Necrotizing Enterocolitis Mortality Research Articles

Association between gastrointestinal perforation and patent ductus arteriosus in extremely-low-birth-weight infants: a retrospective study of our decade-long experience.

Management of persistently patent ductus arteriosus (PDA) in extremely low-birth-weight infants (ELBWIs) requires attention due to the risk of tissue hypoperfusion. We investigated the association between PDA and gastrointestinal perforation. We performed a retrospective chart review from 2012 to 2021. Preterm (≤ 32weeks) ELBWIs with PDA after birth who developed necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and idiopathic gastric perforation were included; ELBWIs with congenital heart disease were excluded. Data were analyzed using chi-squared tests with Yates; correction, and Student's t test. Five hundred thirty-five preterm ELBWIs were analyzed, including 20 with NEC, 22 with FIP, and 1 with gastric perforation. In NEC and FIP, the ductus arteriosus remained open in 40% (4/10) and 63.6% (14/22) of cases, respectively, and cyclo-oxygenase inhibitor treatment showed poor efficacy (p = 0.492 and 0.240). The incidence of perforation in NEC (4/9 vs. 6/11, p = 0.653), mortality in NEC (3/4 vs. 3/6, p = 0.895) and FIP (6/14 vs. 3/8, p = 0.838) did not differ according to whether the PDA persisted or resolved. The presentation of PDA did not affect the mortality or morbidity of ELBWIs. However, it is essential to consider the possibility of gastrointestinal perforation due to decreased organ blood flow caused by ductal steal.

The Outcome of Blood Transfusions in Conservative and Surgical Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

In necrotizing enterocolitis (NEC), blood transfusions (BTs) are a disputed factor concerning the etiology and the outcome. We assessed retrospectively the effects of preonset BT on the outcome of NEC and spontaneous intestinal perforation (SIP). With ethical consent, we reviewed the hospital records of 113 neonates from 2002 to 2019 with surgical NEC (NECs) (n = 57), conservatively treated NEC (NECc) (n = 20), and SIP (n = 36). The onset was defined as the day of surgery (NECs and SIP) or diagnosis (NECc). The effects of preonset BT (total, beyond 48 hours, and within 48 hours) were compared with the effects of birth weight (BW), gestational age (GA), intracerebral hemorrhage, respiratory distress syndrome, septicemia, and patent ductus arteriosus. Main outcome measure was 2-week mortality, and secondary measures were small intestinal loss and days on parenteral nutrition (PN). Overall mortality (8.9%) was predicted independently by BT total and BT beyond 48 hours, risk ratio (RR) = 1.1 to 1.2 (95% confidence interval [CI] = 1.0-1.4), p = 0.01 to 0.02, and BW and GA, RR = 0.7 to 1.0 (95% CI = 0.5-1.0), p = 0.02 to 0.04. Mortality in NECs (12%) was predicted by BT total and BT beyond 48 hours only, RR = 1.1 to 1.2 (95% CI = 1.0-1.5), p = 0.03 to 0.04. BT within 48 hours of onset did not predict mortality. No factors were related with secondary outcome measures or with mortality in patients with SIP or NECc. In NECs, preoperative BT and BT given more than 48 hours before surgery were correlated with slightly increased 2-week mortality but not with small intestinal loss or duration of PN.

Extended-spectrum beta-lactamase (ESBL) producing Enterobacterales in stool surveillance cultures of preterm infants are no risk factor for necrotizing enterocolitis: a retrospective case\u2013control study over 12\xa0years

PurposeMicrobial dysbiosis has been found preceding necrotizing enterocolitis (NEC) in preterm infants; thus, we aimed to investigate whether there is evidence that neonates with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) positive stool cultures are at higher risk for NEC at the NICU.MethodsWe included very preterm inborn infants of ≤ 32 weeks of gestational age being fecal carriers of ESBL-E and compared them with 1:1 matched (gestational age, birth weight, gender and year) controls tested negative for ESBL-E in the stool between 2005 and 2016. An association with NEC was defined as the first detection of ESBL-E before or at the time of definite diagnosis of NEC.ResultsDuring the study period, we diagnosed 217 infants with a total of 270 ESBL-E. We identified ten different species with ESBL-producing Klebsiella oxytoca being the most common one (46%) followed by Klebsiella pneumoniae (19%), and Citrobacter freundii (17%). Ten out of 217 infants had any kind of NEC in the case group compared to two of the controls (p < 0.01), but only four cases with predefined criteria were associated with NEC ≥ stage IIa (1.8 vs. 0.5%, p = 0.089, OR 4.1, CI95% 0.45–36.6). NEC mortality rate was 2/8 (25%).ConclusionsWe observed a threefold increase of ESBL-E in stool surveillance cultures during study time and germs were dominated by ESBL-producing Klebsiella spp. There was no evidence that preterm infants colonized with ESBL-E in the stool were at higher risk for definite NEC.

Trends in incidence and outcomes of necrotizing enterocolitis over the last 12 years: A multicenter cohort analysis

ObjectiveWe sought to describe changes in the incidence and mortality of necrotizing enterocolitis (NEC) and associated surgical management strategies for very low birth weight (VLBW) infants. MethodsData were prospectively collected on VLBW infants (≤1500 g or < 29 weeks) born 2006 to 2017 and admitted to 820 U.S. centers. NEC was defined by the presence of at least one clinical and one radiographic finding. Trends analyses were performed to assess changes in incidence and mortality over time. ResultsOf 473,895 VLBW infants, 36,130 (7.6%) were diagnosed with NEC, of which 21,051 (58.3%) had medical NEC and 15,079 (41.7%) had surgical NEC. Medical NEC decreased from 5.3% to 3.0% (p < 0.0001). Surgical NEC decreased from 3.4% to 3.1% (p = 0.06). Medical NEC mortality decreased from 20.7% to 16.8% (p = 0.003), while surgical NEC mortality decreased from 36.6% to 31.6% (p < 0.0001). In the surgical cohort, the use of primary peritoneal drainage (PPD) versus initial laparotomy rose from 23.2% to 46.8%. ConclusionThe incidence and mortality of both medical and surgical NEC have decreased over time. Changes in surgical management during this time period included the increased utilization of primary peritoneal drainage. Type of studyPrognosis study. Level of evidenceLevel II.

Laparoscopy to Assist Surgical Decisions Related to Necrotizing Enterocolitis in Preterm Neonates.

Aim of the Study: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that mainly affects preterm infants. Despite advancements in neonatal care, mortality of NEC remains high and controversies exist regarding the most appropriate time for surgical intervention and challenging of diagnosing NEC. Using a pig model of NEC, we aimed to examine if laparoscopy is feasible for diagnosis of NEC. Methods: Preterm caesarean-delivered piglets (n = 42) were fed with increasing amounts of infant formula up to 5 days to induce NEC. On days 3-5, we examined the intestine by laparoscopy under general anesthesia. The bowel was examined by tilting the pigs from supine position to the left and right side. Macroscopic NEC lesions were identified and graded according to a macroscopic scoring system, then a laparotomy was performed to rule out any organ injury and missed NEC lesions. Results: Visible NEC lesions (scores 4-6) were found in 26% (11/42) of the piglets. A positive predictive value of 100% was found for laparoscopy as a diagnostic marker of NEC in both colon and the small intestine. One piglet had a higher NEC score in the small intestine found at laparotomy, than at laparoscopy, resulting in a sensitivity of 67%, and a specificity of 100% for the small intestine. Conversely, both the sensitivity and specificity for colon was 100%. Acceptable levels of agreement was found, with minimal proportional bias in both colon and the small intestine for laparoscopy and laparotomy. Ultrasound examination had a lower sensitivity of 67% and specificity of 63%. All piglets were respiratory and circulatory stable during the procedure. Conclusions: In preterm piglets, laparoscopy is a feasible tool to diagnose NEC with a high positive predictive value and a high specificity.

Lactoferrin Reduces Necrotizing Enterocolitis Severity by Upregulating Intestinal Epithelial Proliferation.

Necrotizing enterocolitis (NEC) is a devastating intestinal illness in premature infants characterized by severe intestinal inflammation. Despite medical interventions, NEC mortality remains alarmingly high, which necessitates improved therapies. Lactoferrin is among the most abundant proteins in human milk and has important immunomodulatory functions. While previous studies have indicated protective effects of lactoferrin against neonatal sepsis and NEC, the underlying mechanism remains unclear. We hypothesize that lactoferrin downregulates inflammation and upregulates proliferation in intestinal epithelium during NEC injury. NEC was induced by hypoxia, gavage feeding of hyperosmolar formula and lipopolysaccharide between postnatal day P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). Lactoferrin (0.3 g/kg/day) was administered once daily by gavage from P6 to P8 in both NEC (NEC + Lac; n = 9) and control mice (Cont + Lac; n = 5). Distal ileum was harvested on P9 and analyzed for disease severity, inflammation, and proliferation. Groups were compared using one-way ANOVA and t-test appropriately; p < 0.05 was considered significant. Compared to NEC group, lactoferrin-treated NEC mice had reduced disease severity, reduced inflammation markers IL-6 and TNF-α expression and increased intestinal stem cell marker Lgr5 + expression. Lactoferrin-treated NEC mice exhibited increased nuclear β-catenin, indicating upregulated Wnt pathway, and increased Ki67 positivity, suggesting enhanced proliferation. Furthermore, lactoferrin administration to control mice did not affect intestinal inflammation as well as Lgr5 + stem cell expression and epithelial proliferation. This supports the safety of lactoferrin administration and indicates that the beneficial effects of lactoferrin are present when intestinal injury such as NEC is present. Lactoferrin administration reduces the intestinal injury in experimental NEC by downregulating inflammation and upregulating cell proliferation. This beneficial effect of lactoferrin in stimulating cell proliferation is mediated by the Wnt pathway. This experimental study provides insights on the mechanism of action of lactoferrin in NEC and the role of lactoferrin in enteral feeding.

Toll-Like Receptor-Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) remains the leading cause of death from gastrointestinal disease in premature infants and attacks the most fragile patients at a time when they appear to be the most stable. Despite significant advances in our overall care of the premature infant, NEC mortality remains stubbornly high. There is no specific treatment for NEC beyond broad-spectrum antibiotics and intestinal resection, and current efforts have focused on preventive strategies. Over the past decade, we have proposed a unifying hypothesis to explain the pathogenesis of NEC in premature infants that suggests that NEC develops in response to an imbalance between exaggerated proinflammatory signaling in the mucosa of the premature gut leading to mucosal injury, which is not countered effectively by endogenous repair processes, and in the setting of impaired mesenteric perfusion leads to intestinal ischemia and disease development. One of the most important pathways that mediates the balance between injury and repair in the premature intestine, and that plays a key role in NEC pathogenesis, is Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide on gram-negative bacteria. This review focuses on the role that the TLR4-mediated imbalance between proinflammatory and anti-inflammatory signaling in the premature intestinal epithelium leads to the development of NEC, and will explore how an understanding of the role of TLR4 in NEC pathogenesis has led to the identification of novel preventive or treatment approaches for this devastating disease.

Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis.

Feeding and systemic hypoxia are major stresses inducing necrotizing enterocolitis (NEC). This study aims to investigate the role of systemic hypoxia in NEC and its effect before and after feeding. Neonatal mice were studied in three groups. Control (N=9): breast feeding; NEC A (N=8), gavage feeding+lipopolysaccharide (LPS)+preprandial hypoxia; and NEC B (N=9), feeding+LPS+postprandial hypoxia. Pimonidazole, a hypoxia marker, was injected intraperitoneally before ileum was harvested for histology and quantitative RT-PCR studies. Statistical analysis was done using the ANOVA and Chi-square test. NEC incidence was 62.5% in NEC A and 88.9% in NEC B. The mortality in NEC B (55.6%) but not A (25%) is significantly higher than control (0%, p<0.05). Pimonidazole staining elevated in both NEC A and B with higher pimonidazole grade in NEC B (p<0.01). Both NEC groups had increased the expression of hypoxia-related genes: HIF-1α, GLUT-1, and PHD-3 with GLUT-1 expressed more in NEC B compared with NEC A (p<0.01). The inflammation marker, IL6, was similarly raised in both NEC A and B. Feeding and postprandial hypoxia synergistically induce intestinal hypoxia in NEC. As feeding increases intestinal oxygen demand, maintaining a balance between intestinal oxygen supply and demand is important to prevent NEC.

Analysis of clinical characteristics of necrotizing enterocolitis in term infants

To investigate the characteristics and outcomes of necrotizing enterocolitis (NEC) in Chinese term infants population. A national neonatal necrotizing enterocolitis network was established. Neonates as having necrotizing enterocolitis with gestation age ≥37 weeks were identified if they met the accepted diagnostic criterion during the study period from Jan 1(st) 2011 to Dec 31(st) 2011. The data of maternal and neonates' characteristics, the comorbidities, the clinical interventions prior to NEC, the clinical courses and radiology results, the medical and surgical treatment and the outcomes were collected. SPSS 19.0 software was used to do statistic analysis. Logistic-regression models were used to analyze the risk factors for death in infants with NEC, odds ratio (OR) and 95% confidence interval (CI) were calculated. There were 231 067 newborn infants, 164 307 of them were term infants, admitted to 95 hospitals in main land China. There were 718 term infants were diagnosed as necrotizing enterocolitis with the incidence of 0.44%. There were 294 term infants cases identified as ≥stage 2 necrotizing enterocolitis for the analysis, including 193 cases of stage 2 and 101 cases of stage 3.The mean gestation age was (39.0±1.3) weeks, and the mean birth weight was(3 087.4±548.3)g. The percentage of small for gestation age was 20.4%. The onset age of NEC was 5 (2-11)d. The percentage of cases received breast milk feeding was 23.7%. The most common comorbidities were sepsis (9.5%, 28/294), asphyxia (9.5%, 28/294), pneumonia (7.8%, 23/294) and congenital megacolon (7.5%, 22/294). The bowel perforation rate was 13.9%. The rate of cases who received surgical treatment was 25.2%(76.6% small intestinal necrosis and 65.8% small intestinal perforation). The mortality rate was 28.9%(the mortality rate were 20.7% and 44.6% in stage 2 and stage 3 NEC, respectively). Noninvasive continuous positive airway pressure treatment for NEC (OR=5.278, 95% CI: 2.058-13.533, P<0.01) and NEC staging 3 (OR=3.156, 95% CI: 1.766-5.642, P<0.01) were statistically significantly associated with mortality of NEC. The term infants with necrotizing enterocolitis usually have the underlying comorbidities. The breastmilk feeding rate is low. Necrotizing enterocolitis remains high mortality in term neonates in Chinese neonatal units. Noninvasive continuous positive airway pressure treatment for NEC is statistically significantly associated with mortality of NEC.

The complete blood cell count in a refined cohort of preterm NEC: the importance of gestational age and day of diagnosis when using the CBC to estimate mortality.

The value of the white blood cell count (WBC) in necrotizing enterocolitis (NEC) is controversial. One reason for this confusion may be that the various WBC lineages change substantially with increasing gestational age and thereby age of NEC onset. This study postulated that if a data set was large enough and the diagnosis of NEC clean enough, absolute WBC counts would facilitate prediction of NEC mortality. The objective of this study was to determine whether absolute WBC counts enhance the prediction of NEC mortality. A de-identified data subset from the Pediatrix national data set specific to the diagnoses of NEC in patients who had a CBC drawn on the day of diagnosis (exclusive of the diagnoses of spontaneous intestinal perforations and congenital anomalies) was the target for analysis. Values of primary interest included: gestation, day of diagnosis, absolute WBC count, platelet count, hematocrit, mortality and the day of diagnosis. Stepwise regression analysis was used to predict mortality. A total of 4059 (79%) survivors and 1107 (21%) infants who died with a diagnosis of medical or surgical NEC were included in the data set. Associations with mortality were found with low gestational age, low platelet count, low hematocrit, high band/segmented neutrophil ratio, earlier day of diagnosis, high birth weight z-score, non-white race, no antenatal steroids in gestations above 24 weeks, absolute lymphocyte count adjusted for gestational age, and absolute monocyte count high and low values. A stepwise regression analysis yielded a receiver-operator curve of 0.819 with a sensitivity of 65% and specificity of 84%. Absolute WBC values enhance prediction of NEC survival when used in combination with readily available data on the day of NEC diagnosis.

Serious Congenital Heart Disease and Necrotizing Enterocolitis in Very Low Birth Weight Neonates

Infants with serious congenital heart disease (CHD) appear to be at increased risk for necrotizing enterocolitis (NEC). This study aimed to quantify the incidence and mortality of NEC among very low birth weight (VLBW) neonates with serious CHD, and identify specific CHD diagnoses at the highest risk for developing NEC. Data were prospectively collected on 257,794 VLBW (401 to 1,500 g) neonates born from 2006 to 2011 and admitted to 674 Vermont Oxford Network US centers. Entries were coded for specific CHD diagnoses and reviewed for completeness and consistency. Survival was defined as alive in-hospital at 1 year or discharge. Of eligible neonates, 1,931 had serious CHD. Of these, 253 (13%) developed NEC (vs 9% in infants without CHD, adjusted odds ratio [AOR] 1.80, p<0.0001). Mortality for neonates with CHD and no NEC was 34%, vs 55% for those with CHD and NEC (p<0.0001). Both groups of CHD patients had higher mortality than infants with NEC without CHD (28%, p<0.0001). Although NEC mortality overall decreases with higher birth weight, mortality for NEC and CHD together does not. The incidence of NEC is significantly higher in VLBW neonates when CHD is present. The mortality of CHD and NEC together is substantially higher than that with each disease alone. Infants with atrioventricular canal appear to have higher risk for developing NEC than other CHD diagnoses. In addition to providing benchmark incidence and mortality data, these findings may have utility in the further study of the pathophysiology of NEC.

Mortality and Management of Surgical Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Prospective Cohort Study

Necrotizing enterocolitis (NEC) is a leading cause of death in very low birth weight (VLBW) neonates. The overall mortality of NEC is well documented. However, those requiring surgery appear to have increased mortality compared with those managed medically. The objective of this study was to establish national birth-weight-based benchmarks for the mortality of surgical NEC and describe the use and mortality of laparotomy vs peritoneal drainage. There were 655 US centers that prospectively evaluated 188,703 VLBW neonates (401 to 1,500 g) between 2006 and 2010. Survival was defined as living in-hospital at 1-year or hospital discharge. There were 17,159 (9%) patients who had NEC, with mortality of 28%; 8,224 patients did not receive operations (medical NEC, mortality 21%) and 8,935 were operated on (mortality 35%). On multivariable regression, lower birth weight, laparotomy, and peritoneal drainage were independent predictors of mortality (p < 0.0001). In surgical NEC, a plateau mortality of around 30% persisted despite birth weights >750 g; medical NEC mortality fell consistently with increasing birth weight. For example, in neonates weighing 1,251 to 1,500 g, mortality was 27% in surgical vs 6% in medical NEC (odds ratio [OR] 6.10, 95% CI 4.58 to 8.12). Of those treated surgically, 6,131 (69%) underwent laparotomy only (mortality 31%), 1,283 received peritoneal drainage and a laparotomy (mortality 34%), and 1,521 had peritoneal drainage alone (mortality 50%). Fifty-two percent of VLBW neonates with NEC underwent surgery, which was accompanied by a substantial increase in mortality. Regardless of birth weight, surgical NEC showed a plateau in mortality at approximately 30%. Laparotomy was the more frequent method of treatment (69%) and of those managed by drainage, 46% also had a laparotomy. The laparotomy alone and drainage with laparotomy groups had similar mortalities, while the drainage alone treatment cohort was associated with the highest mortality.

Mortality associated with laparotomy-confirmed neonatal spontaneous intestinal perforation: A prospective 5-year multicenter analysis

BackgroundSpontaneous intestinal perforation (SIP) has been recognized as a distinct disease entity. This study sought to quantify mortality associated with laparotomy-confirmed SIP and to compare it to mortality of laparotomy-confirmed necrotizing enterocolitis (NEC). MethodsData were prospectively collected on 177,618 very-low-birth-weight (VLBW, 401–1500g) neonates born between January 2006 and December 2010 admitted to US hospitals participating in the Vermont Oxford Network (VON). SIP was defined at laparotomy as a focal perforation of the intestine without features suggestive of NEC or other intestinal abnormalities. The primary outcome was in-hospital mortality. ResultsAt laparotomy, 2036 (1.1%) neonates were diagnosed with SIP and 4076 (2.3%) with NEC. Neonates with laparotomy-confirmed SIP had higher mortality (19%) than infants without NEC or SIP (5%, P=0.003). However, laparotomy-confirmed SIP patients had significantly lower mortality than those with confirmed NEC (38%, P<0.0001). Mortality in both NEC and SIP groups decreased with increasing birth weight and mortality was significantly higher for NEC than SIP in each birth weight category. Indomethacin and steroid exposure were more frequent in the SIP cohort than the other two groups (P<0.001). ConclusionsIn VLBW infants, the presence of laparotomy-confirmed SIP increases mortality significantly. However, laparotomy-confirmed NEC mortality was double that of SIP. This relationship is evident regardless of birth weight. The variant mortality of laparotomy-confirmed SIP versus laparotomy-confirmed NEC highlights the importance of differentiating between these two diseases both for clinical and research purposes.

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

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

Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

The Risk of Necrotizing Enterocolitis After Indomethacin Tocolysis

Tocolytic agents such as indomethacin are commonly used to prevent preterm delivery despite little evidence of proven benefit. Administration of postnatal indomethacin in preterm infants seems to be associated with an increased incidence of necrotizing enterocolitis (NEC). It has been hypothesized that antenatal indomethacin (AI), which readily crosses the placenta, may also increase the risk for NEC in preterm infants. This historical cohort study was designed to investigate the association between AI and NEC in preterm infants. The cohort included preterm infants at 23 to 32 weeks' gestational age without major congenital anomalies who had been admitted to a hospital NICU (neonatal intensive care unit) between 2004 and 2006. The investigators reviewed and abstracted maternal and neonatal data in medical records for preterm infants. Bivariate analyses, multivariate logistic regression, and propensity score analysis were used to determine the association between AI exposure within 15 days before delivery (predictor variable) and NEC (with NEC defined as modified Bell's stage 2a or higher) in the first 15 days of life (early NEC)—the primary outcome variable. Of the 628 infants who met inclusion criteria, 63 received AI and 28 developed early NEC. Exposure of mothers to AI was significantly associated with multiple gestation, white race, antenatal corticosteroids, and magnesium sulfate. In neonates, AI exposure was associated with lower birth weight and gestational age, a need for an umbilical arterial catheter, respiratory distress syndrome, postnatal vasopressors and antibiotics, patent ductus arteriosus, sepsis, NEC, intraventricular hemorrhage, and mortality. Multivariate logistic regression showed an association between AI exposure and the development of early NEC; the adjusted odds ratio was 7.193, with a 95% confidence interval of 2.514–20.575 (which represents a number needed to harm of 5). The association of AI and early NEC remained significant when multivariate logistic regression was repeated using AI exposure within 5 days before delivery as the predictor variable, when analyses were stratified according to gestational age, and on propensity score analysis. These findings show that multiple clinical factors, including AI, are associated with NEC in preterm infants in the first 15 days of life. Exposure to AI in preterm infants in the first 15 days of life may contribute to the morbidity and mortality of NEC.

Mortality of necrotizing enterocolitis expressed by birth weight categories

Purpose Low birth weight is the most important risk factor for developing necrotizing enterocolitis (NEC). We aimed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC. Methods Five hundred eleven centers belonging to the Vermont Oxford Network prospectively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006. The primary outcome variable was in-hospital mortality. Results Birth weight was divided into 4 categories by 250-g increments. The NEC risk ( P < .001) and mortality ( P < .001) decreased with higher birth weight category. Necrotizing enterocolitis was associated with a significant odds ratio for death for each category ( P < .001). Across groups, the odds ratio for NEC mortality increased with higher birth weight category (category 1 = 1.6 vs category 4 = 9.9; P < .001). Conclusion The in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category. Although the risk and absolute mortality of NEC decrease with higher birth weight, the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight. These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers.

Necrotizing Enterocolitis: Risk Factor Analysis and Role of Gastric Residuals in Very Low Birth Weight Infants

Necrotizing enterocolitis (NEC) usually occurs in very low birth weight infants and is the most common gastrointestinal emergency in the neonatal intensive care unit. Inasmuch as NEC mortality and morbidity are extremely high, early diagnosis becomes essential. Increased gastric residuals are used to define NEC stage, but studies on qualitative and quantitative residual features as markers of NEC risk are still lacking. The primary goal of this analysis was evaluation of the role of gastric residuals in early identification of patients at risk for NEC. The secondary goal was investigation of NEC risk factors, besides prematurity and birth weight. In a case-control study, NEC patients were matched with control infants by gestational age and birth weight. Feeding tolerance was assessed by maximum gastric residual volume, maximum residual as percentage of previous feeding, and residual appearance. Mortality and NEC risk factors were also evaluated. In all, 844 very low birth weight infants were admitted to the neonatal intensive care unit during the study period, with an overall mortality before discharge of 14.6%. NEC frequency was 2%. Patent ductus arteriosus was significantly associated with NEC. Mean maximum residual from birth to NEC onset and maximum residual as percentage of the corresponding feed volume were significantly higher in patients than in control infants, as was the percentage of infants with hemorrhagic residuals. Gastric residuals are a marker of feeding intolerance, and bloody residuals seem to be the best predictor for NEC. For early detection of very low birth weight infants at risk for NEC, both gastric residual volumes and bloody residuals represent an early relevant marker.

The Experience of Surgical Treatment of Necrotizing Enterocolitis

Purpose: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder of the intestine, causing high mortality and morbidity. We investigated the single center experience about the operative indication, treatment method, and mortality in NEC. Methods: The medical records of infants (＜1 year old) who underwent the operation due to complications of NEC at the Asan Medical Center from Jan 1997 to Dec 2007 were retrospectively reviewed. Results: Among 49 patients (M：F = 34：15), 37 underwent the operation at acute phase of NEC, average 26.43±35.43 days after birth (3∼168), due to pneumoperitoneum in 23, clinical deterioration in 12 and abdominal mass in 2. Average gestational age was 234.64±38.27 days (161∼279) and birth weight was 2,061.38±999.49 g (563∼3,740). The extent of necrosis was classified grossly as focal in 14 cases, multifocal in 14 and panintestinal in 9 and the operative methods were enterostomy in 30 patients, resection and anastomosis in 6 and open drainage in 1. Thirteen patients (35.1%) were expired - 8 (21.6%) died of necrotizing enterocolitis and 5 died of other causes. The other 12 patients underwent operation for stricture after NEC at average 81.17±77.22 days after birth (32∼317). Average gestational age was 240.83±34.4 days (173∼280) and birth weight was 2,089.83±862.47 g (710∼3,200). Eight patients underwent resection and anastomosis including stricture and 4 patients underwent enterostomy. Conclusion: Resection and enterostomy was the preferred procedure but resection and anastomosis did not increase morbidity or mortality. Quite a number of patients suffered from the stricture after NEC.

Trends in infant mortality from necrotising enterocolitis in England and Wales and the USA

Necrotising enterocolitis (NEC) is a devastating disease that affects up to 5% of infants in neonatal units and overall affects 0.5–5/1000 live births1 (33/1000 very-low-birthweight (VLBW) infants2). Mortality remains high...