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Objective: To evaluate the effect of oral Lactobacillus reuteri (L reuteri) first on the incidence and severity of Necrotising enterocolitis (NEC) and second on sepsis., Design: Prospective randomised controlled study., Setting: Tertiary neonatal intensive care unit., Patients and Interventions: Preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 g were included (n=400). Infants in the first group were given 100 million CFU/day (5 drops) of lyophilised L reuteri (DSM 17938) mixed in breast milk or formula, starting from first feeding until discharge. Participants in the control group were given a placebo., Main Outcome Measures: To determine and compare the frequency of NEC and/or death after 7 days, frequency of proven sepsis, rates of feeding intolerance and duration of hospital stay., Results: There was no statistically significant difference between groups in terms of frequency of NEC stage ≥2 (4% vs 5%; p=0.63) or overall NEC or mortality rates (10% vs 13.5%; p=0.27). Frequency of proven sepsis was significantly lower in the probiotic group compared to the control group (6.5% vs 12.5%; p=0.041). A significant difference was also observed with regard to rates of feeding intolerance (28% vs 39.5%; p=0.015) and duration of hospital stay (38 (10-131) vs 46 (10-180) days; p=0.022)., Conclusions: Our results show that oral L reuteri does not seem to affect the overall rates of NEC and/or death in preterm infants followed up in the neonatal intensive care unit, and significant reductions were observed in the frequency of proven sepsis, rates of feeding intolerance and duration of hospital stay., Trial Registration Number: NCT01531179.

Aim: To evaluate the efficacy of orally administered Saccharomyces boulardii (S. boulardii) for reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low-birth-weight (VLBW) infants., Methods: A prospective, randomised controlled trial was conducted in infants with gestational age ≤32 weeks and birth weight ≤1500 g. The study group received S. boulardii supplementation, and the control group did not. The primary outcomes were death or NEC (Bell's stage ≥2), and secondary outcomes were feeding intolerance and clinical or culture-proven sepsis., Results: A total of 271 infants were enrolled in the study, 135 in the study group and 136 in the control group. There was no significant difference in the incidence of death (3.7% vs. 3.6%, 95% CI of the difference, -5.20-5.25; p = 1.0) or NEC (4.4% vs. 5.1%, 95% CI, -0.65-5.12; p = 1.0) between the groups. However, feeding intolerance and clinical sepsis were significantly lower in the probiotic group compared with control., Conclusion: Although Saccharomyces boulardii supplementation at a dose of 250 mg/day was not effective at reducing the incidence of death or NEC in VLBW infants, it improved feeding tolerance and reduced the risk of clinical sepsis., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: The pathophysiology of necrotizing enterocolitis (NEC) includes the massive production of endogenous cytokines with exaggerated activation of inflammatory pathways. Colchicine has been used as an anti-inflammatory agent. The aim of this study was to investigate the possible beneficial effects of colchicine in a neonatal rat model of NEC., Materials and Methods: We randomly divided rat pups into three groups: a control group, a saline-treated NEC group, and a colchicine-treated NEC group. We induced NEC by hyperosmolar enteral formula feeding and exposure to hypoxia/reoxygenation after cold stress. Intestinal samples were harvested for biochemical and histopathologic analyses., Results: The grade of intestinal injury of pups in the saline-treated NEC group was significantly higher than in the control and colchicine-treated groups (P < 0.001 and 0.003, respectively). The median level of intestinal malondialdehyde was significantly higher in the saline-treated NEC group compared with the control group (P = 0.006) or the colchicine-treated NEC group (P = 0.015). We observed significantly higher activity levels of intestinal superoxide dismutase and glutathione peroxidase in the colchicine-treated NEC group compared with the saline-treated NEC group (P = 0.033 and 0.030, respectively). The tissue levels of tumor necrosis factor-α and interleukin-1β were significantly higher in the saline-treated NEC group compared with the colchicine-treated NEC group (P < 0.001 and 0.003, respectively)., Conclusions: We observed that in this model of NEC, colchicine had favorable effects on intestinal histologic and biochemical changes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators., Objectives: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC)., Methods: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4°C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis., Results: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-α levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001)., Conclusions: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To investigate the value of fecal calprotectin in diagnosis and predicting severity of necrotizing enterocolitis (NEC) in preterm infants., Methods: A prospective controlled study was conducted including preterm infants with stage 2 to 3 NEC, and birth weight and gestational age-matched controls. Fecal samples were obtained both at the time of NEC diagnosis and 3-5 days later from the patients, and at similar postnatal age from controls., Results: Twenty-five infants with stage 2 to 3 NEC and 25 controls were enrolled. Median fecal calprotectin concentrations were 1,282 and 365 µg/g at diagnosis in infants with NEC and controls, respectively. Fecal calprotectin levels of infants with NEC were significantly higher than those of the control group both in the first and second samples. Although the fecal calprotectin levels gradually decreased from the time of diagnosis to the second sampling time in stage 2 NEC, in stage 3 NEC fecal calprotectin concentrations increased to a higher level. A fecal calprotectin value of 792 µg/g was found to be 76% sensitive and 92% specific for the diagnosis of definite NEC., Conclusion: Fecal calprotectin increases in infants with NEC and serial measurements may be useful as a noninvasive prognostic marker for progression of disease.

Objective: Our aim was to determine the relationship between red blood cell transfusion and necrotising enterocolitis (NEC) in all admitted very low birth weight (VLBW) infants with or without transfusion., Study Design: All VLBW neonates were categorised into five groups: (i) subjects that developed NEC <48 h after transfusion (n = 15); (ii) subjects that developed NEC >48 h after transfusion (n = 31); (iii) subjects that were never transfused but developed NEC, (n = 50); (iv) subjects that were transfused but did not develop NEC, (n = 250) and (v) subjects that were neither transfused nor developed NEC (n = 301)., Results: A group of 647 infants were enrolled in the study. Mean gestational age and birth weight of the patients were 29 ± 3.1 weeks and 1157 ± 237 g, respectively. The mean age at the onset of NEC in the NEC groups were 20 ± 2.3 days, 12 ± 3 days and 11 ± 2.6 days, respectively (P < 0.05). The mean interval from the last transfusion to the onset of NEC was 16.8 ± 8.8 h in group 1 and 240 ± 50 h in group 2 (P < 0.05)., Conclusion: In this study, we sought to evaluate all VLBW infants, whether they received a transfusion or not. We suggest that transfusion associated NEC exists, but many other factors influence this multifactorial disease. The age of NEC onset was later in transfused vs non-transfused patients, whereas the interval between transfusion and NEC was shorter in transfused vs non-transfused patients., (© 2012 The Authors. Transfusion Medicine © 2012 British Blood Transfusion Society.)

Background/purpose: Hypoxia and ischemia appear to play an important role in the pathogenesis of necrotizing enterocolitis (NEC), which may be related to oxygen-derived free radical formation. This study was designed to evaluate the role of oxidative stress and potentially beneficial effects of N-acetylcysteine (NAC) in a neonatal rat model of NEC., Methods: Thirty Wistar albino rat pups were randomly divided into 3 groups: group 1, control; group 2, NEC and saline; and group 3, NEC and NAC treatment. Necrotizing enterocolitis was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at 4°C and oxygen. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis., Results: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than that in other groups (P ≤ .05). Intestinal superoxide dismutase activities in group 3 were significantly higher than that in group 2 (P = .018). Intestinal tissue tumor necrosis factor α levels were significantly reduced with NAC treatment in group 3 compared with group 2 (P < .003)., Conclusions: It is likely that oxidative stress and inflammatory mediators contribute to the pathogenesis of NEC and that NAC has a protective effect on intestinal injury through its antiinflammatory and antioxidant properties., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 prospective follow-up study was conducted in a cohort of VLBW preterm infants enrolled in a randomized 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 standard 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., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Oxidative stress has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). In this study, we compared the global oxidant/antioxidant status by measuring total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in preterm infants with NEC and with control preterms., Methods: Forty-one preterm neonates with NEC (stage 1 [group 1; n = 23] and stages 2 and 3 [group 2; n = 18]) and age-matched 36 healthy preterm controls (group 3) were included in this study. Blood samples were obtained both at the time of NEC diagnosis and 72 hours after for the evaluation of TAC and TOS. Serum levels of TAC, TOS, and OSI in patients with NEC were compared with controls., Results: Demographic characteristics were comparable in all 3 groups. Preterm neonates in group 2 (with stages 2 and 3 NEC) had the highest TOS levels and OSI (P < .001 vs both groups 1 and 3). There was no difference in TAC levels among the groups (P = .26)., Conclusions: Our findings demonstrated that although TAC levels were similar in all 3 groups, oxidant stress mechanisms were activated in preterm neonates with definite NEC (stages 2 and 3 NEC). Premature neonates with increased levels of TOS and OSI were associated with severity of NEC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/aim: Intestinal fatty acid binding protein (I-FABP) is found within cells at the tip of the intestinal villi, an area commonly injured in necrotizing enterocolitis (NEC). In this study, we aimed to investigate the value of serum I-FABP in early diagnosis and predicting severity of NEC., Methods: This prospective study was conducted between April 2009 and November 2009. The preterm infants with suspected NEC were included in the study. These infants were divided into two groups according to their final diagnoses; Group 1: Stage 1 NEC and Group 2: Stages 2-3 NEC (Group 2a: Stage 2 NEC, Group 2b: Stage 3 NEC). Healthy preterms were assigned to control group (Group 3). Serial blood samples were obtained from the patients at symptom onset, 24h and 72 h later. One blood sample was taken from the controls. Serum I-FABP levels were compared among the groups., Results: Initial serum I-FABP concentrations were 324.0±165.8 pg/ml, 764.7±465.1 pg/ml, and 360.2±439.5 pg/ml in Group 1, Group 2a, and Group 2b, respectively, and all were significantly higher than those of the control group (76.9±115.9 pg/ml) (p<0.001). The serum I-FABP levels gradually decreased from the onset of the disease to 72nd hour in Group 1 and Group 2a (p=0.001). In Group 2b I-FABP concentrations slightly decreased at 24th hour of the disease and increased thereafter, but the difference was not significant (p=0.06)., Conclusion: Serial measurements of I-FABP levels may be a useful marker for early diagnosis and prediction of disease severity in NEC., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background/objective: 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., Subjects/methods: 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)., Results: 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)., Conclusions: 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)