Risk Of Necrotizing Enterocolitis Research Articles

Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis

Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants. To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds. This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023. First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group). The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk. Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group. The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted. ClinicalTrials.gov Identifier: NCT01702805.

A Bayesian Reanalysis of the Overall and Sex-Disaggregated Results of the Neonatal Oxygenation Prospective Meta-Analysis (NeOProM)

Data from the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) indicate that targeting a higher (91–95%) versus lower (85–89%) pulse oximeter saturation (SpO2) range may reduce mortality and necrotizing enterocolitis (NEC) and increase retinopathy of prematurity (ROP). Aiming to re-evaluate the strength of this evidence, we conducted a Bayesian reanalysis of the NeOProM data. We used Bayes factors (BFs) to evaluate the likelihood of the data under the combination of models assuming the presence vs. absence of effect, heterogeneity, and moderation by sex. The Bayesian reanalysis showed moderate evidence in favor of no differences between SpO2 targets (BF10 = 0.30) in death or major disability, but moderate evidence (BF10 = 3.60) in favor of a lower mortality in the higher SpO2 group. Evidence in favor of differences was observed for bronchopulmonary dysplasia (BPD) (BF10 = 14.44, lower rate with lower SpO2), severe NEC (BF10 = 9.94), and treated ROP (BF10 = 3.36). The only outcome with moderate evidence in favor of sex differences was BPD. This reanalysis of the NeOProM trials confirmed that exposure to a lower versus higher SpO2 range is associated with a higher mortality and risk of NEC, but a lower risk of ROP and BPD. The Bayesian approach can help in assessing the strength of evidence supporting clinical decisions.

Biomarkers and predictors of postoperative necrotizing enterocolitis in neonates with duct-dependent congenital heart defects undergoing cardiac surgery: a cohort study

The development of necrotizing enterocolitis (NEC) in neonates with duct-dependent congenital heart defects (CHD) who underwent cardiac surgery is accompanied by high mortality. Analysis of predictors is necessary for understanding the pathophysiology of NEC and development of approaches for prevention to achieve favorable outcomes of cardiac surgery. The purpose of the study was to develop a prognostic model for predicting the development of NEC after cardiac surgery in neonates with duct-dependent CHD. Methods. A prognostic cohort study was performed that included full-term neonates with duct-dependent CHD who underwent cardiac surgery at the Almazov National Medical Research Center from January 2021 to September 2023. The outcome was the development/absence of stage IB-III NEC in the postoperative period. Biomarkers of NEC (intestinal fatty acid binding protein (i-FABP, ng/ml), claudin-3 (CLDN3, ng/ml), calprotectin (CALPR, ng/ml), ischemia modified albumin (IMA, ng/ml), vascular endothelial growth factor A (VEGF A, pg/ml)) were measured by ELISA in the blood serum before cardiac surgery and 12-14 hours after surgery. We also analyzed clinical characteristics of neonates, C-reactive protein levels, complete blood count, abdominal ultrasound, ejection fraction (EF, Teicholtz) in the preoperative and postoperative periods, surgical parameters, P(v-a)CO2/C(a-v)O2 upon arrival from the operating room, vasoactive inotropic score (VIS) and arterial blood lactate levels in the first 24 hours after surgery. The association between predictors and the development of NEC after cardiac surgery was assessed using univariate and multivariate logistic regression analysis. Internal validation of the model was performed using 10-fold cross-validation. Results. During the observation period, 187 neonates underwent surgical treatment of duct-dependent CHD, of which 32 children developed stage IB-III NEC in the postoperative period (17.1%), two neonates required surgical treatment of NEC (6.3%). After meeting the non-inclusion and exclusion criteria, two groups of patients were formed: a main group (30 neonates who developed stages IB-III NEC in the postoperative period, of which stage III NEC was in one neonate) and a comparison group (40 neonates without NEC). Groups were comparable by types of CHD. Predictors associated with NEC (univariate analysis): intrauterine growth retardation (IUGR), formula feeding before surgery, high levels of IMA before on the first postoperative day (POD), procedures performed before surgery (Rashkind procedure/valvuloplasty/stenting), lower EF in in the early postoperative period, a higher maximum level of VIS in the first 24 hours after surgery, as well as a higher level of IR in the superior mesenteric artery (SMA) and thickening of the intestinal wall on the first postoperative day (POD) Independent preoperative predictors of NEC (AUC of model 0.885, specificity 0.867): IUGR (OR 32.2 (1.4-730.3), p=0.029), formula feeding (OR 12.6 (2.6-60.2), p=0.002), IMA level before surgery (OR 1.03 (1.01-1.04), p=0.004), CLDN3 level before surgery (OR 0.5 (0.3-0.9), p=0.013). Independent early postoperative predictors of NEC: IMA level on 12-14 hour after surgery (OR 1.02 (1.01-1.03), p=0.030), P(v-a)CO2/C(a-v)O2 immediately after surgery (OR 2.3 (1.2-4.4), p=0.008), IR>0.93 in SMA (OR 7.2 (1.6-32.4), p=0.011) and thickness of intestinal wall by ultrasound on POD 1 (OR 4.9 (1.3-19.2), p=0.021). Adding of VEGF A level (12-14 hour after surgery, negatively associated with NEC) to the model increased the specificity, but the predictor was not significant. AUC of postoperative model 0.862, specificity 0.800. The final model included preoperative (IUGR, formula feeding) and postoperative predictors (IMA, P(v-a)CO2/C(a-v)O2, IR of SMA>0.93, intestinal wall thickness), AUC=0.921, specificity 0.83. Conclusion. The identified predictors indirectly indicate the role of hypoxia in the pathophysiology of NEC in term neonates with duct-dependent CHD. Breast milk feeding/mixed feeding in the preoperative period may help reduce the risk of NEC in the postoperative period. Low levels of CLDN3 before surgery were associated with the development of NEC, but the interpretation of the result is controversial.

Analysis of Risk Factors for Necrotizing Enterocolitis (NEC) in Newborns: A Systematic Literature Review

Necrotizing enterocolitis (NEC) is a serious condition in newborns involving inflammation and intestinal necrosis. A number of risk factors have been identified, which complexly interact and contribute to the development of this condition. An in-depth understanding of these risk factors has major implications for the prevention, diagnosis and management of NEC in newborns. Babies born prematurely, especially before 32 weeks' gestation, have a higher risk of developing NEC. Low birth weight, regardless of prematurity status, remains a significant independent risk factor. Imbalances in blood circulation, especially in the intestines, can increase the risk of NEC. Hypotension and other medical conditions that affect blood flow to the intestines can be potential triggers. Infection and inflammation, both systemic and local, play a central role in the development of NEC. Bacterial contamination in the digestive tract can trigger an inflammatory response that contributes to the pathophysiological process of NEC. Formula feeding, especially in premature infants, is associated with an increased risk of NEC. The importance of providing exclusive breastfeeding and introducing foods slowly to protect the newborn's intestinal health. Excessive use of antibiotics or without clear indications can change the balance of intestinal microflora and increase the risk of NEC. The importance of judicious selection and use of antibiotics to minimize negative impacts on gut health.

Clinical Dilemma Involving Treatments for Very Low-Birth-Weight Infants and the Potential Risk of Necrotizing Enterocolitis: A Narrative Literature Review.

Necrotizing enterocolitis (NEC) is a critical gastrointestinal emergency with substantial morbidity and mortality risks, especially for very low-birth-weight (VLBW) infants, and unclear multifactorial pathophysiology. Whether common treatments for VLBW infants increase the NEC risk remains controversial. Indomethacin (utilized for patent ductus arteriosus) offers benefits but is concerning because of its vasoconstrictive impact on NEC susceptibility. Similarly, corticosteroids used to treat bronchopulmonary dysplasia may increase vulnerability to NEC by compromising immunity and altering the mesenteric blood flow. Histamine-2 receptor blockers (used to treat gastric bleeding) may inadvertently promote NEC by affecting bacterial colonization and translocation. Doxapram (used to treat apnea) poses a risk of gastrointestinal disturbance via gastric acid hypersecretion and circulatory changes. Glycerin enemas aid meconium evacuation but disrupt microbial equilibrium and trigger stress-related effects associated with the NEC risk. Prolonged antibiotic use may unintentionally increase the NEC risk. Blood transfusions for anemia can promote NEC via interactions between the immune response and ischemia-reperfusion injury. Probiotics for NEC prevention are associated with concerns regarding sepsis and bacteremia. Amid conflicting evidence, this review unveils NEC risk factors related to treatments for VLBW infants, offers a comprehensive overview of the current research, and guides personalized management strategies, thereby elucidating this clinical dilemma.

Efficacy and Safety of Bifidobacterium longum Supplementation in Infants: A Meta-Analysis of Randomized Controlled Trials.

Strategies to stabilize and support overall infant health by increasing the number of Bifidobacterium longum in the infant gut are of interest, but few studies have systematically addressed this issue. We aimed to evaluate the efficacy and safety of Bifidobacterium longum use in infants using meta-analysis. We searched PubMed, EMBASE, Cochrane Library of Systematic Reviews, and SinoMed for publications until 27 July 2022. The main outcomes of interest were weight gain, risk of necrotizing enterocolitis (NEC), and adverse events. Two authors independently performed study screening, risk of bias assessment, and data extraction. Outcome data were extracted from each included study and combined using mean difference (MD) or risk ratio (RR) and finally combined using a fixed-effect model or random-effect model. A total of 4481 relevant studies were identified, of which 15 were found to be eligible for randomized controlled trials and were included in the meta-analysis. The combined extracted data showed that the intervention group containing Bifidobacterium longum had a significantly lower risk of NEC (RR = 0.539, 95% CI: 0.333, 0.874) compared to the control group. There was no statistical difference between the intervention and control groups regarding weight gain (MD = 0.029, 95% CI: -0.032, 0.090), the occurrence of adverse events (RR = 0.986, 95% CI: 0.843, 1.153), and serious adverse events (RR = 0.881, 95% CI: 0.493, 1.573). Bifidobacterium longum may significantly reduce the risk of NEC in infants as well as being safe; thus, further research evidence is needed on whether there is a benefit on weight gain.

Identification of omega-3 oxylipins in human milk-derived extracellular vesicles with pro-resolutive actions in gastrointestinal inflammation.

Premature infants (PIs) are at risk of suffering necrotizing enterocolitis (NEC), and infants consuming human milk (HM) show a lower incidence than infants receiving formula. The composition of HM has been studied in depth, but the lipid content of HM-derived small extracellular vesicles (HM sEVs) remains unexplored. Identifying these molecules and their biological effects has potential for the treatment of intestinal disorders in PIs and could contribute to the development of HM-based fortified formulas. We isolated HM sEVs from HM samples and analyzed their oxylipin content using liquid chromatography coupled to mass spectrometry, which revealed the presence of anti-inflammatory oxylipins. We then examined the efficacy of a mixture of these oxylipins in combating inflammation and fibrosis, in vitro and in a murine model of inflammatory bowel disease (IBD). HM-related sEVs contained higher concentrations of oxylipins derived from docosahexaenoic acid, an omega-3 fatty acid. Three anti-inflammatory oxylipins, 14-HDHA, 17-HDHA, and 19,20-DiHDPA (ω3 OXLP), demonstrated similar efficacy to HM sEVs in preventing cell injury, inducing re-epithelialization, mitigating fibrosis, and modulating immune responses. Both ω3 OXLP and HM sEVs effectively reduced inflammation in IBD-model mice, preventing colon shortening, infiltration of inflammatory cells and tissue fibrosis. Incorporating this unique cocktail of oxylipins into fortified milk formulas might reduce the risk of NEC in PIs and also provide immunological and neurodevelopmental support.

Identification and evaluation of probiotic potential of Bifidobacterium breve AHC3 isolated from chicken intestines and its effect on necrotizing enterocolitis (NEC) in newborn SD rats.

Necrotizing enterocolitis (NEC) is a severe intestinal disease of the newborn infants, associated with high morbidity and mortality. It has been reported that Bifidobacterium could protect the intestinal barrier function and reduce the risk of NEC. This study aimed to evaluate the probiotic potential of Bifidobacterium strains isolated from the chicken intestines and its effect on necrotizing enterocolitis in newborn SD rats. Out of 32 isolates, B. breve AHC3 not only exhibited excellent probiotic potential, including tolerance to artificial simulated gastric conditions, adhesion to HT-29 cells, antioxidant capacity and antibacterial activity, but also possessed reliable safety. Additionally, NEC model was established to further investigate the effect of B. breve AHC3 on necrotizing enterocolitis in newborn SD rats. It was illustrated that administration of B. breve AHC3 significantly not only reduced the incidence of NEC (from 81.25% to 34.38%) (P< 0.05), but also alleviated the severity of ileal injury (P< 0.05). Compared with NEC model, B. breve AHC3 could significantly decrease the level of proinflammatory factor TNF-α (P< 0.05) and increase the level of antiinflammatory factor IL-10 (P< 0.05) in the ileum of NEC rats. Through the intervention of B. breve AHC3, the gray value of inducible nitric oxide synthase (iNOS) in intestinal tissue of NEC rats was significantly reduced (P< 0.05). It was indicated that B. breve AHC3 exhibited prominent probiotic potential and reliable safety. In the neonatal SD rat model of NEC, B. breve AHC3 had an available protective effect on the intestinal injury of NEC, which might be related to reducing the inflammatory reaction in the ileum and inhibiting the expression of iNOS in intestinal tissue cells. B. breve AHC3 could be used as a potential treatment for human NEC.

Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004–2007 vs 2014–2016)

ObjectiveTo investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.DesignRegistry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage...

Time of Delivery Contributes to Mortality and Morbidity in Preterm Infants

Introduction: Knowledge about the time of birth and its impact on premature infants is essential when planning perinatal and neonatal care and resource allocation. We studied the time of birth and its contribution to early death and morbidity in preterm infants. Methods: We explored the time and mode of birth of infants with birthweight of <1,500 g and gestational age of <32+^0/7 weeks. Additionally, we divided the infants into three groups stratified by their time of birth, i.e., during office hours, evening, and nighttime and assessed associations between these groups and mortality and morbidity. Results: The study comprised 1,610 infants of whom 156 (10%) died during their stay in neonatal intensive care unit. The highest number of deliveries occurred on Fridays (21%, n = 341/1,610), primarily due to high number of cesarean sections. Deliveries peaked on workdays at 10 a.m. and 2:00 p.m. Mortality was lowest among infants born on Fridays (6%, n = 21/341) and highest on Mondays (13%, n = 28/218). Intraventricular hemorrhage (IVH) (odds ratio [OR]: 1.50, 95% CI: 1.10–2.03, p = 0.010) and necrotizing enterocolitis (NEC) (OR: 2.11, 95% CI: 1.13–3.91, p = 0.019) were more common among infants born at nighttime. These associations attenuated after adjustment for covariates. Conclusion: Deliveries of premature infants peaked on Fridays. Mortality was lower among those born on Fridays, compared with Mondays. Many low-risk deliveries on Fridays may decrease, and the tendency to postpone high-risk deliveries to Mondays, increase the proportional risk of mortality. Indication of higher risk of IVH and NEC among infants born during nighttime may be due to different patient population.

Complications and Outcomes of Nutritional Guidelines Implementation in Low Birth Weight Infants

Background: Necrotizing enterocolitis (NEC) is one of the most disastrous complications of premature infants. Using preterm feeding protocols can decrease NEC risk and improve feeding intolerance. Objective: To compare the rate of NEC and other comorbidities between low-birth-weight (LBW) infants that received a Bhumibol Adulyadej Hospital (BAH) standardized feeding protocol and those that underwent previous nutritional practice. Materials and Methods: A quasi-experimental study was conducted at neonatal intensive care unit (NICU) in BAH, Thailand. Participants were LBW newborns delivered at BAH between December 1, 2018 and March 31, 2020. The subjects were divided into the control group who underwent previous nutritional practice and the study group who were implemented with a new nutritional guideline. Primary outcome was NEC rate. Secondary outcomes were preterm complications such as neonatal sepsis, catheter-related bloodstream infection, parenteral nutrition-associated liver disease, osteopenia of prematurity, and intraventricular hemorrhage. Feeding achievement outcomes and growth outcome parameters were also evaluated. Results: Data were analyzed on 71 infants in the control group and 68 infants in the study group. The rate of NEC was not different between the two groups with 7% in the control versus 5.9% in the study (p=1.000). In addition, other preterm complications were not different between groups. However, the time to reaching full enteral feeding was shorter in the study group at 14 in the control versus 10 in the study (p&lt;0.001). Day of life when the fortification start was significantly earlier in the study group at 15.5 in the control versus 12 in the study (p=0.008). Other feeding achievement outcomes also improved, which was evidenced by fewer parenteral nutrition (PN) days at 11.55 in the control versus 7.0 in the study (p=0.004) and shorter duration of indwelling central line at 9.5 in the control versus 7 in the study (p=0.001). Conclusion: Initiation of the new nutritional guideline produced a lower rate of NEC as compared to previous practice. Furthermore, the time to full enteral feeding, PN days, and central line days were decreased without increasing other preterm complications. Keywords: Low birth weight; Nutrition; Complication; NEC

Association of anemia and platelet activation with necrotizing enterocolitis with or without sepsis among low birth weight neonates: a case-control study.

This study aims to evaluate the value of the proportion of large platelets (PLCR) and platelet crit (PCT) in predicting necrotizing enterocolitis (NEC) in low birth weight (LBW) neonates. A total of 155 LBW (<2,500 g) neonates with NEC, who were admitted to the neonatal intensive care unit (NICU) of the hospital from January 1, 2017, to November 30, 2019, were included in the case group. According to the 1:3 case-control study design, a total of 465 LBW neonates without NEC (three for each LBW neonate with NEC), who were admitted to the NICU and born ≤24 h before or after the birth of the subjects, were included in the control group. During the study period, a total of 6,946 LBW neonates were born, of which 155 had NEC, including 92 who also had sepsis. Neonatal sepsis was the most important risk factor and confounding factor for NEC in LBW neonates. Further stratified analysis showed that in LBW neonates without sepsis, anemia [P = 0.001, odds ratio (OR) = 4.367, 95% confidence interval (CI): 1.853-10.291], high PLCR (P < 0.001, OR = 2.222, 95% CI: 1.633-3.023), and high PCT (P = 0.024, OR = 1.368, 95% CI: 1.042-1.795) increased the risk of NEC and the receiver operating characteristic curve area of PLCR, sensitivity, specificity, and cutoff value were 0.739, 0.770, 0.610, and 33.55, respectively. The results showed that 2/100 LBW neonates were at risk for NEC, and the stratified analysis of the confounding factors of sepsis identified the risk factors of NEC in LBW neonates. This study first reported the significance of PLCR in the early prediction of NEC occurrence in LBW neonates without sepsis.

The Association of Human Milk Proportion with the Clinical Outcomes of Necrotizing Enterocolitis in Preterm Infants: A Retrospective Study.

Human milk (HM) has been associated with a lower risk of necrotizing enterocolitis (NEC). However, the association of precise HM proportion with the outcome of NEC remains unclear. A total of 77 cases and 154 matched controls were included in this study. The samples were divided into three groups based on the HM proportion of the total enteral intake before NEC onset: ≥70% (HHM), <70% (LHM), and 0% (NHM). The study cohort did not show a significant association between different HM proportions and NEC risk. The adjusted odds ratio (OR) for the highest versus the lowest intake was 0.599. In the prognosis of NEC, different HM proportions significantly affected weight gain, the timing of NEC onset, diagnosis time, hospitalization cost, and the severity of NEC (p < 0.05). Our findings support the beneficial effects of HM on reducing NEC in preterm infants, particularly when a greater proportion of HM of the total enteral intake is included in their feeding. Additionally, the study indicates that preterm infants fed with lower proportions of HM of the total enteral feeding are more prone to experiencing severe cases of NEC.

Pre-operative enteral feeding in single-ventricle CHD patients and necrotising enterocolitis risk.

Enteral feeding prior to cardiac surgery has benefits in pre-operative and post-operative patient statuses. In 2020, to increase pre-operative feeding for single-ventricle patients prior to stage 1 palliation, an enteral feeding algorithm was created. The aim of this study is to monitor the impact of our practice change with the primary outcome of necrotising enterocolitis incidence from birth to 2 weeks following surgical intervention. This is a single-site, retrospective cohort study including patients from 1 March, 2018 to 1 July, 2022. Variables assessed include demographics, age at cardiac surgery, primary cardiac diagnosis, necrotising enterocolitis pre-operative and 2 weeks post-operative cardiac surgery, feeding route, feeding type, volume of trophic enteral feeds, and near-infrared spectroscopy. Following implementation of a pre-operative enteral feeding algorithm, the rate of neonates fed prior to surgery increased (39.5-75%, p = .001). The feedings included a mean volume of 28.24 ± 11.16 ml/kg/day, 83% fed breastmilk only, 44.4% tube fed, and 55.5% of infants had all oral feedings. Comparing enterally fed neonates and those not enterally fed, the necrotising enterocolitis incidence from birth to 2 weeks post-op was not significantly increased (p = 0.926). As a result of implementing our feeding algorithm, the frequency of infants fed prior to stage I Norwood or Hybrid surgeries increased to 75%, and there was no significant change in the incidence of necrotising enterocolitis. This study confirmed that pre-operative enteral feeds are safe and are not associated with increased incidence of necrotising enterocolitis.

Prediction of GutCheck NEC and Its Relation to Severity of Illness and Measures of Deterioration in Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) risk has been shown to arise from multiple sources and risk awareness may be supported using bedside tools. The purpose of this research was to examine the extent to which GutCheck NEC was associated with scores for clinical deterioration, severity of illness, and clinical outcome, and further to examine how scores might improve NEC prediction. A retrospective, correlational case-control study with infant data from 3 affiliated neonatal intensive care units was conducted. Of 132 infants (44 cases, 88 controls), most were 28 weeks of gestation at birth and less (74%). Median age at NEC onset was 18 days (range: 6-34 days), with two-thirds diagnosed before 21 days. At 68 hours of life, higher GutCheck NEC scores were associated with NEC requiring surgery or resulting in death (relative risk ratio [RRR] = 1.06, P = .036), associations that persisted at 24 hours prior to diagnosis (RRR = 1.05, P = .046), and at the time of diagnosis (RRR = 1.05, P = .022) but showed no associations for medical NEC. GutCheck NEC scores were significantly correlated with pediatric early warning scores (PEWS) ( r > 0.30; P < .005) and SNAPPE-II scores ( r > 0.44, P < .0001). Increasing numbers of clinical signs and symptoms were positively associated with GutCheck NEC and PEWS at the time of diagnosis ( r = 0.19, P = .026; and r = 0.25, P = .005, respectively). GutCheck NEC provides structure to streamline assessment and communication about NEC risk. Yet, it is not intended to be diagnostic. Research is needed on how GutCheck NEC impacts timely recognition and treatment.

A systematic review and meta-analysis of the role of Doppler ultrasonography of the superior mesenteric artery in detecting neonates at risk of necrotizing enterocolitis.

The role of postnatal Doppler measurements of the superior mesenteric artery (SMA) in detecting neonates at risk of necrotizing enterocolitis (NEC) remains uncertain; therefore, we systematically reviewed and meta-analyzed the existing evidence regarding the usefulness of SMA Doppler measurements in detecting neonates at risk for NEC. We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and we included studies which reported the following Doppler ultrasonography indices: peak systolic velocity, end-diastolic velocity, time average mean velocity, differential velocity, pulsatility index (PI) and resistive index. Eight studies were eligible for inclusion in the meta-analysis. Evidence suggested that, during the first postnatal day, neonates who developed NEC had a significantly higher peak systolic velocity (mean difference of 2.65cm/s (95% confidence interval [CI] 1.23, 4.06, overall effect Z=3.66, P<0.001)), higher PI (mean difference of 1.52 (95% CI 0.00, 3.04, Z=1.96, P=0.05)) and higher resistive index (mean difference of 1.09 (95% CI 0.59, 1.60, Z=4.24, P<0.001)), compared to neonates who did not develop NEC. However, our findings do not support a strong association between the Doppler ultrasound indices and development of NEC at the time of disease onset. This meta-analysis suggests that first postnatal day SMA Doppler parameters, namely peak systolic velocity, PI and resistive index, are higher in neonates who develop NEC. On the other hand, the aforementioned indices are of uncertain significance once the diagnosis of NEC has been established.

Viral Infections and Neonatal Necrotizing Enterocolitis: A Meta-analysis.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting preterm infants. Studies implicate viral infections in etiopathogenesis. To summarize the association of viral infections with NEC by systematic review and meta-analysis. We searched Ovid-Medline, Embase, Web of Science, and Cochrane databases in November 2022. We included observational studies that examined the association between viral infections and NEC in newborn infants. We extracted data regarding the methodology, participant characteristics, and outcome measures. We included 29 and 24 studies in the qualitative review and meta-analysis, respectively. The meta-analysis demonstrated a significant association between viral infections and NEC (odds ratio [OR], 3.81, 95% confidence interval: 1.99-7.30, 24 studies). The association remained significant after excluding the outliers (OR, 2.89 [1.56-5.36], 22 studies) and studies with poor methodology (OR, 3.33 [1.73-6.43], 22 studies). In subgroup analysis based on participants' birth weight, studies including very low birth weight infants only (OR, 3.62 [1.63-8.03], 8 studies) and non-very low birth weight infants only (OR, 5.28 [1.69-16.54], 6 studies) showed a significant association. In subgroup analysis based on specific viruses, infection with rotavirus (OR, 3.96 [1.12-13.95], 10 studies), cytomegalovirus (OR, 3.50 [1.60-7.65], 5 studies), norovirus (OR, 11.95 [2.05-69.84], 2 studies), and astrovirus (OR, 6.32 [2.49-16.02], 2 studies) was significantly associated with NEC. Heterogeneity of the included studies. Viral infection is associated with an increased risk of NEC in newborn infants. We need methodologically sound prospective studies to assess the effect of preventing or treating viral infections on NEC incidence.

Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.

Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants. To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. We included randomised controlled trials (RCTs) and quasi-RCTs comparing prebiotics with placebo or no prebiotics in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants. The primary outcomes were NEC and all-cause mortality, and the secondary outcomes were late-onset invasive infection, duration of hospitalisation since birth, and neurodevelopmental impairment. Two review authors separately evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference (MD), with associated 95% confidence intervals (CIs). The primary outcomes of interest were NEC and all-cause mortality; our secondary outcome measures were late-onset (> 48 hours after birth) invasive infection, duration of hospitalisation, and neurodevelopmental impairment. We used the GRADE approach to assess the level of certainty of the evidence. We included seven trials in which a total of 705 infants participated. All the trials were small (mean sample size 100). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were potential sources of bias in three of the trials. The studied prebiotics were fructo- and galacto-oligosaccharides, inulin, and lactulose, typically administered daily with enteral feeds during birth hospitalisation. Meta-analyses of data from seven trials (686 infants) suggest that prebiotics may result in little or no difference in NEC (RR 0.97, 95% CI 0.60 to 1.56; RD none fewer per 1000, 95% CI 50 fewer to 40 more; low-certainty evidence), all-cause mortality (RR 0.43, 95% CI 0.20 to 0.92; 40 per 1000 fewer, 95% CI 70 fewer to none fewer; low-certainty evidence), or late-onset invasive infection (RR 0.79, 95% CI 0.60 to 1.06; 50 per 1000 fewer, 95% CI 100 fewer to 10 more; low-certainty evidence) prior to hospital discharge. The certainty of this evidence is low because of concerns about the risk of bias in some trials and the imprecision of the effect size estimates. The data available from one trial provided only very low-certainty evidence about the effect of prebiotics on measures of neurodevelopmental impairment (Bayley Scales of Infant Development (BSID) Mental Development Index score < 85: RR 0.84, 95% CI 0.25 to 2.90; very low-certainty evidence; BSID Psychomotor Development Index score < 85: RR 0.24, 95% 0.03 to 2.00; very low-certainty evidence; cerebral palsy: RR 0.35, 95% CI 0.01 to 8.35; very low-certainty evidence). The available trial data provide low-certainty evidence about the effects of prebiotics on the risk of NEC, all-cause mortality before discharge, and invasive infection, and very low-certainty evidence about the effect on neurodevelopmental impairment for very preterm or VLBW infants. Our confidence in the effect estimates is limited; the true effects may be substantially different. Large, high-quality trials are needed to provide evidence of sufficient validity to inform policy and practice decisions.

Platelet transfusions in preterm infants: current concepts and controversies-a systematic review and meta-analysis.

Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.

The Detrimental Effects of Peripartum Antibiotics on Gut Proliferation and Formula Feeding Injury in Neonatal Mice Are Alleviated with Lactobacillus rhamnosus GG.

Peripartum antibiotics can negatively impact the developing gut microbiome and are associated with necrotizing enterocolitis (NEC). The mechanisms by which peripartum antibiotics increase the risk of NEC and strategies that can help mitigate this risk remain poorly understood. In this study, we determined mechanisms by which peripartum antibiotics increase neonatal gut injury and evaluated whether probiotics protect against gut injury potentiated by peripartum antibiotics. To accomplish this objective, we administered broad-spectrum antibiotics or sterile water to pregnant C57BL6 mice and induced neonatal gut injury to their pups with formula feeding. We found that pups exposed to antibiotics had reduced villus height, crypt depth, and intestinal olfactomedin 4 and proliferating cell nuclear antigen compared to the controls, indicating that peripartum antibiotics impaired intestinal proliferation. When formula feeding was used to induce NEC-like injury, more severe intestinal injury and apoptosis were observed in the pups exposed to antibiotics compared to the controls. Supplementation with the probiotic Lactobacillus rhamnosus GG (LGG) reduced the severity of formula-induced gut injury potentiated by antibiotics. Increased intestinal proliferating cell nuclear antigen and activation of the Gpr81-Wnt pathway were noted in the pups supplemented with LGG, suggesting partial restoration of intestinal proliferation by probiotics. We conclude that peripartum antibiotics potentiate neonatal gut injury by inhibiting intestinal proliferation. LGG supplementation decreases gut injury by activating the Gpr81-Wnt pathway and restoring intestinal proliferation impaired by peripartum antibiotics. Our results suggest that postnatal probiotics may be effective in mitigating the increased risk of NEC associated with peripartum antibiotic exposure in preterm infants.