Intestinal Oxygenation and Survival After Surgery for Necrotizing Enterocolitis: An Observational Cohort Study.

OBJECTIVE: To assess whether regional intestinal oxygen saturation (rintSO2) and regional cerebral oxygen saturation (rcSO2) measurements aid in estimating survival of preterm infants after surgery for NEC. SUMMARY OF BACKGROUND DATA: Predicting survival after surgery for NEC is difficult yet of the utmost importance for counseling parents. METHODS: We retrospectively studied prospectively collected data of preterm infants with surgical NEC who had available rintSO2 and rcSO2 values measured via near-infrared spectroscopy 0-24 hours preoperatively. We calculated mean rintSO2 and rcSO2 for 60-120 minutes for each infant. We analyzed whether preoperative rintSO2 and rcSO2 differed between survivors and non-survivors, determined cut-off points, and assessed the added value to clinical variables. RESULTS: We included 22 infants, median gestational age 26.9 weeks [interquartile range (IQR): 26.3-28.4], median birth weight 1088 g [IQR: 730-1178]. Eleven infants died postoperatively. Preoperative rintSO2, but not rcSO2, was higher in survivors than in non-survivors [median: 63% (IQR: 42-68) vs 29% (IQR: 21-43), P < 0.01), with odds ratio for survival 4.1 (95% confidence interval, 1.2-13.9, P = 0.02) per 10% higher rintSO2. All infants with rintSO2 values of >53% survived, whereas all infants with rintSO2 <35% died. Median C-reactive protein [138 mg/L (IQR: 83-179) vs 73 mg/L (IQR: 12-98), P < 0.01), lactate [1.1 mmol/L (IQR: 1.0-1.6) vs 4.6 mmol/L (IQR: 2.8-8.0), P < 0.01], and fraction of inspired oxygen [25% (IQR: 21-31) vs 42% (IQR: 30-80), P < 0.01] differed between survivors and non-survivors. Only rintSO2 remained significant in the multiple regression model. CONCLUSIONS: Measuring rintSO2, but not rcSO2, seems of added value to clinical variables in estimating survival of preterm infants after surgery for NEC. This may help clinicians in deciding whether surgery is feasible and to better counsel parents about their infants' chances of survival.

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

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

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion.

Importance: There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions. Objective: To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions. Design, Setting, and Participants: This is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (≤1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020. Exposures: Donor sex and mean donor age. Main Outcomes and Measures: The primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight. Results: In total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (P for interaction = .005) and between female donor and number of transfusions (P for interaction < .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased. Conclusions and Relevance: These findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.

Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study.

BACKGROUND: Therapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes. METHODS: We did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit. FINDINGS: 6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2-0·9] in the fed group vs 1·1% [0·7-1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference -11·6% [95% CI -14·0 to -9·3]; p<0·0001), higher survival to discharge (5·2% [3·9-6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1-10·8]; p<0·0001), and shorter neonatal unit stays (-2·2 [-3·0 to -1·2] days; p<0·0001) compared with the unfed group. INTERPRETATION: Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia. FUNDING: UK National Institute for Health Research Health Technology Assessment programme 16/79/13.

C-reactive protein/albumin ratio is a prognostic indicator for predicting surgical intervention and mortality in neonates with necrotizing enterocolitis.

PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC). METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI). RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p < 0.0001] and mortality [AUC 0.66 (95% CI 0.54-0.77); p = 0.0150], respectively. CONCLUSIONS: A CRP/ALB ratio of ≥ 3 on day 2 is indicative of a critical pathway in neonates with radiologically confirmed, non-perforated NEC. This could be used as an additional criterion to guide parental counselling in NEC for surgical intervention and mortality.

Neonatal surgical outcomes: a prospective observational study at a Tertiary Academic Hospital in Johannesburg, South Africa.

PURPOSE: The neonatal period is the most vulnerable period for a child. There is a paucity of data on the burden of neonatal surgical disease in our setting. The aim of this study was to describe the frequency with which index neonatal surgical conditions are seen within our setting and to document the 30-day outcome of these patients. METHODS: This was a single-centre prospective observational study in which all neonates with paediatric surgical pathology referred to the paediatric surgical unit with a corrected gestational age of 28 days were included. RESULTS: Necrotising enterocolitis was the most frequent reason for referral to the paediatric surgical unit (n = 68, 34.34%). Gastroschisis was the most frequent congenital anomaly referred (n = 20, 10.10%). The overall morbidity was 57.58%. Surgical complications contributed to 18.51% of morbidities. The development of gram negative nosocomial sepsis was the most frequent cause of morbidity (n = 98, 50.78%). Mortality at 30 days was 21.74% (n = 40). Sepsis contributed to mortality in 35 patients (87.5%), 16 of which had gram negative sepsis. CONCLUSION: Gram-negative sepsis was a major contributing factor in the development of morbidity and mortality in our cohort. Prevention and improvement in infection control are imperative if we are to improve outcomes in our surgical neonates.

Incomplete resection of necrotic bowel may increase mortality in infants with necrotizing enterocolitis.

BACKGROUND: Infants with advanced necrotizing enterocolitis (NEC) often need surgical resection of necrotic bowel. We hypothesized that incomplete resection of NEC lesions, signified by the detection of necrotic patches in margins of resected bowel loops, results in inferior clinical outcomes. METHODS: We reviewed the medical records of infants with surgical NEC in the past 15 years for demographic, clinical, and histopathological data. We also developed statistical models to predict mortality and hospital stay. RESULTS: Ninety infants with surgical NEC had a mean (±standard error) gestational age of 27.3 ± 0.4 weeks, birth weight 1008 ± 48 g, NEC onset at 25.2 ± 2.4 days, and resected bowel length of 29.2 ± 3.2 cm. Seventeen (18.9%) infants who had complete resection of the necrosed bowel had fewer (4; 23.5%) deaths and shorter lengths of hospital stay. In contrast, a group of 73 infants with some necrosis within the margins of resected bowel had significantly more (34; 46.6%) deaths and longer hospital stay. The combination of clinical and histopathological data gave better regression models for mortality and hospital stay. CONCLUSION: In surgical NEC, incomplete resection of necrotic bowel increased mortality and the duration of hospitalization. Regression models combining clinical and histopathological data were more accurate for mortality and the length of hospital stay. IMPACT: In infants with surgical NEC, complete resection of necrotic bowel reduced mortality and hospital stay. Regression models combining clinical and histopathological information were superior at predicting mortality and hospital stay than simpler models focusing on either of these two sets of data alone. Prediction of mortality improved with the combination of antenatal steroids, chorioamnionitis, and duration of post-operative ileus, with severity of inflammation and hemorrhages in resected intestine. Length of hospital stay was shorter in infants with higher gestational ages, but longer in those with greater depth of necrosis or needing prolonged parenteral nutrition or supervised feedings.

Effect of Feeding Strategies on the Development of Fulminant Necrotizing Enterocolitis.

INTRODUCTION: Necrotizing enterocolitis (NEC) causes significant neonatal morbidity. A subset of infants experience precipitous decline and death from fulminant-NEC (F-NEC). We sought to determine the effect of feeding practices on the development of this more virulent form of NEC. MATERIALS AND METHODS: Premature neonates developing Bell's stage II or III NEC between May 2011 and June 2017 were reviewed. Infants were stratified as having NEC or F-NEC, defined as NEC-totalis or NEC causing rapid decline and death within 72 hours. Risk factors extracted included demographics, gestational age, and weight at NEC diagnosis. Feeding data extracted included age at first feed, caloric density, type of feed (breast milk or formula), and whether full volume feeds were reached. Univariate analysis and multivariate analysis were performed. RESULTS: A total of 98 patients were identified, of which 80 were included. In total, 57 patients had NEC and 23 had F-NEC. Reaching full volume feeds was associated with F-NEC on both univariate and multivariate analysis (37.9 vs. 4.5%; odds ratio: 67, 95% confidence interval: 6.606-2041, p = 0.003). Infants developing F-NEC achieved full feeds earlier (22.5 vs. 19.8 days, p = 0.025) on univariate but not multivariate analysis. There was no difference in the rates of NEC and F-NEC among infants receiving breast milk (standard or fortified) or formula (standard or increased caloric density; p = 0.235). CONCLUSION: Among premature neonates with NEC, reaching full volume feedings was associated with a nearly 70-fold increased risk of F-NEC. Assuming it was possible to predict an infant's development of NEC, alternative feeding regimens might reduce the risk of F-NEC in this population.

Trends in Perinatal Practices and Neonatal Outcomes of Very Low Birth Weight Infants during a 16-year Period at NEOCOSUR Centers.

OBJECTIVE: To describe trends in mortality, major morbidity, and perinatal care practices of very low birth weight infants born at NEOCOSUR Neonatal Network centers from January 1, 2001, through December 31, 2016. STUDY DESIGN: A retrospective analysis of prospectively collected data from all inborn infants with a birthweight of 500-1500 g and 23-35 weeks of gestation. RESULTS: We examined data for 13 987 very low birth weight infants with a mean birth weight of 1081 ± 281 g and a gestational age of 28.8 ± 2.9 weeks. Overall mortality was 26.8% without significant changes throughout the study period. Decreases in early onset sepsis from 6.3% to 2.8% (P <.001), late onset sepsis from 21.1% to 19.5% (P = .002), retinopathy of prematurity from 21.3% to 13.8% (P <.001), and hydrocephalus from 3.8% to 2.4% (P <.001), were observed. The incidence for bronchopulmonary dysplasia decreased from 17.3% to 16% (P = .043), incidence of severe intraventricular hemorrhage was 10.4%, necrotizing enterocolitis 11.1%, and periventricular leukomalacia 3.8%, and did not change over the study period. Administration of antenatal corticosteroids increased from 70.2% to 82.3% and cesarean delivery from 65.9% to 75.4% (P <.001). The use of conventional mechanical ventilation decreased from 67.7% to 63.9% (P <.001) and continuous positive airway pressure use increased from 41.3% to 64.3% (P <.001). Survival without major morbidity increased from 37.4% to 44.5% over the study period (P <.001). CONCLUSIONS: Progress in perinatal and neonatal care at network centers was associated with an improvement in survival without major morbidity of very low birth weight infants during a 16-year period. However, overall mortality remained unchanged.

ELBW infants receive inadvertent sodium load above the recommended intake.

BACKGROUND: To determine total sodium load, including inadvertent load, during the first 2 postnatal weeks, and its influence on serum sodium, morbidity, and mortality in extremely low birth weight (ELBW, birth weight <1000 g) infants and to calculate sodium replacement models. METHODS: Retrospective data analysis on ELBW infants with a gestational age <28 + 0/7 weeks. RESULTS: Ninety patients with a median birth weight of 718 g and a median gestational age of 24 + 6/7 weeks were included. Median sodium intake during the first 2 postnatal weeks was 10.2 mmol/kg/day, which was significantly higher than recommended (2-5 mmol/kg/day). Sodium intake did not affect the risk for hypernatremia. Each mmol of sodium intake during the first postnatal week was associated with an increased risk of bronchopulmonary dysplasia (45%) and higher-grade intraventricular hemorrhage (31%), during the second postnatal week for necrotizing enterocolitis (19%), and during both postnatal weeks of mortality (13%). Calculations of two sodium replacement models resulted in a decrease in sodium intake during the first postnatal week of 3.2 and 4.0 mmol/kg/day, respectively. CONCLUSIONS: Sodium load during the first 2 postnatal weeks of ELBW infants was significantly higher than recommended owing to inadvertent sodium intake and was associated with a higher risk of subsequent morbidity and mortality, although the study design does not allow conclusions on causality. Replacement of 0.9% saline with alternative carrier solutions might reduce sodium intake. IMPACT: Sodium intake in ELBW infants during the first 2 postnatal weeks was twofold to threefold higher than recommended; this was mainly caused by inadvertent sodium components. High sodium intake is not related to severe hypernatremia but might be associated with a higher morbidity in terms of BPD, IVH, and NEC. Inadvertent sodium load can be reduced by replacing high sodium-containing carrier solutions with high levels of sodium with alternative hypotonic and/or balanced fluids, model based.

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

OBJECTIVE: We 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. METHODS: Data 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. RESULTS: Of 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%. CONCLUSION: The 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 STUDY: Prognosis study. LEVEL OF EVIDENCE: Level II.

Long-term outcomes of severe surgical necrotizing enterocolitis.

PURPOSE: We sought to describe long-term outcomes of infants with severe surgical necrotizing enterocolitis (NEC). METHODS: Data were collected on infants with surgical NEC (2009-2018). Severe surgical NEC was defined by extensive bowel loss with residual bowel length <30 cm, and "NEC totalis" was identified per operative report. Post-operative management and long-term outcomes were assessed, including enteral autonomy, severe neurodevelopmental disability, and educational attainment. RESULTS: Of 268 infants with surgical NEC, 41 (15%) had severe surgical NEC, and 14/41 were identified as "NEC totalis". Zero severe NEC vs. 8 (57%) "NEC totalis" patients were placed on comfort measures following initial surgery (p < 0.001). Twenty-five patients (93%) with severe NEC survived vs 3/6 with "NEC totalis" (p < 0.001). The 28 survivors (68%) were followed for a median (IQR) duration of 8(4,10) years. Nine (32%) with severe NEC were weaned from parenteral nutrition. Eight (29%) had ≥1 marker for severe neurodevelopmental disability, and 11/16(69%) (7-16 years) were attending school at last follow-up. CONCLUSION: Long-term survival is excellent following initial discharge, and achievement of enteral autonomy is feasible in patients with severe surgical NEC. The majority of patients who survive do not have severe neurodevelopmental disability and participate in school. Given current survivals and outcomes, focus on measured residual bowel length may be more appropriate than the subjective term "NEC-totalis." TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level II.

Contemporary Outcomes for Infants with Necrotizing Enterocolitis-A Systematic Review.

OBJECTIVE: To develop an accurate understanding of outcomes for necrotizing enterocolitis (NEC) to inform parental counseling, clinical care, and research agendas. STUDY DESIGN: A systematic review of recent (January 2010-January 2018) large cohort studies reporting outcomes of infants who developed NEC. Only studies reporting national, regional, or multicenter outcomes of NEC in high income countries were included. Outcomes assessed were mortality, neurodevelopmental outcome, and intestinal failure. Meta-analyses were used to generate summary statistics for these outcomes. RESULTS: Of 1375 abstracts, 38 articles were included. Overall mortality was 23.5% in all neonates with confirmed NEC (Bell stage 2a+) (95% CI 18.5%-28.8%), 34.5% (30.1%-39.2%) for neonates that underwent surgery for NEC, 40.5% (37.2%-43.8%) for extremely low birthweight infants (<1000 g), and 50.9% (38.1%-63.5%) for extremely low birthweight infants with surgical NEC. Studies examining causes of neonatal mortality showed NEC is responsible for around 1 in 10 of all neonatal deaths. Neurodevelopmental disability was reported in 4 studies at between 24.8% and 61.1% (1209 total NEC cases). Three studies reported intestinal failure with an incidence of 15.2%-35.0% (n = 1370). The main limitation of this review is the lack of an agreed definition for diagnosing NEC and the differences in the way that outcomes are reported. CONCLUSIONS: Mortality following NEC remains high. These contemporary data inform clinical care and justify ongoing research efforts. All infants with NEC should have long-term neurodevelopmental assessment. Data on the long-term risk of intestinal failure are limited. TRIAL REGISTRATION: CRD42018094791.

Evaluation of parenteral nutrition-associated liver disease in surgical infants for necrotizing enterocolitis.

The purpose of this study was to determine the factors associated with parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC) and followed up the postoperative outcomes for long term parenteral nutrition (PN).This study included a retrospective review of 87 infants with NEC and managed surgically from July 2007 to May 2017 at the Children's Hospital, Chongqing Medical University. Clinical data and procedure information were collected and analyzed.Among the infants included, 16.1% of patients developed PNALD. Multivariable logistic regression analysis revealed progressive clinical deterioration (OR, 5.47; 95% CI, 1.10-26.96; P = .037) was independent risk factor for PNALD whereas congenital heart disease (OR, 0.068; 95% CI, 0.008-0.55; P = .012) presentation served as a protective factor.The current data suggested the distinct disease process for cardiac patients with NEC, which might help in the prevention and treatment of PNALD for patients with NEC.

Novel useful markers for follow-up of necrotizing enterocolitis: endocan and interleukin-33.

Objectives: To ascertain the diagnostic value of endocan and interleukin (IL)-33 in infants with necrotizing enterocolitis (NEC) and to compare their effectiveness with C-reactive protein (CRP) and interleukin-6 (IL-6).Methods: Eighty-four preterm infants including control (n = 42) and NEC (n = 42) were eligible. Blood samples were obtained from infants in the NEC for the assessment of CRP, IL-6, endocan, and IL-33 serum levels at the time of diagnosis (first day), at the third and seventh days of NEC. Endocan, IL-33, CRP, and IL-6 serum levels were measured at the 14th day of life in the control group.Results: Serum levels of endocan, IL-33, CRP, and IL-6 were significantly higher in the NEC group compared to the control group at the first, third, and seventh days (p < .05). IL-33 and endocan levels continued to rise in the consequent days in patients with stage III NEC (p < .05). Serum endocan and IL-33 levels gradually increased in patients who underwent surgery (p < .05). Serum endocan levels were higher in patients with stage III NEC than those in the stage II NEC at the diagnosis.Conclusions: Serum levels of IL-33 and endocan can be used as markers in the diagnosis and follow-up of NEC.

Outcome of Very Preterm Infants With Early Optimal Nutrition Strategy: A Comparative Cohort Study.

BACKGROUND: Aggressive nutrition may benefit early growth; nevertheless, effects on neurodevelopmental outcomes are unclear. We planned a descriptive analytical study to compare survival without neurodevelopment disability (NDD) at 1 year in 2 groups during 2 time epochs-before and after implementation of early optimal nutrition strategies. NDD was defined as any one of the following: mental and/or motor development quotient < 85 at 12 months of age, corrected for prematurity; Denver Developmental Screening Test abnormal/suspect in even 1 domain out of the 4 domains; seizures; requirement of hearing aid; or blindness in 1 or both eyes. We also compared mortality, survival without bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage, periventricular leukomalacia, sepsis, metabolic bone disease (MBD), and extrauterine growth restriction (EUGR). METHODS: Preterm neonates born between 27 and 32 weeks' gestation were included. The prospective study group (AO) was recruited after implementation of early optimal nutrition policy. The comparative retrospective cohort (BO) received nutrition based on clinicians' decisions. Both groups were followed up using a structured plan till 1 year corrected age. RESULTS: 137 neonates were enrolled in AO and 151 in the BO cohort. There was no statistically significant difference in survival without NDD at 1 year-75.5% in AO vs 72.1% in BO, odds ratio 0.84 (95% CI 0.5-1.6). Babies who received early optimal nutrition had less NEC, EUGR, and ROP requiring laser therapy but more MBD. CONCLUSION: There was no difference in survival without NDD in early optimal nutrition cohort compared to the cohort before implementation of the nutrition strategy. Short-term benefits themselves may justify the need for early optimal nutrition.

Preventive strategies and factors associated with surgically treated necrotising enterocolitis in extremely preterm infants: an international unit survey linked with retrospective cohort data analysis.

OBJECTIVES: To compare necrotising enterocolitis (NEC) prevention practices and NEC associated factors between units from eight countries of the International Network for Evaluation of Outcomes of Neonates, and to assess their association with surgical NEC rates. DESIGN: Prospective unit-level survey combined with retrospective cohort study. SETTING: Neonatal intensive care units in Australia/New Zealand, Canada, Finland, Israel, Spain, Sweden, Switzerland and Tuscany (Italy). PATIENTS: Extremely preterm infants born between 240 to 286 weeks' gestation, with birth weights<1500 g, and admitted between 2014-2015. EXPOSURES: NEC prevention practices (probiotics, feeding, donor milk) using responses of an on-line pre-piloted questionnaire containing 10 questions and factors associated with NEC in literature (antenatal steroids, c-section, indomethacin treated patent ductus arteriosus and sepsis) using cohort data. OUTCOME MEASURES: Surgical NEC rates and death following NEC using cohort data. RESULTS: The survey response rate was 91% (153 units). Both probiotic provision and donor milk availability varied between 0%-100% among networks whereas feeding initiation and advancement rates were similar in most networks. The 9792 infants included in the cohort study to link survey results and cohort outcomes, revealed similar baseline characteristics but considerable differences in factors associated with NEC between networks. 397 (4.1%) neonates underwent NEC surgery, ranging from 2.4%-8.4% between networks. Standardised ratios for surgical NEC were lower for Australia/New Zealand, higher for Spain, and comparable for the remaining six networks. CONCLUSIONS: The variation in implementation of NEC prevention practices and in factors associated with NEC in literature could not be associated with the variation in surgical NEC incidence. This corroborates the current lack of consensus surrounding the use of preventive strategies for NEC and emphasises the need for research.

Acute kidney injury in newborns with necrotizing enterocolitis: risk factors and mortality / Daño renal agudo en recién nacidos con enterocolitis necrotizante: factores de riesgo y mortalidad

Abstract Background: Both necrotizing enterocolitis and acute kidney injury are tightly related conditions, which independently increase mortality in newborns. Necrotizing enterocolitis is an inflammatory disease with a systemic repercussion that leads to inflammatory kidney changes predisposing to renal damage. Methods: This study assessed risk factors for the development of acute kidney injury in patients diagnosed with necrotizing enterocolitis and compared mortality between patients with or without acute kidney injury. Thirty-nine patients with the diagnosis of necrotizing enterocolitis were included, regardless of the gestational age. Results: Of 39 patients, 38.5% developed acute kidney injury. Survival showed to be significantly lower in patients with acute kidney injury (54.4 days) when compared to newborns without acute kidney injury (76.22 days; p = 0.014). Mortality in patients with acute kidney injury was 46.7%, increasing up to 62.5% with severe kidney damage. The hazard ratio for mortality was 4.708 for acute kidney injury (p = 0.025). The severity of enterocolitis showed to be an independent risk factor in developing acute kidney injury and severe kidney injury (odds ratio [OR] = 1.841, p = 0.034 and OR = 1.917, p = 0.027, respectively). Conclusions: Newborns with necrotizing enterocolitis should be evaluated for early recognition of acute kidney injury. Prospective studies with a higher number of patients are needed to identify modifiable risk factors to impact in the prevention of these conditions.

Resumen Introducción: La enterocolitis necrosante y el daño renal agudo son condiciones íntimamente relacionadas que incrementan independientemente la mortalidad en recién nacidos. La enterocolitis necrosante es una enfermedad inflamatoria sistémica que desencadena cambios renales inflamatorios, predisponiendo el desarrollo de daño renal. Métodos: Se analizaron los factores de riesgo para el desarrollo de daño renal agudo en pacientes con diagnóstico de enterocolitis necrosante y se comparó la mortalidad entre los pacientes sin daño renal y los pacientes con daño renal agudo. Se incluyeron 39 pacientes con diagnóstico de enterocolitis necrosante, independientemente de la edad gestacional. Resultados: De los 39 pacientes, el 38.5% desarrolló daño renal agudo. La sobrevida de los que desarrollaron daño renal agudo (54.4 días) mostró ser significativamente menor al compararse con los recién nacidos que no presentaron daño renal (76.22 días; p = 0.014). La mortalidad en los pacientes con daño renal agudo fue del 46.7%, que se incrementó hasta el 62.5% en aquellos con daño renal grave. El riesgo de mortalidad fue de 4.708 para daño renal agudo (p = 0.025). La gravedad de la enterocolitis necrosante demostró ser un factor de riesgo independiente para el desarrollo de daño renal agudo y de daño renal agudo severo (razón de momios [RM] = 1.841; p = 0.034 y RM = 1.917; p = 0.027, respectivamente). Conclusiones: Los recién nacidos con diagnóstico de enterocolitis necrosante deben ser evaluados para reconocer de forma temprana la presencia de daño renal agudo. Se requiere de estudios prospectivos con mayor número de pacientes para identificar factores de riesgo modificables que puedan impactar en la prevención de estas patologías.

Comparison of Acute Abdominal Surgical Outcomes of Extremely-Low-Birth-Weight Neonates according to Differential Diagnosis.

BACKGROUND: Improvements in perinatal intensive care have improved survival of extremely-low-birth-weight (ELBW) neonates, although the risk of acute abdomen has increased. The differential diagnosis resulting in abdominal surgery can be categorized into necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), meconium-related ileus (MRI), and meconium non-related ileus (MNRI). The purpose of this study was to review our experience with abdominal surgery for ELBW neonates, and to evaluate characteristics and prognosis according to the differential diagnosis. METHODS: Medical records of ELBW neonates treated between 2003 and 2015 were retrospectively reviewed. RESULTS: Of 805 ELBW neonates, 65 (8.1%) received abdominal surgery. The numbers of cases by disease category were 29 for NEC, 18 for SIP, 13 for MRI, and 5 for MNRI. Ostoma formation was performed in 61 (93.8%) patients; primary anastomosis without ostoma was performed in 4 (6.2%). All patients without ostoma formation experienced re-perforation of the anastomosis site. Seven patients had 30-day postoperative mortality (6 had NEC). Long-term survival of the surgical and non-surgical groups was not statistically different. NEC was a poor prognostic factor for survival outcome (P = 0.033). CONCLUSION: Abdominal surgery for ELBW neonates is feasible. Ostoma formation can lead to reduced complications compared to primary anastomosis.