Necrotizing Enterocolitis In Very Low Birth Weight Infants Research Articles

Effects of synbiotics on necrotizing enterocolitis and full enteral feeding in very low birth weight infants: A double-blind, randomized controlled trial.

Necrotizing enterocolitis (NEC) is a multifactorial disease primarily affecting infants with very low birth weight (VLBW). Research has shown that the pathogenesis of NEC is associated with abnormal bacterial colonization. Synbiotics, dietary supplements containing probiotics (beneficial bacteria) and prebiotics (non-digestible food), can alter the gut microbiome. A double-blind, randomized controlled trial was conducted to assess the efficacy of PediLact®, an oral drop multi-strain synbiotic containing Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium infantis, on nutritional parameters and the occurrence of NEC in VLBW neonates. In this study, 118 VLBW neonates from neonatal intensive care units were randomly allocated in a 1:1 ratio to receive either a synbiotic or a placebo. The synbiotic administration continued until the infant was fully fed. The primary outcomes were the occurrence of NEC and the number of days required to achieve full enteral feeding. Log-binomial regression and ANOVA/ANCOVA models were used for analysis. In the group that received the synbiotic, the incidence of NEC decreased significantly (adjusted RR = 0.22, 95% CI: 0.07-0.72, P value = .01; adjusted RD = -0.22, 95% CI: -0.33 to -0.12, P value < .001; NNT = 5). Additionally, feeding intolerance was less frequent in this group (adjusted RR = 0.27, 95% CI: 0.14-0.51, P value < .001; NNT = 3). Furthermore, consumption of the synbiotic was associated with significant weight gain (approximately 40 g) in infants (adjusted SMD = 0.63; 95% CI: 0.26-1.00, P value < .001). The duration of hospitalization and the time required to reach full enteral feeding were also significantly shorter in the synbiotic group (by approximately 3 days). No serious side effects were reported. Prescribing multi-strain synbiotics reduces the incidence of NEC in VLBW infants and has beneficial effects on breastfeeding tolerance and weight gain velocity. Therefore, physicians may consider prescribing synbiotics to VLBW neonates.

Phototherapy: a new risk factor for necrotizing enterocolitis in very low birth weight preterm infants? aretrospective case-control study.

To investigate the association between phototherapy (PT) and the development of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. A retrospective case-control study was conducted on VLBW infants with or without NEC (stage IIA or greater) born at ≤35 weeks' gestation in a tertiary hospital over 7 years. Sample size calculation, trend test, as well as univariate and multiple logistic regression analyses were employed. A total of 824 VLBW infants were reviewed, with 74 cases and 122 controls finally enrolled. The odds of NEC increased with the duration and number of PT sessions. Exposure to >120 h and >4 instances of PT were significantly associated with NEC in multivariate analysis. This is the first study suggesting a potential association between PT and development of NEC in VLBW infants. This association needs further exploration.

Primary Peritoneal Drainage Versus Laparotomy for Perforated Necrotizing Enterocolitis in Very-Low-Birth-Weight Infants: A Retrospective Cohort Study at an Academic Center in Saudi Arabia.

Background and objective Necrotizing enterocolitis (NEC) is a detrimental complication of the gastrointestinal tract amongpreterm infants with very low birth weight (VLBW) and is associated with high morbidity and mortality. About one-third of these cases require surgical intervention due to intestinal perforation. The preferred method for the surgical management of perforated NEC is still a matter of controversy. In light of this, we aimed to compare the outcomes of treating perforated NEC in VLBW infants with primary peritoneal drainage (PPD) versus laparotomy. Method We conducted a retrospective chart review of VLBW infants with perforated NEC treated at King Abdulaziz University Hospital between January 1, 2015, and March 31, 2020. Results Twenty-seven infants with perforated NEC were identified; 12 were managed initially with PPD, and 15 underwent laparotomy. There was no difference between groups in terms of postoperative outcomes, length of hospital stay, or mortality before discharge. Among infants managed with PPD,50%(5/10) underwent second drainage and survived, while 33%(4/12) underwent laparotomy. Conclusion We identified no difference in postoperative outcomes and mortality between managing perforated NEC in VLBW infants with either PPD or laparotomy. However, randomized clinical trials with larger sample sizes and defined outcome measures are needed for reaching definitive conclusions.

Prolonged antibiotic therapy increased necrotizing enterocolitis in very low birth weight infants without culture-proven sepsis.

ObjectivesWe aimed to identify the factors associated with necrotizing enterocolitis (NEC) and to assess the associations of the initial empirical antibiotic therapy (IEAT) duration and antibiotic therapy duration/hospital stay ratio (A/H ratio) before NEC with subsequent NEC in very low birth weight (VLBW) infants with gestational age less than 32 weeks without proven sepsis.MethodsA retrospective study was conducted at the NICU of the First Affiliated Hospital of Medical University of Anhui province from June 2015 to May 2022, and 567 VLBW infants with gestational age less than 32 weeks were included in the study. We divided the VLBW infants into those with and without NEC according to modified Bell’s criteria. We then used descriptive statistics to identify the factors associated with NEC and multivariate analyses to evaluate the associations of IEAT duration and A/H ratio with the occurrence of NEC.ResultsOf the 567 VLBW neonates admitted to our center, 547 survived and reached the normal discharge criteria. Fifty-one infants (8.99%) were diagnosed as showing NEC. Infants with NEC had a longer total parenteral nutrition time, total enteral nutrition time, and IEAT duration, as well as a higher A/H ratio than those without NEC. In multivariate analyses adjusted for the other factors, IEAT duration was associated with an increased odds of NEC [odds ratio (OR) = 1.267; 95% confidence interval (CI), 1.128–1.423], and the A/H ratio was also associated with increased odds of NEC (OR = 8.718; 95% CI, 2.450–31.030). For the A/H ratio, the area under the curve (AUC) was 0.767 and the ideal cutoff was 0.357, and the sensitivity and specificity were 0.843 and 0.645, respectively.ConclusionProlonged antibiotic therapy may increase the risk of NEC in VLBW infants with a gestational age of fewer than 32 weeks and should be used with caution.

Cost-effectiveness of probiotics for necrotizing enterocolitis prevention in very low birth weight infants.

To examine the cost-effectiveness of prophylactic probiotics on necrotizing enterocolitis (NEC) prevention in very low birth weight (VLBW) infants. We built a decision-analytic model using TreeAge. Effectiveness was assessed using quality-adjusted life-years (QALY). Primary outcome was an incremental cost-effectiveness ratio (ICER) expressed as cost per QALY gained. Costs were expressed in 2017 US dollars. Deterministic and probabilistic sensitivity analyses (SA) were performed. For the base case analysis, the ICER of probiotics versus no probiotics for the prevention of NEC in VLBW infants was $1868/QALY. SA revealed that probiotics became cost-saving at a NEC rate of 6.5% and higher or with incremental NEC cost of $37,500 or higher. Our model demonstrated that prophylactic probiotics were a cost-effective strategy in NEC reduction. SA confirmed that the model is customizable to various clinical settings and thus, can aid in understanding the economic impact of this intervention.

Associations between Red Blood Cell Transfusions and Necrotizing Enterocolitis in Very Low Birth Weight Infants: Ten-Year Data of a Tertiary Neonatal Unit.

Background and Objective: Necrotizing enterocolitis (NEC) remains an important cause of mortality in preterm neonates. There are many risk factors for NEC; however, probably the most controversial one is red blood cell transfusions (RBCT). The data concerning the link between NEC and RBCT has been conflicting. Therefore, we aimed to analyze the association between NEC and RBCT in Neonatal Intensive Care Unit (NICU) at the Hospital of Lithuanian University of Health Sciences. Materials and Methods: We used the Very Low Birth Weight (VLBW) Infants database to match all infants with ≥2a Bell’s stage NEC admitted between 1 January 2005 and 31 December 2014 (n = 54) with a control group (n = 54) of similar gestational age and birth weight and without NEC. We analyzed the charts of these infants and performed statistical analysis on 20 clinical variables including RBCT. Results: The main clinical and demographic characteristics did not differ between the two groups. All variables associated with RBCT (receipt of any RBCT, the number of transfusions and the volume transfused in total) were significantly higher in the NEC group both before the onset of NEC and throughout the hospitalization. RBCT increased the odds of NEC even after adjustment for confounding factors. In addition, we found that congenital infection was more abundant in the NEC group and increased the odds of NEC 2.7 times (95% confidence interval CI (1.1, 6.3), p = 0.024). Conclusions: A higher number and the total volume of RBCT are associated with an increased risk of NEC in VLBW infants. The presence of congenital infection might identify the infants at risk.

Efficacy of Bifidobacterium Species in Prevention of Necrotizing Enterocolitis in Very-Low Birth Weight Infants. A Systematic Review.

Necrotizing enterocolitis (NEC) is one of the most common and serious gastrointestinal diseases in preterm infants. The aim of this systematic review examines the effects of probiotics on preventing NEC in very-low birth weight (VLBW) infants with a focus on the Bifidobacterium species and its strains. A systematic review of randomized trials and retrospective studies analyzing the use of probiotics to prevent NEC in VLBW infants was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (1996-2016). Trials reporting NEC involving preterm infants who were given Bifidobacterium alone in the first month of life were included in the systematic review. Nine studies were suitable for inclusion. Nine studies involving VLBW infants were analyzed for strain specific effects of Bifidobacterium for the prevention of NEC ≥ Stage II. B breve showed some benefit in infants < 34 weeks GA with relative risk (RR) of 0.43 (95% confidence interval [CI]: 0.21-0.87) p = 0.019, but not in neonates < 28 weeks. B lactis greatly reduced the incidence of NEC with a RR 0.11 (95% CI: 0.03-0.47), p = < 0.001. B bifidum was not widely studied but resulted in no cases of NEC. Bifidobacterium proved to be statistically significant in reducing the incidence of NEC in preterm infants.

A quality improvement initiative to reduce necrotizing enterocolitis across hospital systems

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local rates of NEC were unacceptably high. We hypothesized that utilizing quality improvement methodology to standardize care and apply evidence-based practices would reduce our rate of NEC. A multidisciplinary team used the model for improvement to prioritize interventions. Three neonatal intensive care units (NICUs) developed a standardized feeding protocol for very low birth weight (VLBW) infants, and employed strategies to increase the use of human milk, maximize intestinal perfusion, and promote a healthy microbiome. The primary outcome measure, NEC in VLBW infants, decreased from 0.17 cases/100 VLBW patient days to 0.029, an 83% reduction, while the compliance with a standardized feeding protocol improved. Through reliable implementation of evidence-based practices, this project reduced the regional rate of NEC by 83%. A key outcome and primary driver of success was standardization across multiple NICUs, resulting in consistent application of best practices and reduction in variation.

Oropharyngeal Administration of Colostrum Increases Salivary Secretory IgA Levels in Very Low-Birth-Weight Infants.

Aim Oropharyngeal administration of colostrum (OAC) has been proposed to provide mother's early milk to very low-birth-weight (VLBW) infants in the first few days of life. The aim of this study was to test the hypothesis that OAC would increase salivary secretory IgA (SsIgA). Patients and Methods Overall, 30 VLBW infants randomized to receive OAC or sterile water had salivary sampling for SsIgA on the day of life (DOL) 2, 7, and 14. The incidence of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) was determined prospectively. Within and between-group comparisons were made by paired and independent samples t-tests. Results Baseline characteristics were similar between groups. SsIgA was higher in OAC versus the control group (p &lt; 0.05) on DOL 7, but not subsequently on DOL 14. There was no difference in LOS or NEC. Conclusion OAC increased SsIgA at DOL 7. A large, multicenter trial is needed to determine if OAC decreases LOS or NEC in VLBW infants.

Probiotics (Lactobacillus acidophilus and Bifidobacterium infantis) prevent NEC in VLBW infants fed breast milk but not formula [corrected

Specific probiotics prevent necrotizing enterocolitis (NEC). A mixture of lactobacilli and bifidobacteria (Infloran) was highly effective in Asian very-low-birth-weight (VLBW) infants. We analyzed the effect of Infloran on NEC, NEC severity, and the influence of enteral feedings (breast milk vs. formula) on NEC prevention in a cohort of European VLBW infants. Infloran was implemented for routine use at our department. VLBW infants receiving probiotics were prospectively followed (2010-2012) and compared with historic controls (2008-2009). Data on NEC, neonatal morbidity, feeding tolerance, and descriptive parameters on NEC cases were analyzed. Infloran had no statistically significant impact on NEC (controls: 24/233 (10.3%); probiotics: 16/230 (7%); P = 0.2). However, NEC was significantly reduced in infants of the probiotics group who were fed any breast milk (20/179 (11.2%) vs. 10/183 (5.5%); P = 0.027), whereas it was ineffective in infants exclusively fed formula (4/54 (7.4%) vs. 6/44 (13.6%); P = 0.345). Occurrence of severe NEC (IIIb), time until full feeds, and gastric residuals were similar. Infloran was of lower efficacy in a European VLBW cohort and showed a reduction of NEC only in infants fed breast milk. Future studies should investigate the influence of feeding formula or breast milk on the effect of probiotics.

Conservative Enteral Feeding Policy and Necrotizing Enterocolitis (NEC) in VLBW Infants: A Single Center Experience

Background: One of the major modifiable risk factor for necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants is related to enteral feeding practices. Objective: The primary outcome was to determine a potential association of slow rates of enteral feed advancement and the incidence of NEC in VLBW infants. Method: Single center retrospective analysis at a tertiary University Children’s

Saccharomyces boulardiifor prevention of necrotizing enterocolitis in preterm infants: a randomized, controlled study

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. A prospective, randomised controlled trial was conducted in infants with gestational age ≤32weeks and birth weight ≤1500g. 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. 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. Although Saccharomyces boulardii supplementation at a dose of 250mg/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.

Probiotics for the prevention of necrotizing enterocolitis in neonates: an 8-year retrospective cohort study

Probiotic therapy has been shown to reduce morbidity and mortality of necrotizing enterocolitis (NEC) in premature infants in several international studies using various probiotic agents. The purpose of this study(*) is to describe our experience of using probiotic therapy in preventing NEC in infants with very low birth weight (VLBW) in a neonatal intensive care unit (NICU) and to evaluate whether our records provide evidence of effectiveness for probiotic therapy. In a retrospective cohort study, the efficacy of probiotic therapy in preventing NEC in VLBW infants was investigated via chart review. A probiotic administration protocol using a three-strain (Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium bifidum) supplement was implemented in August 2007. Patients admitted to the NICU from August 2003 through July 2011 were screened. Primary outcomes are the morbidity and mortality of NEC. The secondary outcomes were severity of NEC and incidence of where infant feeds were stopped but NEC was not diagnosed (NEC scare). There was a significant increased baseline risk of NEC development in the probiotics group, including younger gestational age, higher incidence of patent ductus arteriosus (PDA) and use of indomethacin. The incidence of NEC is similar between the control group (2·8%) and probiotics group (2·4%) (hazard ratio, 1·15; 95% confidence interval [CI], 0·42, 3·12). Mortality of NEC is also not statistically different. Incidence of NEC scare was decreased from 2·8% in control group to 1·4% in probiotics group, although the difference was not statistically significant (P=0·38). Our findings suggest that probiotics are safe in NEC prevention in VLBW infants. We had no cases of infection related to the strains of bacteria used in our product. With the low incidence of NEC (2·8%) and NEC scare (2·8%) in our cohort, we do not have enough power to detect any change in outcome, particularly as our study was observational. However, it is hoped that our data give useful information for others on probiotic prophylactic therapy in the routine clinical management of VLBW infants.

Enteral L‐Arginine Supplementation for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Neonates

Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal disease in premature infants and has high mortality and morbidity. Endothelial nitric oxide is an important regulator of vascular perfusion and is synthetized from the amino acid L-arginine. Hypoargininemia is frequently observed in preterm neonates and may predispose them to NEC. Our objective was to determine the effect of enteral L-arginine supplementation on the incidence and severity of NEC in very low birth weight (VLBW) neonates. We conducted a parallel blind randomized pilot study, comprising VLBW neonates with birth weight ≤1500 g and gestational age ≤34 weeks. VLBW neonates were randomly assigned to receive enteral L-arginine supplementation (1.5 mmol/kg/d bid) between the 3rd and 28th day of life or placebo. Diagnosis and classification of NEC were done according to modified Bell's criteria. Eighty-three neonates were randomized to the arginine (n = 40) or placebo (n = 43) group. No adverse effects were observed in neonates receiving L-arginine supplementation. The incidence of NEC stage III was significantly lower in the arginine-supplemented group (2.5% vs 18.6%, P = .030). Enteral L-arginine supplementation of 1.5 mmol/kg/d bid can be safely administered in VLBW neonates from the 3rd to the 28th day of life. Enteral L-arginine supplementation appears to reduce the incidence of stage III NEC in VLBW infants. Larger studies are needed to further evaluate the effect of L-arginine supplementation in preventing NEC in VLBW infants.

Cord blood epidermal growth factor as a possible predictor of necrotizing enterocolitis in very low birth weight infants

To evaluate epidermal growth factor (EGF) levels in cord blood as a possible marker for predicting the subsequent development of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. A total of 241 VLBW infants (38 infants developed NEC and 203 had no NEC) were enrolled. EGF concentrations were measured by enzyme-linked immunosorbent assay. VLBW infants who subsequently developed NEC had significantly lower cord serum concentrations of EGF than those who did not (p < 0.0001). Moreover, cord blood concentrations of EGF were significantly lower in infants with stage III than those with stage II or I NEC (p < 0.001). Logistic regression analysis demonstrated that low cord blood EGF was independently associated with the subsequent risk of NEC (OR = 0.978 [95% CI: 0.959-0.997]; p = 0.02). Low cord blood EGF concentrations may predict the subsequent development of NEC in VLBW infants.

Ranitidine Therapy Increases the Risk of Sepsis and Necrotizing Enterocolitis in Very Low Birthweight Infants: Prospective Multicenter Study

Background and aims: Gastric acidity is a major non-immune defense mechanism against infections. In adults and children treated with gastric acidity inhibitors (GAI) there is evidence of an increased risk of intestinal and extraintestinal infections. These drugs are being increasingly used in the neonatal period. To investigate the possible association between GAI and infections or necrotizing enterocolitis (NEC) in very-low-birthweight (VLBW) newborns.Methods: VLBW consecutively observed in Neonatal Intensive Care Units for at least 8 weeks were evaluated and the effect of GAI exposure on the rate of infections and NEC was analysed.Results: As many as 274 VLBW infants were evaluated 183 not exposed to GAI and 91 received ranitidine. The main clinical and demographic characteristics were not different between the two groups. The rate of infections was significantly higher in neonates receiving ranitidine (34/91) compared to subjects not receiving GAI (18/183, p< 0.001). The number of infants presenting sepsis (23/91 vs 16/183), pneumonia (4/91 vs 1/183), urinary tract infections (7/91 vs 1/183) was significantly higher in the newborns receiving ranitidine than in controls (p< 0.05). The risk of infections (OR 5.47, 95% CI 2.9-10.4) and NEC (OR 6.58, 95% CI 1.7-25.0) were significantly increased in neonates exposed to ranitidine.Conclusions: Ranitidine therapy is associated with an increased risk of infections and NEC in VLBW infants. Neonatologists need to consider that the benefits of treatment outweigh the potential risk.

Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial

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.

Oral Probiotics to Prevent Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a devastating intestinal condition primarily affecting very-low-birth-weight (VLBW) premature newborns. Some studies have linked it to feeding practices. Evidence from two clinical trials suggests that orally administered probiotics reduce the incidence of NEC in VLBW infants, but the optimal strains, dosage, duration, and timing of treatment have not been determined. Now, in …

Historical Perspectives

Perhaps the least well understood of the disorders of prematurity is necrotizing enterocolitis (NEC). Although it is not certain when this problem initially was observed, it was well described in 1964 by Berdon and coworkers at Babies Hospital in New York, (1) with amplification from the same group in slightly later publications. (2)(3) A group in Seattle also contributed important observations of a significant number of survivors in a comparatively large series (4) and an increased frequency of the disorder in the late 1960s. (5) The role of radiographic interpretation was emphasized in these later reports, with pneumatosis intestinalis considered the hallmark of the disorder. It subsequently was emphasized that a provisional diagnosis was required before pneumatosis was evident to allow for medical rather than surgical intervention. (6) Even in the early reports, the very low-birthweight (VLBW) infant (<1,500 g) born before 32 weeks’ gestation seemed to be particularly susceptible, although larger and more mature infants also could be affected. Both then and now, NEC was and is a disorder of uncertain etiology. (7)(8) The role of bowel ischemia seemed to be paramount, with bacterial infection and method of feeding being other important contributors. Although infection seemed to be important, it was not possible to isolate a responsible organism in many cases. Despite this, the periodicity of the disorder in nurseries and the ability to reduce the incidence by infection control measures (9) was highly suggestive of the potential importance of infection (possibly viral). The ability of human milk to protect against NEC in the VLBW infant is well established, (10) and minimal enteral nutrition over several days also has been shown to decrease the incidence of NEC in VLBW infants. (11) At one point, the idea that NEC was a form of inflammatory …

Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants

Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants