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AbstractBackgroundMethodsResultsConclusionNecrotizing enterocolitis (NEC) is an inflammatory and necrotizing intestinal emergency that occurs in preterm infants and low birth weight newborns; however, no specific serum biomarkers for the diagnosis of NEC has been identified so far.Serum samples were collected from healthy neonatal controls and patients with NEC newly admitted to the Children’s Hospital of Chongqing Medical University. ELISA was used to measure serum PK2 levels, and ROC curve analysis was sued to evaluate the diagnostic efficacy of PK2 and other clinical biomarkers.Serum PK2 levels in the NEC group (n = 53) were significantly lower than those in the control group (n = 18), but increased to near-normal levels after the postoperative recovery period. The NLR value of NEC group was higher than that of control group (P < 0.05). There was no significant difference in WBC and PLT count between NEC group and control group (P > 0.05). Serum CRP and PCT levels in NEC group were significantly higher than those in control group (P < 0.001 for CRP and P < 0.05 for PCT, respectively). After surgery, serum CRP, NLR and PCT levels were lower than before surgery, while serum PK2 levels were higher than before surgery (P < 0.05). The areas under the ROC curve (AUC) of PK2, PCT and CRP for the diagnosis of NEC were 0.837, 0.662 and 0.552, respectively. The AUC of PK2 combined with PCT, PK2 combined with CRP, and PK2 combined with PCT and CRP were 0.908, 0.854 and 0.981, respectively. PK2 exhibited the highest diagnostic efficacy for NEC.PK2 has higher diagnostic efficacy than PCT and CRP in the diagnosis of NEC; the combination of PK2 and PCT or CRP can significantly improve its diagnostic efficiency, especially when the three are combined at the same time. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to determine clinical correlates of moderate to severe bronchopulmonary dysplasia (BPD) in preterm infants following surgical necrotizing enterocolitis (NEC). Study Design This is a retrospective, single-center cohort study comparing patients with moderate to severe BPD to patients with non/mild BPD among surgical NEC infants. BPD was defined by NIH 2001 consensus definition. Results Of 92 consecutive neonates with surgical NEC, 77% (71/92) had moderate/severe BPD and 22% (21/92) had non/mild BPD. The patent ductus arteriosus (PDA) was significantly higher in those developing moderate/severe BPD (67.6% [48/71]) than non/mild BPD (28.6% [6/21]; p = 0.001). Postoperatively, infants with moderate/severe BPD had more severe acute kidney injury (AKI; 67.6 [48/71] vs. 28.6% [6/21]; p = 0.001), were intubated longer (40.5 [interquartile (IQR): 12, 59] vs. 6 days [IQR: 2, 13]; p <0.001), received more parenteral nutrition (109 [IQR: 77, 147] vs. 55 days [IQR: 19, 70]; p <0.001), developed higher surgical morbidity (46.5 [33/71] vs. 14.3% [3/21]; p = 0.008), had more intestinal failure (62.5 vs. 13.3%; p <0.001), required a longer hospital stay (161 [IQR: 112, 186] vs. 64 days [IQR: 20, 91]; p <0.001), and were more likely to need home oxygen. In a multivariable analysis, lower birth weight (OR = 0.3, [95% confidence interval (CI): 0.1–0.5]; p = 0.001), PDA (OR = 10.3, [95% CI: 1.6–65.4]; p = 0.014), and longer parenteral nutritional days (OR = 8.8; [95% CI: 2.0–43.0]; p = 0.005) were significantly and independently associated with higher odds of moderate/severe versus non-/mild BPD. Conclusion Development of moderate/severe BPD occurred in the majority of preterm infants with surgical NEC in this consecutive series. Preterm infants with moderate/severe BPD were more likely to have a PDA before NEC. Development of moderate/severe BPD was associated with significantly greater burden and duration of postoperative morbidity following surgical NEC. Identifying surgical NEC infants at increased risk of moderate/severe BPD and developing lung protection strategies may improve surgical NEC outcomes. Key Points Three-fourths of preterm infants experienced severe lung injury following surgical NEC. The infants with severe moderate/severe BPD were most likely associated with greater duration of postoperative morbidity. There is need to understand and develop lung protective strategies in infants with surgical NEC. [ABSTRACT FROM AUTHOR]

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction. Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data. [ABSTRACT FROM AUTHOR]

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

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B. On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15–0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02–3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26–6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death. [ABSTRACT FROM AUTHOR]

Background: We have recently noted some sonographic features in necrotizing enterocolitis that have received little or no attention in the current literature. These include thickening of the mesentery, hyperechogenicity of intraluminal intestinal contents, abnormalities of the abdominal wall, and poor definition of the intestinal wall. It has been our impression that the above four sonographic findings are generally seen in neonates with more severe necrotizing enterocolitis and may be useful in predicting outcome. Objectives: The aim of this study is, firstly, to review a large series of neonates, known to have clinical NEC, to document how frequently the above four sonographic features occur in neonates with necrotizing enterocolitis and, secondly, to determine whether they are predictive of outcome. Materials and methods: We retrospectively analyzed the clinical, radiographic, sonographic, and surgical findings in neonates with necrotizing enterocolitis between 2018 and 2021. The neonates were categorized into two groups based on outcome. Group A included neonates with a favorable outcome defined as successful medical treatment with no surgical intervention. Group B included neonates with an unfavorable outcome defined as failed medical treatment requiring surgery (for acute complications or late strictures) or death because of necrotizing enterocolitis. The sonographic examinations were reviewed with attention to the features of mesenteric thickening, hyperechogenicity of intraluminal intestinal contents, abnormalities of the abdominal wall, and poor definition of the intestinal wall. We then determined the association of these four findings with the two groups. Results: We included 102 neonates with clinical necrotizing enterocolitis: 45 in group A and 57 in group B. Neonates in group B were born at a significantly earlier gestational age (median 25 weeks, range 22–38 weeks) and had a significantly lower birth weight (median 715.5 g, range 404–3120 g) than those in group A (median age 32 weeks, range 22–39 weeks, p = 0.003; median weight 1190 g, range 480–4500 g, p = 0.002). The four sonographic features were present in both study groups but with different frequency. More importantly, all four were statistically significantly more frequently present in neonates in group B compared to group A: (i) mesenteric thickening, A = 31 (69%), B = 52 (91%), p = 0.007; (ii) hyperechogenicity of intestinal contents, A = 16 (36%), B = 41 (72%), p = 0.0005; (iii) abnormalities of the abdominal wall, A = 11 (24%), B = 35 (61%), p = 0.0004; and (iv) poor definition of the intestinal wall, A = 7 (16%), B = 25 (44%), p = 0.005. Furthermore, the proportion of neonates with more than two signs was greater in group B compared to group A (Z test, p < 0.0001, 95% CI = 0.22–0.61). Conclusion: The four new sonographic features described were found to occur statistically significantly more frequently in those neonates with an unfavorable outcome (group B) than in those with a favorable outcome (group A). The presence or absence of these signs should be included in the sonographic report to convey the radiologists concern regarding the severity of the disease in every neonate, suspected or known to have necrotizing enterocolitis, as the findings may impact further medical or surgical management. [ABSTRACT FROM AUTHOR]

ObjectivesNeonatal necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that primarily affects preterm and very low birth weight infants, with high morbidity and mortality. We aim to build a reliable prediction model to predict the risk of NEC in preterm and very low birth weight infants.MethodsWe conducted a retrospective analysis of medical data from infants (gestational age

BACKGROUND: Minimal enteral feeding after birth has been developed as a strategy to enhance the functional maturation of the gastrointestinal tract. This study aimed to examine the relationship between the duration of minimal enteral feeding and time to regain birth weight in extremely low-birth-weight infants. METHODS: This retrospective study included all extremely low-birth-weight infants born between January 2018 and December 2020. Infants with major congenital anomalies and conditions requiring surgery and those who died or received palliative care in the first 10 days of life were excluded from the analysis. Minimal enteral feeding courses were categorized as extended if the feeding was continued for > 72 hours and short if the feeding was < 72 hours. The primary measured outcome was the time taken to regain birth weight. RESULTS: Of 217 study infants, 180 received an extended minimal enteral feeding for > 72 h. The median time to regain birth weight was not significantly different between the extended and short minimal enteral feeding groups, median (IQR) was 10 (7–13) versus 8 (6–11), respectively (p = 0.15). Extended minimal enteral feeding is associated with a significant increase in the mean duration of the total parenteral nutrition, (21.3±10 versus 17.2±9.3 days; p = 0.021). Infants with prolonged minimal enteral feeding courses experienced non-significantly higher levels of necrotizing enterocolitis, late-onset sepsis, and retinopathy of prematurity. CONCLUSIONS: Extended minimal enteral feeding in extremely low-birth-weight infants may not affect the time taken to regain birth weight. [ABSTRACT FROM AUTHOR]

Background: Survival without major comorbidities remains low among extremely low birthweight (ELBW) infants. An exclusive human milk diet (EHMD) has shown clinical benefits among infants born weighing ≤1,250 g. Methods: Our objective was to determine the associations between an exclusive human milk diet (EHMD) or a diet containing cow milk-based products (CMBD) and common morbidities and mortality among infants born weighing ≤750 g. We conducted a systematic review with individual participant data meta-analysis. After a PubMed search (Jan 2000 to Feb 2022), authors from eligible RCT and observational studies were invited to contribute their data. EHMD was compared to a CMBD, including formula (CMBD+f). Sensitivity analyses compared an EHMD and a base diet of human milk fortified with cow milk-based fortifiers (CMBDf). Adjusted odds ratios (aOR) reported are from complete cases. Results: Six studies were included, totaling 879 infants born between 2007-2015 and weighing ≤750 g. Infants fed an EHMD (n=449) had reduced odds of developing necrotizing enterocolitis (NEC), surgical NEC, and bronchopulmonary dysplasia (BPD) compared to those fed a CMBD+f (n=430). Similar reductions were observed when an EHMD was compared with CMBD-f (n=78). Additionally, an EHMD was associated with 50% lower odds of scoring affirmatively on a mortality and morbidity index (MMI) compared to CMBD+f. Conclusions: In this study, infants born ≤750 g have reduced odds of developing several major comorbidities than those fed cows milk-based nutritional products, even with a base diet of human milk. Registry Number: PROSPERO, identifier: CRD42022319031 [ABSTRACT FROM AUTHOR]

We sought to determine the clinical and histopathological factors linked with intestinal repair and its correlation with clinical outcomes in preterm infants following surgical necrotizing enterocolitis (NEC). A retrospective study has compared clinical and histopathological characteristics between preterm infants with histopathological reparative changes versus non-reparative changes in resected intestinal tissue following surgical treatment of NEC. Reparative changes were defined as microscopic evidence of neovascularization, increased fibroblasts or myofibroblasts, and epithelial regeneration during histopathological examination of the most affected area of resected intestinal tissue. The infants with reparative changes (53/148) had significantly lower median birth weight (725 [650−963] vs. 920 [690−1320]; p =.018), higher likelihood of patent ductus arteriosus (38/53 [71.7%] vs. 48/95 [50.5%]; p =.012), longer TPN days (99 [56−147] vs. 76.5 [39−112.5]; p =.034), higher CRP levels (7.3 [3.2−13] vs. 2.6 [1.1−7.8]; p =.011) at NEC onset, and more short bowel syndrome (27/53 [54.0%] vs. 28/95 [32.2%]; p =.012). Those with reparative changes also received more Penrose drain therapy (21/53 [39.6%] vs. 14/95 [14.7%]; p =.011) and had a longer median time to laparotomy (108 h [28−216] vs. 24 [12−96]; p =.003). Epithelial regeneration observed in 6/53 (11.3%) infants lagged fibroblast proliferation and neovascularization changes in the submucosa/muscularis intestinal layers. On a multivariable logistic regression model which included histopathological and clinical factors, inflammation with a percentage <25% area involvement, time from NEC diagnosis to surgery, and Apgar score < 6 at 5 min were independently and significantly associated with higher odds reparative changes. In neonates with surgical NEC, the histopathological findings in the resected bowel are significantly associated with clinical characteristics, other histopathological findings, and outcomes. The presence of reparative changes consistent with healing is significantly associated with Apgar score, Penrose drain therapy, longer time from NEC diagnosis to surgery, and lower burden of inflammation in the resected bowel tissue in multivariable analyses. Routine histopathological grading of resected bowel and optimal use of Penrose drain therapy warrant further investigation in the care of neonates with surgical NEC. [ABSTRACT FROM AUTHOR]

Background and Objectives: To assess whether the use of intravenous immunoglobulin (IVIG) in late‐preterm and term newborns with haemolytic disease of the newborn (HDN) is associated with an increased risk of necrotizing enterocolitis (NEC). Materials and Methods: A retrospective cohort study was conducted in a tertiary centre. Infants with HDN during early neonatal period (<7 days) who were of ≥34 weeks' gestation and born between January 2019 and October 2021 were included. Propensity score, interaction as well as univariate and multiple logistic regression analyses were employed. Results: One‐thousand two‐hundred and fifty‐nine infants with HDN were enrolled, of whom 192 (15.3%) received IVIG. NEC was diagnosed in 29 (2.3%) patients with 5 (2.6%) in the IVIG group and 24 (2.2%) in the non‐IVIG group. No significant association between IVIG administration and confirmed NEC was observed using univariate analysis (p > 0.05). The possible predictors of NEC, as assessed by multivariate analysis, were caesarean delivery, haemoglobin on admission <130 g/L and patent ductus arteriosus (PDA). There was no interactive effect of IVIG against NEC for prematurity, low birth weight, caesarean delivery, haemoglobin on admission <130 g/L and PDA. Conclusions: In late‐preterm and term infants with HDN, there was no evidence that the early use of IVIG led to the development of NEC. [ABSTRACT FROM AUTHOR]

BackgroundGlobally, the incidence of necrotizing enterocolitis (NEC) varies between 6 and 15% of all neonates admitted to the neonatal intensive care unit (NICU). Though necrotizing enterocolitis is a multifactorial and life-threatening disease, low birth prematurity is the single cause. Therefore, determining the time to presentation and its predictors of necrotizing enterocolitis were the main goals of this investigation.Materials and methodsAn institution-based retrospective follow-up study was conducted among 747 low birth weight (LBW) neonates admitted to the neonatal intensive care unit of Felege Hiwot comprehensive specialized Hospital from 1 January 2017 to 30 December 2019. The sample size was calculated by using the STATA package. Data were entered into Epi data version 3.1 and exported to STATA version 14 for analysis. The log-rank test and the Kaplan–Meier estimator were used to display the survival probability and differences between groups. At a significance threshold of 5%, Cox proportional hazard regression was performed to determine the net independent predictors of necrotizing enterocolitis.ResultThe overall incidence rate was 0.86 per 1,000 person-days (95% CI: 0.67, 1.14) with a 6.8% (95% i: 5.2, 8.9) proportion of necrotizing enterocolitis among low birth weight neonates. Preeclampsia [adjusted hazard ratio (AHR);1.92 (95% CI: 1.03–3.58)], premature rapture of membrane [AHR; 2.36 (95%, CI: 1.19–4.69)], perinatal asphyxia [AHR; 4.05 (95%, CI: 2.04–8.60)], gestational age between 28 and 32 weeks [AHR; 3.59 (95% CI: 1.01–8.83)], and birth weigh less than 1,000 g [AHR; 5.45 (95% CI: 3.84–9.12) were the independent predictors of necrotizing enterocolitis.ConclusionWithin the first 1–7 days of a newborn’s life, necrotizing enterocolitis was most common. It was discovered that preeclampsia, premature rupture of membrane, perinatal asphyxia, gestational age of 28–32 weeks, and birth weight less than 1,000 g were predictors of its occurrence.

Necrotizing enterocolitis (NEC) is a digestive disease that frequently occurs in premature infants with low gestational age and low birth weight, and seriously threatens the life of NEC patients. NEC pathogenesis is recognized to be affected by multiple factors, such as preterm birth, formula feeding and low birth weight. As a popular object for the past decades, intestinal flora is commonly used in NEC‐related studies, and intestinal disorder is considered as a critical risk factor for the occurrence and development of NEC. The colonization of abnormal microbiota into gastrointestinal micro‐ecosystem can easily lead to the damage of intestinal mucosal barrier, destruction of immune function, inflammatory reaction and further the occurrence of NEC. Although it is a low‐cost and safe way to prevent and treat the NEC by early intervention of oral probiotics to regulate the intestinal homoeostasis, more studies in the future are still encouraged to narrow the gap between theoretical guidance and practical application. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study is to evaluate risk factors for NEC using an identical twin model. In this case-control study, all monochorionic twin pairs born in our center in 2002–2020 were retrospectively reviewed for NEC. Potential risk factors for NEC were studied. For within-pair comparison, outcomes were compared between affected and unaffected twins. Within-pair analyses showed that the twin with NEC had a lower birth weight compared to its unaffected co-twin (1100 (913–1364) vs. 1339 (1093–1755) grams). Median gestational age at birth and birth weight were lower in twin pairs in the NEC-group compared to the no-NEC group, 29.1 weeks (27.8–30.8) versus 33.6 (30.7–36.0) and 1221 g (1010–1488) versus 1865 (1356–2355) respectively. Twin pregnancies in the NEC-group were more often complicated by twin-to-twin transfusion syndrome compared to the no-NEC-group (70 % (14/20) vs. 49 % (472/962)), particularly when treated with amnioreduction. This unique population of identical twins confirms that preterm neonates with a relatively lower birth weight are more prone to develop NEC compared to their co-twin, regardless of other genetic, maternal and obstetrical factors. • MC twins with low birth weight are more prone to NEC regardless of gestational age, genetic, maternal or obstetrical factors. • NEC occurred more frequently in TTTS twins treated with amnioreduction. • This nested case-control study reveals that neonates with lower birth weight are more prone to NEC compared to their co-twin. • More attention to timely risk assessment and preventing NEC is needed in MC twins and neonates born with lower birth weight. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is a serious disease in neonates and requires surgical treatment in cases with complications. The purpose of this study was to review outcomes of NEC patients treated by various procedures during an 11-year period. Patients and Methods: A retrospective cohort study of patients with NEC treated at Khon Kaen Hospital between January 2009 and December 2019 was conducted. Medical records of patients were abstracted for clinical characteristics and presentations, laboratory findings, radiologic studies and results of treatment. Results: Seventy-three NEC patients (40 males and 33 females) was available for the study. Sixty-one cases (84%) were managed by medical treatment and 12 cases (16.4%) required surgery because of complications due to intestinal perforation and peritonitis. Of the 12 surgical NEC, 10 cases (83%) were premature (median gestational age, 29 weeks) and 10 were low birth weight infants (median birth weight, 1263 grams). Nine cases (75%) had a serious condition treated by primary peritoneal drainage (PPD) and 4 cases survived (44%). Three cases underwent primary exploratory laparotomy (PEL) -- 2 had necrotic bowel resection with enterostomy, and one had primary anastomosis -- and only one survived. The overall mortality of surgical NEC was 60% (7 of 12 cases), and the mortality rate of medical NEC was 12% (7 of 61 cases). Conclusion: NEC patients with serious complications including intestinal perforation and peritonitis require surgical treatment. PPD was done more common than PEL because of severely -- ill patients with extremely and very low birth weight. The overall mortality of surgical NEC remains high, at 50%. [ABSTRACT FROM AUTHOR]

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Objective  The aim of this study is to identify causes of neonatal intensive care unit (NICU) death in extremely low birth weight (ELBW) infants less than 1,000 g admitted in Chinese tertiary NICUs. Study design  We retrospectively collected data on 607 ELBW infants from 39 level III NICUs from July 2016 to June 2019. The primary causes of death were compared among different gestation age, postnatal age groups, and areas with variable economic status. Results  Among all 607 ELBW NICU deaths, 47.1% were multiple gestation with high rate of in vitro fertilization (IVF) (43.3%); 53.4 and 34.1% received any or full course of antenatal corticosteroid (ACS). The most common causes of ELBW NICU death were respiratory distress syndrome-related neonatal respiratory failure (RDS-NRF, 43.5%), severe infection (19.1%), necrotizing enterocolitis or bowel perforation (9.4%), severe central nervous system injury (8.4%), and bronchopulmonary dysplasia-related respiratory failure (BPD-NRF, 7.7%). Causes of ELBW NICU death varied across postnatal age groups. RDS-NRF was the leading cause of early neonatal death, while severe infection in late neonatal death and BPD in postneonatal EBLW NICU death. RDS-NRF, severe brain injury, and asphyxia were most likely to die at early neonatal age (median age [interquartile range], 2 [0–5], 6 [3–9], and 3 [1–6] days, respectively) while severe infection and necrotizing enterocolitis (NEC) at late neonatal age, BPD-NRF at postneonatal age. Conclusion  In Chinese tertiary NICUs, the major causes of death in extremely low birth weight infants were RDS, infection, NEC, brain injury and BPD, and they varied with postnatal age. Developing specific prevention strategies for identified causes of death in ELBW NICU may potentially improve ELBW survival. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. Survivors may suffer both short‐ and long‐term morbidities. Current evidence suggests that the incidence of NEC can be reduced by standardizing the care delivery in addressing key risk factors including an altered gut microbiome, use of formula milk, hyperosmolar feeds, and unrestricted use of high‐risk medications Methods: Since 2014, the department has a workgroup who analyzed all cases of NEC within a month of diagnosis to identify preventable risk factors. Existing evidence‐based quality improvement strategies were revised and new ones were implemented sequentially over the next 4 years. These strategies include (1) a standardized feeding protocol, (2) early initiation of enteral feeding using human milk, (3) optimization of the osmolality of preterm milk feeds using standardized dilution guidelines for additives, and (4) promotion of healthy microbiome by use of probiotics, early oral care with colostrum and by restricting high‐risk medications and prolonged use of empirical antibiotics Results: Baseline characteristics of the patients including sex, gestational age, and birth weight were similar during the study period. After implementing the evidence‐based practices successively over 4 years, the incidence of NEC in very‐ low birth‐weight (VLBW) infants dropped from 7% in 2014 to 0% (P <.001) in 2018. The duration of parenteral nutrition, use of central line, and days to full feeds were also reduced significantly (P <.05) Conclusion: Adopting evidence‐based best practices resulted in a significant decrease in the incidence of NEC and improved the nutrition outcomes in VLBW infants. [ABSTRACT FROM AUTHOR]

Objectives: This study is aimed at determing the pattern and treatment outcome of neonatal gastrointestinal surgical emergencies. Study Design: Prospective Descriptive study. Setting: DHQ Teaching Hospital Sahiwal. Period: January 2018 to December 2019. Material & Methods: All neonates (<28 days old) who underwent surgery for acute gastrointestinal emergency during the study period were included. Newborns more than 28 days and diseases such as esophageal atresia, esophageal atresia with trachea-esophageal fistula, diaphragmatic hernia, omphalocele, gastroschisis and infantile hypertophic pyloric stenosis were not included in the study. Results: A total of 104 cases of neonatal gastrointestinal surgical emergency were included in the study. The most common cause was anorectal malformation 37(35.57%), followed by intestinal atresia 26(25.0%), Hirschsprung disease 13(12.50%), necrotizing enterocolitis 9(8.65%), intestinal malrotation 8(7.69%), meconium ileus 7(6.73%) and others 4(3.84%). Males were 59(56.73%), females 45(43.26%) and male to female ratio 1.3:1. Mean weight was 2.62kg, ranging from 1.5 to 4.4kg. Post-operative complications were septicemia 26(25.0%), wound infection 17(16.34%), respiratory problems 19(18.26%). Mortality rate in necrotizing enterocolitis was 55.55%, meconium ileus 42.85% and intestinal atresia 38.46%. Mortality rate in premature neonates was 48.0% and mature 12.65%. Overall mortality rate was 21.15%. Conclusions: Anorectal malformation is the commonest cause of neonatal gastrointestinal surgical emergency. Necrotizing enterocolitis, intestinal atresia and meconium ileus are the neonatal surgical diseases with high mortality rate. Surgical outcome depends on the complexity of the disease. Sepsis, late presentation, prematurity and low birth weight are significant contributory factors for high morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of probiotics in prevention of necrotizing enterocolitis (NEC) among low birth weight (LBW) preterm neonates. Study Design: Randomized controlled trial. Setting: Department of Pediatric Medicine, Unit-II, Services Hospital, Lahore. Period: September 2019 to February 2020. Material and Methods: A total of 260 LBW preterm neonates were enrolled. All the neonates were allocated to 2 groups with equal number of cases (130 in each group). Group-A was given probiotics whereas placebo was administered in Group-B. All the cases were admitted and follow ups were made up until 7th day. Occurrence of NEC was recorded among both groups. Results: Out of a total of 260 LBW preterm neonates, 142 (54.6%) were male and118 (45.4%) female. Overall, mean age was noted to be 1.48+0.50 days. Table-I shows that there was no statistical difference among neonates of both study groups in terms of age, gestational age and birth weight (p>0.05). Five (3.8%) neonates in Group-A and 14 (10.8%) in Group-B were found to have NEC. Efficacy of treatment in Group-A was significantly higher in comparison to Group-B. Conclusion: Probiotics are effective in the prevention of NEC in preterm LBW neonates. Prophylactic usage of probiotics among preterm neonates is noted to be helpful in avoiding development of NEC. [ABSTRACT FROM AUTHOR]

Background: Necrotizing Enterocolitis (NEC) is a major cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU), yet the global incidence of NEC has not been systematically evaluated. We conducted a systematic review and meta-analysis of cohort studies reporting the incidence of NEC in infants with Very Low Birth Weight (VLBW).Methods: The databases searched included PubMed, MEDLINE, the Cochrane Library, EMBASE and grey literature. Eligible studies were cohort or population-based studies of newborns including registry data reporting incidence of NEC. Incidence were pooled using Random Effect Models (REM), in the presence of substantial heterogeneity. Additional, bias adjusted Quality Effect Models (QEM) were used to get sensitivity estimates. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Funnel plots as appropriate for ratio measures were used to assess publication bias.Results: A systematic and comprehensive search of databases identified 27 cohort studies reporting the incidence of NEC. The number of neonate included in these studies was 574,692. Of this 39,965 developed NEC. There were substantial heterogeneity between studies (I2 = 100%). The pooled estimate of NEC based on REM was 7.0% (95% CI: 6.0-8.0%). QEM based estimate (6.0%; 95% CI: 4.0-9.0%) were also similar. Funnel plots showed no evidence of publication bias. Although, NEC estimates are similar across various regions, some variation between high and low income countries were noted. Meta regression findings showed a statistically significant increase of NEC over time, quantified by the publication year.Conclusion: Seven out of 100 of all VLBW infants in NICU are likely to develop NEC. However, there were considerable heterogeneity between studies. High quality studies assessing incidence of NEC along with associated risk factors are warranted. [ABSTRACT FROM AUTHOR]

The intestinal microbiome is the genetic material from microorganisms residing in the intestinal tract. Very low-birthweight infants (VLBW; birth weight ≤1500 g) are a physiologically compromised population undergoing a unique period of initial intestinal microbiome establishment. Evidence supports a connection between the intestinal microbiome and gastrointestinal illness that disproportionately affects VLBW infants. Necrotizing enterocolitis, an inflammatory and often necrotic condition of the intestine, and late-onset sepsis, a bloodstream infection occurring after 3 days of life, are thought to be associated with delayed or abnormal intestinal microbiome development. Here, we review the determinants, or factors, that influence the VLBW infant's intestinal microbiome and discuss clinical implications. PubMed, Web of Science, EMBASE, and CINAHL were systematically searched for publications addressing factors with the potential to affect the intestinal microbiome of VLBW infants. Results indicate that infant's age and weight, mode of delivery, antibiotic exposure, medication use, feeding regime, environment, and perinatal-/infant-associated factors may be important determinants of the microbiome in this vulnerable population. Clinicians have opportunities to support positive development of the VLBW infant's intestinal microbiome through antibiotic stewardship, support of human milk feeding, and hygienic care practices. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether observational studies comparing laparotomy versus peritoneal drainage for surgical treatment of necrotizing enterocolitis (NEC) in preterm infants differ from randomized controlled trials (RCTs) of the same interventions. Further, in the absence of sufficient RCT evidence, it is uncertain how best to use existing observational data to guide clinical decision making.Methods: We performed a systematic review and meta-analysis of articles comparing laparotomy versus peritoneal drainage for preterm infants with NEC. Two authors independently searched PubMed and the Cochrane Database of Systematic Reviews, from 1 January 1990 to 1 May 2017 and selected articles that: (1) included low birthweight (<2500 g) or preterm (<37-week gestation) infants, (2) compared laparotomy versus peritoneal drainage for NEC, and (3) reported all-cause mortality (primary outcome) in both groups. The same two authors extracted data about study outcomes and about study quality, which was assessed using the Consolidated Standards of Reporting Trials (CONSORT) checklist for reporting of RCTs and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for reporting of observational studies. Random-effects meta-analysis was used to generate weighted odds ratios (OR).Results: Twenty-five observational studies and two RCTs met all eligibility criteria. Outcomes were reported for 16,288 patients: 16,103 from observational studies and 185 from RCTs. Meta-analysis of observational studies demonstrated significantly lower mortality after laparotomy, as compared to peritoneal drainage (pooled OR 0.54, 95% CI 0.34-0.84). In contrast, RCTs demonstrated no difference in mortality (pooled OR 0.85, 95% CI 0.47-1.54). In post hoc analyses, observational studies were separated into two subgroups: low versus high quality of reporting, based on the STROBE checklist. Observational studies with low quality of reporting significantly favored laparotomy (pooled OR 0.38, 95% CI 0.18-0.81). In contrast and similar to RCTs, observational studies with high quality of reporting showed no difference in mortality (pooled OR 0.67, 95% CI 0.37-1.19).Conclusions: Neither RCTs nor observational studies with high quality of reporting demonstrate differences in mortality when preterm infants with surgical NEC are managed with laparotomy or peritoneal drainage. While RCTs remain a gold standard for evaluation of therapies, results from high quality observational studies may approximate the results of RCTs and might guide clinical practice until adequate RCT evidence is available. [ABSTRACT FROM AUTHOR]

Introduction. Necrotizing enterocolitis is a disorder characterized by the ischemic necrosis of intestinal mucosa. It is the most serious gastrointestinal disease affecting neonates, with high morbidity and mortality rates, mainly among premature newborns. The purpose of this study is to describe the clinical and anatamopathological characteristics of deceased newborns with necrotizing enterocolitis, diagnosed at a high-complexity hospital. Methodology. This is a descriptive retrospective study of 21 cases of medical-scientific autopsies performed at a high-complexity hospital in northeastern Colombia, with anatomo-pathological findings of necrotizing enterocolitis, performed between January 2013 and July 2017. Results 85.7% of the newborns were pre-term, and the same percentage had weight at birth below 2.5 kilograms. Regarding the mothers' background, 14.3% displayed a spectrum of hypertensive disorders associated with pregnancy, and 23.8% had maternal infections. The three most frequent locations of necrotizing enterocolitis were the ileum, ascending colon and transverse colon. Discussion. According to some authors, up to 85% of all cases of necrotizing enterocolitis occur in premature patients, especially in babies with extremely low weight at birth. There are forms of necrotizing enterocolitis that occur in full term babies, and they are generally associated with contributing factors, which is consistent with the findings of this study. Conclusions. This study of a Colombian population is consistent with other descriptions of the global population, where necrotizing enterocolitis arises more frequently in pre-term newborns and low weight at birth. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusion improves cardiorespiratory status of preterm infants by increasing circulating hemoglobin, improving tissue oxygenation, and reducing cardiac output. However, RBC transfusion itself has also been suggested to negatively affect short-term outcomes such as intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in premature infants. Purpose: This study aimed to analyze the relationship between RBC transfusion and short-term outcomes in very low birth weight (VLBW) infants (birth weight, <1,500 g). Methods: We retrospectively reviewed the medical records of VLBW infants admitted to the Soonchunhyang University Bucheon Hospital between October 2010 and December 2017. Infants who died during hospitalization were excluded. The infants were divided into 2 groups according to RBC transfusion status. We investigated the relationship between RBC transfusion and short-term outcomes including BPD, ROP, NEC, and IVH. Results: Of the 250 enrolled VLBW infants, 109 (43.6%) underwent transfusion. Univariate analysis revealed that all shortterm outcomes except early-onset sepsis and patent ductus arteriosus were associated with RBC transfusion. In multivariate analysis adjusted for gestational age, birth weight and Apgar score at 1 minute, RBC transfusion was significantly correlated with BPD (odds ratio [OR], 5.42; P<0.001) and NEC (OR, 3.40; P= 0.009). Conclusion: RBC transfusion is significantly associated with adverse clinical outcomes such as NEC and BPD in VLBW infants. Careful consideration of the patient's clinical condition and appropriate guidelines is required before administration of RBC transfusions. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal administration of mother's colostrum in early days has an immunoprotective effect in preterm infants.Objectives: Our aim was to study the effect of oropharyngeal administration of mother's milk (OPAMM) on decreasing the incidence of nosocomial sepsis.Methods: In a pilot prospective randomized study on preterm (<32 weeks gestation and 1500 g weight) infants, we compared OPAMM practice (applying 0.2 mL of mother's colostrum or milk prior to gavage feeding until full oral feeding is reached) with regular gavage feeding. The primary outcome was incidence of culture-proven nosocomial sepsis. Secondary outcomes included bacterial colonization of the gastrointestinal tract, feeding intolerance, time to reach full feeding, incidence of necrotizing enterocolitis, ventilator-associated pneumonia, duration of respiratory support, incidence of bronchopulmonary dysplasia (BPD), length of hospital stay, and neonatal mortality.Results: The outcomes of 200 neonates (100 in each group) were analyzed. OPAMM practice did not significantly reduce the incidence of culture proven nosocomial sepsis (8% vs 13%, P = 0.35). Infants in the OPAMM group had a significantly lower growth of Klebsiella species in the oropharyngeal pouch, borderline lower incidence of ventilator-associated pneumonia, shorter duration of oxygen therapy, less episodes of feeding intolerance, reached full feeding earlier, and had a shorter length of hospital stay. OPAMM practice did not affect the incidence of necrotizing enterocolitis, BPD, or neonatal mortality.Conclusion: OPAMM prior to gavage feeding does not reduce the incidence of nosocomial sepsis but had beneficial effects on early achievement of feeding, and early hospital discharge in preterm very low-birth-weight infants. [ABSTRACT FROM AUTHOR]

Necrotizing 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. 1) 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. A 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. NEC 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. In VLBW infants with NEC, lower birth weight and antenatal antibiotics administration were independently associated with the need for surgical intervention. • Necrotizing enterocolitis affects very low birth weight infants with a high incidence and mortality. • Finding risk factors and modifiable interventions that increase the necessity of surgery is crucial. • Birth weight <750 g and receiving prenatal antibiotics were associated with an increased risk of surgery requirement. • Those requiring surgery had significantly higher morbidity and mortality than the ones receiving medical treatment. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to show the effects of routine vs. selective fortification of human milk (HM) on short-term growth and metabolic parameters.Methods: Single-centre retrospective pre-post cohort study in India. Preterm infants ≤32 weeks' gestation and weighing ≤1500 g were included. Routine fortification: pre-fixed feed volume (100 ml/kg/day in our unit) at which fortification was done. Selective fortification: feed volume was gradually optimized till 180-200 ml/kg/day. If weight gain was below the expected threshold (<10 g/kg/day), then fortification was considered. Primary outcome measure was rate of growth till discharge.Results: The median rate of weight gain (g/kg/day) in the routine fortification group [10.8 (3.3, 17.1)] was comparable with that in the selective fortification group [8.4 (0, 14.2), p = 0.6]. Serum phosphorus showed a significantly higher value (5.9 vs. 4.8, p = 0.03), while rest of the metabolic parameters showed a trend towards a favourable outcome in the selective fortification group. Adverse outcomes showed a trend towards decreased feed intolerance, necrotizing enterocolitis, and sepsis in the selective fortification group.Conclusions: Selective fortification had a comparable growth rate and showed a trend towards better metabolic parameters and lesser adverse outcomes compared with routine fortification of HM. [ABSTRACT FROM AUTHOR]

Introduction: Milk curd obstruction is a rare, yet important cause of neonatal bowel obstruction that has been seldom reported in the literature. The presentation has evolved over time: Initially being seen in formula-fed term babies, to now being more prevalent in premature babies that require milk fortification. We present a case series of four patients treated for the condition at our institution and report that there may be additional contributing factors that have not been previously described. Method: Case notes of four patients that were diagnosed with milk curd obstruction over a one-year period were retrospectively analysed. Data collected included: gender, gestational age at birth, birth weight, pre-existing gastro-intestinal pathology, previous surgeries, feeding regimens used as well as the management and outcomes of milk curd obstruction. Results: All patients included in the series were premature, with three being classified as extremely low birth weight (ELBW). All babies received fortified expressed breast milk feeds. Three patients were treated for necrotising enterocolitis (NEC) prior to being diagnosed with milk curd obstruction. Two patients had undergone surgery for abdominal pathology ahead of their diagnosis. Three of the four babies required operative management for milk curd obstruction, whilst one was successfully managed conservatively. There were no mortalities. Conclusion: Previous gastrointestinal pathology as well as previous surgery may be associated with the development of milk curd obstruction. Milk curd obstruction is becoming an increasingly significant cause of neonatal bowel obstruction and further research and investigation is required to establish patterns of causation. [ABSTRACT FROM AUTHOR]

Supplementation of probiotics to very low birth weight (VLBW) infants has been extensively studied, with multiple meta-analyses reporting probiotics decrease the risk of necrotizing enterocolitis (NEC) and death. Despite availability of this evidence, the decision to initiate routine probiotic supplementation to preterm infants continues to be a complex one. There are uncertainties regarding the use of probiotics, including selecting the appropriate product, dose and target population. Additionally, availability of specific probiotic products and regulatory oversight varies by country, raising concerns regarding the safety and efficacy of specific probiotic products. In this review, we summarize the latest evidence on probiotic use in preterm infants and discuss considerations that may help guide clinicians who are considering routine probiotic supplementation. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in preterm infants, but specific therapies remain scarce. Recent studies have demonstrated an association between caffeine exposure and less frequent AKI in the first 7-10 days after birth. We hypothesized that patients with necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) would provide a better natural model of AKI to evaluate this association.Methods: We reviewed all premature patients diagnosed with NEC or SIP at our institution from 2008 to 2014. AKI was defined by change in serum creatinine using the neonatal Kidney Disease: Improving Global Outcomes definition. Caffeine was prescribed for apnea of prematurity and caffeine exposure was determined by chart review.Results: A total of 146 patients with NEC/SIP were reviewed. Of these, 119 (81.5%) received caffeine, and 91 (62.3%) developed AKI. AKI occurred less frequently in patients who received caffeine than in those who did not (55.5% vs. 92.6%; odds ratio (OR) 0.10; 95% confidence interval (CI) 0.02-0.44). This association persisted in multivariable models after adjustment for potential confounders (adjusted OR 0.08; 95% CI 0.01-0.42; number needed to be exposed to caffeine to prevent one case of AKI = 2.6). Although baseline serum creatinine did not differ by caffeine exposure, patients receiving caffeine had lower peak creatinine (median 1.0 mg/dl vs. 1.5 mg/dl; p = 0.008) and absolute creatinine change (median 0.42 mg/dl vs. 0.68 mg/dl; p = 0.003) than those who did not.Conclusions: Caffeine exposure in preterm infants with NEC/SIP is associated with decreased incidence and severity of AKI. [ABSTRACT FROM AUTHOR]

Aim:  The main purpose of this study was to investigate if necrotizing enterocolitis (NEC) has a different presentation and outcome in patients with congenital heart defect (CHD) (cardiogenic NEC) from those without (classical NEC).Materials and Methods:  A systematic review of the literature on the characteristics of infants with NEC and CHD was performed by three independent investigators using a defined strategy (PubMed, Cochrane, Embase, and Web of Science). A meta-analysis was conducted on studies comparing NEC in infants with CHD and non-CHD infants using RevMan 5.3.Results:  Systematic review: Of 7,291 abstracts screened, 126 full-text articles were analyzed and 51 studies were included. NEC had an incidence of 5.1% in CHD infants (7,728/151,046, range 0-24%) and 0.8% in non-CHD infants (26,430/3,256,891, range 0.1-8.9%; p < 0.0001). In very low birth weight infants, NEC occurred in 6.3% of CHD patients (6,361/100,454pts) and in 8.9% of non-CHD (23,201/257,794pts; p < 0.0001). In CHD cases, NEC occurred before cardiac surgery in 48% cases and surgery for NEC was required in 31% infants (2,037/6,683). Meta-analysis: In eight comparative studies, the incidence of NEC was higher in CHD infants (6%, 768/13,145) than in infants with no CHD (0.9%, 32,625/3,354,323pts; p < 0.00001, odds ratio [OR] 1.84, 95% confidence interval [CI] 1.7-1.9). The overall mortality was higher in infants with CHD and NEC (38%, 243/640) than in those without CHD (27%, 6651/24810; p < 0.00001, OR 3.4, 95% CI 2.8-4.1).Conclusion:  This is the first evidence-based study showing that infants with cardiogenic NEC have different demographics and outcomes than those with classical NEC. The risk of developing NEC and the mortality rate are higher among infants with CHD than in those without. Conversely, the need for intestinal surgery is lower in babies with cardiogenic NEC than in those with classical NEC. Further studies are needed to establish preventative and management interventions that are specific to infants with or at risk of developing cardiogenic NEC. [ABSTRACT FROM AUTHOR]

Objective: In our study, we aimed to evaluate the risk factors that influenced development of necrotizing enterocolitis (NEC) in preterm babies born at a gestational age below 32 weeks who were being followed up in our neonatal intensive care unit. Method: Babies who were born at a gestational age below 32 weeks in our hospital were evaluated in terms of perinatal (maternal hypertension/preeclampsia, antenatal Doppler US abnormality, intrauterine growth restriction, delayed/premature membrane rupture) and postnatal risk factors for the development of NEC. Demographic and clinical characteristics of the babies, in-hospital follow-up period, presence of respiratory distress, perinatal asphyxia, prsence of hemodynamically ptent ductus arteriosus, inotropic support, ventilator support, caffeine treatment, presence of central catheter, erythrocyte suspensio, nevidenced/clinical sepsis, and nutritional statıs were recorded. IBM SPSS Statistics 21,0 program was used for statistical evaluation. Results: Eighty-five preterm babies were included in our study. The birth weighst and gestational weeks of the subjects were found to be 1190 (380-1650) gs and 29 (21-31) weeks, respectively. The birth weight and gestational week were found to be significantly lower in the subjects who developed necrotizing enterocolitis compared to the subjects who did not (p:0.005; p:0.035). The incidence of NEC was found to be 11.7% (n:10) in preterm babies. Doppler ultrasonography revealed abnormal findings in five of the subjects who developed NEC and in 12 of the subjects who did not develop NEC; this difference was statistically significant (p:0.002). Surgical laparotom, and surgical resection were performed in five infants. Penrose drain was inserted in one infant at bedside. The mean birth weight and gestational week of these cases were found to be significantly lower compared to the ones who did not require surgery (p:0.015; p:0.042). In 3.5% of the babies tranfusion-rlated NEC was detected. The mortaişty rate in infants who developed NEC was 40 percent. Conclusion: Especially premature babies with lower gestational week and and very low birth weight, whom cannot tolerate minimal enteral feeding, and have abnormal Doppler ultrasound findings or blood transfusion history should be monitored more carefully. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is among the most serious gastrointestinal emergency in very low birth weight (VLBW), extremely low birth weight (ELBW) and extremely low gestational age neonates (ELGAN), affecting 7-14% of these neonates. Despite extensive research, the underlying aetiology of NEC still remains blurred. Due to high mortality, morbidity and its delayed presentation, early detection of NEC is considered to be lifesaving. A number of biomarkers have been studied for early detection and prediction of severity of NEC but till date, no ideal marker has been discovered. Molecular techniques like proteomic and metabolomic have recently emerged in the field for the development of biomarkers for early detection and understanding the pathophysiology of NEC. We did literature search for identifying all biomarkers that have been used for the detection of NEC and, in this review article, we discuss these biomarkers along with the available current evidence. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to understand the clinical characteristics of preterm neonatal necrotizing enterocolitis (NEC) to improve the medical management level.Methods: The clinical characteristics of preterm NEC infants with low birth weight (LBW, ≥ 1500 g) and very low birth weight (VLBW, < 1500 g) were compared. Then, clinical information, including demographics, surgical interventions and morbidity, were collected.Results: A total of 149 preterm NEC infants (60 with VLBW and 89 with LBW) were enrolled. Their median birth weight and gestational age were 1600 g and 31 weeks, respectively. Respiratory support and surfactant therapy were more frequent in VLBW infants (90% vs. 38% and 75% vs. 21.3%) than in LBW infants. In addition, 70.5% of these infants were fed by formula before the NEC occurred. Prematurity-associated morbidities were significantly higher in VLBW infants. Furthermore, 12.8% of all NEC infants died at discharge, and mortality was more prevalent in VLBW infants (21.7% vs. 6.7%). The most frequently received surgeries were enterostomy (n = 58), primary anastomosis (n = 42), and peritoneal drainage (n = 2). Multifocal, localized and pan-intestinal disease occurred in 77.5%, 19.6% and three infants, respectively. Furthermore, postoperative complications occurred more frequently in VLBW infants.Conclusion: The overall mortality was 12.8% for infants who had a larger mean gestational age and birth weight, when compared to that in developed countries. Higher rate of formula feeding might be an important risk factor for NEC development. Furthermore, mortality and morbidities, especially nutrition-associated complications, were more frequent in VLBW infants. [ABSTRACT FROM AUTHOR]

Background  We previously showed, in a single-center study, that early heart rate (HR) characteristics predicted later adverse outcomes in very low birth weight (VLBW) infants. We sought to improve predictive models by adding oxygenation data and testing in a second neonatal intensive care unit (NICU). Methods  HR and oxygen saturation (SpO 2) from the first 12 hours and first 7 days after birth were analyzed for 778 VLBW infants at two NICUs. Using multivariate logistic regression, clinical predictive scores were developed for death, severe intraventricular hemorrhage (sIVH), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (tROP), late-onset septicemia (LOS), and necrotizing enterocolitis (NEC). Ten HR-SpO 2 measures were analyzed, with first 12 hours data used for predicting death or sIVH and first 7 days for the other outcomes. HR-SpO 2 models were combined with clinical models to develop a pulse oximetry predictive score (POPS). Net reclassification improvement (NRI) compared performance of POPS with the clinical predictive score. Results  Models using clinical or pulse oximetry variables alone performed well for each outcome. POPS performed better than clinical variables for predicting death, sIVH, and BPD (NRI > 0.5, p  < 0.01), but not tROP, LOS, or NEC. Conclusion  Analysis of early HR-SpO 2 characteristics adds to clinical risk factors to predict later adverse outcomes in VLBW infants. [ABSTRACT FROM AUTHOR]

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated.

The article presents case study of male neonate was born by Cesarean section because of oligohydramnios at 25 weeks and 5 days of gestation with a birth weight of 572 g. It mentions he was hemodynamically stable on a ventilator and tolerated full enteral feeding until 40 days of age when he presented with abdominal distension, vomiting, and melena.

Background:Clostridium difficile is a gram-positive, anaerobic spore-forming, toxin-producing bacillus, which is one of the most common causes for health care-associated infections. High colonization rates in clinically asymptomatic neonates and infants have been described, although most studies go back to the early 1980 and 1990s, and were carried out in term and late preterm infants. Objectives: The aim of our study was to determine both the impact and time course of C. difficile colonization in a cohort of very low birth weight infants (VLBWI) in an era of PCR-based technologies for diagnosis. Methods: Stool samples of VLBWI were analyzed for the presence of C. difficile strains in regular intervals during the hospital stay by PCR ribotyping. Analysis was continued throughout the first 2 years of life. Results: A 32% C. difficile colonization rate during the first 2 years of life and an in-hospital colonization rate of 8% was found in a cohort of 190 VLBWI. C. difficile colonization occurred mainly in the first 6 months of life, which was similar to term neonates. In-hospital colonization accounted for only a small percentage of cases with no detection of hypervirulent strains. Also, C. difficile colonization was not related to an adverse outcome in this VLBWI cohort. Oral lactoferrin of bovine origin and treatment with piperacillin/tazobactam were negatively correlated with C. difficile colonization in our study. Conclusions:C. difficile colonization in our cohort of VLBWI was significantly lower than has been described in the literature and was not related to an adverse outcome. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to delineate whether patient-related or prescriber-related factors account for the prolongation of antibiotic therapy beyond 48 h in premature infants whose initial blood cultures are negative.Methods: Retrospective review of infants born <29 weeks born between January 2011 and December 2012. Infants who had positive blood cultures or who died in the first 48 h were excluded from analysis. Antibiotic courses were categorized as prolonged if antibiotics were continued for greater than 48 h and not prolonged if antibiotics were stopped by 48 h. Neonatologists were classified as high prescribers if they prolonged antibiotics for more than the median rate for the overall group.Results: Seventeen of 59 (29%) infants had empiric antibiotics continued for greater than 48 h despite negative blood cultures. Both patient-related factors and the neonatologist at 48 h of life were significantly associated with prolongation of antibiotics. Patient-related factors associated with prolongation of empiric antibiotics were positive maternal Group B streptococcus (GBS) status (5/17 versus 4/42); p = .054), white blood count >25,000 (7/17 versus 1/42); p < .001), rupture of membranes (ROM) duration (187 ± 253 h versus 47 ± 89 h; p = .015). Increased number of risk factors was associated with increased likelihood of prolongation. Risk factors for sepsis were similar between high and low prescribing neonatologists with high prescribers prolonging antibiotics with a lower number of risk factors.Conclusions: The decision to prolong empiric antibiotics in culture negative preterm infants is related both to patient and prescriber-related factors. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a neonatal surgical emergency with potentially devastating consequences. Pre-term infants of very low birth weight are most at risk with several genetic and environmental risk factors identified. The local microbial environment plays a key role in early life to help reduce the risk of NEC. Breast milk has also shown to be protective. The disease is characterized by infection, inflammation and ischaemia of the bowel that can extend from a small segment to most of its length. The diagnosis is made based on clinical, biochemical and radiological features with perforation the most widely accepted indication for surgery. When conservative management fails, a laparotomy is indicated with the aim of resecting necrotic bowel and preserving intestinal length. Complications include strictures, stoma morbidity, short-bowel syndrome and poor neurodevelopmental outcomes. Preventative strategies include the use of probiotics and encouraging the use of breast milk. [ABSTRACT FROM AUTHOR]

Background Analysis of subtle vital sign changes could facilitate earlier treatment of acute inflammatory illnesses. We previously showed that high cross-correlation of heart rate and oxygen saturation (XCorr-HR-SpO2) occurs in some very low birthweight (VLBW) infants with sepsis, and hypothesized that this corresponds to apnea. Methods In 629 VLBW infants, we analyzed XCorr-HR-SpO2 in relation to central apnea with bradycardia and desaturation (ABD), BD with or without central apnea (BD), and percent time in periodic breathing (PB) throughout the neonatal intensive care unit (NICU) stay (75 infant-years). We reviewed 100 days with extremely high XCorr-HRSpO2 (>0.7) and control days for clinical associations. Next, we identified all cases of late-onset septicemia (LOS) and necrotizing enterocolitis (NEC) and analyzed change in XCorr-HR-SpO2 before diagnosis. Results Mean XCorr-HR-SpO2 was ~0.10, and increasing XCorr-HR-SpO2 was associated with increasingABD, BD, andPB (correlation coefficients>0.93).Days withmaximumXCorr- HR-SpO2>0.7weremore likely to have an adverse event than control days (49%versus 13%). In 93 cases of LOS or NEC, there was a 67% increase in XCorr-HR-SpO2 in the 24-hour period prior to diagnosis compared with the previous day (p < 0.01). Conclusion High XCorr-HR-SpO2 is associated with apnea and adverse events including LOS and NEC. [ABSTRACT FROM AUTHOR]

Background: The multifactorial pathology and broad clinical presentation of necrotizing enterocolitis (NEC) development in premature infants make prediction of disease onset extremely challenging. Over the past decade, packed red blood cell (PRBC) transfusions have been temporally linked to the development of NEC in severely anemic preterm infants, although this issue is highly controversial.Purpose: In this case study, we describe events of an extremely low birth-weight infant who developed NEC complicated by pneumoperitoneum after receiving multiple PRBC transfusions. Specifically, we describe mesenteric tissue oxygenation trend changes as measured by continuous near-infrared spectroscopy (NIRS) technology.Methods: As part of a larger prospective, observational investigation, this infant was monitored with NIRS (INVOS 5100C; Medtronic, Boulder, Colorado) before, during, and 48 hours following PRBC transfusions.Results: The infant demonstrated severe, prolonged, and persistent reductions in mesenteric tissue oxygenation following blood transfusions, yet routine physiologic monitoring did not indicate intestinal hypoperfusion or impending NEC onset.Implications For Practice: This report demonstrates the ability of NIRS to capture possible tissue ischemia during early stages of NEC that may help guide bedside therapeutic interventions.Implications For Research: Larger cohort studies to evaluate the ability of NIRS to capture early tissue ischemia are essential to validate the feasibility of adding this technology as a routine clinical bedside tool.Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx. [ABSTRACT FROM AUTHOR]

Background: Fear of necrotizing enterocolitis (NEC) has perpetuated delayed initiation and slow advancement of enteral feeding in very low birth weight (VLBW) infants with inherent risks of parenteral alimentation. The objective of this study was to assess effect of early total enteral feeding (ETEF) on day of achievement of full enteral feeds, feed intolerance, NEC and sepsis.Methods: In total, 208 stable VLBW neonates (28-34 weeks) admitted during 6 month periods of three consecutive years were enrolled. First phase (n = 73) constituted the 'before' phase with standard practice of initial intravenous fluid therapy and slow enteral feeding. The second prospective phase (n = 51) consisted of implementation of ETEF with infants receiving full enteral feeds as per day's fluid requirement since Day 1 of life. The third phase (n = 84) was chosen to assess the sustainability of change in practice.Results: Day of achievement of full feeds was significantly earlier in Phases 2 and 3 compared with Phase 1 (8.97 and 5.47 vs. 14.44 days, respectively, p = 0.0001). Incidence of feed intolerance was comparable between Phases 1 and 2 (22 vs. 14%, p = 0.28), with marked reduction in incidence of NEC (14 vs. 4%, p = 0.028). There was a significant decrease in sepsis, duration of parenteral fluid and antibiotic therapy as well as hospital stay with comparable mortality.Conclusion: In stable preterm VLBW infants, ETEF is safe and has the benefit of optimizing nutrition with decrease in sepsis, NEC and hospital stay. [ABSTRACT FROM AUTHOR]

Background To evaluate peritoneal drainage (PD) and laparotomy ± resection/ostomy (LAP) as initial approaches to the surgical management of necrotizing enterocolitis (NEC) in premature, extremely low birth weight (ELBW) infants. Methods Kids' Inpatient Database (2003-2012) was searched for cases of NEC ( International Classification of Diseases, ninth revision, Clinical Modification [ICD-9-CM] 777.5x) in premature (<37 weeks), extremely low birth weight (<1000 g) infants. Infants were admitted at <28 days of life. Propensity score (PS)-matched analyses were performed, using end points of hospital mortality, length of stay (LOS), and cost of hospitalization. Cases were matched 1:1 on 48 confounding variables (demographic, clinical, and hospital characteristics and 39 comorbidities). Results On PS-matched comparison, PD had higher survival versus LAP, P = 0.0009. LOS and cost were higher for PD versus LAP, P < 0.003. Survival rates did not differ between PD + LAP and PD-only treatments. LOS and cost were higher for PD + LAP versus PD-only, P < 0.02. PD + LAP infants had higher survival versus LAP, P = 0.0193. LOS and cost were higher for PD + LAP, P < 0.005. Conclusions A risk-adjusted PS-matched analysis of operative management in premature, ELBW infants with NEC found higher survival rates associated with PD placement versus LAP, whether PD was used as definitive treatment or with subsequent LAP even after controlling for potential contributors to selection bias (i.e., stability influencing management preference). [ABSTRACT FROM AUTHOR]

Background: Lactoferrin (LF) is present in breast milk and have numerous properties including antimicrobial, antiviral, antifungal, and anticancer. Recent studies have emphasized the role of LF in neonatal care Aims and objective: To evaluate the various roles of LF in neonatal care in preterm infants. Search methods: The literature search was done for this systematic review by searching the electronic database namely Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS), SCIWIN (Scientific World Index), Google Scholar, Latin American and Caribbean Health Sciences Information System (LILACS), Index Medicus for the Eastern Mediterranean Region (IMEMR), Index Medicus for the South-East Asian Region (IMSEAR), Western Pacific Region Index Medicus (WPRIM), various sites for ongoing trials namely clinical trial registry (www.clinicaltrials.gov, www.controlled-trials.com, Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au), Indian Clinical Trials Registry (http://ctri.nic.in/Clinicaltrials), and the World Health Organization (WHO) International Clinical Trials Registry, and Platform (http://www.who.int/ictrp/search/en/) and abstracts of conferences namely proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research, and European Society for Pediatric Research). Results: Nine eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Six duplicate publications were excluded from review. Four studies were excluded due to nonfulfillment of inclusion criteria. All of the studies had more than one outcome of interest. Four studies showed reduction in late onset sepsis (LOS), one showed reduction in invasive fungal infection (IFI), three showed significant decrease in incidence of necrotizing enterocolitis (NEC), one showed reduction in NEC scares, and two showed decrease in mortality, and one showed decrease in combined death and/or NEC. Only one study evaluated role of LF for ventilator-associated pneumonia (VAP) reduction and showed lower rate of VAP. Still the role of LF in Bronchopulmonary dysplasia (BPD) and Retinopathy of prematurity (ROP) is unclear. Conclusion: LF has shown to be promising agent for reduction of LOS and NEC. The role of LF in prevention of neonatal mortality, BPD, and ROP needs further studies. The trials that are going on around the world may be able to give reply of this question in future [ABSTRACT FROM AUTHOR]

Purpose: Very low birth weight infants (VLBWIs) are at risk of surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI). We conducted this study to verify whether the timing of stoma closure and that of enteral nutrition establishment after stoma closure in VLBWIs differ among the most common disorders. Methods: A retrospective multicenter study was conducted at 11 institutes. We reviewed the timing of stoma closure and enteral nutrition establishment in VLBWIs who underwent stoma creation for intestinal disorders. Results: We reviewed the medical records of 73 infants: 21 with NEC, 24 with FIP, and 25 with MRI. The postnatal age at stoma closure was 107 (28-359) days for NEC, 97 (25-302) days for FIP, and 101 (15-264) days for MRI ( p = 0.793), and the postnatal age at establishment of enteral nutrition was 129 (42-381) days for NEC, 117 (41-325) days for FIP, and 128 (25-308) days for MRI ( p = 0.855). The body weights at stoma closure were 1768 (620-3869) g for NEC, 1669 (1100-3040) g for FIP, and 1632 (940-3776) g ( p = 0.614) for MRI. There were no significant differences among the three groups. Conclusions: The present study revealed that the time and body weights at stoma closure and the postoperative restoration of bowel function in VLBWIs did not differ among the three diseases. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate the effect of sex on survival and short-term outcomes of very low-birthweight infants ( VLBWI) born in Japan. Methods This study included VLBWI who were admitted to neonatal intensive care units participating in the Neonatal Research Network of Japan, between 2003 and 2012. The primary outcome was a composite of mortality or any major morbidity, including neurologic injury, bronchopulmonary dysplasia ( BPD), necrotizing enterocolitis ( NEC), or retinopathy of prematurity requiring treatment. Results The composite primary outcome was worse in male infants. Male infants were also more likely to develop BPD. This difference reached statistical significance in neonates born at ≥26 weeks of gestation. In contrast, significant difference in the incidence of NEC was more likely to be seen at 23-25 weeks of gestation. Conclusion Male neonates are more likely to die and are at a higher risk of respiratory and gastrointestinal complications than female neonates. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants and continues to be a major cause of morbidity and mortality. The incidence of NEC as well as mortality from the disease has persisted at unacceptably high levels for decades as current understanding of the cause remains incomplete. Identifying infants at risk and preventing NEC are mainstays of care. This article briefly examines disease presentation and treatment, identifies gaps in current understanding of disease pathology, and highlights new research that may lead to a decrease in the incidence of NEC in the future. [ABSTRACT FROM AUTHOR]

Background: Data on long-term consequences of neonatal pain is limited.Aim: To assess whether perinatal factors, later pain experience and pain coping strategies are associated with altered pain threshold, pain tolerance and pain intensity in adolescents born preterm.Study Design: Observational, longitudinal study (Project on Preterm and SGA-infants, POPS-19).Subjects: We analyzed data of 412 adolescents at the age of 19years, who were born at a gestational age<32weeks or with a birth weight<1500g.Outcome Measures: Participants performed a standardized cold pressor test to assess pain threshold, tolerance and intensity. Furthermore, they completed a pain coping questionnaire (PCQ).Results: In univariate analysis, female gender and necrotizing enterocolitis (NEC) were associated with lower pain tolerance, indicated by reaching the ceiling time of 180s in ice water (females 19% vs males 29%, NEC 7% vs no NEC 25%). Female gender was associated with higher pain intensity (mean difference 0.58; 95%CI 0.21; 0.95) and lower pain threshold (log rank test p 0.007). In a multivariate Cox regression analyses, emotion focused avoidance pain coping style was significantly associated with lower pain threshold (hazard ratio HR 1.38; 95%CI 1.02; 1.87) and pain tolerance (HR 1.72; 95%CI 1.21; 2.42). NEC was significantly associated with lower pain threshold (HR 1.47; 95%CI 1.01; 2.14) and pain tolerance (HR 1.63; 95%CI 1.09; 2.41).Conclusion: In adolescence, maladaptive pain coping strategy was associated with lower pain threshold, pain tolerance and higher pain intensity. NEC was associated with altered pain response in adolescents born preterm. [ABSTRACT FROM AUTHOR]