Prophylactic probiotics for prevention of necrotizing enterocolitis in very low birth weight newborns. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial. Effects of bifidobacterium breve supplementation on intestinal flora of low birth weight infants. Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind, placebo-controlled, randomized study. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial. Enteral feeding of premature infants with Saccharomyces boulardii. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Lack of effect of Lactobacillus on gastrointestinal bacterial colonization in premature infants. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Enteral feeding of premature infants with Lactobacillus GG. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates.
Our study showed that enteral administration of prophylactic probiotics in neonatal intensive care setup could significantly reduce morbidity due to necrotising enterocolitis in very low birth weight newborn. It also helps in establishing early full enteral feeding and reduces hospital stay. Colonization by Candida 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 Candida species in preterm, very low birth weight (i.e., < 1500-g) neonates during their stay in a neonatal intensive care unit.
                Over a 12-month period, a prospective, randomized, 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 randomly 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.
                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 Candida strains. No adverse effects potentially associated with the probiotic were recorded.
                Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates. 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.
                A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor), Dicofarm, Rome, Italy) in a dose of 6 x 10(9) colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo.
                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.
                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 populations.
                Copyright 2002 S. Karger AG, Basel Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants.
                To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates.
                Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis.
                Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth).
                First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.
                Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.
                Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates.
                isrctn.org Identifier: ISRCTN53107700. To investigate the colonisation with Bifidobacterium breve of the bowels of very low birthweight (VLBW) infants.
                The adverse effects of B breve were examined in 66 VLBW infants (preliminary study). A prospective randomised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years. Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants. The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody.
                In the preliminary study there were no side effects attributable to the bacteria. Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73% at 2 weeks of age, but only 12% in the control group. Early administration of B breve significantly decreased aspirated air volume from the stomach and improved weight gain.
                B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants, probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules. It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases. Because bacterial populations develop during the first day of life, the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants.
                The effects of oral administration of Bifidobacterium breve (B. breve) supplements were studied in a controlled trial with low birth weight infants (average birth weight 1489 g). The infants were divided into three groups: Group A and B received a dose of 1.6 x 10(8) cells of B. breve supplement twice a day, commencing either from several hours after birth (group A) or 24 h after birth (group B). Group C, the control group, received no supplement.
                There were no significant differences in birth weight, treatment with antibiotics, and the starting time of breast-feeding among the three groups. A Bifidobacterium-predominant flora was formed at an average of 2 weeks after birth in group A and at an average of 4 weeks after birth in group B, while no Bifidobacterium was isolated in eight out of 10 infants in group C during the observation period of 7 weeks. In comparison between group A and B, Bifidobacterium was detected significantly earlier in group A, and the number of Enterobacteriaceae present in the infants at 2 weeks after birth was significantly lower in group A.
                The results of the present study suggest that very early administration of B. breve to low birth weight infants is useful in promoting the colonization of the Bifidobacterium and the formation of a normal intestinal flora. 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, randomized 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 (log(10) values per g of fecal wet weight: probiotic, 8.18 + 0.54 [standard 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 (log(10) 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. The identification of probiotic species involved in gut homeostasis and their potential therapeutic benefits have led to an interest in their use for preventing necrotizing enterocolitis (NEC). Although bifidobacterium and lactobacilli sp. have been used to reduce the incidence of NEC in clinical trials. Lactobacillus sporogenes has not been used in the prevention of NEC in very low-birth weight infants yet. The objective of this study was to evaluate the efficacy of orally administered L sporogenes in reducing the incidence and severity of NEC in very low-birth weight (VLBW) infants.
                A prospective, blinded, randomized controlled trial was conducted in preterm infants with a gestational age of <33 weeks or birth weight of <1500 g. VLBW infants who survived to start enteral feeding were randomized into two groups The infants in the study group were given L. sporogenes with a dose of 350,000,000 c.f.u. added to breast milk or formula, once a day, starting with the first feed until discharged. The infants in the control group were fed without L. sporogenes supplementation. The primary outcome measurement was death or NEC (Bell's stage ≥2).
                A total of 221 infants were studied: 110 in the study group and 111 in the control group. There was no significant difference in the incidence of death or NEC between the groups. Feeding intolerance was significantly lower in the probiotics group than in the control group (44.5% (n: 49) vs 63.1% (n: 70), respectively; P=0.006).
                L. sporogenes supplementation at the dose of 350,000,000 c.f.u/day is not effective in reducing the incidence of death or NEC in VLBW infants, however, it could improve the feeding tolerance.
                © 2011 Macmillan Publishers Limited All rights reserved Saccharomyces boulardii (SB) is a yeast that acts both as a probiotic and as a polyamine producer. Probiotics prevent the overgrowth of pathogens in the gut while polyamines enhance intestinal maturation. The aim of this randomized study was to investigate the ability of SB to modify the gut microbial ecology and its function.
                A total of 87 healthy babies with gestational age 28-32 weeks were studied. They were randomly assigned to receive a preterm formula to which SB or maltodextrins was added for 30 days. Evaluations were made on the following: SB tolerance and weight gain, faecal flora analysis, intestinal D-xylose absorption and faecal lipid excretion.
                SB was well tolerated by the infants. There was no difference in weight gain between the two groups. Median log of colony forming units per gram of faeces for Escherichia coli and enterococci was significantly lower in the SB group [E. coli: 2.67 (0.045) vs. 2.75 (0.058), P<0.001; enterococci: 2.14 (0.359) vs. 2.19 (0.138), P<0.05]. On the other hand, the number of bifidobacteria and staphylococci in the stools was significantly higher in the SB group [bifidobacteria: 2.65 (0.083) vs. 2.27 (0.075), P<0.001; staphylococci: 1.23 (0.869) vs. 0.6 (0.281), P<0.001]. D-Xylose and lipid absorption was not improved by SB [median blood D-xylose: 1.5 (0.4) mmol/l vs. 1.35 (0.3) mmol/l, P>0.1; median stool steatocrit: 64% (3.05%) vs. 65% (2.72%) P>0.5].
                An SB-supplemented formula is well tolerated by preterm infants, it has a beneficial effect on stool flora bringing it closer to that of breast fed babies but it does not improve D-xylose or lipid gut absorption. We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.
                A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (<1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (>or= stage 2).
                Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (>or= stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (>or= stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species.
                Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants. Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms. Thirty premature infants were matched by birth weight and gestational age, randomized and fed double blind either lactobacilli-containing formula or non-lactobacilli-containing formula within 72 hours of delivery. The two study groups were screened weekly by culture for stool lactobacilli, for gram-negative bacteria and for antibiotic resistance of these bacteria. Lactobacilli were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli (P less than 0.001). Gram-negative enteric organisms were isolated during 40 of the 86 weeks (47%) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks (49%) for patients not receiving lactobacilli. There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates (4 of 40 vs. 0 of 28). These results suggest that facultative gram-negative enteric bacterial colonization, with either total or aminoglycoside-resistant strains, is not decreased by oral feedings of Lactobacillus acidophilus in premature infants. 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.
                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.
                In a bicentric, double-blind, randomized 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.
                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.
                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 clinicaltrials.gov as NCT 00290576. The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants.
                A prospective, blinded, randomized, multicenter controlled trial was conducted at 7 NICUs in Taiwan, to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants (birth weight: <1500 g). Very low birth weight infants who survived to start enteral feeding were eligible and were assigned randomly to 2 groups after parental informed consent was obtained. Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus, added to breast milk or mixed feeding (breast milk and formula), twice daily for 6 weeks. Infants in the control group were fed with breast milk or mixed feeding. The clinicians caring for the infants were blinded to the group assignment. The primary outcome measurement was death or necrotizing enterocolitis (Bell's stage >or=2).
                Four hundred thirty-four infants were enrolled, 217 in the study group and 217 in the control group. The incidence of death or necrotizing enterocolitis (stage >or=2) was significantly lower in the study group (4 of 217 infants vs 20 of 217 infants). The incidence of necrotizing enterocolitis (stage >or=2) was lower in the study group, compared with the control group (4 of 217 infants vs 14 of 217 infants). No adverse effect, such as sepsis, flatulence, or diarrhea, was noted.
                Probiotics, in the form of Bifidobacterium and Lactobacillus, fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis. 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 randomised 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. Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae.
                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.
                In a prospective randomized 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.
                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).
                The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth. 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.
                Neonates < or =1500 g birth weight were randomized 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 graded according to Bell's criteria.
                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.
                Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population.