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 Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. The politics of probiotics: probiotics, necrotizing enterocolitis and the ethics of neonatal research Probiotics supplementation increases intestinal blood flow velocity in extremely low birth weight preterm infants A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants. Bacillus clausii for Prevention of Late-onset Sepsis in Preterm Infants: A Randomized Controlled Trial. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Effect of Bifidobacterium breve M-16V Supplementation on Fecal Bifidobacteria in Preterm Neonates - A Randomised Double Blind Placebo Controlled Trial [Effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria in preterm infants]. Effects of Bifidobacterium lactis Bb12 Supplementation on Intestinal Microbiota of Preterm Infants: a Double-Blind, Placebo-Controlled, Randomized Study Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO study. Early versus Late Enteral Feeding in Preterm Intrauterine Growth Restricted Neonates with Antenatal Doppler Abnormalities: An Open-Label Randomized Trial Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. The nutritional iodine supply of Belgian neonates is still insufficient Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. Synbiotics for decreasing incidence of necrotizing enterocolitis among preterm neonates – a randomized controlled trial The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial. Slow versus rapid enteral feed in preterm neonates with antenatal absent end diastolic flow Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome Effect of early feeding on maturation of the preterm infant's small intestine. Enteral feeding of premature infants with Lactobacillus GG. Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants
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 BACKGROUND Colonization by C and ida species is the most important predictor of the development of invasive fungal disease in preterm neonates , and the enteric reservoir is a major site of colonization . We evaluated the effectiveness of an orally supplemented probiotic ( Lactobacillus casei subspecies rhamnosus ; Dicoflor [ Dicofarm spa ] ; 6 x 10(9 ) cfu/day ) in the prevention of gastrointestinal colonization by C and ida species in preterm , very low birth weight ( i.e. , < 1500-g ) neonates during their stay in a neonatal intensive care unit . METHODS Over a 12-month period , a prospect i ve , r and omized , blind , clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit . During the first 3 days of life , the neonates were r and omly assigned to receive either an oral probiotic added to human ( maternal or pooled donors ' ) milk ( group A ) or human milk alone ( group B ) for 6 weeks or until discharge from the NICU , if the neonate was discharged before 6 weeks . On a weekly basis , specimens obtained from various sites ( i.e. , oropharyngeal , stool , gastric aspirate , and rectal specimens ) were collected from all patients for surveillance culture , to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract . RESULTS The incidence of fungal enteric colonization ( with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site ) was significantly lower in group A than in group B ( 23.1 % vs. 48.8 % ; relative risk , 0.315 [ 95 % confidence interval , 0.120 - 0.826 ] ; P = .01 ) . The numbers of fungal isolates obtained from each neonate ( P = .005 ) and from each colonized patient ( P = .005 ) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001 - 1500 g. There were no changes in the relative proportions of the different C and ida strains . No adverse effects potentially associated with the probiotic were recorded . CONCLUSIONS Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by C and ida species among very low birth weight neonates 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 determine whether probiotics supplementation affects intestinal blood flow velocity in extremely low birth weight neonates . Study Design : In this r and omized , double-blind , placebo-controlled study , probiotics were added to the first enteral feeding and continued until discharge or 34 weeks postmenstrual age . Pulsed Doppler was used to measure prepr and ial and postpr and ial ( at 30 and 60 min ) time-averaged mean velocity ( TAMV ) , peak systolic velocity ( PSV ) and end diastolic velocity ( EDV ) during the second week of life after ⩾7 days of probiotics supplementation . Result : A total of 31 infants were studied , 15 were r and omized to the probiotic and 16 to the placebo groups . There was a significant postpr and ial increase in TAMV for the probiotic vs the placebo group ( P=0.035 ) , with PSV and EDV showing a trend . Demographic and clinical variables were similar between the groups . Conclusion : Probiotics administration significantly increases postpr and ial intestinal blood flow in extremely low birth weight preterm neonates when compared with the placebo group 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 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 Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG )  and 49 received placebo .  The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed < or = 1000 g , presumably because of more frequent suspensions of enteral feeding , more courses of antibiotic treatment , or both . CONCLUSIONS Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576 Background Probiotic supplementation significantly reduces the risk of necrotising enterocolitis ( NEC ) and all cause mortality  in preterm neonates . Independent quality assessment is important before introducing routine probiotic supplementation in this cohort . Aim To assess product quality , and confirm that Bifidobacterium breve ( B. breve ) M-16V supplementation will increase fecal B. breve counts without adverse effects . Methods and Participants Strain identity ( 16S rRNA gene sequencing ) , viability over 2 year shelf-life were confirmed , and microbial contamination of the product was ruled out . In a controlled trial preterm neonates ( Gestation <33 weeks ) ready to commence or on feeds for < 12 hours were r and omly allocated to either B. breve M-16V ( 3 × 109 cfu/day ) or placebo ( dextrin ) supplementation  until the corrected age 37 weeks . Stool sample s were collected before ( S1 ) and after 3 weeks of supplementation ( S2 ) for study ing fecal B. breve levels using quantitative PCR ( Primary outcome ) . Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II . Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests , and McNemar and Wilcoxon signed-rank tests for paired comparisons . Results A total of 159 neonates ( Probiotic : 79 , Placebo : 80 ) were enrolled . Maternal and neonatal demographic characteristics were comparable between the groups . The proportion of neonates with detectable B. breve increased significantly post intervention : Placebo : [ S1:2/66 ( 3 % ) , S2 : 25/66 ( 38 % ) , p<0.001 ] Probiotic : [ S1 : 29/74 ( 40 % ) , S2 : 67/74 ( 91 % ) , p<0.001 ] . Median S1 B. breve counts in both groups were below detection ( < 4.7 log cells.g−1 ) , increasing significantly in S2 for the probiotic group ( log 8.6 ) while remaining < 4.7 log in the control group ( p<0.001 ) . There were no adverse effects including probiotic sepsis and no deaths . NEC≥Stage II occurred in only 1 neonate ( placebo group ) . Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates . Trial Registration Australia New Zeal and Clinical Trial Registry ACTRN 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 ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants . In particular , the colonization of preterm infants by bifidobacteria is delayed . A double-blind , placebo-controlled , r and omized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota . Both culture-dependent and culture-independent approaches were used to study the gut microbiota . Bifidobacterial numbers , determined by fluorescence in situ hybridization , were significantly higher in the probiotic than in the placebo group ( log10 values per g of fecal wet weight : probiotic , 8.18 + 0.54 [ st and ard error of the mean ] ; placebo , 4.82 + 0.51 ; P < 0.001 ) . A similar trend for bifidobacterial numbers was also obtained with the culture-dependent method . The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae ( log10 values of CFU per g of fecal wet weight : probiotic , 7.80 + 0.34 ; placebo , 9.03 + 0.35 ; P = 0.015 ) and Clostridium spp . ( probiotic , 4.89 + 0.30 ; placebo , 5.99 + 0.32 ; P = 0.014 ) than the infants in the placebo group . Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population . However , the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia 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 of the study Enteral feeding in preterm neonates with intrauterine growth restriction ( IUGR ) and absent or reversed end diastolic flow ( AREDF ) on umbilical artery ( UA ) Doppler is delayed owing to an increased risk of necrotizing enterocolitis ( NEC ) . Delaying enteral feeding with longer duration of parenteral nutrition ( PN ) carries an increased risk of sepsis . Objectives To study early versus late feeding in preterm IUGR neonates for time required to attain sufficient feed volume to discontinue PN and increased risk of NEC or feed intolerance ( FI ) . Design Open-label r and omized controlled trial . Setting Tertiary care neonatal unit and fetal-maternal medicine unit in India . Participants Preterm intrauterine growth restricted neonates ' ≤32 weeks with AREDF on UA Doppler enrolled from 1 January 2014 to 31 July 2015 . Intervention R and omized to receive early or late feeding using mothers own or donor breast milk as per a feed initiation and advancement protocol . Primary outcome Time in days required to attain sufficient feed volume allowing discontinuation of PN and incidence of NEC in neonates fed early versus late . Results There were 77 eligible neonates . Sixty-two neonates were included and stratified as extreme preterm ( 27 - 29 weeks ) ( n = 20 ) and very preterm ( 30 - 32 weeks ) ( n = 42 ) . Ten extreme preterm and 21 very preterm neonates were r and omized to each early feeding and late feeding arm . There was a significantly faster attainment of sufficient feeds in the early feeding arm of both the stratified groups [ extreme preterm : median 14 days ( Interquartile range IQR : 12 - 15 ) compared with 18 days ( IQR : 18 - 20 ) , hazard ratio ( HR ) : 1.59 , 95 % CI : 0.626 - 4.078 ; very preterm : 12 days ( IQR : 10 - 14 ) as compared with 16 days ( IQR 15 - 17 ) , HR : 1.89 , 95 % CI : 1.011 - 3.555 ] . There was no difference in the incidence of NEC , FI and combined outcome of NEC and FI . Conclusion Early feeding in preterm IUGR neonates with AREDF on antenatal UA Doppler allowed earlier discontinuation of PN , allowing birth weight to be regained earlier and did not increase the incidence of NEC and FI 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 Abstract . Belgium used to be affected by mild iodine deficiency . Improvement in iodine nutrition has been recently documented in schoolchildren in Belgium in spite of the absence of any systematic programme of iodine supplementation . The question arises as to whether this ' silent iodine prophylaxis ' affected also the neonates . A total of 185 r and om urine sample s were collected from 90 full term and 65 preterm neonates in Brussels on day 5 and repeated on day 30 in 30 preterms who were bottle-fed with iodine-enriched formula-milk . The iodine content was also determined in 58 sample s of breast-milk on day 5 . The median urinary iodine on day 5 in full term neonates was 86 µg/l , which is markedly higher than the figure of 48 µg/L reported 15 years previously in neonates in the same area but still much lower than normal for this age group ( 150–200 µg/l ) . The mean iodine content of breast-milk was 78 µg/l , which is unchanged as compared to 15 years ago and is about 66 % of normal . Finally , the median urinary iodine increased from 60 µg/l on day 5 to 150 µg/l on day 30 in preterms bottle-fed with iodine-enriched formula-milk . Conclusion : the status of iodine nutrition has also improved spontaneously in Belgian neonates but has not yet normalised . Lactating and probably pregnant women remain clearly iodine deficient . The iodine-enriched formula-milk for preterms is efficient in correcting their iodine deficiency . National measures are urgently required for correction of iodine deficiency in Belgium OBJECTIVE To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense , thereby reducing both the incidence and severity of  necrotizing enterocolitis ( NEC ) in preterm neonates . STUDY DESIGN Neonates < or = 1500 g birth weight were r and omized to either receive a daily feeding supplementation with a probiotic mixture ( Bifidobacteria infantis , Streptococcus thermophilus , and Bifidobacteria bifidus ; Solgar , Israel ) of 10(9 ) colony forming units (CFU)/day or to not receive feed supplements .  NEC was grade d according to Bell 's criteria . RESULTS For 72 study and 73 control infants , respectively , birth weight ( 1152 + /- 262 g vs 1111 + /- 278 g ) , gestational age ( 30 + /- 3 weeks vs 29 + /- 4 weeks ) , and time to reach full feeds  ( 14.6 + /- 8.7 days vs 17.5 + /- 13.6 days ) were not different . The incidence of NEC was reduced in the study group ( 4 % vs 16.4 % ; P=.03 ) . NEC was less severe in the probiotic-supplemented infants ( Bell 's criteria 2.3 + /- 0.5 vs 1.3 + /- 0.5 ; P=.005 ) . Three of 15 babies who developed NEC died , and all NEC-related deaths occurred in control infants . CONCLUSION Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population 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 BACKGROUND AND AIM Intestinal flora of preterms , dominantly presents with decreased amounts of physiological microbiota . This double blinded r and omized control trial compared the stool of bottle fed preterms , r and omized to receive lactobacillus rhamnosus GG ( LGG ) 6x109or placebo with formula feeding . STUDY DESIGN 46 enterally fed preterms were r and omized to receive probiotics or placebo within 0 - 3days after birth . All personnel were blinded to treatment assignment . Faecal sampling  was preformed at day 7 , 21 , 42 . Presence of LGG colonization , somatic growth and length of hospital stay were recorded . RESULTS 60 patients were initially identified and enrolled but after exclusion criteria were applied , 21 babies were analyzed in the probiotic group and 26 in the placebo group . The number of lactobacillus were significantly higher ( p=0.014 ) on day 7 , and 21 ( p=0.024 ) in the study group , and so was the number of enterobacteriaceae on all study days ( p=0.004 , p=0.000 , p=0.000 ) , and Enterococcus sp on day 21 ( p=0.000 ) . The amount of sample s positive for staphylococci was significantly higher in the study group , on days 7 and 42 ( p=0.001 and 0.011 ) . We did not show a significant difference in weight gain upon discharge between the groups p=0.567 , 95 % CI ( -168 ; 305 ) or mean of hospital stay p=0.421 95 % CI ( -13.43;5.71 ) . CONCLUSIONS A preterm infant formula with an addition of probiotics leads to a rapid growth of LGG in the gut of bottle fed infants , but does not decrease the amount of pathogenic organisms , nor increase weight gain during enteral feeding , or decrease length of hospital stay 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 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 To determine the response of the preterm infant 's intestine to entire feedings at different postnatal ages , we recorded results of manometry of the gastroduodenum and determined fasting plasma concentrations of gastrin , gastric inhibitory peptide , neurotensin , and peptide YY three times in each of two groups : 27 preterm infants were r and omly assigned to receive hypocaloric enteral nutrition on postnatal days 3 to 5 ( early feeding ) or on  days 10 to 14 ( late feeding ) . Initial observations ( study 1 ) were performed by the fifth postnatal day ; study 2 was performed on days 10 to 14 , and study 3 on days 24 to 28 . Early-fed infants received hypocaloric feedings immediately after study 1 ; late-fed infants did not receive enteral feedings until the completion of study 2 . Although motor activity and fasting gastrointestinal peptide concentrations did not differ between groups at study 1 , at study 2 early-fed infants had significantly more mature motor patterns than did babies not being fed . Early-fed infants also had significantly higher plasma concentrations of gastrin and gastric inhibitory peptide than did late-fed infants ; neurotensin and peptide YY values were similar in both groups . By the time of study 3 , when late-fed infants had also received enteral feedings , gut development was not different in the two groups . However , early-fed infants were able to tolerate full oral nutrition sooner , had fewer days of feeding intolerance , and had shorter hospital stays . Thus the provision of early hypocaloric nutrition was associated with earlier nutrition of preterm infants ' intestinal function and result ed in improved feeding tolerance . These findings support the use of early feedings in preterm infants The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so , does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae , enterococci , yeasts or staphylococci , and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome . Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge . The infants were r and omised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks . The clinical features of the two groups of infants were similar . Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants . However , colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants Docosahexaenoic acid ( DHA ) is an essential fatty acid ( FA ) important for health and neurodevelopment . Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes . Most supplementation strategies have focused on increasing DHA content in mother ’s milk or infant formula . However , extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA , so blood levels decline rapidly after birth . Our objective was to develop a DHA supplementation strategy to overcome these barriers . This double-blind , r and omized , controlled trial determined feasibility , tolerability and efficacy of daily enteral DHA supplementation ( 50 mg/day ) in addition to st and ard nutrition for preterm infants ( 24–34 weeks gestational age ) beginning in the first week of life .  Blood FA levels were analyzed at baseline , full feedings and near discharge in  DHA ( n = 31 ) or placebo supplemented ( n = 29 ) preterm infants . Term peers ( n = 30 ) were analyzed for comparison . Preterm infants had lower baseline DHA levels ( p < 0.0001 ) . Those receiving DHA had a progressive increase in circulating DHA over time ( from 3.33 to 4.09 wt% or 2.88 to 3.55 mol% , p < 0.0001 ) while placebo-supplemented infants ( receiving st and ard neonatal nutrition ) had no increase over time ( from 3.35 to 3.32 wt% or 2.91 to 2.87 mol% ) . Although levels increased with additional DHA supplementation , preterm infants still had lower blood DHA levels than term peers ( 4.97 wt% or 4.31 mol% ) at discharge ( p = 0.0002 ) . No differences in adverse events were observed between the groups . Overall , daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants Background & Aims : Feeding intolerance because of functional gastrointestinal dysmotility and parenteral nutrition-associated cholestasis ( PNAC ) are common problems in preterm , very-low-birth-weight ( VLBW ) infants . This double-blind , r and omized , placebo-controlled study aim ed to assess the effectiveness of “ high-dose ” oral erythromycin as a prokinetic agent in decreasing the incidence of PNAC . Two secondary end points , including the time to achieve full enteral feeding and the duration of parenteral nutrition , were also evaluated . Methods : Infants consecutively admitted to the neonatal unit were r and omized to receive erythromycin ( 12.5 mg/kg/dose every 6 hours for 14 days ) or an equivalent volume of normal saline ( placebo ) if they attained less than half the total daily fluid intake ( < 75 mL/kg/day ) as milk feeds on day 14 of life . Results : Of 182 VLBW infants enrolled , 91 received erythromycin  . The incidence of PNAC was significantly lower in erythromycin-treated infants ( 18/91 ) compared with placebo infants ( 37/91 ; P = .003 ) . Treated infants achieved full enteral nutrition significantly earlier ( mean , 10.1 ; SE , 1.7 days ; P < .001 ) , and the duration of parenteral nutrition was also significantly decreased by 10 days ( P < .001 ) . Importantly , fewer infants receiving erythromycin had 2 or more episodes of septicemia ( n = 4 ) compared with placebo patients ( n = 13 , P = .03 ) . No serious adverse effect was associated with erythromycin treatment . Conclusions : High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded
Other benefits included fewer episodes of feed intolerance , better weight gain and growth velocity , decreased transition time from orogastric to breast feeds , and increased postpr and ial mesenteric flow .
There were no adverse effects of probiotic supplementation .
Probiotics reduced the time to full enteral feeds  in preterm neonates .
INTRODUCTION The optimization of enteral nutrition is a priority in preterm neonates worldwide .
Probiotics are known to improve gut maturity and function in preterm neonates .
To our knowledge , previous systematic review s have not adequately assessed the effects of probiotic supplementation on enteral nutrition in preterm neonates .
OBJECTIVE We assessed the evidence on effects of probiotics on enteral nutrition in preterm neonates .