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Introduction: Necrotizing enterocolitis (NEC) is a severe gastrointestinal problem that predominantly affects premature babies. The aim of this retrospective study was to evaluate patients who underwent surgical treatment for NEC and newborns who initially recovered with medical treatment but later developed a stricture and required surgery. Materials and Methods: We analyzed patients diagnosed with NEC between January 2009 and December 2021. Our study included patients who developed strictures after initially receiving medical treatment for NEC and subsequently underwent surgery. Demographic findings, mother's age, gestational weeks, birth weight, type of birth, postnatal age at NEC diagnosis, pH, first C-reactive protein (CRP) after onset of symptoms, leukocytes, hemoglobin and thrombocytes at the onset of NEC, echocardiography results, age at surgery, blood values before surgery, surgery technique, and outcomes were retrospectively analyzed. Results: Out of 40 patients who underwent primary surgery for NEC during the newborn period, 6 patients underwent surgery after initially receiving medical treatment. The female-to-male ratio was 15/31, and the median gestational age was 29 weeks. The median mother's age was 30 years, and the median birth weight was 1097g. The median postnatal age at NEC onset was 6 days (range 2-39). Echocardiography was performed in 43 patients, with 6 showing normal results and 28 having congenital cardiac anomalies. The median surgery day for patients who underwent primary surgery for NEC was 19 days (range 2-90). Ileostomy was performed in 26 patients, colostomy in 8 patients, and ileostomy plus colostomy in 1 patient. Surgery was conducted in 6 out of 392 patients who developed post- NEC strictures after initial medical treatment. Comparison between post-NEC stricture patients and those who underwent surgery for NEC revealed significant differences only in the age at surgery (p=0.024). Conclusion: Patients who clinically experience NEC should be considered for the development of strictures, especially in cases of prolonged feeding intolerance, distention, gastric residual, and rectal bleeding. Therefore, close follow-up and multidisciplinary approaches are crucial, and contrast barium radiography should be the initial diagnostic step. [ABSTRACT FROM AUTHOR]

Introduction: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. Methods: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98–99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. Results: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55–0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). Conclusion: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged. [ABSTRACT FROM AUTHOR]

Introduction: Necrotizing enterocolitis (NEC) is a fatal disease with up to 20% mortality rates. Identifying risk factors for NEC may reduce NEC incidences. This study aims to investigate NEC-related risk factors in preterm infants. Methods: We included 27 preterm infants with NEC and 35 infants without NEC among the preterm newborns (n=1669) hospitalized in the Duzce University School of Medicine neonatal intensive care unit between 2009 and 2021. Parametric numeric data were calculated using the independent sample's t-test. Two-sample comparisons of nonparametric data were performed using the Mann-Whitney test. Pearson chi-square, Yates correction, and Fisher's exact test were also used to evaluate the categorical data. Results: Our results agree with previous studies regarding some of these findings: birth weight is lower in the NEC group (1.37±0.49 kg) than in the non-NEC group (18.3±6.5 kg) (p=0.009), with statistically similar gestational age. We couldn't show the association between NEC and multiple gestations, chorioamnionitis, preeclampsia, Apgar scores, patent ductus arteriosus, mechanical ventilation, pre-NEC red blood cell, or fresh frozen plasma transfusions. In the NEC group, thrombocyte levels before NEC were significantly lower (98 [9-2253]) (/x10³ mm³) than in the control group (222 [17-345]) (/x10³ mm³) (p=0.012). In addition, mortality rates (22.2% vs. 2.9%, respectively) (p=0.037), use of vasopressors (29.6% vs. 2.9%, respectively) (p=0.008) were markedly higher in the NEC group than in the non-NEC group. Additionally, lower birth weight (NEC group: 1367.25±493.62 vs. non-NEC group: 1831.71±651.62) (p=0.009), prolonged use of antibiotics (NEC group: 24% vs. non-NEC group: 0%) (p=0.004), and poor circulation (NEC group: 84% vs. non-NEC group: 3%) (p<0.001) were statistically significant variables. Discussion and Conclusion: NEC increases the mortality rates in preterm infants. The use of vasopressors, low birth weight, poor circulation, and antibiotics are significant risk factors for NEC, and low thrombocyte levels can lead to the prediction of NEC. [ABSTRACT FROM AUTHOR]

Introduction: Disruptions of the gut microbiota of preterm infants admitted to the neonatal intensive care unit (NICU) during the first 2 weeks of life are of critical importance. These infants are prone to various complications, including necrotizing enterocolitis (NEC) and sepsis. Studying the gut microbiota will improve outcomes in preterm infants. In the present study, we examined the gut microbiota of preterm infants admitted to the NICU in the first month of life. Methods: Neonates admitted to the NICU were recruited, and stool samples were collected weekly from the seventh day of the infant's life until the 30th day of life. DNA was extracted using a DNeasy Powersoil DNA isolation kit. 16S rRNA gene sequencing targeting the V3-V4 region was performed using the MiSeq platform. Sequenced reads were processed on DADA2 pipeline to obtain an amplicon sequence variant (ASV) table. All bioinformatic and statistical analyses were performed using different packages in the R statistical framework. Results: Fourteen preterm infants were recruited, and 48 samples were collected. Alpha diversity metrics, observed ASV count, and Shannon index were found to have no differences in any clinical variables. Permutational multivariate analysis of variance (PERMANOVA) showed discrimination of neonates by gestational age and administration of probiotics. Differential abundance analysis showed a decreased abundance of Bifidobacterium Breve in extremely preterm infants (gestational age <28 weeks) compared to moderate preterm infants (gestational age 29-32 weeks). Supplementation with probiotics decreased Acinetobacter and increased Bifidobacterium in the gut of preterm neonates regardless of gestational age. Conclusion: Gestational age and probiotic supplementation alter the gut microbiota of preterm infants admitted to the NICU. [ABSTRACT FROM AUTHOR]

BackgroundPrematurity and congenital heart disease (CHD) are the leading causes of neonatal mortality and morbidity. Limited data are available about the outcomes of premature infants with severe CHD.MethodsWe queried The National Inpatient Database using ICD-10 codes for premature patients (

IntroductionDisruptions of the gut microbiota of preterm infants admitted to the neonatal intensive care unit (NICU) during the first 2 weeks of life are of critical importance. These infants are prone to various complications, including necrotizing enterocolitis (NEC) and sepsis. Studying the gut microbiota will improve outcomes in preterm infants. In the present study, we examined the gut microbiota of preterm infants admitted to the NICU in the first month of life.MethodsNeonates admitted to the NICU were recruited, and stool samples were collected weekly from the seventh day of the infant’s life until the 30th day of life. DNA was extracted using a DNeasy Powersoil DNA isolation kit. 16S rRNA gene sequencing targeting the V3–V4 region was performed using the MiSeq platform. Sequenced reads were processed on DADA2 pipeline to obtain an amplicon sequence variant (ASV) table. All bioinformatic and statistical analyses were performed using different packages in the R statistical framework.ResultsFourteen preterm infants were recruited, and 48 samples were collected. Alpha diversity metrics, observed ASV count, and Shannon index were found to have no differences in any clinical variables. Permutational multivariate analysis of variance (PERMANOVA) showed discrimination of neonates by gestational age and administration of probiotics. Differential abundance analysis showed a decreased abundance of Bifidobacterium Breve in extremely preterm infants (gestational age

Objective Antenatal steroids are commonly used to stimulate fetal lung maturation, particularly in pregnancies at risk of early preterm labor. This study aimed to compare the effects of administering betamethasone at a 12- versus 24-hour interval on perinatal outcomes. Study Design This retrospective study included 423 early preterm births from 26 +0/7 to 33 +6/7 weeks of gestation. Patients received betamethasone at either a 12- or 24-hour dosing interval. Results When all patients in each group were evaluated together, there was no statistically significant difference between both groups for complications of prematurity, including respiratory distress syndrome (RDS). When the two groups were divided by gestational age (GA), the 32 +0/7 to 33 +6/7 -week group that received betamethasone at a 24-hour interval had statistically lower 1- and 5-minute APGAR scores (p = 0.06 and p = 0.02, respectively). They also had a greater need for neonatal intensive care unit (NICU), NICU length of stay, RDS, and need for surfactant (p = 0.20, p = 0.09, p = 0.27, and p = 0.23, respectively) than did the infants at 32 +0/7 to 33 +6/7 weeks, who received betamethasone at a 12-hour interval. In the group with GA between 28 +0/7 and 29 +6/7 weeks, the 1-minute APGAR score was lower (p = 0.22), and the durations of hospital stay, and mechanical ventilation were longer (p = 0.048, p = 0.21, respectively) in the 24-hour interval group. No statistically significant difference was observed for all parameters in other GA groups. Conclusion A 12-hour dosing interval for betamethasone appears to be more appropriate, as it results in a reduction in some neonatal complications and provides a short dose interval. Key Points RDS is reduced when betamethasone is used 12 hours apart. When betamethasone is used 12 hours apart, the need for surfactant is reduced. The use of betamethasone 12 hours apart is advantageous with its short dose interval. [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]

Objective: To find out the frequency of necrotizing enterocolitis (NEC) in preterm infants and to compare the frequency of NEC in preterm infants with formula feed versus breast feed. Study Design: Cross-sectional study. Setting: Department of Pediatric Medicine, Ghazi Khan Medical College, Dera Ghazi Khan, Pakistan. Period: January 2022 to June 2022. Material & Methods: A total of 174 preterm infants were enrolled. The NEC was diagnosed as abdominal distention or intolerance to nasogastric feed with pneumatosis intestinalis/portal venous gas or free intraperitoneal air which was confirmed by abdomen X-ray. At the time of enrollment, gestational age and weight were recorded. All preterm neonates were called for follow up every week for 4 weeks to diagnose NEC. Results: Of these 174 study cases, 101 (58.0 %) were male patients while 73 (42.0 %) were female patients. Mean gestational age of our study cases was 30.48 ± 3.24 weeks. Of these 174 study cases, 102 (58.6%) mothers were illiterate. Breastfeeding was noted in 74 (42.5%) infants while formula feeding was recorded among 100 (57.5%) infants. The NEC was reported among 61 (35.1%) cases whereas NEC in breastfeeding cases was found in 14 (18.9%) and 47 (47.0%) infants with formula feeding. Conclusion: High frequency of NEC was observed among preterm infants given formula feeding in comparison to breastfed preterm infants. Significant linkage of NEC was noted with gender, maternal literacy, birth weight and pattern of feeding. [ABSTRACT FROM AUTHOR]

To determine the association of placental pathology with the severity of necrotizing enterocolitis (NEC) in preterm infants. This single-center matched case-control study included infants with NEC (n = 107) and gestational age and birth weight-matched controls (n = 130), born between 2013 and 2020. Placentas were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Acute histologic chorioamnionitis with the fetal response was significantly more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). On regression model, infants with multiple placental pathologies (OR 2.16; 95% CI 1.01 − 4.73; p = 0.04) and maternal vascular malperfusion (OR 2.2; 95% CI 1.12 − 4.51; p = 0.02) had higher odds of either medical or surgical NEC than controls. Infants with multiple placental lesions, including placental inflammatory and vascular lesions, were at higher risk of medical or surgical NEC in the postnatal period. [ABSTRACT FROM AUTHOR]

Preterm infants have increased morbidity and mortality due to immature physiology and neonatal complications. Necrotizing enterocolitis (NEC) is a devastating gastrointestinal complication that affects morbidity and mortality in preterm infants. The authors present an adaptation of Neuman's systems model called the NEC systems model to explore intrinsic and extrinsic factors leading to NEC in preterm infants. The literature was searched for theoretical models to guide exploration of neonatal disease influenced by the environment. Neuman's Systems Model provides a holistic approach to care of the system, offering a foundation to develop frameworks to examine preterm infants in their environment with associated stressors. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictive value of serum amyloid A (SAA), C-reactive protein (CRP), platelet distribution width (PDW) and neutrophil/lymphocyte ratio (NLR) for the timing of neonatal necrotizing enterocolitis (NEC) surgery.Methods: 70 children with NEC who were admitted to Foshan Maternal and Child Health Hospital from January 2019 to January 2022were selected, and they were divided into surgery group with 35 cases and non-surgery group with 35 cases according to treatment methods. Clinical data of children with NEC were collected, and the levels of serum SAA, CRP, peripheral blood PDW and NLR in the two groups were detected. Univariate and multivariate Logistic regression were used to analyze the influencing factors of neonatal NEC surgery. The predictive value of serum SAA, CRP, peripheral blood PDW and NLR on the timing of neonatal NEC surgery was analyzed by receiver operating characteristic (ROC) curve. Results: The gestational age ≥37 weeks and the proportion of weight ＞2500 g at diagnosis in the surgery group were lower than those in the non-surgery group, the proportion of weight 1500～2500 g at diagnosis, poor mental response, abdominal distension, weak bowel sound and the levels of serum SAA, CRP, peripheral blood PDW and NLR were higher than those in the non-surgery group (all P＜0.05). Multivariate Logistic regression analysis showed that weight＞2500 g at diagnosis was an independent protective factor for neonatal NEC surgery, poor mental response, abdominal distension, weak bowel sound and increased levels of serum SAA, CRP, PDW and NLR were independent risk factors for neonatal NEC surgery (all P＜0.05). ROC curve analysis showed that the area under the curve (AUC) of the combination of serum SAA, CRP, peripheral blood PDW and NLR in predicting the timing of neonatal NEC surgery was greater than that of each indicator alone. Conclusion: The increase levels of serum SAA, CRP, peripheral blood PDW and NLR are closely related to neonatal NEC surgery, and the combined value of these four indicators in predicting the timing of neonatal NEC surgery is higher [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to determine the clinical and histopathological factors associated with intestinal hemorrhage and its correlation with clinical outcomes in neonates with surgical necrotizing enterocolitis (NEC). METHODS: A retrospective study compared clinical and histopathology information in neonates following surgical NEC with severe hemorrhage and those with mild/moderate hemorrhagic lesions seen on resected intestine pathology. RESULTS: The infants with severe hemorrhage (Grade 3-4, 81/148, 54.7%) had significantly lower exposure to antenatal steroids (52.5 % vs 76.9 %; p = 0.004), had higher gestational age (28.5 weeks [7.14] vs. 26.58 [2.90]; p = 0.034), lost more bowel length (p = 0.045), had higher CRP levels at 2 weeks (p = 0.035), and had less intestinal failure ([30.3 % vs 52.5 %]; p = 0.014) than mild/moderate (Grade 0–2, 67/148, 45.2%) hemorrhage group. Those with severe hemorrhage had significantly higher mean inflammation score (2.67 [0.94] vs. 1.63 [0.92]; p = <0.001), higher necrosis scores (1.95 [1.28] vs. 1.49 [1.35]; p = 0.037), higher neovascularization (p = 0.01), higher fibroblasts (p = 0.023) and higher lymphocyte percentages up to 48 hours (p < 0.05) following NEC than mild/ moderate hemorrhage group. On multivariable regression, less exposure to antenatal steroids (OR 0.18 [95% CI 0.05–0.58]; p = 0.005), higher inflammation (OR 3.7 [95% CI 2.09–7.32]; p = 0.001), and lymphocyte count on the day of onset/24 hours following NEC (OR 1.06 [95% CI 1.02–1.11]; p = 0.005) were independently associated with a higher odd of severe intestinal hemorrhage. CONCLUSION: The surgical NEC infants with intestinal hemorrhage were less likely to have antenatal steroid exposure but had higher inflammation grade and lymphocyte counts following NEC onset on multivariable regression modeling. [ABSTRACT FROM AUTHOR]

Objective To investigate gestational age (GA) specific hematological and transfusion response patterns in preterm infants following necrotizing enterocolitis (NEC) Design A retrospective study comparing hematological/transfusion information in three GA groups’ infants: Group A ≤ 28 weeks. Group B 28–32 weeks, Group C > 32 weeks following necrotizing enterocolitis. Results Group A infants responded with significantly higher WBC count, thrombocytopenia, higher absolute neutrophil, and higher absolute monocyte and lower absolute lymphocyte counts following NEC onset, received more blood transfusions before NEC onset (59.8 versus 30.0%; p = .007), and had higher odds of surgical NEC (OR 3.39 [95% CI 1.19–10.38]; p = .02) than group C. One unit increase in absolute lymphocyte count on the day, and 24 h following NEC was significantly associated with lower surgical NEC odds than groups C. Conclusion The infant’s in-group A had significantly different hematological response patterns following NEC than infants with higher gestational age (groups B and C). [ABSTRACT FROM AUTHOR]

The American Academy of Pediatrics recommends the use of donor human milk in infants when mother's own milk is not available. Our objective was to analyze whether the use of donor human milk in preterm, very-low-birth-weight (VLBW, <1500 g) infants affected the rates of necrotizing enterocolitis, duration of parenteral nutrition (PN), growth, culture-positive sepsis, length of hospital stay, and mortality in an urban NICU population with low exclusive breast-feeding rates. A retrospective cohort study was conducted comparing two 2-year epochs of VLBW neonates before and after the introduction of donor breast milk in our neonatal intensive care unit (NICU). With the introduction of donor human milk, there was a significant reduction in the rate of necrotizing enterocolitis (NEC) (5% vs. 13%; p = 0.04) and less severe NEC as defined by Stage III based on the Modified Bell Staging Criteria (10% to 3%; p = 0.04). In the donor milk era, there was earlier initiation of enteral feeding (2.69 days vs. 3.84; p = 0.006) and a more rapid return to birthweight (9.5 days. 10.9 days; p = 0.006). In this study, a change in practice to the use of donor breast milk in a population with low rates of human milk provision was associated with earlier initiation of enteral feeding, faster return to birth weight, and a reduced incidence of NEC. [ABSTRACT FROM AUTHOR]

BACKGROUND: To determine the clinical implications and gestation age-specific diagnostic predictability of pneumatosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A retrospective study on abdominal radiographs comparing clinical and radiological information in infants with and without pneumatosis. RESULT: Our findings disproved our hypothesis. Pneumatosis was seen more frequently in infants with higher gestational age [28.4 (26.1–32.4) vs. 26.4 (24.3–29) weeks; p < 0.001] and birth weight [1110 (762–1768) vs. 770 (645–1022) grams; p < 0.001] and were more likely delivered vaginally (39.1% vs. 21.7%, p = 0.01). Portal venous gas was seen frequently on radiographs (10.3% vs. 0%, p < 0.001), but not pneumoperitoneum (20.7% vs. 36.7%, p = 0.02). Infants with pneumatosis frequently developed acute kidney injury, with higher serum creatinine (16.5% vs. 4.5%, p = 0.02) and frequent oliguria (12.9% vs. 2.7 %; p = 0.043) and had higher C-reactive protein levels at 24 and 96 hours (p < 0.002). Receiver operating curves for pneumatosis showed GA >28 weeks and birth weight > 1000 gm to have a sensitivity of 58.6% and specificity of 72.5%. CONCLUSION: Contrary to our hypothesis, infants who developed pneumatosis during NEC were more mature with a higher gestational age and birth weight than those who did not. [ABSTRACT FROM AUTHOR]

Introduction: Several studies showed advantages in outcomes for very-low-birth-weight (VLBW) female infants. It has been suggested that recent advances in perinatal care might have benefited boys relatively more than girls, making differences disappear. Objectives: The aims of the study were (1) to determine if sex differences in survival and survival without morbidity in VLBW infants are still present in the context of more advanced perinatal care and (2) to know whether these differences are consistent throughout gestational age (GA). Methods: Retrospective cohort study in seven countries participating in the Spanish SEN1500 and the South American NEOCOSUR neonatal networks. We included VLBW infants 24–30 weeks' GA, born alive without major congenital anomalies (2013–2016). Major morbidity, survival, and survival without morbidity were compared between male and female infants overall and stratified by GA. Results: 10,565 patients were included: 5,620 (53.2%) males and 4,945 (46.8%) females. Female infants exhibited a lower incidence rate ratio (95% CI) of respiratory distress syndrome: 0.91 (0.88, 0.94), necrotizing enterocolitis: 0.83 (0.74, 0.93), major brain damage: 0.79 (0.72, 0.86), moderate-severe bronchopulmonary dysplasia (BPD): 0.77 (0.72, 0.83), higher survival: 1.03 (1.01, 1.05), survival without BPD: 1.11 (1.07, 1.16), survival without major brain damage: 1.05 (1.02, 1.08), and survival without major morbidity: 1.14 (1.07, 1.21). Survival and survival without morbidity were almost consistently favourable to females throughout GA. Conclusions: Our findings suggest that perinatal results continue to be favourable for VLBW female infants in the context of current perinatology, and that they are almost consistent throughout GA. [ABSTRACT FROM AUTHOR]

Background Necrotizing enterocolitis (NEC) is a prematurityrelated complication of the gastrointestinal tract that affects 3-15% of preterm infants. Due to its atypical signs and symptoms, NEC is often diagnosed late, leading to mortality and morbidity. Objective To describe the incidence, characteristics, and survival rate of preterm infants with NEC in the Neonatal Unit of Dr. Cipto Mangunkusumo Hospital. Methods This prospective cohort study was conducted on preterm infants born in Dr. Cipto Mangunkusumo Hospital in 2019 who had NEC Bell stage 2 or higher. Subjects were recruited consecutively. The NEC was classified into either early-onset (<14 days of life) or late-onset (=14 days of life). We identified the risk factors of mortality and survival using multiple Cox regression. Results Within the study period, 55/639 preterm infants born in Dr. Cipto Mangunkusumo Hospital were diagnosed with NEC. Mean gestational age was 31.16 (SD 2.63) weeks and mean birth weight was 1,378.12 (SD 438.26) grams. The median age at NEC diagnosis was 6 (range 0-24) days. The most common symptoms were gastrointestinal bleeding (29.09%) and abdominal distension (29.09%). Plain abdominal radiographs showed dilated bowels in 92.72%, thickened intestinal walls in 83.63%, and pneumatosis intestinalis in 61.81% of subjects. Positive blood cultures were found in 63.63% of subjects, with Staphylococcus epidermidis and Klebsiella pneumoniae being the predominant organisms. Median survival was 27 days and 31 days for infants born at <32 weeks and =32 weeks gestational age, respectively (P=0.37). Median survival was 27 and 28 days in infants with early-onset and late-onset NEC, respectively (P=0.07), and 23 and 28 days in infants with birth weight of <1,000 grams and =1,000 grams, respectively (P=0.14). Conclusion The incidence of NEC among preterm infants born in Dr. Cipto Mangunkusumo Hospital in 2019 was 8.6%. The survival rate of infants with NEC was 27.27%. Early-onset and late-onset NEC have similar mortality rates. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease which mostly occurs in very low birth weight (VLBW) infants. In addition to decreasing gestational age (GA) or birth weight (BW), artificial formula, delayed initiation or rapidly advanced feeding, severe anemia and systemic infections were associated with NEC. Several studies demonstrated that breast milk, standardized feeding advancement regimens and treatment of anemia are associated with less incidence of NEC. It is not known if including all these interventions in one multifaceted program will lead to significant reduction in NEC. The NICU team at The George Washington University Hospital created a multifaceted interdisciplinary quality improvement project to tackle several aspects of NEC prevention that addressed researched risk factors for NEC. The program was made of four quality improvement protocols: 1) Standardized Structured Feeding Program, 2) Feeding Intolerance Management Algorithm, 3) Enteral Osmolality Control Tool, and 4) Packed Red Blood Cell (RBC) Standardized Transfusion Protocol. This time-series, quasi experimental study design examined the differences in the incidence of NEC between infants with BW < 1500 g who were admitted to the GW Hospital NICU before and after the program implementation. Data from 408 VLBW infants were included in the study. Although not statistically significant, there was a decreasing trend of NEC incidence in the post-implementation group (n = 199) compared to the pre-implementation group (n = 209), (3.5% vs. 5.3%, p = 0.88). The trend in the incidence of NEC declined further after the introduction of RBC transfusion protocol which was introduced ten month after starting the other elements of the program. Integration of the multifaceted quality improvement program may be associated with a decline in the occurrence of NEC. Further analysis with a larger sample size is required to determine if the changes seen are statistically significant. [ABSTRACT FROM AUTHOR]

The article presents a rare case study of strangulated bowel obstruction in a very low birthweight infant caused by an idiopathic congenital band (ICB). It is reported that operative findings revealed a necrotic bowel due to strangulation by an anomalous band, which was excised. It further emphasizes the importance of considering ICB as a cause of bowel obstruction in preterm infants.

Background: Necrotizing enterocolitis (NEC) is a devastating disease in preterm infants with significant morbidities, including neurodevelopmental impairment (NDI). This study aimed to investigate whether NEC is associated with (1) brain volume expansion and white matter maturation using diffusion tensor imaging analysis and (2) NDI compared with preterm infants without NEC. Methods: We included 86 preterm infants (20 with NEC and 66 without NEC) with no evidence of brain abnormalities on trans-fontanelle ultrasonography and magnetic resonance imaging at term-equivalent age (TEA). Regional brain volume analysis and white matter tractography were performed to study brain microstructure alterations. NDI was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III) at 18 months of corrected age (CA). Results: Preterm infants with NEC showed significantly high risk of motor impairment (odds ratio 58.26, 95% confidence interval 7.80–435.12, p < 0.001). We found significantly increased mean diffusivity (MD) in the splenium of corpus callosum (sCC) (p = 0.001) and the left corticospinal tract (p = 0.001) in preterm infants with NEC. The sCC with increased MD showed a negative association with the BSID-III language (p = 0.025) and motor scores (p = 0.002) at 18 months of CA, implying the relevance of sCC integrity with later NDI. Conclusion: The white matter microstructure differed between preterm infants with and without NEC. The prognostic value of network parameters of sCC at TEA may provide better information for the early detection of NDI in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Recently, blood monocyte concentration has been introduced as an inventive biomarker for necrotizing enterocolitis (NEC) in low birth weight neonate; therefore, we aimed to examine and compare blood monocyte counts in preterm neonates with and without NEC. Methods: A case-control study was conducted on 160 preterm neonates in Tehran during 2017. In this study, medical records and laboratory findings of 80 neonates with NEC (case) and 80 neonates (control), who were randomly chosen from among neonates who had survived NEC, were reviewed and CBC outcomes were compared between the groups. Results: We compared 80 cases and 80 controls. The mean gestational age in the NEC and control group was 30.78 ± 2.33 and 31.41 ± 2.16 weeks, respectively. The birth weights in the NEC and control group were 1500 ± 488 and 1562 ± 360 g, respectively. The mean age for developing NEC was 14.14 ± 13.9 days. The absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) did not differ statistically significantly between the two groups. The mean absolute white blood cells (WBC) in the NEC and control group were 11368 ± 7957 and 8268 ± 7505, respectively; absolute WBC was significantly different between the two groups (P = 0.001). The mean absolute monocyte count (AMC) in the NEC and control group were 262 ± 193 and 518 ± 691, respectively; the difference in absolute WBC was significant between the two groups (P = 0.002). Receiver operating characteristic of AMC values showed a diagnostic accuracy of 0.693 (95% CI: 0.612-0.773) for NEC and 0.738 (95% CI: 0.627-0.850) for stage II and III NEC. Conclusion: The result of this study suggest that the concentration of blood monocyte could be an indicator for NEC in the preterm neonate. However, this result should be confirmed by other studies. [ABSTRACT FROM AUTHOR]

Introduction:  Very preterm infants (VPIs) surgically treated for necrotizing enterocolitis (NEC) are at risk of growth retardation. The aim of this study was to demonstrate and compare growth during the first 6 years of life in VPIs with stoma after NEC surgery with VPIs without NEC surgery.Materials and Methods:  We included all VPIs surgically treated due to NEC at the Odense University Hospital from August 1, 2004, to July 31, 2008. Outcome on growth was compared with a group of VPIs without NEC. The VPIs with NEC were identified searching the local database using the International Classification of Diseases, 10th Revision diagnosis of NEC (DP77.9). Data on growth were collected from medical files and if not present, the parents reported the data.Results:  Nineteen VPIs, surgically treated due to NEC, survived to 6 years of age. Median gestational age was 283/7 weeks (245/7-313/7). Median age at NEC surgery and stoma formation was 2.3 weeks (0.1-6.3) and median age at stoma closure was 2.5 months corrected age (CA) (postmenstrual age 36 weeks to CA 6.7 months). Compared with the non-NEC group, VPIs with NEC and stoma demonstrated poor growth, especially in head circumference (HC) with no increase in growth velocity before the time of stoma closure between 2.5- and 3-month CAs.Conclusion:  Our findings demonstrate poor growth in VPIs after NEC surgery and improved HC growth after stoma closure. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal fatty acid-binding protein (I-FABP) is located in the apex of mature enterocytes and released into circulation; once the injury of enterocyte happens, its circulating levels are considered an early and sensitive marker of intestinal ischemia as in necrotizing enterocolitis (NEC); because of its small molecular weight, it can be detected in urine. Aims: The aim was to study the usefulness of both serum and urine I-FABP in early diagnosis of NEC and to correlate the serum and urinary levels. Settings and Design: This study was case–control design. Methods: Simultaneous serum and urine samples obtained at the onset of symptoms, in 40 preterms with suspected NEC, with gestational age ± 27.70 weeks and birth weight ± 1.11 kg, i.e., 20 preterms diagnosed at Stage I, 12 preterms at Stage II, and 8 preterms at Stage III, were compared with age- and weight-matched preterms with no NEC. Statistical Analysis: The collected data were tabulated, coded, and then analyzed using the computer program Statistical Package for the Social Science (SPSS version 22). Results: Serum levels of I-FABP in NEC cases were significantly higher than the control group, with a mean of 6005.77 ± 6384.77 and 1480.79 ± 1276.48 pg/ml, respectively (P < 0.001). Urine levels of I-FABP in NEC cases were significantly higher than the control group, with a mean of 5009.22 ± 3941.64 and 2677.62 ± 2257.29 pg/ml, respectively (P = 0.04). Both serum and urine I-FABP levels not only in Stage II are significantly higher than Stage I but also in Stage III are significantly higher than Stage I and II (P < 0.001, P = 0.03, respectively), which showed significant positive correlation with stages of NEC (r = 0.618; P < 0.001; r = 0.306; P = 0.049, respectively). Both serum and urine I-FABP levels had a highly significant positive correlation with each other (r = 0.406 P < 0.0001). Receiving operating characteristic curve showed an area under the curve of 0.92 and 0.81 for serum and urine I-FABP, respectively. Conclusions: Whether serum or urinary I-FABP is valuable in the diagnosis and prediction of NEC and strongly correlated with the disease severity and with each other. [ABSTRACT FROM AUTHOR]

Objective  Citrulline synthesized by healthy enterocytes and decreases with injury. This work aimed to study plasma citrulline concentrations (CITs) as a biomarker to differentiate among infants presenting with early nonspecific signs and symptoms of necrotizing enterocolitis (NEC) with those who will develop NEC. Further to study the correlation between posttreatment CIT with time to full feeds (TTFF) and length of stay (LOS). Study Design  This is a prospective study which included infants < 32 weeks gestational age (GA) with 9 infants each in Group 1 (stage 2/3 NEC), Group 2 (with stage 1 NEC-like presentation), and Group 3 (healthy GA-matched infants). CIT was measured in Groups 1 and 2 within 24 hours of presentation and again in Group 1 after treatment. Results  The three groups were similar in clinical characteristics. Median CIT (µmol/L) in Group 1 (15.4 [interquartile range, IQR: 7.3–18.0]) was lower than Group 2 (22.2 [IQR: 18.3–27.3], p  = 0.02) and Group 3 (24.9 [IQR: 19.8–31.9], p  = 0.009). Posttreatment CIT in Group 1 did not correlate with TTFF (r  = 0.15; p  = 0.69) and LOS (r  =  − 0.33; p  = 0.38). Conclusion  CIT was lower in infants with NEC as compared with healthy controls and those infants with nonspecific signs of NEC. CIT after treatment does not correlate with TTFF and LOS. Key Points Citrulline is produced by enterocytes. It is decreased in infants with necrotizing enterocolitis early in disease. It can be used as a biomarker for early diagnosis of necrotizing enterocolitis. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis(NEC) is the most significant gastrointestinal emergency in neonates, particularly affecting those who are premature. Neonatal appendicitis is highly uncommon in term infants and its diagnosis is typically incidental. The clinical presentation of newborn appendicitis is nonspecific and usually mimics that of NEC. Pneumatosis intestinalis is a finding that is extremely specific to NEC; it is very surprising to observe this finding in a patient with acute appendicitis. A 2730-g male infant was born at 39 weeks gestation to a 33-year-old mother. 30 minutes after delivery, the patient exhibited grunting and respiratory distress and was subsequently admitted to the Neonatal Intensive Care Unit. On the 7th day, the patient developed nutrition intolerance. The feeding was discontinued and the nasogastric catheter was switched to free drainage. Abdominal examination and laboratory parameters were not significant, but direct abdominal radiographs showed findings suggesting pneumatosis intestinalis. NEC was considered and the antibiotics were revised accordingly. The department of pediatric surgery was consulted as the patient's abdominal examination and radiographs showed abnormalities suggestive of advanced NEC. The patient was taken into operation, gangrenous appendicitis was detected and an appendectomy was performed. When considering the differential diagnosis of NEC in neonatal patients, especially in term infants, clinicians should be mindful of acute appendicitis. In this study, we present a case of neonatal appendicitis, which is relatively common in pediatric cases but uncommon in the neonatal period, presenting as atypical NEC. [ABSTRACT FROM AUTHOR]

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: Recently, the correlation between necrotizing enterocolitis (NEC) and packed cell transfusion (PCT) has been identified. Evidence shows that 25 - 35% of NEC cases are associated with PCT. Objectives: this study aimed to determine the association between PCT and feeding tolerance in healthy preterm newborns. Methods: Materials and Methods: This clinical trial was performed on preterm infants, admitted to the neonatal intensive care unit (NICU) of Mofid Children's Hospital, Tehran, Iran, from April 2017 to May 2018. A total of 70 healthy premature infants (birth weight < 1500 g and gestational age < 32 weeks) with enteral feeding, who required PCT, were included in this study. The eligible infants were divided into two groups by block randomization. In the intervention group (n = 35), breastfeeding was withheld only during PCT and then continued as usual. On the other hand, in the control group (n = 35), feeding was performed as usual, regardless of PCT. Feeding tolerance within the first 72 hours post-transfusion was compared between the two groups. Sick newborns were excluded from the study. Data analysis was performed in SPSS version 20. Results: The mean gestational age, birth weight, and postnatal age of the neonates were 30.13 weeks, 1245.71 g, and 17 days in the intervention group and 29.97 weeks, 1169.43 g, and 15.46 days in the control group, respectively; there was no significant difference between the two groups. Except for pre-transfusion hemoglobin and hematocrit levels, other characteristics of the two groups were similar. Feeding tolerance was reported in 32 (91.2%), 33 (94.73%), and 34 (97.1%) newborns at 24, 48, and 72 hours post-transfusion in both groups, without any significant difference. There was no significant difference between neonates with and without feeding tolerance in either of the groups. Conclusions: According to the present results, withholding feeding during PCT is not necessary in healthy preterm neonates with a good general condition, and continued breastfeeding seems to be a safe option. [ABSTRACT FROM AUTHOR]

Introduction: Critical aspects of time of feed initiation, advancement, and volume of feed increment in preterm neonates remain largely unanswered. Methods: Medline , Embase, CENTRAL and CINAHL were searched from inception until 25th September 2020. Network meta-analysis with the Bayesian approach was used. Randomized controlled trials (RCTs) evaluating preterm neonates ≤32 weeks were included. Feeding regimens were divided based on the following categories: initiation day: early (<72 h), moderately early (72 h–7 days), and late (>7 days); advancement day: early (<72 h), moderately early (72 h–7 days), and late (>7 days); increment volume: small volume (SV) (<20 mL/kg/day), moderate volume (MoV) (20–< 30 mL/kg/day), and large volume (≥30 mL/kg/day); and full enteral feeding from the first day. Sixteen regimens were evaluated. Combined outcome of necrotizing enterocolitis (NEC) stage ≥ II or mortality before discharge was the primary outcome. Results: A total of 39 studies enrolled around 6,982 neonates. Early initiation (EI) with moderately early or late advancement using MoV increment enteral feeding regimens appeared to be most efficacious in decreasing the risk of NEC or mortality when compared to EI and early advancement with SV increment (risk ratio [95% credible interval]: 0.39 [0.12, 0.95]; 0.34 [0.10, 0.86]) (GRADE–very low). Conclusions: Early initiated, moderately early, or late advanced with MoV increment feeding regimens might be most appropriate in decreasing the risk of NEC stage ≥II or mortality. In view of the certainty of evidence being very low, adequately powered RCTs evaluating these 2 strategies are warranted. [ABSTRACT FROM AUTHOR]

Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that antenatal magnesium sulfate use is associated with favorable neurodevelopmental outcomes in preterm infants. However, there are concerns regarding the effects of antenatal magnesium sulfate on neonates, especially regarding gastrointestinal morbidities. This study aims to explore the effects of antenatal magnesium sulfate on intestinal morbidities requiring surgery in preterm infants. This was a retrospective cohort study of 181 preterm infants who were born at less than 28 weeks of gestational age. Subjects were categorized as infants exposed to antenatal magnesium sulfate and those not exposed to antenatal magnesium sulfate. Antenatal magnesium sulfate was associated with a decreased risk of surgical conditions of the intestine (OR 0.393, 95% CI 0.170–0.905). The multivariate analysis showed that the duration of antenatal magnesium sulfate use was associated with surgical conditions of the intestine (adjusted OR 0.766, 95% CI 0.589–0.997). In the <26 weeks of gestational age subgroup, the use of antenatal magnesium sulfate was significantly associated with decreased intestinal morbidities requiring surgery (adjusted OR 0.234, 95% CI 0.060–0.922). Antenatal magnesium sulfate use appears to have a protective effect on intestinal morbidities requiring surgery in preterm infants in a duration-dependent manner. Association of antenatal magnesium sulfate use and decreased intestinal morbidities requiring surgery was more distinct in preterm infants <26 weeks of gestational age. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to describe the 30-day mortality, neurodevelopmental outcome and composite outcome (mortality or abnormal neurodevelopmental outcome) of neonates with necrotizing enterocolitis (NEC), requiring neonatal intensive care (NICU) admission, in a resource-restricted environment.Methods: All neonates admitted to Tygerberg Hospital, NICU, with a presumptive diagnosis of NEC Bell stage IIB or more, over a 5-year period, were included.Results: One hundred and thirty-five neonates were included with a mean gestational age of 29 ± 2.7 weeks and mean birth weight of 1185 g ± 446 g. The 30-day mortality was 52%, neurodevelopment abnormalities occurred in 35% of survivors and adverse composite outcome in 63%. The 30-day mortality and adverse composite outcome risk were increased by small for gestational age, shock, metabolic acidosis, inotrope requirement and first feed >9 days after surgery.Conclusion: In resource-restricted environments, mortality and abnormal neurodevelopmental outcome of neonates with NEC, remain high. However, outcomes are comparable with international literature. Neonates with NEC, requiring NICU admission and surgery, require neurodevelopmental follow-up. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the expression of CD64 and CD11b neutrophils in neonates with necrotizing enterocolitis (NEC) and to evaluate the diagnostic value of CD64 and CD11b in identifying NEC in neonates. Methods: A total of 138 newborns, admitted to our neonatal intensive care unit from October 2018 to March 2020, were recruited in this study. The subjects were divided into the NEC and control groups, according to the method of case-control. The expression of CD64, CD11b, and C-reactive protein (CRP) was measured in the peripheral blood, the sensitivity and specificity of each index in diagnosing NEC were compared, and their diagnostic value was examined. Results: The corrected gestational age of the NEC and control groups was 32.29 ± 1.85 and 33.24 ± 1.98 weeks, respectively. The mean birth weight of the two groups was 1654 ± 373 and 1746 ± 400 g, respectively. Also, the mean age at sampling was 11.6 ± 3.11 and 11.7 ± 3.14 days in the NEC and control groups, respectively. Gender, corrected gestational age, mean birth weight, and sampling age were not significantly different between the groups (P > 0.05). The CD64 and CD11b expression levels were higher in the NEC group, compared to the control group (P < 0.01). Comparison of the NEC group by stage showed that the CD64 and CD11b indices were the highest in stage III, followed by stage II and stage I (P = 0.01). However, both indices showed a downward trend during the recovery period (P < 0.01). A CD64 level ≥ 0.71, a CD11b level of 1.94, and a CRP level ≥ 7.38 were considered as the best diagnostic criteria. The highest exponential sensitivity (82.7%) was attributed to the CD64 index, followed by CD11b (50.8%) and CRP (39.1%). The highest sensitivity (89%) was obtained by a combination of two indices (one positive index); also, when both indices were positive, the highest specificity (87%) was reported. The sensitivity of combined indices for NEC diagnosis in stage I, II and III were 84.4%, 95.7%, and 92.9%, respectively. Conclusions: The expression levels of CD64 and CD11b neutrophils in neonatal NEC increased and was associated with the severity of NEC. Monitoring of changes in the two indices had a clinical value in the diagnosis of NEC. In conclusion, the combined use of these two indices can be more valuable in the diagnosis of neonatal NEC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to study the association of clinical variables obtainable before delivery for severe neonatal outcomes (SNO) and develop a clinical tool to calculate the prediction probability of SNO in preterm prelabor rupture of membranes (PPROM). Methods: This was a prospective study from October 2015 to May 2018. We included singleton pregnancies with PPROM and an estimated fetal weight (EFW) two weeks before delivery. We excluded those with fetal anomalies or fetal death. We examined the association between SNO and variables obtainable before delivery such as gestational age (GA) at PPROM, EFW, gender, race, body mass index, chorioamnioitis. SNO was defined as having at least one of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or neonatal death. The most parsimonious logistic regression models was constructed using the best subset selection model approach, and receiver operator curves were utilized to evaluate the prognostic accuracy of these clinical variables for SNO. Results: We included 106 pregnancies, 42 had SNO (39.6%). The EFW (area under the receiver operating characteristic curve [AUC]=0.88) and GA at PPROM (AUC=0.83) were significant predictors of SNO. The addition of any of the other variables did not improve the predictive probability of EFW for the prediction of SNO. Conclusions: The EFW had the strongest association with SNO in in our study among variables obtainable before delivery. Other variables had no significant effect on the prediction probability of the EFW. Our findings should be validated in larger studies. [ABSTRACT FROM AUTHOR]

Background: Necrotising Enterocolitis (NEC) is a devastating neonatal disease. A temporal association between red cell transfusion and NEC has been recognized and there have been concerns about the effects of feeding during transfusion. We aimed to assess the effect of different enteral feeding regimens on splanchnic oxygenation in preterm infants receiving red cell transfusions.Methods: This was an open, multi-arm, parallel-group, randomised controlled trial conducted in a single centre in Australia. We compared three different enteral feeding regimes during a single red cell transfusion in preterm infants < 35 weeks gestational age at birth. Infants were randomised to either: (1) Withholding enteral feeds for 12 h from the start of transfusion or; (2) Continuing enteral feeds or; (3) Restriction of enteral feed volume to 120 ml/kg/day (maximum 20 kcal/30 ml) for 12 h. The primary outcome was mean splanchnic-cerebral oxygenation ratio (SCOR) and mean splanchnic fractional oxygen extraction (FOE) before (1 h prior), during (1 h into transfusion) and after (end of transfusion; 12 and 24 h post) transfusion.Results: There were 60 transfusion episodes (20 transfusion episodes in each group) included in the analysis. 41 infants with a median gestational age at birth of 27 weeks (range 23-32 weeks) were enrolled. The median postnatal age was 43 days (range 19-94 days) and the median pre-transfusion haematocrit was 0.27 (range 0.22-0.32). All three groups were similar at baseline. There were no differences in mean SCOR and mean splanchnic FOE at any of the pre-specified time points. There were also no differences in clinical outcomes. There were no episodes of NEC in any infant. Across all groups the mean SCOR increased from the start to the end of each transfusion (0.97 [CI95% 0.96-0.98] vs 1.00 [CI95% 0.99-1.01]; p = 0.04) and the mean FOE decreased from the start to the end of each transfusion (0.22 [CI95% 0.21-0.23] vs 0.17 [CI95% 0.16-0.18]; p < 0.001).Conclusions: There were no differences in splanchnic oxygenation when enteral feeds were either withheld, continued or restricted during a transfusion. However, the successful conduct of this study supports the feasibility of a large trial powered to assess clinical outcomes.Trial Registration: ANZCTR, ACTRN12616000160437. Registered 10 February 2016, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370069. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to study the role of oropharyngeal administration of colostrum (OAC) in very-low-birth-weight infants for reducing necrotizing enterocolitis (NEC). Study Design  In this randomized controlled trial, 117 infants were enrolled, 59 were randomized to OAC group and 58 to routine care group. Infants with birth weight ≤ 1,250 g and/or gestational age ≤ 30 weeks were enrolled. Infants in OAC group received maternal colostrum (0.2 mL), 0.1 mL on either side, after 24 hours of postnatal life and were given every 2 hour for the next 72 hours irrespective of the enteral feeding status of the neonate. The primary outcome of the study was the incidence of NEC (stage 2 or 3). Results  Baseline characteristics were comparable between the two groups. There was no significant reduction in the incidence of NEC in OAC group (0 [0%] vs. 3 [7.1%]; p  = 0.11). There was significant reduction of 7 days of hospital stay in OAC group (34.2 ± 5.7 vs. 41.5 ± 6.7 days; p  = 0.04).The incidence of early-onset sepsis, late-onset sepsis, blood culture positive sepsis, and ventilator-associated pneumonia were comparable between the two groups. Conclusion  OAC is safe and reduces the duration of hospital stay. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality. Serum biomarkers to aid diagnosis, such as intestinal fatty acid binding protein (IFABP) and calprotectin, are actively being investigated; however, the normative values of these markers among healthy premature and term infants remains unknown. We sought to identify normative values for the serum concentrations of IFABP and calprotectin across gestational (GA) and post-menstrual age.Methods: We collected serum from infants (24-40 weeks GA) in the first week of life and at multiple time points in a sub-cohort of premature infants (24-29 weeks GA), excluding sepsis or known intestinal disease. IFABP and calprotectin were measured using ELISA. Groups were compared with descriptive statistics and mixed effects linear regression.Results: One hundred twelve infants had specimens in the first week of life, and 19 premature infants had longitudinal specimens. IFABP concentration in the first week of life was low and did not differ across gestational ages. Longitudinally, IFABP increased 4% per day (P < 0.001). Calprotectin concentration in the first week of life was more variable. An inverse relationship between day of life and calprotectin level was found in the longitudinal cohort (P < 0.001).Conclusions: Serum IFABP and calprotectin fluctuate over time. Infants had low levels of IFABP during the first week of life, independent of gestational age, and levels increased longitudinally in premature infants. Calprotectin levels generally declined over time. Normative data for infants is necessary to establish meaningful cut-off levels for clinical use. [ABSTRACT FROM AUTHOR]

Objective  A temporal relationship has been reported between necrotizing enterocolitis, anemia, and red blood cell transfusion (RBCT) in preterm neonates. However, the mechanism underlying this association is not clearly defined. Intestinal (I-) and liver (L-) fatty acid binding proteins (FABPs) have been proposed as plasma markers for the detection of acute intestinal injury. This study aimed to investigate the effect of anemia and RBCT on intestinal injury in preterm neonates by measuring serum I-FABP and L-FABP levels. Study Design  A prospective cohort study including preterm neonates with gestational age <32 weeks and/or birth weight <1,500 g and requiring erythrocyte transfusions for anemia after day 15 of life was conducted. Stable growing preterm infants with hemoglobin values ≥ 10 g/dL were taken as controls. I-FABP and L-FABP levels of the neonates with anemia were compared with levels of the control group. In addition, pretransfusion I-FABP and L-FABP levels of the neonates with anemia were compared with posttransfusion levels. Results  In total, 39 infants transfused for anemia and 20 controls were enrolled. L-FABP levels were significantly higher in neonates with anemia compared with controls (p  < 0.001), whereas I-FABP (p  = 0.695) was not different. L-FABP and I-FABP levels were similar before and after transfusion in neonates with anemia. L-FABP levels before transfusion were negatively correlated with pretransfusion hemoglobin levels (p  < 0.001). Conclusion  Anemia is associated with intestinal injury documented by increased L-FABP levels in preterm infants, and this injury is more severe with lower hemoglobin levels. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) in neonates is devastating, and risk-factor identification is crucial. This study aimed to evaluate risk factors for NEC in different gestational age (GA) groups. Methods: Risk factors associated with NEC were investigated using a retrospective case-control design. Patients with Bell's Stage NEC ≥ II were divided into three groups based on GA: I, 34 weeks with congenital heart disease were more likely than controls to have NEC. Conclusion: Intrahepatic cholestasis of pregnancy and meconium aspiration syndrome may be new risk factors for NEC.

Purpose: Necrotizing enterocolitis (NEC), a leading cause of mortality and morbidity in preterm neonates, lacks a reliable biomarker. Citrulline is primarily produced by enterocytes and correlates with intestinal function. Serum citrulline concentration (CIT) is routinely measured in routine newborn screening (NBS). The purpose of the study is to test if CIT from NBS may predict the occurrence of NEC and whether it correlates with the time to full feeds (TTFF) and length of stay (LOS), serving as a biomarker of NEC and intestinal health.Methods: In a retrospective case control study conducted on neonates with gestational age of 26-32 weeks, we compared CIT levels between cases (neonates with NEC) and controls (next-born neonate). NBS was collected within first 24 h, at day 5 and when the neonates achieved full feeds and were compared using non-parametric tests.Results: There was no difference in CIT between the controls and cases on day 1 [11.42 (7.42-14.84 vs. 11.93 (6.85-18.8) µmol/L, p = 0.55], on day 5 [11.99 (7.99-16.55) vs. 13.70 (7.42-26.83) µmol/L, p = 0.05], or at full feeds [14.86 (6.85-25.69) vs. 15.7 (7.42-26.26) µmol/L, p = 0.87]. CIT on day 1 did not correlate with TTFF (r = 0.08, p = 0.53) or LOS (r = 0.23, p = 0.06), respectively).Conclusions: CIT from routine NBS does not serve as a biomarker to predict NEC in preterm neonates. [ABSTRACT FROM AUTHOR]

Background: Only few studies have quantitated the frequencies of immune cells in the small bowel mucosa and submucosa during gestation. The aims of this study were to describe the frequencies of T and B cells, eosinophils and mast cells in the normal small bowel mucosa and submucosa (NSB) in relation to gestational age (GA) and in the uninvolved small bowel (USB) of premature newborns with necrotizing enterocolitis (NEC). Methods: We obtained 36 NSB specimens (GA 12–41 weeks) and 8 NEC-USB specimens (GA 24–32 weeks) from autopsies and surgeries and performed immunostaining for CD3, CD79a, BMK-13 and tryptase as well as the histochemical stains giemsa and toluidine blue. Qualitative histological evaluation and two different quantitative cell-samplings were performed using digital imaging analysis with both TissuemorphDP® and newCAST® software. Linear regression analysis was performed with cell frequency as the dependent variable and GA and USB as the independent variables. Results: In the NSB specimens, we found significant linear correlations between cell frequencies and GA for all examined cell types, though B cell frequencies reached a plateau midway through gestation. In the USB cases, submucosal mast cell frequencies were higher than in the NSB specimens, while T cell frequencies were lower. In USB of NEC patients, we found a significant increase of mast cells and a significant decrease of T cells compared to NSB. Conclusion: Throughout gestation, we found an increase of all examined immune cell types in the normal small bowel, while the number of B cells came to a standstill at midway. Future studies should examine subtypes of T cells and also include histiocytes. A larger amount of small bowel specimens, covering the full gestational age, would be of great value. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is one of the most prevalent digestive emergencies in neonates, leading to mortality and morbidity in premature neonates. Since there is no specific test for NEC diagnosis, only clinical symptoms and radiological findings are used for diagnosis. Therefore, if a reliable biomarker found to detect NEC, it can help to reduce the mortality and morbidity; hence, the present study evaluated the stool calprotectin levels in the infected and noninfected neonates weighing <1500 g. Methods: This case-control study was performed on 35 neonates with NEC and 35 healthy neonates. Demographic information and calprotectin levels were measured, and the values were recorded and compared between the two groups. Results: The results of this study revealed that the level of stool calprotectin in the case group with the mean of 459.66 ± 172.63 was significantly higher than the control group with the mean of 103.03 ± 30.97 (P < 0.001). Furthermore, the level of calprotectin had a significant relation with the severity of the disease. Moreover, this biomarker can be a good diagnostic criterion for detecting NEC (cutoff >176 μg/g, sensitivity = 97.14%, Specificity = 100%, P < 0.0001). Conclusion: Given that the level of calprotectin in the stool was not associated with factors such as the sex of neonate, gestational age, birth weight, and type of delivery, it appears that stool calprotectin level can be used as a reliable biomarker for NEC diagnosis. [ABSTRACT FROM AUTHOR]

Background To examine whether polymorphisms in the VEGFA gene lead to low VEGFA production in peripheral blood and increased risk of NEC in the Chinese Han population. Material and methods Thirty NEC patients and 80 control subjects were enrolled. Six VEGFA single-nucleotide polymorphisms (SNPs) were performed using the SEQUENOM MassARRAY platform assay. The concentration of VEGFA in the plasma was measured using an enzyme-linked immunosorbent assay. Results The rs699947 and rs833061 VEGF-A SNPs were found to be associated with low plasma levels and high risk of NEC. Conclusion Our results suggested that, if validated in larger studies, screening for VEGFA SNPs and plasma levels might be useful as a risk factor for NEC in the future. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of caffeine infusion on superior mesenteric artery (SMA) blood flow velocities (BFV) in preterm infants.Methods: Prospective observational study on 38 preterm neonates 28-33+6 weeks gestation, who developed apnea on their first day of life, and caffeine citrate infusion was initiated at a loading dose of 20 mg/kg, followed by a maintenance dose of 5-10 mg/kg/day. Duplex ultrasound measurements of SMA BFV were recorded: peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI), at 15 min before, 1-, 2- and 6-h after caffeine loading dose, and 2 h after two maintenance doses.Results: There was a significant reduction in PSV 1-h (p = .008), a significant decrease in EDV 1- and 2-h (p = .000 and p = .005, respectively) and a significant increase in RI 1- and 2-h (p = .003 and p = .005, respectively) following caffeine loading dose, as compared to values before caffeine infusion. No significant effect of caffeine maintenance doses on SMA BFV was observed (p > .05).Conclusion: Blood flow in SMA is significantly reduced after caffeine citrate infusion at a loading dose of 20 mg/kg. This effect continues for at least 2 h. Meanwhile, SMA BFV seems not affected by maintenance doses. [ABSTRACT FROM AUTHOR]

Objective  We examined the effects of magnesium sulfate on non-neurologic neonatal outcomes with respect to cord blood magnesium level. Study Design  We conducted a secondary analysis of the Maternal-Fetal Medicine Units Beneficial Effects of Antenatal Magnesium (MFMU BEAM) trial comparing the upper and lower quintiles of cord blood magnesium level. Outcomes included cerebral palsy (CP), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios (aORs) of each outcome, controlling for gestational age (GA), birth weight, and treatment group (TG). Results  A total of 1,254 women of the 2,444 included in the BEAM trial had cord blood magnesium levels recorded. GA and birth weight were lower and TG was more common in the upper quintile cohort (p  < 0.001). Neonates in the upper quintile were more likely to have severe NEC (OR, 2.41, 95% confidence interval [CI]: 1.11–5.24), ROP (OR, 1.65, 95% CI: 1.05–2.59), and BPD (OR, 1.70, 95% CI: 1.04–2.73). Adjustment for covariates demonstrated no difference in the NEC, ROP, and BPD rates, although there was a decrease in rates of mental disability index < 70 which was not seen in the unadjusted analysis (aOR, 0.49, 95% CI: 0.25–0.99). Conclusion  Higher cord blood magnesium levels do not appear to have adverse non-neurologic effects on the neonate and may demonstrate improvement in neurologic outcomes. [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]

Objective  We aimed to compare the rates of "surfactant treated respiratory disease" and other neonatal morbidities among moderately preterm (MPT) infants exposed to no, partial, or a complete course of antenatal corticosteroids (ANS). Study Design  This observational cohort study evaluated MPT infants (29 0/7 –33 6/7 weeks' gestational age), born between January 2012 and November 2013 and enrolled in the "MPT Registry" of the National Institute of Child Health and Human Development Neonatal Research Network. Results  Data were available for 5,886 infants, including 676 with no exposure, 1225 with partial, and 3,985 with a complete course of ANS. Among no, partial, and complete ANS groups, respectively, there were significant differences in rates of delivery room resuscitation (4.1, 1.4, and 1.2%), surfactant-treated respiratory disease (26.5, 26.3, and 20%), and severe intracranial hemorrhage (3, 2, and 0.8%). Complete ANS course was associated with lower surfactant-treated respiratory disease, compared with partial ANS (odds ratio [OR] 0.62; 95% confidence interval [CI] 0.52–0.74), and no ANS groups (OR 0.52; 95% CI 0.41–0.66) on adjusted analysis. Conclusion  In MPT infants, ANS exposure is associated with lower delivery room resuscitation, surfactant-treated respiratory disease, and severe intracranial hemorrhage; with the lowest frequency of morbidities associated with a complete course. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intestinal disorders are common in very low‐birthweight infants. The purpose of this study was to evaluate the impact of prophylactic oral Gastrografin® (diatrizoate acid) on meconium‐related ileus (MRI) in extremely preterm infants. Methods: This was a retrospective case–control study of infants born extremely preterm at <28 weeks of gestation and treated with diatrizoate acid (prophylactic group) or not (control group) in the periods 2007–2014 and 2000–2009, respectively. In the 2007–2014 period, 120 infants received prophylactic diatrizoate acid solution. From the 165 infants in the control group, we selected 120 infants matched for gestational age. Cases of death before 72 h of life or congenital abnormalities were excluded. Intestinal disorders, time until full enteral feeding, duration of hospital stay, mortality rate, and neurodevelopmental outcome were compared. Results: MRI occurred in six infants in the control group and in none of the infants in the prophylactic group (P = 0.039). Median time until full enteral feeding was 25 versus 22 days (P < 0.01), hospital stay was 142 versus 126 days (P < 0.01), and mortality rate for infants aged 24–27 weeks was 8.2% versus 0% (P = 0.021), respectively. Conclusions: Prophylactic oral diatrizoate acid reduced MRI in extremely preterm infants without side‐effects and decreased the mortality rate of infants born at 24–27 weeks, and is thus beneficial in extremely preterm infants. [ABSTRACT FROM AUTHOR]