The effect of neutral oligosaccharides on fecal microbiota in premature infants fed exclusively with breast milk: A randomized clinical trial.

OBJECTIVE: This study was designed to compare the efficacy and safety of enteral supplementation of a prebiotic mixture (SCGOS/LCFOS) on faecal microbiota in very premature infants who fed exclusively with human-milk. METHODS: This double-center randomized control trial was conducted from December 2012 to November 2013 in the tertiary Neonatal Intensive Care Units of the Isfahan University of Medical Sciences. Fifty preterm infants (birth weight ≤1500 g who were not fed with formula) were randomly allocated to have enteral (tube feeding) supplementation with a prebiotic mixture (SCGOS/LCFOS; 9:1) or receive no prebiotics. FINDINGS: The primary outcome (e.g., the effect of the prebiotic mixture on fecal microbiota pattern) was clearly different between the two groups. Despite greater coliforms colony counts in first stool cultures in the prebiotic group (Group P) (P = 0.67), coliforms were significantly lower in the third stool cultures in the Group P (P < 0.001). Furthermore, despite the much higher Lactobacillus colony counts, in the first stool cultures, in the control group (Group C) (P = 0.005); there was a trend toward significantly increased Lactobacillus colony counts in the Group P during the study, but the difference between Lactobacillus colony counts, in the third stool cultures, between two groups was no longer statistically significant (P = 0.11). Interestingly, the median length of hospital stay was significantly less in the Group P (16 [12.50-23.50] vs. 25 [19.50-33.00] days; P = 0.003). CONCLUSION: This suggests that it might have been "the complete removal of formula" which manifests a synergistic effect between nonhuman neutral oligosaccharides (prebiotics) and human oligosaccharides, which in turn, led to the rapid growth of beneficial Lactobacillus colonies in the gut of breast milk-fed preterm infants, while decreasing the number of pathogenic coliforms microorganisms. Therefore, further studies with larger sample sizes are recommended to investigate the issue.

Prebiotics for the management of hyperbilirubinemia in preterm neonates.

OBJECTIVE: We evaluated if prebiotics have benefits for the management of hyperbilirubinemia in preterm neonates. METHODS: Preterm neonates were entered into the study when enteral feeding volume met 30 mL/kg/day. They randomly received a mixture of short-chain galacto-oligosacarids/long-chain fructo-oligosacarids or distilled water (placebo) for 1 week. Total serum bilirubin level was measured by transcutaneous bilirubinometry. Stool frequency and meeting full enteral feeding during the study period were considered as secondary outcomes. RESULTS: Twenty-five neonates in each group completed the trial. Bilirubin level was decreased with the prebiotic (-1.3 ± 1.8 mg/dL, p = 0.004), but not placebo (-0.1 ± 3.3 mg/dL, p = 0.416). Peak bilirubin level was lower with the prebiotic than placebo (8.3 ± 1.7 versus 10.1 ± 2.2 mg/dL, p = 0.003). Stool frequency was increased with the prebiotic (0.7 ± 1.9 defecation/day, p = 0.014), but not with placebo (0.6 ± 1.5 defecation/day, p = 0.133). Average stool frequency (2.4 ± 0.4 versus 1.9 ± 0.5 defecation/day, p = 0.003) and frequently of meeting full enteral feeding (60% versus 16%, p = 0.002) were higher with the prebiotic than placebo. CONCLUSIONS: Prebiotic oligosaccharides increase stool frequency, improve feeding tolerance and reduce bilirubin level in preterm neonates and therefore can be efficacious for the management of neonatal hyperbilirubinemia.

The Effect of Neutral Oligosaccharides on Reducing the Incidence of Necrotizing Enterocolitis in Preterm infants: A Randomized Clinical Trial.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most destructive diseases associated with conditions of neonatal prematurity. Supplementation with enteral prebiotics may reduce the incidence of NEC, especially in infants who fed exclusively with breast-milk. Therefore, we compared the efficacy and safety of enteral supplementation of a prebiotic mixture (short chain galacto-oligosaccharides/long chain fructo-oligosaccharides [SCGOS/LCFOS]) versus no intervention on incidence of NEC in preterm infants. METHODS: In a single-center randomized control trial 75 preterm infants (birth weight [BW] ≤1500 g, gestational age ≤34 weeks and were not fed with formula) on 30 ml/kg/day volume of breast-milk were randomly allocated to have enteral supplementation with a prebiotic mixture (SCGOS/LCFOS; 9:1) or not receive any prebiotic. The incidence of suspected NEC, feeding intolerance, time to full enteral feeds, duration of hospitalization were investigated. RESULTS: Differences in demographic characteristics were not statistically important. SCGOS/LCFOS mixture significantly reduced the incidence of suspected NEC, (1 [4.0%] vs. 11 [22.0%]; hazard ratio: 0.49 [95% confidence interval: 0.29-0.84]; P = 0.002), and time to full enteral feeds (11 [7-21] vs. 14 [8-36] days; P - 0.02]. Also duration of hospitalization was meaningfully shorter in the prebiotic group (16 [9-45] vs. 25 [11-80]; P - 0.004]. Prebiotic oligosaccharides were well tolerated by very low BW (VLBW) infants. CONCLUSIONS: Enteral supplementation with prebiotic significantly reduced the incidence of NEC in VLBW infants who were fed exclusively breast-milk. This finding suggests that it might have been the complete removal of formula which caused a synergistic effect between nonhuman neutral oligosaccharides (prebiotic) and human oligosaccharides.