Cases Of Necrotizing Enterocolitis Research Articles

Trends and risk factors analysis of NEC in preterm infants over 9 years

BackgroundInvestigating the trend of changes in the occurrence of necrotizing enterocolitis (NEC) in preterm infants during 9 years and analyzing the risk factors of NEC with the purpose of providing reference for clinical diagnosis and treatment of NEC.MethodsClinical data of NEC in preterm infants with Bell’s stage ≥ II from January 2013 to December 2021 in the Neonatology Department of the Third Affiliated Hospital of Zunyi Medical University was retrospectively analyzed. Trends in the occurrence of NEC in preterm infants were analyzed by the trend chi-square test. Subsequently, the general data (sex, gestational age, singleton or multiple births, birth weight, serum albumin, alkaline phosphatase, sepsis, blood transfusion, mechanical ventilation, RDS, arterial catheterization) and perinatal data (intrauterine distress, turbid amniotic fluid, premature rupture of membranes, mode of delivery, fetal heart abnormalities, diabetes mellitus) were collected; then, the risk factors for NEC were analyzed by univariate and multivariate logistic-regression analysis.ResultsIn the past 9 years, 77 cases of NEC occurred, with the incidence rate of 1.95%, and the incidence of NEC in preterm infants has been increasing year by year (P < 0.05). The results of univariate analysis showed that the morbidity of NEC in preterm infants was associated with premature rupture of membranes, blood transfusion, sepsis, and the of serum albumin (P < 0.05). Multivariate logistic regression analysis revealed that blood transfusion (OR = 2.232, 95% CI: 1.012–4.923) and sepsis (OR = 0.899, 95% CI: 0.809–3.915) were independent risk factors of NEC in preterm infants, while high serum albumin (OR = 0.899, 95% CI: 0.809–3.915) was an independent protective factor of NEC in preterm infants.ConclusionThe morbidity of NEC is gradually increasing. Inhibition of infection and limitation of blood transfusion are effective measures to reduce the occurrence of NEC. Meanwhile, high serum albumin is a protective factor for NEC.

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 new classification for surgical NEC during exploratory laparotomy: introduction and reproducibility assessment.

Variability in necrosis patterns and operative techniques in surgical necrotizing enterocolitis (NEC) necessitates a standardized classification system for consistent assessment and comparison. This study introduces a novel intraoperative reporting system for surgical NEC, focusing on reliability and reproducibility. Analyzing surgical NEC cases from January 2018 to June 2023 at two tertiary neonatal and pediatric surgery units, a new classification system incorporating anatomical details and intestinal involvement extent was developed. Its reproducibility was quantified using kappa coefficients (κ) for interobserver and intraobserver reliability, assessed by four specialists. Furthermore, following surgery, the occurrence of mortality and enteric autonomy were evaluated on the basis of surgical decision-making of the novel intraoperative classification system for surgical NEC. In total, 95 patients with surgical NEC were included in this analysis. The mean κ value of the intra-observer reliability was 0.889 (range, 0.790-0.941) for the new classification, indicating excellent agreement and the inter-observer reliability was 0.806 (range, 0.718-0.883), indicating substantial agreement. The introduced classification system for surgical NEC shows high reliability, deepening the understanding of NEC's intraoperative exploration aspects. It promises to indicate operative strategies, enhance prognosis prediction, and substantially facilitate scholarly communication in pediatric surgery. Importantly, it explores the potential for a standardized report and may represent a step forward in classifying surgical NEC, if pediatric surgeons are open to change.

A Nomogram for Predicting Surgical Risk in Neonates with Necrotizing Enterocolitis: A Retrospective Cohort Study.

To construct a nomogram that predicts the risk of surgery in patients with necrotizing enterocolitis (NEC). This retrospective cohort study recruited patients diagnosed with NEC at the Children's Hospital of Soochow University from 2013 to 2023. The neonates were divided into conservative and surgical-treatment groups. Univariate and multivariate logistic regressions were performed to identify factors influencing surgical risk, and a predictive model was constructed. This study comprised 154 cases of NEC, 103 cases (66.9%) in the conservative group and 51 cases (33.1%) in the surgical group. Multivariate logistic regression analysis revealed that increased bloody stools [odds ratio (OR) 5.066; 95% confidence interval (CI) 1.7396-14.7532; p = 0.0029), oxygen inhalation (OR 1.8278; 95% CI 1.2113-2.7581; p = 0.0041), use of vasoconstrictors (OR 4.4446; 95% CI 1.7157-11.5137; p = 0.0021), portal venous gas (OR 4.5569; 95% CI 1.6324-12.7209; p = 0.0038), and blood sodium (OR 0.8339; 95% CI 0.7477-0.9301; p = 0.0011) were independent factors of surgical risk. The area under the nomogram's receiver operating characteristic (ROC) curve was 0.886. Decision curve analysis (DCA) and calibration curves demonstrated good predictive performance for the nomogram. The nomogram effectively assessed the risk of surgical intervention in NEC patients, providing new insights and references for diagnosing and treating NEC.

A prospective evaluation of the risk factors and utility of GutCheckNEC scoring system to predict necrotizing enterocolitis in preterm newborns, in a tertiary care centre in North India

Background: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease of neonate with high fatality. GutCheckNEC scoring system can be used in predicting NEC and decrease NEC rate. Aims: To assess risk factors and use scoring system GutCheckNEC in predicting necrotising enterocolitis. Methods: A prospective observational study with preterms, birth weight &lt;1500grams was done. Risk factor assessment was done using GutCheckNEC and serial scorings were done. Descriptive analyses of the various risk factors assessed were done. Results: 51 babies included, with gestational age 24 to 35 weeks (Median (IQR) 30+2 (27+2, 31+6), birth weight 500 to 1500 grams (Median (IQR) – 1105 (893, 1300). 9 NEC cases, 6(11.5%) confirmed NEC and 2(22%) were surgical NEC. Absence of ANS, HsPDA and late onset sepsis were risk factors. The median (IQR) scoring at 72 hrs., 86 hrs., 7 days, 14days, 21days and 28 days were 34 (31, 38), 34 (30, 39), 34 (26, 43), 31 (23, 35), 35 (23, 38), 35 (30, 40). The median risk for developing NEC was high (33-36) on all days except day 14, when it was moderate (20-32). The sensitivity and specificity for a cut off &gt;32 at 86hours was 85.7% and 48.5% (PPV – 26.1%, NPV – 94%) for medical NEC and 100% and 44.7% (PPV – 8.7%, NPV – 100%) respectively for surgical NEC. Conclusion: Hence we conclude that GUTCHECK can help in early prediction of NEC and prevention of NEC.

Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Optimal timing of delivery for growth restricted fetuses with gastroschisis: A decision analysis.

Our objective was to determine the optimal timing of delivery of growth restricted fetuses with gastroschisis in the setting of normal umbilical artery (UA) Dopplers. We designed a decision analytic model using TreeAge software for a hypothetical cohort of 2000 fetuses with isolated gastroschisis, fetal growth restriction (FGR), and normal UA Dopplers across 34-39weeks of gestation. This model accounted for costs and quality adjusted life years (QALYs) for the pregnant individual and the neonate. Model outcomes included stillbirth, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), short gut syndrome (SGS), neonatal sepsis, neonatal death, and neurodevelopmental disability (NDD). We found 38weeks to be the optimal timing of delivery for minimizing overall perinatal mortality and leading to the highest total QALYs. Compared to 37weeks, delivery at 38weeks resulted in 367.98 more QALYs, 2.22 more cases of stillbirth, 2.41 fewer cases of RDS, 0.02 fewer cases of NEC, 1.65 fewer cases of IVH, 0.5 fewer cases of SGS, 2.04 fewer cases of sepsis, 11.8 fewer neonatal deaths and 3.37 fewer cases of NDD. However, 39weeks were the most cost-effective strategy with a savings of $1,053,471 compared to 38weeks. Monte Carlo analysis demonstrated that 38weeks was the optimal gestational age for delivery 51.70% of the time, 39weeks were optimal 47.40% of the time, and 37weeks was optimal 0.90% of the time. Taking into consideration a range of adverse perinatal outcomes and cost effectiveness, 38-39weeks gestation is ideal for the delivery of fetuses with gastroschisis, FGR, and normal UA Dopplers. However, there are unique details to consider for each case, and the timing of delivery should be individualized using shared multidisciplinary decision making.

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...

Complicated Necrotizing Enterocolitis in a full-term Infant – A Case Report

Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder primarily affecting preterm infants. However, cases of NEC in full-term infants are relatively rare but can present with unique challenges and clinical features. We present a case report of a full-term baby who developed perforation due to necrotizing enterocolitis shortly after birth. The infant underwent surgery and transverse colostomy was made. Over the course of treatment, the infant showed gradual improvement and was discharged home after a hospital stay of 16 days. This case highlights the atypical presentation of NEC in a full-term infant, underscoring the importance of early recognition and prompt intervention. Although NEC is commonly associated with preterm infants, it should be considered as a potential diagnosis in full term neonates presenting with gastrointestinal symptoms. Clinicians should maintain a high index of suspicion for NEC in these cases to ensure timely management and reduce the risk of complications.

Occurrence of Neonatal Necrotizing Enterocolitis in Premature Neonates and Gut Microbiota: A Case-Control Prospective Multicenter Study.

Necrotizing enterocolitis (NEC) is still one of the leading causes of neonatal death. The present study reports the data from a French case-control prospective multicenter study. A total of 146 preterm neonates (PNs) with or without NEC were included. Bacterial 16S rRNA gene sequencing was performed on stool samples (n = 103). Specific culture media were used to isolate Escherichia coli, Clostridium butyricum, and Clostridium neonatale, and strains were phenotypically characterized. The gut microbiota of PNs was dominated by Firmicutes and Proteobacteria, and five enterotypes were identified. The microbiota composition was similar between NEC cases and PN controls. However, differences were observed in the relative abundance of Lactobacillus genus, which was significantly lower in the NEC group, whereas that of the Clostridium cluster III was significantly higher (p < 0.05). Within enterotypes, several phylotypes were significantly more abundant in NEC cases (p < 0.05). Regarding perinatal factors, a statistical association was found between the gut microbiota and cesarean delivery and antifungal therapy. In NEC cases and PN controls, the carriage rates and virulence genes of uropathogenic E. coli were equivalent based on culture. No correlation was found between E. coli, C. butyricum, and C. neonatale carriages, beta-lactam resistance, and antibiotic treatment. At disease onset, our data support a microbiota dysbiosis between NEC and control infants at the genus level. In addition, it provides valuable information on bacterial antimicrobial susceptibility.

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.

Age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm and low birthweight infants: a systematic review

ObjectiveReview of age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm (≤32 weeks) and/or very low birthweight (VLBW, ≤1500 g) infants.DesignPreregistered review undertaken according...

Time to first passage of meconium and defecation frequency preceding necrotizing enterocolitis in preterm infants: a case–control study

Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case–control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13–65] vs. 30 h [IQR 9–66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99–1.03], 1.16 [0.86–1.55] and 0.97 [0.72–1.31], resp.).Conclusion: In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC.What is Known:• Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment.• Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease.What is New:• Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.

Reduction in regulatory T cells in preterm newborns is associated with necrotizing enterocolitis

BackgroundDespite multifactorial pathogenesis, dysregulation of inflammatory immune response may play a crucial role in necrotizing enterocolitis (NEC). Regulatory T cells (Tregs) are involved in immune tolerance early in life. We aimed to investigate the predicting role of Tregs in developing NEC in neonates at high risk.MethodsWe studied six newborns with a diagnosis of NEC (cases) in comparison with 52 controls (without NEC). We further classified controls as neonates with feeding intolerance (FI) and neonates without it (FeedTol). The rate of female and male neonates (sex defined as a biological attribute) was similar. We analyzed the blood frequency of Tregs (not overall numbers) at three time points: 0–3 (T0), 7–10 (T1), and 27–30 (T2) days after birth by flow cytometry. Neonates’ sex was defined based on the inspection of external genitalia at birth.ResultsWe observed, at T0, a significantly lower frequency of Tregs in NEC cases (p < 0.001) compared with both FI (p < 0.01) and FeedTol controls (p < 0.01). Multivariate analysis reported that the occurrence of NEC was independently influenced by Treg frequency at birth (ß 2.98; p = 0.039).ConclusionTregs frequency and features in the peripheral blood of preterm neonates, early in life, may contribute to identifying neonates at high risk of developing NEC.ImpactRegulatory T cells may play a pivotal role in regulating the immune response in early life. Reduction of Tregs in early life could predispose preterm newborns to necrotizing enterocolitis.Early markers of necrotizing enterocolitis are still lacking. We demonstrated a predicting role of assessment of regulatory T cells in the diagnosis of this gastrointestinal emergency.Early identification of newborns at high risk of necrotizing enterocolitis through measurement of regulatory T cells may guide clinicians in the management of preterm newborns in order to reduce the development of this severe condition.

Rhesus alloimmunization is correlated to necrotizing enterocolitis and respiratory distress: A tertiary center experience

Background Rh alloimmunization occurs in pregnant women who do not express the red blood cell Rh antigen phenotype but carry a fetus that does. The mainstay of treatment is intrauterine blood transfusion (IUT). Necrotizing enterocolitis (NEC) is a rapidly progressive and life-threatening emergency that most commonly affects preterm neonates. It has been noticed that NEC has a predilection toward neonates with rhesus hemolytic disease (RHD) compared to neonates without RHD, particularly among the late preterm to near-term population with a moderate to severe grade of RHD. Methodology This is a retrospective cohort study that included all neonates delivered in our hospital between January 2015 and December 2021,who received IUT due to Rh-isoimmunization, and the control group consisted of neonates, who did not have Rh-isoimmunization and no history of IUT. Neonates were excluded from the study if they met our exclusion criteria. Results During a 7-year study period, a total of 144 neonates were included in the study. Of those, 72 neonates had RHD and received IUT (group 1), while 72 neonates did not have RH isoimmunization and did not receive IUT (group 2). Maternal and neonatal demographic data were similar between the two groups, except for birth weight, which was higher in group 1 (2.49 vs. 2.31 kg, P = 0.025). Ten cases developed NEC (13.89%) in group 1, while there were no cases of NEC in the other group (P = 0.001). We also found that the initial hemoglobin level was lower in group 1 (135.4 vs. 174.3 g/dL) with a P value of &lt;0.001. The duration of respiratory support was significantly higher in group 1 (2.27 vs. 0.319 days; P = 0.006). Neonatal sepsis was more in group 1 (19.44 vs. 1.39%; P = 0.002). There was no significant difference between the two groups in terms of respiratory distress syndrome, intraventricular hemorrhage, and retinopathy of prematurity. Conclusion Neonates with rheus hemolytic disease (RHD) who undergo IUT are at a higher risk of developing NEC and prolonged course of respiratory support. Extra cautions may be necessary when advancing feeding in these patients. A well-designed multicenter prospective trial with an adequate sample size is recommended to validate our result.

Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA− strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.

Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis

BackgroundPreterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested potential positive effects on cognitive outcomes but raised concerns about some increased neonatal morbidities. These studies and recent recommendations for DHA supplementation generated controversy owing to the lack of balance between DHA and arachidonic acid (ARA; n-6 LCPUFA). ObjectivesTo identify the effect of enteral supplementation of DHA, with and without ARA, on necrotizing enterocolitis (NEC) in very preterm infants. MethodsA systematic review of randomized and controlled trials compared enteral LCPUFAs with placebo or no supplementation in very preterm infants. We searched PubMed, Ovid-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINHAL databases from inception to July 2022. Data were extracted in duplicate using a structured proforma. A meta-analysis and metaregression with random-effects models were used. The interventions evaluated were DHA alone vs. that combined with ARA, source of DHA, dose, and supplement delivery methods. Methodological qualities and risk of bias were assessed using the Cochrane risk-of-bias tool. ResultsFifteen randomized clinical trials (RCTs) included 3963 very preterm infants with 217 cases of NEC. Supplementation with DHA alone increased NEC (2620 infants; RR: 1.56; 95% CI: 1.02, 2.39) with no evidence of heterogeneity (I2 = 0.0%, P = 0.46). Multiple metaregression revealed significant reduction in NEC when ARA was supplemented with DHA (aRR 0.42; 95% CI: 0.21, 0.88). The source of DHA, dose, and feeding type revealed no associations with NEC. Two RCTs supplemented high-dose DHA to lactating mothers. There was a significant increase in risk of NEC with this approach (1148 infants; RR: 1.92; 95% CI: 1.02, 3.61) with no evidence of heterogeneity (I2 = 0.0, P = 0.81). ConclusionsSupplementation with DHA alone may increase risk of NEC. Concurrent supplementation with ARA needs to be considered when adding DHA to preterm infants’ diet.

Impact of Delayed Time to Antibiotics in Medical and Surgical Necrotizing Enterocolitis.

This study investigated whether delayed receipt of antibiotics in infants with necrotizing enterocolitis (NEC) is associated with disease severity. In this retrospective, single-center cohort study of infants diagnosed with NEC over 4 years, we compared the timing of antibiotic administration in infants (time order placed to time of receipt) in medical and surgical NEC. Cases were independently reviewed, then various clinical factors were compared. Of 46 suspected cases, 25 were confirmed by a panel of radiologists with good interrater reliability (ICC 0.657; p < 0.001). Delays in antibiotic receipt were 1.7× greater in surgical than medical NEC cases (p = 0.049). Every hour after order entry increased the adjusted odds of surgical NEC by 2.4 (1.08−5.23; p = 0.032). Delayed antibiotic receipt was more common in infants with surgical than medical NEC. Larger studies will be needed to investigate if optimizing antibiotic expediency could improve intestinal outcomes.

Impact of breast milk miR-155 on the health of preterm neonates

Background. Breast milk (BM) is an important source of microRNAs (miRs). MicroRNAs are highly resistant to gastrointestinal enzymes and are well absorbed in the intestine. MiR-155 is one of the most expressed miR of BM. Currently, the effect of miR-155 of BM on the health of preterm neonates has not been almost studied. The objective was to determine the effect of miR-155 of BM on the health of preterm neonates. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We determined the level of miR-155 in the BM of 44 mothers of exclusively breastfed children. In parallel, we evaluated gene expression of the transcription factor FOXP3 in buccal smears of all neonates. Three comparison groups were selected: group 1 consisted of 32 newborns of up to 37 weeks of gestation; group 2 — of 30 preterm newborns on artificial feeding; control group — of 12 full-term breastfed newborns. Results. The gestational age median in group 1 was 33 (31; 34) weeks; in group 2 — 32.5 (32; 35) weeks; it was higher in the control group (p &lt; 0.001) — 40 (39; 41) weeks. Neonatal encephalopathy as the main diagnosis occurred more often among full-term newborns (p &lt; 0.001). Children of groups 1 and 2 did not differ significantly in the frequency of respiratory distress syndrome and the duration of the necessary respiratory support (p &gt; 0.05). In group 2 compared to group 1, manifestations of necrotizing enterocolitis were detected significantly more often (p &lt; 0.05): 30.0 ± 8.4 % vs 9.4 ± 5.2 %. The results of evaluating the miR-155 expression level in the BM of mothers of group 1 children prove that the corresponding indicator in the control group was exceeded by an average of 6.2 (4.1; 9.2) times (p &lt; 0.001). Analysis of FOXP3 levels in buccal smears showed that all preterm newborns had significantly lower FOXP3 levels than that of full-term neonates (&lt; 0.001). However, the expression of this factor was the lowest in group 2 (&lt; 0.001): 0.08 (0.04; 0.16) c.u. in group 2 vs 0.21 (0.14; 0.38) c.u. in group 1. We found a direct moderate correlation between the expression levels of miR-155 of the BM and the FOXP3 in the mucosal cells of breastfed preterm neonates: r = 0.442 (p = 0.014). A significant decrease was noted in the expression of FOXP3 in children with necrotizing enterocolitis (0.11 (0.04; 0.25) c.u.) compared to newborns without such pathology (0.22 (0.09; 0.91) c.u.) (p &lt; 0.05). Conclusions. The results of the study confirm a lower number of necrotizing enterocolitis cases among preterm breastfed babies. BM of mothers, whose children were born prematurely, has a higher level of miR-155 expression, which promotes FOXP3 expression of mucous membranes. Thus, it is likely that miR-155 of BM stimulates maturation and maintains the level of T-reg cells of the mucous membranes that prevents the development of necrotizing enterocolitis in premature infants.

Enterocolite Necrotizante Grave em Recém-Nascido A Termo: Relato de Caso

Necrotizing enterocolitis (NEC) is an important cause of mortality in the neonatal intensive care unit, and a rare finding in term neonates. We report a case of NEC in a 15 day old term neonate who presented to urgency care with fever and abdominal distension. He had a severe course of illness with pneumoperitoneum and hemodynamic instability and required surgical intervention with extensive intestinal resection. This case is particular due to the absence of classical risk factors for NEC (congenital cardiopathy, perinatal hypoxia, cow milk protein allergy) and to the more severe clinical presentation than most cases of NEC in term patients. Furthermore, the late start of symptoms and small intestine necrosis rather than colonic were unusual. NEC diagnosis is a challenge in term neonates due to the unspecific signs and symptoms it can present and its low prevalence in this group.