvasive biomarker to predict LOS at a pre clinical stage , because VOC reflect the composition and activity of intestinal microbial communities . Methods : In a prospect i ve multicenter study , fecal sample s were collected daily from infants with a gestational age of < 30 weeks .  VOC signatures of fecal sample s from infants with LOS , collected up to 5 days before diagnosis , were analyzed by means of an electronic nose technology ( Cyranose 320 ) and compared to matched controls . Results : Fecal VOC profiles of infants with LOS ( n = 36 ) could be discriminated from controls ( n = 40 ) at 3 days ( area under the curve [ ±95 % confidence interval ] , P value , sensitivity , specificity ; 70.2 [ 52.2–88.3 ] , 0.033 , 57.1 % , 61.5 % ) , 2 days ( 77.7 [ 62.7–92.7 ] , 0.050 , 75.0 % , 70.8 % ) , and 1 day ( 70.4 [ 49.6–91.3 ] , 0.037 , 64.3 % , 64.3 % ) before the onset of LOS . Conclusions : Fecal VOC profiles of preterm infants with LOS could be discriminated from matched controls , up to 3 days before clinical onset of the disease , underlining the hypothesis that intestinal microbiota may play an etiological role in LOS . Notably , VOC profiling is clinical ly feasible and the potential of this technique in the early detection of LOS needs to be confirmed in future studies BACKGROUND & AIMS Recent studies have suggested that the gut microflora has metabolic effects . We aim ed to evaluate postnatal growth in preterm infants who received different probiotic supplements  , and to assess the safety of probiotic administration . METHODS This prospect i ve , r and omized , double-blind , controlled trial was performed at three tertiary care neonatal units . Preterm infants were r and omly assigned to receive daily supplementation over 4 - 6 weeks with placebo ( group C ) or probiotics ( group P ) . Group P comprised three subgroups : P1 received Bifidobacterium lactis , P2 received Bifidobacterium longum , and P3 received B. lactis and B. longum . We assessed postnatal growth during the supplementation period and up to a corrected gestational age ( GA ) of 41 weeks when body composition was assessed using whole-body dual-energy X-ray absorptiometry . Aerobic and anaerobic blood cultures were performed on suspicion of late-onset sepsis . RESULTS The study comprised 199 preterm infants with a mean GA of 29.1 ± 1.4 weeks and a mean birth weight of 1173 ± 210 g , who received a placebo  ( group C , n = 52 )  or probiotics  ( group P , n = 147 ) from the first week of life . At the end of the supplementation period , no statistically significant differences were seen between the groups in relation to the mean body weight ( group C = 1906 ± 23 g , group P = 1875 ± 14 g , p = 0.25 ) , length , or head circumference . The incidence rates of necrotizing enterocolitis and late-onset sepsis were similar in the two groups . At the corrected GA of 41 weeks , there were no differences between the groups with respect to anthropometric measurements or body composition analysis . CONCLUSIONS Preterm infants receiving  Bifidobacterium supplements did not exhibit better postnatal growth compared with those who received placebo treatment . No adverse effects were associated with probiotic administration . Registered under Clinical Trials.gov Identifier no. NCT01379417 Background : Feeding preterm infants human  milk has a beneficial effect on the risk of late-onset sepsis ( LOS ) . Due to lack of microbiological st and ards , practice s such as pasteurization of mother ’s own milk differ widely among neonatal intensive care units worldwide . Objectives : To investigate whether pasteurization of mother ’s own milk for very-low-birth-weight ( VLBW ) infants influences the incidence and severity of infection-related outcomes . Methods : In this r and omized controlled trial , preterm infants ( gestational age < 32 weeks and /or birth weight < 1,500 g ) received either raw or pasteurized mother ’s own milk during the first 8 weeks of life . The primary outcome was the incidence of proven LOS . A dose-response relation was verified , i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother ’s own milk . Results : This study included 303 VLBW infants ( mean birth weight : 1,276 g ; mean gestational age : 29 weeks ) whose baseline and nutritional characteristics were similar . The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk : 22/151 ( 0.15 , CI : 0.08–0.20 ) and 31/152 ( 0.20 , CI : 0.14–0.27 ) , respectively ( RR : 0.71 ; 95 % CI : 0.43–1.17 ) . A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS , regardless of the type of feeding . Conclusion : For preterm infants , pasteurization of mother ’s own milk shows a trend towards an increase in infectious morbidity , although no statistical significance was reached . Practice s should focus on collection , storage and labeling procedures to ensure the safety and quality of expressed milk 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 ) Background : The increase in invasive fungal infections ( IFIs ) in neonatal intensive care unit ( NICU ) is jeopardizing the survival of preterm neonates . Probiotics modulating the intestinal microflora of preterm neonates may minimize enteral fungal colonization . Aims : This study was to examine whether probiotic supplementation in neonates reduced fungal septicemia . Material s and Methods : This prospect i ve , r and omized , double blind trial investigating the  supplementation of preterm infants with a probiotic  was done from May 2012 to April 2013 , with 112 subjects r and omized into two groups . Primary outcome : Decreased fungal colonization in gastrointestinal tract . Others : Incidence of late onset septicemia ; duration of the primary hospital admission ; number of days until full enteral feeds established . Results : Full feed establishment was earlier in probiotics group compared to placebo group ( P = 0.016 ) . The duration of hospitalization was less in the probiotic group ( P = 0.002 ) . Stool fungal colonization , an important outcome parameter was 3.03 ± 2.33 × 105 colony formation units ( CFU ) in the probiotics group compared to 3 ± 1.5 × 105 CFU in the placebo group ( P = 0.03 ) . Fungal infection is less in the study group ( P = 0.001 ) . Conclusion : The key features of our study were reduced enteral fungal colonization , reduce invasive fungal sepsis , earlier establishment of full enteral feeds , and reduced duration of hospital stay in the probiotics group To assess the impact of a h and hygiene protocol , using h and washing , alcohol h and rub and gloves when caring for preterm infants born after 31 weeks of gestation , on the incidence of neonatal late onset sepsis ( LOS ) 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 : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age <33 weeks or birthweight < 1,500 g were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration  of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population CONTEXT Temperature instability is a serious but potentially preventable morbidity in preterm infants . Admission temperatures below 36 ° C are associated with increased mortality and late onset sepsis . OBJECTIVE The goal of our quality -improvement effort was to increase preterm infants ' admission temperatures to above 36 ° C by preventing heat loss in the immediate postnatal period . DESIGN This quality -improvement initiative used the rapid-cycle Plan-Do- Study -Act approach . Preterm infants born at less than 33 weeks ' gestation with very low birth weight less than 1500 g who were born at a Regional Level III Neonatal Intensive Care Unit ( NICU ) in San Jose , CA , were enrolled . Our intervention involved st and ardizing the management of thermoregulation from predelivery through admission to the NICU . Data on admission temperature were collected prospect ively . MAIN OUTCOME MEASURES The primary outcome measure was hypothermia , defined as temperature below 36 ° C on admission to the NICU . RESULTS The hypothermia rate was reduced from 44 % in early 2006 to 0 % by 2009 . There was a slight increase to 6 % in 2010 . Subsequently , with further real-time feedback , we were able to sustain 0 % hypothermia through 2011 . Our hypothermia rate remained substantially lower than state and national hypothermia benchmarks that have shown moderate improvement over the same period . CONCLUSION We reduced hypothermia in very low-birth-weight infants using a st and ardized protocol , multidisciplinary team approach , and continuous feedback . Sustaining improvement is a challenge that requires real-time progress evaluation of outcomes and ongoing staff education OBJECTIVE To evaluate the effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria among preterm infants in the neonatal intensive care unit ( NICU ) . METHODS A double-blind , r and omized , placebo-controlled trial was carried out in the preterm infants who were transferred to the NICU immediately after birth . These infants were stratified by whether they were breastfed and then r and omized into test group and control group . The test group was given probiotics from the day when enteral feeding began , while the control group was treated conventionally without probiotics . The two groups were compared in terms of the colonization with extended-spectrum beta-lactamase-producing bacteria , as assessed by rectal swabs on days 1 , 3 , 7 , and 14 after birth , and the incidence of diseases . RESULTS Rectal colonization with drug-resistant bacteria was found in the test group ( n=119 ) and control group ( n=138 ) on days 1 , 3 , 7 , and 14 after birth . There were no significant differences in the incidence of late-onset sepsis and necrotizing enterocolitis between the two groups ( P>0.05 ) . Among non-breastfed infants , the test group had significantly decreased rectal colonization with drug-resistant bacteria compared with the control group on day 14 after birth ( 71.1 % vs 88.9 % ; P=0.04 ) . No probiotic-related adverse events were observed in the study . CONCLUSIONS Oral administration of probiotics may reduce rectal colonization with drug-resistant bacteria in preterm infants under certain conditions and shows good safety OBJECTIVE . This study compared the effects of immediate ( ICC ) and delayed ( DCC ) cord clamping on very low birth weight ( VLBW ) infants on 2 primary variables : bronchopulmonary dysplasia ( BPD ) and suspected necrotizing enterocolitis ( SNEC ) . Other outcome variables were late-onset sepsis ( LOS ) and intraventricular hemorrhage ( IVH ) . STUDY DESIGN . This was a r and omized , controlled unmasked trial in which women in labor with singleton fetuses < 32 weeks ’ gestation were r and omly assigned to ICC ( cord clamped at 5–10 seconds ) or DCC ( 30–45 seconds ) groups . Women were excluded for the following reasons : their obstetrician refused to participate , major congenital anomalies , multiple gestations , intent to withhold care , severe maternal illnesses , placenta abruption or previa , or rapid delivery after admission . RESULTS . Seventy-two mother/infant pairs were r and omized . Infants in the ICC and DCC groups weighed 1151 and 1175 g , and mean gestational ages were 28.2 and 28.3 weeks , respectively . Analyses revealed no difference in maternal and infant demographic , clinical , and safety variables . There were no differences in the incidence of our primary outcomes ( BPD and suspected NEC ) . However , significant differences were found between the ICC and DCC groups in the rates of IVH and LOS . Two of the 23 male infants in the  DCC group had IVH versus 8 of the 19 in the ICC group . No cases of sepsis occurred in the 23 boys in the DCC group , whereas 6 of the 19 boys in the ICC group had confirmed sepsis . There was a trend toward higher initial hematocrit in the infants in the DCC group . CONCLUSIONS . Delayed cord clamping seems to protect VLBW infants from IVH and LOS , especially for male infants OBJECTIVE Late-onset sepsis ( occurring after 3 days of age ) is an important problem in very low birth weight ( VLBW ) infants . To determine the current incidence of late-onset sepsis , risk factors for disease , and the impact of late-onset sepsis on subsequent hospital course , we evaluated a cohort of 6956 VLBW ( 401 - 1500 g ) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period ( 1998 - 2000 ) . METHODS The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospect i ve registry of all VLBW neonates admitted to participating centers within 14 days of birth . Exp and ed infection surveillance was added in 1998 . RESULTS Of 6215 infants who survived beyond 3 days , 1313 ( 21 % ) had 1 or more episodes of blood culture-proven late-onset sepsis . The vast majority of infections ( 70 % ) were caused by Gram-positive organisms , with coagulase-negative staphylococci accounting for 48 % of infections . Rate of infection was inversely related to birth weight and gestational age . Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus , prolonged ventilation , prolonged intravascular access , bronchopulmonary dysplasia , and necrotizing enterocolitis . Infants who developed late-onset sepsis had a significantly prolonged hospital stay ( mean length of stay : 79 vs 60 days ) . They were significantly more likely to die than those who were uninfected ( 18 % vs 7 % ) , especially if they were infected with Gram-negative organisms ( 36 % ) or fungi ( 32 % ) . CONCLUSIONS Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors . Strategies to reduce late-onset sepsis and its medical , social , and economic toll need to be addressed urgently 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 Background : Probiotics are live microbes that colonize the gastrointestinal tract and benefit the host . Preterm infants develop abnormal patterns of bowel colonization , and only a few clinical trials have reported the outcomes of preterm infants treated with probiotics .  Purpose : We investigated the rate of colonization of Lactobacillus and the clinical variables affecting the colonization in preterm infants . Methods : Infants with gestational age less than 37 weeks treated at Ewha Womans University Hospital between March 2003 and July 2004 were eligible .  Lactobacillus acidophilus ( containing 108 CFU ) was supplemented orally , mixed with breast milk or formula divided into three doses a day . Stool sample s were collected before and 14 days after supplementation of the probiotic . Stool sample s were anaerobically cultured on Rogosa agar and identified by Gram stain , catalase test and glucose fermentation test . Clinical characteristics were analyzed . Results : Seventy-three patients with an average gestational age of 33.0 ± 2.5 weeks were studied . Meconium was cultured in 46 patients and Lactobacillus was not detected .  Probiotic supplementation began on 3.4 ± 6.8 days , and after 14 days of supplementation , Lactobacillus was cultured in an average of 3.01 × 108 CFU in the stool of 37.0 % ( 27/73 ) of the patients . There was a tendency towards an increased incidence of sepsis in the Lactobacillus– group ( p = 0.082 ) . In the Lactobacillus+ group , a striking increase in feeding tolerance was detected . Conclusion : In preterm infants , with the administration of probiotics , 37 % of the preterm infants  had Lactobacillus colonized in the gastrointestinal tract and improved feeding tolerance . A double-blind study is in progress for further investigation into the effect on other systemic diseases in premature infants BACKGROUND Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants . Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin , an antimicrobial protein processed from cow 's milk , prevents infections and associated complications . OBJECTIVE To determine whether or not enteral supplementation with bovine lactoferrin ( The Tatua Cooperative Dairy Company Ltd , Morrinsville , New Zeal and ) reduces the risk of late-onset infection ( acquired > 72 hours after birth ) and other morbidity and mortality in very preterm infants . DESIGN R and omised , placebo-controlled , parallel-group trial . R and omisation was via a web-based portal and used an algorithm that minimised for recruitment site , weeks of gestation , sex and single versus multiple births . SETTING UK neonatal units between May 2014 and September 2017 . PARTICIPANTS Infants born at < 32 weeks ' gestation and aged < 72 hours at trial enrolment . INTERVENTIONS Eligible infants were allocated individually ( 1 : 1 ratio ) to receive enteral bovine lactoferrin ( 150 mg/kg/day ; maximum 300 mg/day ) or sucrose ( British Sugar , Peterborough , UK ) placebo ( same dose ) once daily from trial entry until a postmenstrual age of 34 weeks . Parents , caregivers and outcome assessors were unaware of group assignment . OUTCOMES Primary outcome - microbiologically confirmed or clinical ly suspected late-onset infection . Secondary outcomes - microbiologically confirmed infection ; all-cause mortality ; severe necrotising enterocolitis ( NEC ) ; retinopathy of prematurity ( ROP ) ; bronchopulmonary dysplasia ( BPD ) ; a composite of infection , NEC , ROP , BPD and mortality ; days of receipt of antimicrobials until 34 weeks ' postmenstrual age ; length of stay in hospital ; and length of stay in intensive care , high-dependency and special-care setting s. RESULTS Of 2203 enrolled infants , primary outcome data were available for 2182 infants ( 99 % ) . In the intervention group , 316 out of 1093 ( 28.9 % ) infants acquired a late-onset infection versus 334 out of 1089 ( 30.7 % ) infants in the control group [ adjusted risk ratio ( RR ) 0.95 , 95 % confidence interval ( CI ) 0.86 to 1.04 ] . There were no significant differences in any secondary outcomes : microbiologically confirmed infection ( RR 1.05 , 99 % CI 0.87 to 1.26 ) , mortality ( RR 1.05 , 99 % CI 0.66 to 1.68 ) , NEC ( RR 1.13 , 99 % CI 0.68 to 1.89 ) , ROP ( RR 0.89 , 99 % CI 0.62 to 1.28 ) , BPD ( RR 1.01 , 99 % CI 0.90 to 1.13 ) , or a composite of infection , NEC , ROP , BPD and mortality ( RR 1.01 , 99 % CI 0.94 to 1.08 ) . There were no differences in the number of days of receipt of antimicrobials , length of stay in hospital , or length of stay in intensive care , high-dependency or special-care setting s. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group . CONCLUSIONS Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection , mortality or other morbidity in very preterm infants . FUTURE WORK Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta- analysis with data from other trials . A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants . TRIAL REGISTRATION Current Controlled Trials IS RCT N88261002 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 22 , No. 74 . See the NIHR Journals Library website for further project information . This trial was also sponsored by the University of Oxford , Oxford , UK . The funder provided advice and support and monitored study progress but did not have a role in study design or data collection , analysis and interpretation Necrotizing enterocolitis ( NEC ) continues to be a major cause of morbidity and mortality in premature infants . Although the pathogenesis of NEC remains unclear , abnormal bacterial colonization has been postulated as playing a central role . Various factors impact bacterial colonization following delivery . Compared to term infants , the bacterial colonization pattern in prematurely born infants is markedly different , with a greater predilection for colonization with pathogenic bacteria . Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment , favoring the growth of commensal bacteria . Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC . These preliminary studies support the need for a large , r and omized , controlled trial to further investigate the role of probiotics in the prevention of NEC
: Probiotic supplementation reduces the risk of LOS in preterm infants
CONTEXT : Late-onset sepsis ( LOS ) is a major cause of mortality and morbidity in preterm infants .
Despite various preventive measures , its incidence continues to remain high , hence the urgent need for additional approaches .
One such potential strategy is supplementation with probiotics .
Currently there are > 30 r and omized controlled trials ( RCTs ) of probiotics in preterm infants that have reported on LOS .