Incidence Of Necrotizing Enterocolitis Research Articles

Next-Generation Probiotic Therapy to Protect the Intestines From Injury.

Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. Some strains of the probiotic Lactobacillus reuteri (L. reuteri) have both antimicrobial and anti-inflammatory properties that may be exploited for the treatment and prevention of different gastrointestinal diseases, including necrotizing enterocolitis (NEC) and Clostridioides difficile (C. difficile) infection. Our laboratory has developed a new delivery system for L. reuteri in which the probiotic is incubated with biocompatible, semipermeable, porous dextranomer microspheres (DM) that can be loaded with beneficial and diffusible cargo. L. reuteri can be induced to form a biofilm by incubating the bacteria on the surface of these microspheres, which enhances the efficacy of the probiotic. Loading the DM with sucrose or maltose induces L. reuteri to produce more biofilm, further increasing the efficacy of the probiotic. Using a rat model of NEC, L. reuteri administered in its biofilm state significantly increases animal survival, reduces the incidence of NEC, preserves gut barrier function, and decreases intestinal inflammation. In a murine model of Clostridiodes difficile infection, L. reuteri administered in its biofilm state decreases colitis when administered either before or after C. difficile induction, demonstrating both prophylactic and therapeutic efficacy. There are currently no FDA-approved probiotic preparations for human use. An FDA-approved phase I clinical trial of L. reuteri in its biofilm state in healthy adults is currently underway. The results of this trial will be used to support a phase 1 clinical trial in neonates, with the goal of utilizing L. reuteri in its biofilm state to prevent NEC in premature neonates in the future.

Risk factors of necrotizing enterocolitis-related mortality in preterm neonates: a preliminary prospective study

Background Necrotizing enterocolitis (NEC) is a prematurity-related complication of the gastrointestinal tract that affects 3-15% of preterm infants. Due to its atypical signs and symptoms, NEC is often diagnosed late, leading to mortality and morbidity.
 Objective To describe the incidence, characteristics, and survival rate of preterm infants with NEC in the Neonatal Unit of Cipto Mangunkusumo Hospital.
 Methods This prospective cohort study was conducted on preterm infants born in Cipto Mangunkusumo Hospital in 2019 who had NEC Bell stage 2 or higher. Subjects were recruited consecutively. NEC was classified into either early-onset (<14 days of life) or late-onset (?14 days of life). We identified the risk factors of mortality and survival using multiple Cox regression.
 Results Within the study period, 55/639 preterm infants born in Cipto Mangunkusumo Hospital were diagnosed with NEC. Mean gestational age was 31.16 (SD 2.63) weeks and mean birth weight was 1,378.12 (SD 438.26) grams. The median age at NEC diagnosis was 6 (range 0-24) days. The most common symptoms were gastrointestinal bleeding (29.09%) and abdominal distension (29.09%). Plain abdominal radiographs showed dilated bowels in 92.72%, thickened intestinal walls in 83.63%, and pneumatosis intestinalis in 61.81% of subjects. Positive blood cultures were found in 63.63% of subjects, with Staphylococcus epidermidis and Klebsiella pneumoniae being the predominant organisms. Median survival was 27 days and 31 days for infants born at <32 weeks and ?32 weeks gestational age, respectively (P=0.37). Median survival was 27 and 28 days in infants with early-onset and late-onset NEC, respectively (P=0.07), and 23 and 28 days in infants with birth weight of <1,000 grams and ?1,000 grams, respectively (P=0.14).
 Conclusion The incidence of NEC among preterm infants born in Cipto Mangunkusumo Hospital in 2019 was 8.6%. The survival rate of infants with NEC was 27.27%. Early-onset and late-onset NEC had similar mortality rates.

Effect of Maternal Diet on Any Necrotizing Enterocolitis in Neonates: A Randomized Double-Blind Study.

Background: The etiology of necrotizing enterocolitis (NEC) is controversially discussed. One of the most recently proposed causes of NEC is an allergy to cow's milk protein. This study was designed to evaluate the effect of a maternal diet without bovine protein on the incidence of any NEC in very low birth weight (VLBW) infants. Materials and Methods: A pilot randomized controlled clinical trial was performed at Akbarabadi Hospital, Tehran, Iran, from December 2019 to July 2020, in women with VLBW infants. One hundred twenty mothers with VLBW neonates were randomly assigned to the intervention or the control group (60 in each). In the intervention group, mothers were given a dairy-free diet during the first 14 days after the newborn's onset of feeding. No special diet was given to the control group. The primary outcome of the study was the rate of any NEC in neonates, which was compared between groups. Any NEC was defined as Bell stage I or greater. Results: The minimum and maximum gestational ages were 26 and 33 weeks, respectively. The minimum birth weight of neonates was 700 g. The two groups did not differ significantly in terms of demographic and preinterventional clinical characteristics. Any NEC was reported in 0% and 10% (5/52) of neonates in the intervention and control groups, respectively; the difference was statistically significant (p = 0.028). The NEC symptoms began ∼34 days after birth. Four cases of NEC were classified as Bell stage I, and one was classified as Bell stage II. No statistical association was registered between sex, gestational age, birth weight, and the onset of feeding with the incidence of any NEC. Conclusion: The use of a cow's milk protein-free diet in mothers and exclusive breastfeeding in preterm VLBW infants may reduce the incidence of NEC. We recommend further studies with larger sample sizes in a multicenter setting. The study was registered at the Iranian Registry of Clinical Trials (IRCT20200415047086N1).

Anti‐CD3 mAb Induced Necrotizing Enterocolitis in Formula‐Fed Neonatal Mice through a Gut Microbiome Colonization Dependent Mechanism

Necrotizing enterocolitis (NEC) is a serious disease that affects the small intestine of premature infants. Previous studies showed that formula feeding is a risk factor for NEC. Furthermore, gut microbiome and T cells are revealed to play a critical role in the pathogenesis of NEC. It has been reported that anti‐CD3 mAb induces T cell activation and small intestinal injury in adult mice. However, how the small intestine of neonatal mice responses to anti‐CD3 mAb treatment is uncertain. In the present study, we aimed to study the susceptibility of dam‐fed and formula‐fed neonatal mice to the anti‐CD3 mAb challenge. For this purpose, mouse pups (P0) were nursed by dam feeding (DF) and formula feeding (FF) respectively. On postnatal day 2, pups were subjected to subcutaneous treatment with 10 mg/kg anti‐CD3ε mAb. They were processed to measure intestinal permeability to FITC‐dextran and euthanized at 24 h after administration of anti‐CD3 mAb. Histology examination showed that FF but not DF pups developed NEC‐like injury in the small intestine after anti‐CD3 treatment. FF Pups were noted to display an increase in mortality, intestinal permeability, and inflammatory mediators upon anti‐CD3 mAb challenge compared to DF pups. Even though the inflammatory markers were increased, the intestinal mucosa in DF pups remains intact after being challenged with anti‐CD3. Remarkably, disruption of postnatal colonization by gavaging streptomycin attenuated NEC incidence in anti‐CD3 mAb‐treated FF pups, suggesting that bacterial colonization plays a role in predisposition of mouse pups by formula feeding to anti‐CD3 mAb‐induced intestinal injury. Taken together, this study provided the first evidence that anti‐CD3 mAb induces NEC‐like injury in neonatal mice receiving FF but not in DF via a microbiome colonization dependent manner. The underlying mechanisms regarding this pathophysiological event are to be studied in the future.

Effect of early feeding regimen in pre-terms with abnormal antenatal dopplers: a prospective analytical COHORT study

Background: 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 various neonatal morbidities.Methods: It was a prospective observational non randomized cohort study. Data was collected prospectively from the NICU records. Neonates fulfilling the inclusion criteria were classified as early feeding regimen and late feeding regimen. A strict feeding regimen was followed. Data was analyzed for primary and secondary outcomes.Results: The 50 neonates were enrolled. Baseline characteristics were comparable. A significantly higher time to full feeds was recorded in the delayed feeding regimen by a mean of 3.9 days. The duration of hospital stay was significantly higher for delayed feeding regimen (+12.7 days). Days of mechanical ventilation were also significantly higher (+1.6 days) in the neonates in delayed feeding group. There was no difference in the incidence of feed intolerance, NEC, incidence of culture positive sepsis and mortality across the two regimens, however neonates in the delayed feeding group needed longer support with parenteral nutrition.Conclusions: Early feeding will lead to earlier time to full feeds and decreased duration of hospital stay without additional increase the incidence of feeding intolerance and NEC in neonates with AEDF/REDF. Individualized feeding strategy in these compromised neonates should be the primary objective to optimize outcomes.

Early Antibiotic Exposure Alters Intestinal Development and Increases Susceptibility to Necrotizing Enterocolitis: A Mechanistic Study.

Increasing evidence suggests that prolonged antibiotic therapy in preterm infants is associated with increased mortality and morbidities, such as necrotizing enterocolitis (NEC), a devastating gastrointestinal pathology characterized by intestinal inflammation and necrosis. While a clinical correlation exists between antibiotic use and the development of NEC, the potential causality of antibiotics in NEC development has not yet been demonstrated. Here, we tested the effects of systemic standard-of-care antibiotic therapy for ten days on intestinal development in neonatal mice. Systemic antibiotic treatment impaired the intestinal development by reducing intestinal cell proliferation, villi height, crypt depth, and goblet and Paneth cell numbers. Oral bacterial challenge in pups who received antibiotics resulted in NEC-like intestinal injury in more than half the pups, likely due to a reduction in mucous-producing cells affecting microbial–epithelial interactions. These data support a novel mechanism that could explain why preterm infants exposed to prolonged antibiotics after birth have a higher incidence of NEC and other gastrointestinal disorders.

Providing the Best Parenteral Nutrition before and after Surgery for NEC: Macro and Micronutrients Intakes.

Necrotizing enterocolitis (NEC) is the main gastrointestinal emergency of preterm infants for whom bowel rest and parenteral nutrition (PN) is essential. Despite the improvements in neonatal care, the incidence of NEC remains high (11% in preterm newborns with a birth weight <1500 g) and up to 20–50% of cases still require surgery. In this narrative review, we report how to optimize PN in severe NEC requiring surgery. PN should begin as soon as possible in the acute phase: close fluid monitoring is advocated to maintain volemia, however fluid overload and electrolytes abnormalities should be prevented. Macronutrients intake (protein, glucose, and lipids) should be adequately guaranteed and is essential in each phase of the disease. Composite lipid emulsion should be the first choice to reduce the risk of parenteral nutrition associated liver disease (PNALD). Vitamin and trace elements deficiency or overload are frequent in long-term PN, therefore careful monitoring should be planned starting from the recovery phase to adjust their parenteral intake. Neonatologists must be aware of the role of nutrition especially in patients requiring long-term PN to sustain growth, limiting possible adverse effects and long-term deficiencies.

The predictors of necrotizing enterocolitis in newborns with low birth weight: A retrospective analysis.

There are needs to investigate the influencing factors of necrotizing enterocolitis (NEC) in low birth weight (LBW) newborns, to provide insights into the clinical management of NEC.This study was a retrospective cohort study. Infants admitted to our hospital from January 1, 2019 to June 30, 2021 were selected. The clinical characteristics of NEC and no-NEC infants were evaluated. Logistic regression analyses were conducted to assess the risk factors of NEC in LBW infants.A total of 192 LBW infants were included, the incidence of NEC in LBW infants was 35.42%. There were significant differences in the congenital heart disease, sepsis, breastfeeding, blood transfusion and probiotics feeding between NEC and no-NEC group (all P < .05), and there were no significant differences in birth weight, gestational age, mother's pregnancy-induced hypertension, premature rupture of fetal membrane, amniotic fluid pollution, fetal asphyxia, neonatal respiratory distress syndrome and mechanical ventilation between NEC and no-NEC group (all P > .05). Congenital heart disease (OR: 2.128, 95% CI: 1.103–3.511), sepsis (OR: 1.630, 95% CI: 1.022–2.549), and blood transfusion (OR: 1.451, 95% CI: 1.014–2.085) were the independent risk factors for NEC in LBW infants, and breastfeeding (OR: 0.494, 95% CI: 0.023–0.928), probiotics feeding (OR: 0.816, 95% CI: 0.782–0.982) were the protective factors for the NEC in LBW infants. The prognosis of NEC infants undergone surgery treatment was better than that of infants undergone conservative treatments (P = .043).The incidence of NEC in LBW is high, which is affected by many factors, and comprehensive interventions targeted on the risk and protective factors should be made to improve the prognosis of LBW infants.

Omitting routine gastric residual checks may help to accelerate enteral feeds and postnatal growth in stable preterm infants.

The prefeed gastric residual check (GRC) when increasing the amounts of feeds given via orogastric and nasogastric tubes as a precaution for necrotizing enterocolitis (NEC) and intestinal intolerance is a routine procedure. However, it is mostly misleading, and recently, there has been a tendency not to check prefeed residuals. We changed our nutrition protocol at the end of 2018 to start minimal enteral feeds (MEFs) and increase feeds without GRCs. We investigated the effects on the incidence of NEC, complications, time to reach full feeds, and growth parameters RESULTS: We compared the results of 60 preterm infants at ≤35 weeks' gestational age (group 1: 2016-2017, cared for with GRC) and 77 preterm infants (group 2: 2019, without routine GRCs). No differences in incidence of NEC and complications were observed. Group 2 started enteral feeds 3 days earlier, reached total feeds 6 days earlier (P < 0.01), and had higher weight (P < 0.01) and head circumference gain (P < 0.01). Extrauterine growth restriction was significantly less for head circumference and also insignificantly less for weight and height. We conclude that starting MEFs earlier and omitting routine GRCs in clinically stable preterm infants accelerate enteral feeds and growth parameters.

Three-hourly versus two-hourly feeding interval in stable preterm infants: an updated systematic review and meta-analysis of randomized controlled trials.

In stable preterm infants (1000-1500g), three-hourly feeding can be followed safely. In infants < 1000g, there is insufficient evidence to advise on an optimal feeding interval, although a 2-h interval might be preferable.Prospero Registration Number: CRD42021246568. • Most of the units follow two-hourly feeding schedules without any evidence. • Recent trials suggest that the three hourly feeding schedules can be safely followed in stable preterm infants. • Low certainty evidence suggests that three-hourly feeding is safe in stable preterm infants (1000-1500 grams). •In infants with birthweight <1000 grams, two-hourly feeding may be considered as it was associated with a shorter time to full feeds in subgroup analysis.

Relationship of Epidermal Growth Factor (EGF) and Insulin-Like Growth Factor-1 (IGF-1) levels in breast milk colostrum with the occurrence of necrotizing enterocolitis in neonates

Background: Colostrum contains various bioactive compounds that have various roles and potentials in preventing the occurrence of necrotizing enterocolitis (NEC). EGF and IGF-1 are growth factors found in breast milk colostrum in the form of polypeptides that play a role in regulating and stimulating cell proliferation and differentiation processes. The purpose of this study was to determine the relationship between EGF and IGF-1 levels in breast milk colostrum with the occurrence of NEC in neonates.&#x0D; Methods: This analytical observational study was conducted at Saiful Anwar Hospital Malang during June-August 2019 on mothers and neonates who were breastfed. Maternal colostrum was collected at 72 hours postpartum, while NEC incidence in infants was determined prospectively. EGF and IGF-1 levels in colostrum were examined using the ELISA method. The data were processed by SPSS 21 program and analyzed using Spearman’s test and logistic regression.&#x0D; Results: 24 mother and baby pair samples were included in the study. The mean level of EGF in maternal colostrum was 466±304 ng/ml, and the mean level of IGF-1 was 1.99±0.96 ng/ml with no significant difference in levels based on gestational age. There is a strong negative correlation between the levels of EGF (r = -0.630; p=0.001) and IGF-1 (r = -0.646; p=0.001) on the occurrence of NEC. With the regression test, there was no significant effect between the levels of IGF-1 (p=0.995) and EGF (p=0.997) on NEC occurrence.&#x0D; Conclusion: EGF and IGF-1 levels have a significant relationship to the occurrence of NEC. The higher levels of EGF and IGF-1 contained in breast milk colostrum reduced the incidence of necrotizing enterocolitis in neonates.

Bifidobacteriumlongum subsp. infantis EVC001 Administration Is Associated with a Significant Reduction in the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants

To assess the effects of Bifidobacteriumlongum subsp. infantis EVC001 (Binfantis EVC001) administration on the incidence of necrotizing enterocolitis (NEC) in preterm infants in a single level IV neonatal intensive care unit (NICU). Nonconcurrent retrospective analysis of 2 cohorts of very low birth weight (VLBW) infants not exposed and exposed to Binfantis EVC001 probiotic at Oregon Health & Science University from 2014 to 2020. Outcomes included NEC incidence and NEC-associated mortality, including subgroup analysis of extremely low birth weight (ELBW) infants. Log-binomial regression models were used to compare the incidence and risk of NEC-associated outcomes between the unexposed and exposed cohorts. The cumulative incidence of NEC diagnoses decreased from 11.0% (n=301) in the no EVC001 (unexposed) cohort to 2.7% (n=182) in the EVC001 (exposed) cohort (P<.01). The EVC001 cohort had a 73% risk reduction of NEC compared with the no EVC001 cohort (adjusted risk ratio, 0.27; 95% CI, 0.094-0.614; P<.01) resulting in an adjusted number needed to treat of 13 (95% CI, 10.0-23.5) for Binfantis EVC001. NEC-associated mortality decreased from 2.7% in the no EVC001 cohort to 0% in the EVC001 cohort (P=.03). There were similar reductions in NEC incidence and risk for ELBW infants (19.2% vs 5.3% [P<.01]; adjusted risk ratio, 0.28; 95% CI, 0.085-0.698 [P=.02]) and mortality (5.6% vs 0%; P<.05) in the 2 cohorts. In this observational study of 483 VLBW infants, Binfantis EVC001 administration was associated with significant reductions in the risk of NEC and NEC-related mortality. Binfantis EVC001 supplementation may be considered safe and effective for reducing morbidity and mortality in the NICU.

Prenatal administration of heparin-binding epidermal growth factor-like growth factor in an experimental model of necrotizing enterocolitis decreased both incidence and severity of the disease.

Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death in premature infants and causes long-term disabilities. Previously, enteral heparin-binding epidermal growth factor-like growth factor (HB-EGF) administered after birth demonstrated decreased incidence and severity of NEC in a neonatal animal model of NEC. We investigated the potential prophylactic strategy of preventing NEC using prenatally administered HB-EGF. An HB-EGF (800 µg/kg/dose) dose was injected into pregnant rats via tail vein or intraperitoneal route 2 hours prior to delivery. After cesarean section (C-section) at 21 days' gestation, the rat pups were subjected to the NEC protocol by inducing stressors: hypoxia, hypothermia, hypertonic feeds, and orogastric gavage of lipopolysaccharide (2 mg/kg). Postnatally, pups were monitored for 96 hours and assessed for the development of clinical and postmortem histological NEC. The experimental NEC incidence in untreated, stressed rat pups was 66%. Compared with untreated pups, the maternal administration of HB-EGF correlated with a significant NEC incidence and severity decrease in rat pups. The strongest decrease was seen when HB-EGF was administered via the intraperitoneal route 2 hours prior to C-section (66% vs 31%, *p<0.05). Prenatal HB-EGF administration significantly increased pups' survival after NEC protocol exposure, with the greatest benefit observed in the group that received HB-EGF intraperitoneally 2 hours before delivery. Prenatal administration of HB-EGF decreases the incidence and severity of NEC, preserves gut barrier function and increases survival. This may represent a novel prophylactic clinical strategy for NEC offered to mothers at risk of delivering a premature infant.

Некротизирующий энтероколит у новорожденных с врожденными пороками сердца: частота и факторы риска

Necrotizing enterocolitis (NEC) is a serious complication in newborns with critical congenital heart disease (CHD), prolonging hospital stay, worsening neurological prognosis, and increasing mortality. The leading role in the pathogenesis of NEC in these infants is the violation of mesenteric perfusion. A decrease in arterial blood oxygenation may be an additional risk factor for intestinal hypoxia. Objective. To assess the incidence and risk factors for NEC in full-term newborns with CHD born in 2019–2021 at the Perinatal Center of Almazov National Research Medical Center. Patients and methods. The article presents an analysis of the frequency and risk factors of NEC in children with CHD born at the Almazov National Medical Research Centre in 2019–2021. In the group of critical and duct-dependent CHD (n = 264), the overall incidence of NEC was 15.9% (42 cases). The frequency of surgical stages of NEC (IIIA) was 1.1% (3 cases). In the preoperative period, there was a trend towards a higher frequency of inotropic therapy in a subgroup of children who subsequently developed NEC. NEC in newborns with duct-dependent CHD developed mainly in the early postoperative period after cardiac surgery. In children with duct-dependent pulmonary blood flow, a higher incidence of NEC after surgery was noted compared to children with duct-dependent systemic blood flow. Conclusion. Risk factors for NEC in the postoperative period were arterial hypotension and hemodynamically significant cardiac arrhythmias. Dysbiosis of the gut microbiota and changes in microbial metabolism may be additional risk factors for NEC in children with CHD. Key words: necrotizing enterocolitis, risk factors, congenital heart disease, cardiopulmonary bypass, intestinal microbiome, metabolomics

Современные подходы к профилактике некротизирующего энтероколита у недоношенных новорожденных

Necrotizing enterocolitis (NEC) is the most life-threatening disease of the gastrointestinal tract in newborns. Current strategies and methods of NEC prevention affect the pathogenetic mechanisms of the disease development. The promotion of breastfeeding and the use of early minimal enteral nutrition with native breast milk are the main links in prevention. Immunoglobulins, antiinflammatory cytokines, and other biologically active substances found in breast milk prevent the development of NEC. A change in diet and the use of donor milk lead to a decrease in the incidence of NEC. The use of antenatal steroids in women at risk of preterm birth, control of hypoxia and normalization of the respiratory parameters also reduce the risk of NEC development. For normal colonization of the intestine, the use of probiotics is recommended. The use of oral antibacterial drugs, which are recommended in some multicomponent methods of prevention, often leads to negative results. The use of oral antifungal drugs in modern neonatology is not excluded. The use of oral immunoglobulins is ineffective. Key words: necrotizing enterocolitis, breast milk, enteral antibiotics, oral antifungal drugs, probiotics

Effect of human milk enriched with human milk-based fortifier (HMBF) versus bovine milk-based fortifier (BMBF) on growth and morbidity among very low birth weight (VLBW) infants – A randomized controlled trial

Introduction: Survival of preterm neonates increased dramatically with the advancement in neonatology services. These infants have high nutritional demands for optimal growth, and human milk alone is insufficient to meet their needs. Hence, fortification of milk has become the standard of care. Bovine milk-based fortifiers (BMBF) are commonly used, but there exists concern regarding the exposure to cow milk protein. Human milk-based fortifier (HMBF) use offers a theoretical advantage from the immunological and gastrointestinal standpoint. We intend to study the effects of HMBF compared to BMBF on growth and morbidity of preterm neonates. Methodology: It is a single-centre, open-labelled, randomized controlled trial (RCT) enrolling very low birth weight (VLBW) neonates of less than 34 weeks of gestation weighing between 1,000 and 1,500 g. Only human milk was used, and infants were randomized to receive either fortifier after reaching 100 ml/kg/day of enteral feeds. Growth and morbidity of preterm neonates were analysed. Results: A total of 50 infants were enrolled (25 in each arm). Weight gain (21.42 vs. 20.84 g/day, p = 0.77) and growth velocity (16.45 vs. 15.85 g/kg/day, p = 0.57) were similar in both groups with no statistical difference. Sepsis (relative risk [RR] = 0.6), feed intolerance (RR = 0.57), necrotizing enterocolitis (NEC) (RR = 0.33) and duration of hospital stay (33 vs. 36 days) were better in the HMBF group than in the BMBF group. Conclusion: Growth velocity was similar in both groups. However, HMBF was well tolerated by neonates with lesser incidence of feed intolerance, NEC, sepsis, and lesser hospital stay duration than in neonates supplemented with BMBF. Given the fewer number of studies, there is a need for well-powered RCTs with a good sample size to fill the knowledge gap.

The impact of a multifaceted quality improvement program on the incidence of necrotizing enterocolitis in very low birth weight infants

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease which mostly occurs in very low birth weight (VLBW) infants. In addition to decreasing gestational age (GA) or birth weight (BW), artificial formula, delayed initiation or rapidly advanced feeding, severe anemia and systemic infections were associated with NEC. Several studies demonstrated that breast milk, standardized feeding advancement regimens and treatment of anemia are associated with less incidence of NEC. It is not known if including all these interventions in one multifaceted program will lead to significant reduction in NEC. The NICU team at The George Washington University Hospital created a multifaceted interdisciplinary quality improvement project to tackle several aspects of NEC prevention that addressed researched risk factors for NEC. The program was made of four quality improvement protocols: 1) Standardized Structured Feeding Program, 2) Feeding Intolerance Management Algorithm, 3) Enteral Osmolality Control Tool, and 4) Packed Red Blood Cell (RBC) Standardized Transfusion Protocol. This time-series, quasi experimental study design examined the differences in the incidence of NEC between infants with BW < 1500g who were admitted to the GW Hospital NICU before and after the program implementation. Data from 408 VLBW infants were included in the study. Although not statistically significant, there was a decreasing trend of NEC incidence in the post-implementation group (n=199) compared to the pre-implementation group (n=209), (3.5% vs. 5.3%, p=0.88). The trend in the incidence of NEC declined further after the introduction of RBC transfusion protocol which was introduced ten month after starting the other elements of the program. Integration of the multifaceted quality improvement program may be associated with a decline in the occurrence of NEC. Further analysis with a larger sample size is required to determine if the changes seen are statistically significant.

The effect of daily probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight

Background:Necrotizing enterocolitis remains a leading cause of morbidity and mortality in premature infants. The role of prophylactic probiotics in its prevention is unclear. This study evaluates the effect of routine probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight in the neonatal intensive care unit.Methods:This retrospective cohort study compared infants cared for at a single institution before and after implementation of routine probiotic administration (2014– 2018). Babies born after July 2016 received probiotics containing Bifidobacterium and Lactobacillus daily until 35 weeks corrected gestational age. Baseline characteristics, necrotizing enterocolitis incidence and severity, infections, mortality, and length of stay were compared between groups.Results:Of the 665 infants included in the study, 310 received probiotics and 355 did not. The 2 groups did not differ with regard to gestational age, birth anthropometrics, mode of delivery, comorbidities, and type of enteral feed. The incidence of necrotizing enterocolitis (Bell’s stage 2 of 3) was similar between groups (4% v. 5%, p = 0.35), as was its severity (p = 0.10). In addition, there were no significant differences in mortality and length of stay between the groups. Significantly fewer infants receiving probiotics developed infections (27% v. 34%, p = 0.046), with the rate of urinary tract infections having the largest reduction.Conclusion:The routine use of Bifidobacterium and Lactobacillus probiotics in infants with very low birth weight did not significantly affect the incidence and severity of necrotizing enterocolitis. However, the use of probiotics was associated with fewer overall infections.

The Administration of Probiotics in Extremely Low-Birth-Weight Infants and the Incidence of Necrotizing Enterocolitis and Mortality: A Systematic Review

Encouraging findings were previously demonstrated in a previous meta-analysis that analyzed the results of randomized controlled trials (RCTs) that investigated the potential favorable effects of probiotics administration in preterm infants to prevent necrotizing enterocolitis (NEC) and feeding intolerance. This evidence has only been linked to low birth-weight infants (&lt;1000 g), while evidence regarding the impact of administration of these modalities for Extremely Low-Birth-Weight Infants (ELBW) infants is still controversial among the different studies in the literature. A systematic review was conducted to retrieve all the relevant randomized controlled trials in the literature that investigated the impact of probiotics administration on the different outcomes in ELBW infants, including the incidence of mortality and NEC. A thorough search was then conducted through the different databases to find the relevant articles.A total of 11 RCTs were included in the present systematic review. All articles were published between 2007 and 2021, with a total of 3225 ELBW infants were included in both the intervention and control groups across the different included trials. Our results indicate that the administration of these modalities does not have a significant impact on these outcomes. However, it has been reported that they enhance the growth rate, especially head growth circumference, which has been reported to be superior to the placebo effect. Further investigations for ELBW should be encouraged to furtherly validate these modalities, although no adverse events have been reported for their administration among trials in the current systematic review.

Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial—the N-forte trial

IntroductionThe mortality rate of extremely low gestational age (ELGA) (born <gestational week 28+0) infants remains high, and severe infections and necrotising enterocolitis (NEC) are common causes of death. Preterm infants...