Surgical NEC Research Articles

Metabolomic analysis to predict the onset and severity of necrotizing enterocolitis

BackgroundNecrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology.MethodsWe conducted a prospective study including preterm infants born at < 34 gestational weeks (GWs) whose urine was longitudinally collected at birth (< 48 h, T0) and at 14 (T1) and 28 days (T2). Neonates were followed for their development of NEC, spontaneous intestinal perforation (SIP), or other GI conditions and compared to those of matched healthy controls. Urine samples were investigated by untargeted metabolomic analysis based on mass-spectrometry.ResultsThirty-five patients with NEC, 5 patients with SIP, 14 patients with other GI diseases and 113 controls were enrolled and selected for metabolomic analysis on the basis of their clinical characteristics and available samples. Considering urine samples at T0, the one-class classification approach was able to correctly classify 16/20 subjects (80%) who developed NEC, 3/3 (100%) who developed SIP and 5/7 subjects (71.4%) with other GI pathologies as not belonging to the control group. Neonates with surgical NEC had higher N-acetylaspartic acid, butyrylcarnitine and propionylcarnitine levels than did those with medical NEC. Considering the time evolution of the urinary metabolome, the NEC and control groups showed differences independently of the time point.ConclusionsThe urinary metabolome is closely associated with the underlying GI disease from birth. Urinary metabolic features characterize NEC patients from healthy controls until 28 days of life. The early urinary metabolome has the potential to predict surgical NEC. Future studies are needed to validate our results.

Maternal, neonatal, and nutritional risk factors for medical and surgical necrotizing enterocolitis.

To identify maternal and neonatal risk factors associated with progression to surgery or death after diagnosis of NEC. Forty-seven demographic and clinical factors were evaluated across 216 validated cases of NEC occurring between 2010-2020. Nutrition at NEC onset was evaluated in 149 cases. The binary outcome of surgical NEC (progressing to surgery or death) vs. medical NEC (resolved with antibiotic/bowel rest) was compared across variables. Elevated CRP, rapidly decreasing platelet counts, inotropic medication, intubation, and positive blood cultures within 24 h of diagnosis were associated with progression to surgery/death. Infants with surgical NEC had higher abdominal circumferences at birth. Maternal milk intake and receipt of human milk fortifiers were associated with medical NEC, and infants receiving fortified, maternal milk showed the lowest progression to surgery/death. The index of suspicion should be heightened for surgical NEC when these risk factors are present.

Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants

Retinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development. To investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks' gestation. This retrospective cohort study was conducted using data from the German Neonatal Network (GNN) and Norwegian Neonatal Network (NNN). The GNN involves 68 and the NNN includes 21 level III neonatal intensive care units. Participants were infants born at a gestation of 22 weeks and 0 days to 28 weeks and 6 days and enrolled in the GNN between January 1, 2009, and December 31, 2022, and NNN between January 1, 2009, and December 31, 2018. Data were analyzed from February through September 2023. Single or multiple episodes of culture-proven sepsis. Any ROP and treatment-warranted ROP. Among 12 794 infants in the GNN (6043 female [47.2%] and 6751 male [52.8%]; mean [SD] gestational age, 26.4 [1.5] weeks) and 1844 infants in the NNN (866 female [47.0%] and 978 male [53.0%]; mean [SD] gestational age, 25.6 [1.5] weeks), the mean (SD) birth weight was 848 (229) g and 807 (215) g, respectively. Any ROP was present in 6370 infants (49.8%) in GNN and 620 infants (33.6%) in NNN, and treatment-warranted ROP was present in 840 infants (6.6%) in GNN and 140 infants (7.6%) in NNN. In both cohorts, there were increasing rates of treatment-warranted ROP with each sepsis episode (no sepsis: 572 of 10 658 infants [5.4%] in GNN and 85 of 1492 infants (5.7%) in NNN; 1 episode: 190 of 1738 infants in GNN [10.9%] and 29 of 293 infants [9.9%] in NNN; 2 episodes: 53 of 314 infants in GNN [16.9%] and 13 of 49 infants [26.5%] in NNN; 3 episodes: 25 of 84 infants [29.8%] in GNN and 3 of 10 infants [30.0%] in NNN). After adjusting for multiple confounders in the GNN dataset, the number of sepsis episodes was associated with ROP and treatment-warranted ROP compared with 0 episodes (1 episode: adjusted odds ratio [aOR], 1.44 [95% CI, 1.27-1.63]; P < .001 and OR, 1.60 [95% CI, 1.31-1.96]; P < .001, respectively; 2 episodes: OR, 1.81 [95% CI, 1.35-2.42]; P < .001 and OR, 2.38 [95% CI, 1.68-3.37]; P < .001, respectively; 3 episodes: OR, 4.39 [95% CI, 2.19-8.78]; P < .001 and OR, 3.88 [95% CI, 2.29-6.55]; P < .001, respectively). These associations were confirmed for any ROP by propensity score matching (for example, the aOR with propensity score matching was 1.76 [95% CI, 1.54-2.02]; P < .001 for 1 episode vs 0 episodes and 1.58 [95% CI, 1.12-2.22]; P = .007 for 3 episodes vs 0 or 1 episode). In the NNN dataset, surgical NEC was associated with treatment-warranted ROP (multivariable analysis: aOR, 3.37 [95% CI, 1.78-6.37]; P < .001). This study found that in the large-scale GNN cohort, recurrent culture-proven sepsis was associated with ROP and treatment-warranted ROP in infants born at less than 29 weeks.

Does the Timing of Surgical Intervention Impact Outcomes in Necrotizing Enterocolitis?

The optimal time for intervention in surgical necrotizing enterocolitis (sNEC) remains to be elucidated. Surgical management varies between peritoneal drain (PD), laparotomy (LAP), and PD with subsequent LAP (PD + LAP). We propose that some infants with surgical NEC benefit from late (>48h) operative intervention to allow for resuscitation. A retrospective comparison of clinical information in infants with sNEC from 2012 to 2022 was performed. Early intervention was defined as less than 48 hours from time of NEC diagnosis to surgical intervention. 118 infants were identified, 92 underwent early intervention (62 LAP; 22 PD; 8 PD + LAP) and 26 underwent late intervention (20 LAP; 2 PD; 4 PD + LAP). Infants with early intervention were diagnosed younger (DOL 8 [6, 15] vs 20 [11, 26]; P=< .05) with more pneumoperitoneum (76% vs 23%; P=< .05). The early intervention group had a higher mortality (35% vs 15%; P=< .05). When excluding infants with pneumoperitoneum, the early intervention group had a higher mortality rate (10/22 (45%), 4/26 (15%); P < .05) and had more bowel resected (29 ± 17cm vs 9 ± 8cm; P < .05), with the same number of patients scoring above 3 on the MD7 criteria. Infants with NEC who underwent early surgical intervention had a higher mortality and more bowel resected. While this study has a provocative finding, it is severely limited by the non-specific 48-hour cut off. However, our data suggests that a period of medical optimization may improve outcomes in infants with sNEC and thus more in-depth studies are needed.

A multicenter matched-cohort analysis of gastroschisis outcomes in infants born before 32 weeks gestation.

To examine neonatal outcomes of infants with gastroschisis born <32 weeks' gestation compared to matched infants without gastroschisis. Retrospective matched-cohort analysis of infants with gastroschisis born <32 weeks' gestation at Children's Hospitals Neonatal Consortium (CHNC) NICUs from 2010 to 2022 compared to gestational age-matched controls. The study included 119 infants with gastroschisis and 357 matched infants; 60% of infants born 29-32 weeks, 23% born 26-28 weeks, and 16% born < 25 weeks. Mortality was not significantly different between groups (11% vs. 9%, p = 0.59). Preterm co-morbidities such as IVH, BPD, ROP, and PVL were similar, as were rates of surgical NEC. Infants with gastroschisis had longer hospital stays (92 vs. 67 days), higher CLABSI and UTIs, and were more likely to need feeding support at discharge. Compared to infants without gastroschisis, infants <32 weeks' gestation with gastroschisis had similar risks for inpatient mortality, NEC, and other preterm co-morbidities.

Prevalence and risk factors associated with the need for surgical intervention due to necrotizing enterocolitis in very low birth weight infants

IntroductionNecrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies affecting very low birth weight (VLBW) infants with an incidence of 6–15 %. Early recognition is crucial. Mortality is high and variable (30–50 %). Those requiring surgical intervention have a higher mortality rate than those who receive medical treatment. Objectives1) To assess the prevalence of surgical NEC and associated risk factors 2) To compare outcomes based on the type of treatment required 3) To estimate the mortality associated with NEC and surgical NEC. MethodsA multicentre retrospective cohort study was designed (level II), including VLBW infants born between 2011 and 2020 in Centers of the Neocosur Network. A multivariate logistic regression analysis was performed to evaluate risk factors associated with the need for surgery. ResultsNEC was diagnosed in 1679 (10.4 %) of 16,131 births in this period. The prevalence of surgery was 25 % (95 % CI 23–27 %). In multivariable analysis, variables associated with an increased risk of surgery requirement were birth weight <750 g (aOR 1.73–95%CI 1.2–2.5) and receiving antenatal antibiotics (aOR 1.54–95%CI 1.09–2.74). Those requiring surgery had significantly higher morbidity and mortality than the ones receiving medical treatment. ConclusionIn VLBW infants with NEC, lower birth weight and antenatal antibiotics administration were independently associated with the need for surgical intervention.

Surgical Necrotizing Enterocolitis – Can We Predict the Need for Gastrostomy Tube Placement?

IntroductionNecrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement. MethodsA single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed. ResultsEighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. ConclusionsGT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.

Clinical impact of analgesic-sedative agents and peri-operative clinical status on white matter brain injury in preterm infants following surgical NEC.

The potential influence of exposure to analgesic-sedative agents (ASA) before, during, and after surgical NEC and peri-operative clinical status on white matter injury (WMI) in preterm infants has not been fully defined, and a comprehensive evaluation may inform future research and clinical interventions. A retrospective study comparing ASA exposure before/during /after surgical NEC and peri-operative clinical status in neonates with and without WMI. Infants with any WMI (grade 2-4, n = 36/67, 53.7%) had a higher number of surgical procedures receiving ASA (5 [IQR: 3, 8] vs. 3 [2, 4]; p = 0.002) and had a longer duration of hypotension during their first (48.0 hours [26.0, 48.0] vs. 15.5 [6, 48]; p = 0.009) and second surgery (20 hours [0, 48h] vs. 0 [0, 22]; p = 0.017), received more hydrocortisone (35% vs.13.3%,p = 0.04) than those without any WMI. There were no differences in fentanyl/morphine/midazolam exposure before/during/after the NEC onset in the two groups.Infants with severe WMI (19/67, 28.3%, grade 3/4) had a higher incidence of AKI (P = 0.004), surgical morbidity (p = 0.047), more surgical procedures (6.5 [3, 10] vs. 4 [2, 5]; p = 0.012), and received higher mean fentanyl doses(p = 0.03) from birth until NEC onset than those without severe WMI. The univariate associations between these factors and severe WMI remained insignificant after multivariable logistic regression. Infants with WMI had more surgical procedures receiving ASA and had a longer duration of hypotension during surgeries. A large multicenter prospective study is needed to understand the full impact of ASA.

Addendum to: Surgical NEC, randomized control trials, missed opportunity.

Addendum to: Surgical NEC, randomized control trials, missed opportunity.

Mortality of necrotizing enterocolitis does not vary across tertiary care children's hospitals

ObjectiveNecrotizing enterocolitis (NEC) continues to have high surgical mortality despite progressive regionalization to children's hospitals. It is unclear whether outcomes for patients with NEC undergoing surgery vary depending on volume of these children's hospitals. This study aimed to examine the relationship between operative outcomes and a hospital's overall NEC patient volume, as well as operative volume for NEC across children's hospitals. MethodsA retrospective, cross sectional analysis was performed using the Pediatric Health Information System (PHIS). NEC patients were identified using ICD-10 codes from 2016-2021. Two hospital volume metrics were used: annual volume of NEC patients treated in the NICU, and annual volume of NEC patients undergoing surgery. Primary outcome was mortality and secondary outcome was complication. Regression models were estimated to determine the association between each volume metric and patient outcomes. ResultsA total of 1780 children who had surgery for NEC from 47 tertiary children's hospitals were included. Overall mortality rate was 23.3%. Median overall and surgical NEC patient volume per hospital were 53 [IQR 41-65] and 11 [IQR 7-16], respectively. A chi-squared test comparing mortality to volume metrics for total NEC volume, and surgical NEC volume showed no significant associations (p=0.07, p=0.74). Simple logistic regression demonstrated total NEC patient volume to have best fit with mortality outcome. ConclusionNo statistically significant association was found between the two volume metrics and discharge mortality. This lack of association suggests that the volume in these tertiary children's hospitals may be higher than the threshold for optimized outcomes. Level of EvidenceIII

Does measuring matter? Abdominal girth changes and the need to operate in necrotizing enterocolitis

IntroductionNecrotizing enterocolitis (NEC) is a disease of prematurity resulting in surgery for approximately 30% of patients. Trends in abdominal distention can assist decision-making. There is no defined abdominal girth change that predicts need for surgery. The aim of this study was to determine any relationship between girth change and surgery for NEC. MethodsAn IRB-exempt review of NEC patients from 2015 to 2020 at a single institution was performed. Inclusion and exclusion criteria were applied. Demographics, daily largest girth, and laboratory data were recorded. Average daily%girth change was calculated, as was largest%change from first girth of NEC episode. Statistical analysis was performed using Mann-Whitney U tests and ROC curve (p<0.05). Results43/178 patients were analyzed. 30% underwent surgery. There was a statistically significant difference in average daily%girth change between medical and surgical patients based on <30 and >30 week gestational age; this significance persisted when analyzing birth weight. Laboratory data was non-contributory. Further subgrouping did not yield appropriate sample sizes for analysis. Threshold to predict surgery was a 1.2% daily girth increase based on ROC analysis. ConclusionAbdominal girth changes differed significantly between medical and surgical NEC. Establishing a threshold for%change in girth would be valuable for NEC management to assist in surgery decision-making; the value found in this study may be within measurement error. However, any girth increase put the patient at risk for surgery. Abdominal girths should continue to be included in surgical decision-making for premature infants with NEC.

Surgical NEC, Randomized Control Trials, Missed Opportunity.

Surgical NEC, Randomized Control Trials, Missed Opportunity.

COGNITIVE OUTCOMES IN CHILDREN WITH CONDITIONS AFFECTING THE SMALL INTESTINE : A SYSTEMATIC REVIEW

It is possible that children who suffer from gastrointestinal (GI) disorders have a less-than-ideal nutritional status, particularly as a result of malabsorption and symptoms that are brought on by a restricted food intake. A cognitive function is any conscious mental action, including thinking, remembering, learning, or utilizing language. Examples of cognitive functions include these. Attention, memory, consideration, the ability to solve problems, and executive abilities such as planning, assessing, supervising, and evaluating are all aspects of cognitive function. Neurodevelopment issues in intestinal failure (IF) children have surfaced. The researchers Hukkinen et al. reviewed the existing research and came to the conclusion that children with IF are at a high risk of delayed psychomotor and cognitive development. However, this conclusion was drawn from a small number of studies that used a variety of research methods. This study reveals that children with IF and surgical NEC are at a greater risk of having bad cognitive outcomes in patients with illnesses affecting the small intestine who require PN. These patients include individuals with conditions such as Crohn's disease and ulcerative colitis.

Reduction of absolute monocyte counts is associated with the severity of preterm necrotizing enterocolitis

ObjectiveNecrotizing enterocolitis (NEC) is characterized by a rich infiltration of macrophages in the intestines, which is derived from monocytes in the blood. The authors aimed to explore the changing trend of absolute monocyte counts (AMC) over time in NEC infants and to verify whether the reduction of AMC correlates with the severity of NEC and whether it can be used to identify infants who need surgery. MethodThe authors collected the clinical data of 66 control and 222 NEC infants. The NEC infants were divided into medical NEC (M-NEC) and surgical NEC (S-NEC). The counting of monocyte and their percentage change were compared at the time of birth, before NEC (baseline), the onset of NEC and after NEC (recovery). In addition, the same comparison was made among stages 1, 2 and 3 of Bell's staging, respectively. ResultsThe authors found that the AMC in NEC infants decreased sharply at the onset. Further comparison was made between 172 cases of M-NEC and 50 cases of S-NEC. It was discovered that the AMC reduced more in S-NEC infants at onset, but it increased more at recovery. In addition, the authors found that among stage 1,2 and 3, stage 3 had the lowest AMC and the largest percentage decrease at the onset. ConclusionThe AMC decreases sharply in NEC infants at onset, and the degree of decline is associated with the severity of NEC. AMC is expected to be a marker of NEC and provide a reference for clinicians in the diagnosis and treatment of NEC.

Surgical treatment for necrotizing enterocolitis: a new score to extreme surveillance.

The time to perform a surgical intervention in necrotizing enterocolitis remains a challenge for the pediatric surgeon. We design a novel score system to predict infants in high risk for the development of surgical necrotizing enterocolitis. A total of 124 consecutively patients diagnosed of NEC at the University Hospital of A Coruña, Spain were included in the study. Associations were analyzed by bivariate and multivariate analysis. We applied multivariate logistic regression modeling to identify factors that could provide accurate risk of surgical NEC. We include not only analytical and radiological parameters or physical examination, but we also analyzed prenatal, sociodemographic, perinatal and peripartum variables that conditioned the presence of predispose factors, which could determine the debut of this entity and in its progression. Patients requiring surgical treatment have presented an antecedent of respiratory distress (worsening of the ventilatory requirements) in the perinatal period, they present higher values of glycemia at diagnosis of the illness, debut with coagulopathy and have in laboratory findings marked neutrophilia. Our score system obtained by combining several parameters could detect infants at risk of developing severe necrotizing enterocolitis improving the morbidity and mortality associated with delay in the surgical treatment.

Correlation of placental pathology with the postoperative outcomes and white matter injury in preterm infants following necrotizing enterocolitis.

To determine the association of placental pathologic lesions with postoperative outcomes, survival, and white matter injury (WMI) in preterm infants with NEC. A retrospective chart review of 107 neonates with NEC (Bell stage > IIa) from Jan 2013- June 2020 was completed. Demographic, clinical, and outcome data were compared between infants with or without placental pathologic lesions. In this cohort, 59/107 (55%) infants had medical NEC, and 48 (45%) had surgical NEC. The infants had a mean gestational age of 28.1±3.7 weeks and a birth weight of 1103±647 g. Maternal vascular malperfusion (82/107, 76.6%) and acute histological chorioamnionitis (42, 39.3%) were the most common pathological placental lesions. Acute histologic chorioamnionitis with fetal inflammatory response was more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). The NEC Infants with WMI on brain MRI scans had a significantly higher incidence of acute histological chorioamnionitis (52% vs. 27.8%; P = 0.04). No significant differences in mortality, length of stay and postoperative outcomes in neonates with and without acute histologic chorioamnionitis with fetal inflammatory response were noted. On unadjusted logistic regression, acute histologic chorioamnionitis without fetal inflammatory response was also associated with higher odds of WMI (OR 2.81; 95% CI 1.05-7.54; p = 0.039). Acute histological chorioamnionitis without fetal inflammatory response was associated with higher odds of WMI in infants with NEC, with no significant impact on mortality and other postoperative outcomes.

Admission temperature and neonatal outcomes - single-centre experience in Saudi Arabia

This study aimed to investigate the association between admission hypothermia (AH), neonatal mortality and major neonatal morbidities in preterm infants <33 weeks' gestation. An additional aim of the study was to examine changes in the prevalence of admission hypothermia after the initiation of a thermoregulation quality improvement (QI) project. This is a retrospective cohort study of preterm infants < 33 weeks' gestation born at King AbdulAziz Medical City Riyadh (KAMC-R) between January 2017 to December 2020. Eight-hundred infants were born during the study period. Four hundred and one infants (50.1%) had an admission temperature of <36.5°C and a further 399 (49.9%) had an admission temperature of >36.5°C. The mortality before discharge was 15.7% in infants with AH compared to 4.8% among those with an admission temperature above 36.5°C. This remained statistically significant after adjustments for gestational age and maternal PET status on a multivariate analysis (P=.001, OR 2.7,95%CI 1.5-4.7). The need for mechanical ventilation (P=.005) and incidence of surgical NEC (P=.030) were significantly different between the two temperature groups. Mean (SD) admission temperature increased from 36.3°C to 36.6°C following the thermoregulation intervention program (P <.001). Admission temperature <36°C is associated with higher mortality in the first week (P=.001, OR 3.3,95% CI (1.7-6.6)) and increased incidence of cystic PVL (P=.04, OR 2.1, CI (1.03-4.3)). Preterm infants with AH suffered higher mortality and greater neonatal morbidities.

Long-Term Outcome of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are complications in preterm infants associated with high morbidity, mortality, impaired growth, and neurodevelopmental (ND) outcomes. Few studies have reported growth or ND outcomes of infants born extremely preterm with NEC/SIP beyond early childhood. Here, we compared anthropometric and ND outcomes, at 10 and 15 years, for children with medical NEC, surgical NEC, SIP, and neither NEC nor SIP. Participants from the prospective longitudinal extremely low gestational age newborns study were evaluated at ages 10 and 15 years for anthropometrics, neurocognition, attention-deficit/hyperactivity disorder, epilepsy, and gross motor function. At age 10 years, 889 children were followed-up (medical NEC = 138, surgical NEC = 33, SIP = 29, no NEC/SIP = 689), and 694 children were followed up-at 15 years. Children with medical NEC had similar weight, BMI, height, and head circumference compared with controls at both 10 and 15 years. At 15 years, children with surgical NEC had lower weight z-score (adjusted β: -0.75, 95% confidence interval [CI]: -1.25 to -0.25), lower BMI z-score (adjusted β: -0.55, 95% CI: -1.09 to -0.01), and lower height z-score (adjusted β: -0.65, 95% CI: -1.16 to -0.14). Children with SIP had lower weight and height z-scores at age 10 years when adjusted for sample attrition, but these differences were not significant when adjusted for confounders. We observed no differences in long-term ND outcomes. Surgical NEC- and SIP-associated growth impairment may persist through late childhood. ND outcomes among school-aged children born extremely preterm with any NEC or SIP are no different from children without NEC/SIP.

Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis

ObjectiveNecrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear.DesignTo further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth.ResultsWe found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants.ConclusionWe confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC.

Predictive factors for the surgical treatment of necrotizing enterocolitis in preterm infants: a single-center retrospective study

BackgroundNecrotizing enterocolitis (NEC) is a gastrointestinal disease that tends to occur in premature infants. Some features may be associated with an increased probability that preterm infants with NEC will require surgical treatment. This study aimed to identify the factors that increased the probability of surgical treatment in infants with NEC.MethodsWe retrospectively analyzed the data of premature infants with NEC who were hospitalized at The Affiliated Hospital of Qingdao University from April 2011 to April 2021. According to the treatments received, these patients were divided into medical NEC group and surgical NEC group. The perinatal characteristics, clinical manifestations, and laboratory values before the onset of NEC were subjected to univariate and multivariate analyses.ResultsA total of 623 preterm infants with NEC (> Bell’s stage I) were included in this study, including 350 (56%) who received surgical treatment and 273 (44%) who received conservative medical treatment. Multivariate analysis showed that lower gestational age (P = 0.001, odds ratio (OR) (95% CI) = 0.91[0.86–0.96]), early occurrence of NEC (P = 0.003, OR (95% CI) = 0.86 [0.77–0.95]), hemodynamically significant patent ductus arteriosus (P = 0.003, OR (95% CI) = 7.50 [2.03–28.47]), and low serum bicarbonate (P = 0.043, OR (95% CI) = 0.863 [0.749–0.995]) were associated with an increased probability of surgical treatment in preterm infants with NEC.ConclusionsOur findings were applied to identify potential predictors for surgical treatment in preterm infants with NEC, which may facilitate early decisive management.