title: Bifidobacterium bifidum OLB6378 Simultaneously Enhances Systemic and Mucosal Humoral Immunity in Low Birth Weight Infants: A Non-Randomized Study Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial Bifidobacterium and enteral feeding in preterm infants: Cluster-randomized trial Nutrition of preterm infants in relation to bronchopulmonary dysplasia The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Probiotics-supplemented feeding in extremely low-birth-weight infants Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. Impact of oral probiotics on neurodevelopmental outcomes in preterm infants Probiotic Supplementation in Preterm: Feeding Intolerance and Hospital Cost Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. Probiotics to minimize the disruption of faecal microbiota in healthy subjects undergoing antibiotic therapy. Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program.
abstract: Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity . Administration of Bifidobacterium bifidum OLB6378 ( OLB6378 ) reduced the incidence of late-onset sepsis in infants . In this non-r and omized study , we aim ed to determine the effect of administration of live OLB6378 on infants ’ humoral immunity . Secondly , we tried to eluci date whether similar effects would be observed with administration of non-live OLB6378 .  Low birth weight ( LBW ) infants weighing 1500–2500 g were divided into three groups : Group N ( no intervention ) , Group L ( administered live OLB6378 concentrate ) , and Group H ( administered non-live OLB6378 concentrate ) . The interventions were started within 48 h after birth and continued until six months of age . Serum immunoglobulin G ( IgG ) levels ( IgG at one month/IgG at birth ) were significantly higher in Group L than in Group N ( p < 0.01 ) . Group H exhibited significantly higher serum IgG levels ( p < 0.01 ) at one month of age and significantly higher intestinal secretory immunoglobulin A ( SIgA ) levels ( p < 0.05 ) at one and two months of age than Group N. No difference was observed in the mortality or morbidity between groups . Thus , OLB6378  administration in LBW infants enhanced humoral immunity , and non-live OLB6378 , which is more useful as a food ingredient , showed a more marked effect than the viable bacteria 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 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 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 Background This study evaluated the benefit of Bifidobacterium bifidum OLB6378 ( B. bifidum ) in very low-birthweight ( VLBW ) infants ( birthweight < 1500 g ) for the acceleration of enteral feeding . Methods A cluster-r and omized , double-blind , placebo-controlled trial was conducted in 19 hospitals , divided into two groups : the B group ( n = 10 hospitals ; B. bifidum given to infants within 48 h of birth ) and the P group ( n = 9 hospitals ; infants received a placebo ) . The primary outcome was establishment of enteral feeding after birth , defined as the postnatal day at which enteral feeding exceeded 100 mL/(kg/day ) . Secondary outcomes were defined as incidence of morbidity and somatic growth before discharge . Results Overall , 283 VLBW infants were enrolled in the study : B group , n = 153 ; and P group , n = 130 . Enteral feeding was established within 21 days after birth in 233 infants , of whom 119 received B. bifidum and 114 received placebo until their bodyweight reached 2000 g. Enteral feeding was established significantly earlier in the B group , at 11.0 ± 3.6 days versus 12.1 ± 3.8days in P group ( P < 0.05 ) . Infant growth during the stay in the neonatal intensive care unit was not different between groups , but the incidence of late-onset sepsis among all enrolled infants was significantly lower in the B group ( 3.9 % , 6/153 ) than in the P group ( 10.0 % , 13/130 ; P < 0.05 ) . No differences were observed in the incidence of other adverse outcomes including mortality . Conclusions B. bifidum in VLBW infants accelerated the establishment of enteral feeding after birth without increasing the incidence of adverse effects Background The pathogenesis of bronchopulmonary dysplasia ( BPD ) is multifactorial . In addition to prenatal inflammation , postnatal malnutrition also affects lung development . Methods A retrospective study was performed to analyse during the first two weeks of life the total , enteral and parenteral nutrition of  premature infants ( < 31 weeks , birth weight ≤1500 g ) born between 08/04 and 12/06 . Results Ninety-five premature infants were analysed : 26 with BPD ( 27 ± 1 weeks ) and 69 without BPD ( 28 ± 1 weeks ) . There was no statistical significant difference in the total intake of fluids , calories , glucose or protein and weight gain per day in both groups . The risk of developing BPD was slightly increased in infants with cumulative caloric intake below the minimal requirement of 1230 kcal/kg and a cumulative protein intake below 43.5 g/kg . Furthermore , the risk of developing BPD was significantly higher when infants had a cumulative fluid intake above the recommended 1840 ml/kg . In infants who developed BPD , the enteral nutrition was significantly lower than in non-BPD infants [ 456 ml/kg ( IQR 744 , 235 ) vs. 685 ( IQR 987 , 511 ) ] . Infants who did not develop BPD reached 50 % of total enteral feeding significantly faster [ 9.6 days vs. 11.5 ] . Conclusions Preterm infants developing BPD received less enteral feeding , even though it was well compensated by the parenteral nutrient supply . Data suggest that a critical minimal amount of enteral feeding is required to prevent development of BPD ; however , a large prospect i ve clinical study is needed to prove this assumption BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation .  Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth Objective : The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight ( ELBW ) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age ( PMA ) . Other important outcome measures , such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated . Study Design : We conducted a multicenter r and omized controlled double-blinded clinical study . The probiotics-supplementation ( PS ) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks ( PMA ) . The control ( C ) group received unsupplemented feedings .  Infant weight and feeding volumes were recorded daily during the first 28 days of study period . Weights were also recorded at 34 weeks PMA . Result : A total of 101 infants were enrolled ( PS 50 versus C 51 ) . There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA ( PS group 58 % versus C group 60 % , ( P value 0.83 ) ) or in the average volume of feeding during 28 days after study entry ( PS group 59 ml kg−1 versus C group 71 ml kg−1 , ( P value 0.11 ) ) . Calculated growth velocity was higher in the PS group compared with the C group ( 14.9 versus 12.6 g per day , ( P value 0.05 ) ) . Incidences of necrotizing enterocolitis ( NEC ) , as well as mortality were similar between the two groups . Conclusion : Although probiotic-supplemented feedings improve growth velocity in ELBW infants , there was no improvement in the percentage of infants with growth delay at 34 weeks PMA . There were no probiotic-related adverse events reported OBJECTIVE To evaluate the growth and neurodevelopment outcomes of very low-birth-weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . STUDY DESIGN This prospect i ve follow-up study was conducted in a cohort of VLBW preterm infants enrolled in a r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Growth outcomes included weight , length , and head circumference . Cognitive and neuromotor development were assessed by using the Bayley Scales of Infant Development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18 to 22 months ' corrected age . RESULTS A total of 221 infants completed the trial protocol . Of the 208 infants eligible for follow-up , 174 infants ( 86 in the probiotics group and 88 in the control group ) were evaluated . There was no significant difference in growth and neurodevelopmental outcomes between the two groups . CONCLUSION Oral probiotic administered to VLBW infants to reduce the incidence and severity of NEC started with the first feed did not affect growth , neuromotor , neurosensory , and cognitive outcomes at 18 to 22 months ' corrected age OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P < .001 ) . The times to reach full enteral feeding were faster ( P < .001 ) , the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants  , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC Abstract Objective : The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . Methods : A prospect i ve follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Cognitive and neuromotor developments were assessed by using the Bayley scales of infant development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18–24 months ’ corrected age . Results : A total of 400 infants completed the trial protocol . Of the 370 infants eligible for follow-up , 249 infants ( 124 in the probiotics group and 125 in the control group ) were evaluated . There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups . Conclusion : Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor , neurosensory and cognitive outcomes at 18–24 months ’ corrected age We hypothesized that giving the probiotic strain Lactobacillus reuteri ( L. reuteri ) DSM 17938 to preterm , formula-fed infants would prevent an early traumatic intestinal inflammatory insult modulating intestinal cytokine profile and reducing the onset of feeding intolerance . Newborn were r and omly allocated during the first 48 h of life to receive either daily probiotic ( 108 colony forming units ( CFUs ) of L. reuteri DSM 17938 ) or placebo for one month . All the newborns underwent to gastric ultrasound for the measurement of gastric emptying time . Fecal sample s were collected for the evaluation of fecal cytokines . Clinical data on feeding intolerance and weight gain were collected . The costs of hospital stays were calculated . The results showed that the newborns receiving  L. reuteri DSM 17938 had a significant decrease in the number of days needed to reach full enteral feeding ( p < 0.01 ) , days of hospital stay ( p < 0.01 ) , and days of antibiotic treatment ( p < 0.01 ) . Statistically significant differences were observed in pattern of fecal cytokine profiles . The anti-inflammatory cytokine interleukin (IL)-10 , was increased in newborns receiving L. reuteri DSM 17938 . Pro-inflammatory cytokines : IL-17 , IL-8 , and tumor necrosis factor (TNF)-alpha levels were increased in newborns given placebo . Differences in the gastric emptying and fasting antral area ( FAA ) were also observed . Our study demonstrates an effective role for L. reuteri DSM 17938 supplementation in preventing feeding intolerance and improving gut motor and immune function development in bottle-fed stable preterm newborns . Another benefit from the use of probiotics is the reducing cost for the Health Care service 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 A novel combination of culturing and DNA-based terminal restriction fragment length polymorphism ( TRFLP ) analysis was used to investigate the effect of probiotics on  antibiotic-induced gut microbiota alterations  to determine if a probiotic preparation containing bifidobacteria and lactobacilli , taken during and after antibiotic therapy , can minimize antibiotic disturbance of faecal microbiota . Healthy subjects administered amoxicillin/clavulanate  were r and omized and concomitantly received a placebo or probiotic mixture . The primary end point was similarity of faecal microbiota as determined by culturing and TRFLP from subjects taking  probiotics  compared to those taking a placebo measured by comparing data from baseline to post-treatment for each subject . TRFLP analysis revealed a high subject to subject variation in the baseline faecal microbiota . The most common antibiotic-induced disturbance was a relative increase in Clostridium , Eubacterium , Bacteroides and Enterobacteraceae . The mean similarity to the baseline increased over time in both treatment groups , although the probiotic group was less disturbed according to both TRFLP and culture data . The culture method revealed that post-antibiotic faecal microbiota in probiotic-consuming subjects were more similar to the baseline microbiota than the control group ( P=0.046 ) . Changes in Enterobactereaceae ( P=0.006 ) and Bifidobacterium ( P=0.030 ) counts were significantly different between the groups . Analysis of TRFLP data reinforced the trend between groups but was not statistically significant ( P=0.066 ) . This study indicates this mixture of probiotics promotes a more rapid return to pre-antibiotic baseline faecal bacterial microbiota RATIONALE Bronchopulmonary dysplasia is the most common morbidity of prematurity , but the validity and utility of commonly used definitions have been question ed . OBJECTIVES To compare three commonly used definitions of bronchopulmonary dysplasia in a contemporary prospect i ve , multicenter observational cohort of extremely preterm infants . METHODS At 36 weeks postmenstrual age , the following definitions of bronchopulmonary dysplasia were applied to surviving infants with and without imputation :  need for supplemental oxygen ( Shennan definition ) , National Institutes of Health Workshop definition , and " physiologic " definition after a room-air challenge . MEASUREMENTS AND MAIN RESULTS Of 765 survivors assessed at 36 weeks , bronchopulmonary dysplasia was diagnosed in 40.8 , 58.6 , and 32.0 % of infants , respectively , with the Shennan , workshop and physiologic definitions . The number of unclassified infants was lowest with the workshop definition ( 2.1 % ) and highest with the physiologic definition ( 16.1 % ) . After assigning infants discharged home in room air before 36 weeks as no bronchopulmonary dysplasia , the modified Shennan definition compared favorably to the workshop definition , with 2.9 % unclassified infants . Newer management strategies with nasal cannula flows up to 4 L/min or more and 0.21 FiO2 at 36 weeks obscured classification of bronchopulmonary dysplasia status in 12.4 % of infants . CONCLUSIONS Existing definitions of bronchopulmonary dysplasia differ with respect to ease of data collection and number of unclassifiable cases . Contemporary changes in management of infants , such as use of high-flow nasal cannula , limit application of existing definitions and may result in misclassification . A contemporary definition of bronchopulmonary dysplasia that correlates with respiratory morbidity in childhood is needed . Clinical trial registered with www . clinical trials.gov ( NCT01435187 )
target: Meta-regression did not show any significant association between the RR for NEC or LOS and the RR for BPD .
  In conclusion , our results suggest that NEC and LOS prevention by probiotics does not affect the risk of developing BPD in preterm infants
background: Probiotic supplementation reduces the risk of necrotizing enterocolitis ( NEC ) and late-onset sepsis ( LOS )  in preterm infants , but it remains to be determined whether this reduction translates into a reduction of other complications .
  We conducted a systematic review and meta- analysis to evaluate the possible role of probiotics in altering the risk of bronchopulmonary dysplasia ( BPD ) .