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Objective Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. Study Design Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z -score < −2. Results Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z -score < 0. Conclusion NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z -score < 0. Key Points We studied 2,940 infants <33 weeks' GA. We assessed NEC. NEC was more frequent in SGA infants. NEC occurred 2 weeks later in SGA infants. NEC was associated with severe growth restriction. [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]

This comprehensive review examines the role of Neutrophil Extracellular Traps (NETs) in pediatric surgery. Focusing on NET formation, functions, and implications, this study highlights their dual impact in infection control and contribution to tissue damage after surgery. It covers the role of NET formation in a range of pediatric conditions including immunothrombosis, formation of peritoneal adhesions, appendicitis, burns, gallstones, tumors, and necrotizing enterocolitis (NEC). The results underscore the significance of NETs in fighting infections and their association with complications like sepsis and delayed wound healing. The breakdown products of NETs as a diagnostic tool of the clinical course of acute appendicitis will also be discussed. Understanding NET formation in the pathophysiology can potentially help to find new therapeutic approaches such as the application of DNase and elastase inhibitors to change the clinical course of various diseases in pediatric surgery such as improvement of wound healing, adhesion formation, NEC, and many more. [ABSTRACT FROM AUTHOR]

Objective To study the predictive value of hemoglobin (Hb) decrease for the occurrence of necrotizing enterocolitis (NEC) in preterm infants with late-onset sepsis (LOS) . Methods Clinical data of 93 LOS preterm infants were collected for retrospective analysis, among which 16 infants developed NEC while 77 infants did not. Based on the decrease in Hb levels from the most recent Hb measurement before LOS occurrence to the initial Hb levels during LOS, the infants were divided into three groups: no Hb decrease (n=15), mild Hb decrease (Hb decrease <15 g/L; n=35), and severe Hb decrease (Hb decrease ≥15 g/L; n=43). Multivariate logistic regression analysis was conducted to explore the predictive factors for NEC secondary to LOS, and the value of Hb decrease in predicting NEC secondary to LOS was evaluated through receiver operating characteristic curve analysis. Results The incidence of NEC in the severe Hb decrease group, mild Hb decrease group, and no Hb decrease group were 26%, 14%, and 0% (P<0.05), respectively. Multivariate logistic regression analysis revealed that a larger Hb decrease was an independent predictive factor for NEC in LOS preterm infants (OR=1.141, 95%CI: 1.061-1.277, P<0.001). Receiver operating characteristic curve analysis showed that the area under the curve for predicting NEC in preterm infants with LOS using Hb decrease (with a cut-off value of 20 g/L) was 0.803, with sensitivity and specificity of 0.69 and 0.78, respectively. Conclusions Hb decrease can serve as an indicator for prediction of NEC in preterm infants with LOS. [ABSTRACT FROM AUTHOR]

Context Many preterm neonates often cannot be fed enterally and hence do not receive the benefits of colostrum. Oropharyngeal application of colostrum is a novel way of harnessing the immunological benefits of colostrum. Randomized controlled trials (RCTs) investigating the efficacy of this approach have shown variable results. Objective The aim of this systematic review was to synthesize available data on the effect of oropharyngeal application of colostrum or mother's own milk (CMOM) in preterm infants. Data Sources Six electronic databases (MEDLINE, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library) were searched until January 13, 2022. Only RCTs comparing oral application of CMOM with placebo/routine care in preterm infants were eligible. Studies enrolling term neonates or administering enteral feeds were excluded. Data Extraction Two investigators independently extracted data using a structured proforma. Data Analysis The Cochrane Risk of Bias 2 tool was used to assess bias. Random-effects meta-analysis was undertaken using RevMan 5.4 software. From 2787 records identified, 17 RCTs enrolling 4106 preterm infants were included. There was no significant difference between groups in incidence of necrotizing enterocolitis (NEC) stage 2 or higher (RR = 0.65; 95%CI, 0.36–1.20; 1089 participants in 12 trials). Application of CMOM significantly reduced the incidence of sepsis (RR = 0.72; 95%CI, 0.56–0.92; 1511 participants in 15 studies) and any stage of NEC (RR = 0.58; 95%CI, 0.37–0.92; 1616 participants in 16 trials). The CMOM group achieved full enteral feeds 1.75 days sooner (95%CI, 0.3–3.2 days; 1580 participants in 14 studies) and had higher weight at discharge (MD = 43.9 g; 95%CI, 3–85 g; 569 participants in 3 studies). There were no statistically significant differences in other outcomes. Conclusions Evidence with low to very low certainty suggests CMOM has a beneficial effect on NEC (any stage), sepsis, and time to full enteral feeds. Given its low cost and minimal risk of harm, routine CMOM use may be considered in preterm neonates. Prospero Registration Number CRD42021262763 [ABSTRACT FROM AUTHOR]

Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8–3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7–5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3–8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC. [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]

The need for high quality evidence is recognized for optimizing practices of parenteral nutrition (PN). The purpose of the present systematic review is to update the available evidence and investigate the effect of standardized PN (SPN) vs. individualized PN (IPN) on protein intake, immediate morbidities, growth, and long-term outcome in preterm infants. A literature search was performed on articles published in the period from 1/2015 to 11/2022 in PubMed and Cochrane database for trials on parenteral nutrition in preterm infants. Three new studies were identified. All new identified trials were nonrandomized observational trials using historical controls. SPN may increase weight and occipital frontal circumference gain and lower the value of maximum weight loss. More recent trials suggest that SPN may easily increase early protein intake. SPN may reduce the sepsis incidence, but overall, no significant effect was found. There was no significant effect of standardization of PN on mortality or stage ≥2 necrotizing enterocolite (NEC) incidence. In conclusion SPN may improve growth through higher nutrient (especially protein) intake and has no effect on sepsis, NEC, mortality, or days of PN. [ABSTRACT FROM AUTHOR]

Preterm birth is a major contributor to neonatal morbidity and mortality. Complications of prematurity such as bronchopulmonary dysplasia (BPD, affecting the lung), pulmonary hypertension associated with BPD (BPD-PH, heart), white matter injury (WMI, brain), retinopathy of prematurity (ROP, eyes), necrotizing enterocolitis (NEC, gut) and sepsis are among the major causes of long-term morbidity in infants born prematurely. Though the origins are multifactorial, inflammation and in particular the imbalance of pro- and anti-inflammatory mediators is now recognized as a key driver of the pathophysiology underlying these illnesses. Here, we review the involvement of the interleukin (IL)-1 family in perinatal inflammation and its clinical implications, with a focus on the potential of these cytokines as therapeutic targets for the development of safe and effective treatments for early life inflammatory diseases. [ABSTRACT FROM AUTHOR]

The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as OS-related neonatal diseases. Due to the physiological immaturity of their antioxidant defenses and to the enhanced antenatal and postnatal exposure to free radicals, preterm infants are particularly susceptible to oxidative damage, and several pathophysiological cascades involved in the development of prematurity-related complications are tightly related to OS. This narrative review aims to provide a detailed overview of the OS-related pathophysiological mechanisms that contribute to the main OS-related diseases during pregnancy and in the early postnatal period in the preterm population. Particularly, focus has been placed on pregnancy disorders typically associated with iatrogenic or spontaneous preterm birth, such as intrauterine growth restriction, pre-eclampsia, gestational diabetes, chorioamnionitis, and on specific postnatal complications for which the role of OS has been largely ascertained (e.g., respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis). Knowledge of the underlying pathophysiological mechanisms may increase awareness on potential strategies aimed at preventing the development of these conditions or at reducing the ensuing clinical burden. [ABSTRACT FROM AUTHOR]

Introduction: Necrotizing enterocolitis (NEC) is a major cause of mortality among premature babies. It has no definitive pathogenesis and no specific treatment. Its prevention remains the most important intervention till now. Aim of the work: To detect the impact of using mother's own milk to feed preterm babies (< 37 weeks) on necrotizing enterocolitis, occurrence of signs of feeding intolerance, sepsis and mortality. Methods: This prospective cohort study enrolled 250 preterm babies (< 37 weeks) whose gestational ages ranged from 27-36 weeks who were admitted to the neonatal intensive care unit (NICU) of Kasr Al-Ainy Hospital, Cairo University soon after birth. Mothers with no contraindication to breast feeding were included in the "case" group and the others were included in "control" group. Results: The mean± SD gestational age of the case group (120 preterm) was 33.12 ± 1.63 weeks and of the control group (130 preterm) was 32.17 ± 1.95 weeks. The mean birth weights of the case and control groups were 1.86 ± 0.49 and 1.55 ± 0.32 kgs, respectively (p= 0.000). The case group showed significant decrease in the incidence of NEC (5% in the case group versus 13% in the control group (p= 0.027). Sepsis incidence also decreased among patients in the case group (37.5% in the case group versus 60% in the control group (p= 0.00). There was no significant difference between the two groups regarding time at which trophic feeding was started but the study group showed significantly shorter duration to reach both minimal enteral nutrition (20cc /kg) (6.85 ± 3.16 days versus 11.20 ± 7.05 days in the control group) (p= 0.000) and full feeds (10.60 ± 3.94 days versus 15.47 ± 8.85 in the control group) (p= 0.000). The mean duration of total parenteral nutrition was significantly shorter in the case group (p= 0.020). The difference between the need for antibiotics in both groups was insignificant (p= 0.353). However, the duration of antibiotic therapy was significantly shorter in the case group (p= 0.000). Conclusion: Preterm mother's own milk feeding (not necessarily exclusively) proved to be protective against NEC, sepsis and poor outcome.

The aim. To acquaint medical practitioners with the case of successful surgical treatment and intensive care of a extremely preterm infant with necrotic enterocolitis, complicated with intestinal perforation and sepsis of mixed bacterial and fungal etiology. Materials and methods. The child was treated in the Neonatal Anesthesiology and Intensive Care Department of Communal Non-commercial Enterprise “City Children’s Hospital No. 5” of Zaporizhzhia City Council. Blood analyses, microbiological, X-ray and ultrasound examinations were performed by indications using the hospital equipment. Results. An extremely preterm, very low birth weight infant underwent nine traumatic surgical interventions for NEC with gastric and intestinal perforation, diffuse peritonitis, and adhesive intestinal obstruction. The child’s condition was complicated by sepsis of mixed bacterial and fungal etiology. Preoperative preparation included antibacterial therapy, infusion therapy with modern balanced polyionic solutions, and inotropic support. During and after surgical interventions, the child underwent multimodal combined anti-stress anesthesia with the use of neuroaxial blocks, prolonged MLV, antibacterial therapy with modern drugs according to the de-escalation principle and microbiological peculiarities of the department, antifungal therapy with reserve drugs, immune replacement therapy, parenteral nutrition and infusion program using blood products according to indications. Despite the child’s critically severe condition and morphofunctional immaturity, the child has survived, has no neurological deficit, and has gained four times his initial body weight. Conclusions. The use of multimodal combined anesthesia with caudal-epidural blocks in the intra- and postoperative periods, adequate respiratory and hemodynamic support, parenteral and early enteral feeding in a deeply premature baby with NEC probably contributed to antinociceptive protection and positive treatment outcome after 9 urgent operations. The reserve antibiotics and antifungal drugs prescription according to de-escalation principle, considering the sensitivity of the bacterial flora to them, bacteriological monitoring and immune replacement therapy, had a positive result in the treatment of sepsis, which complicated the course of NEC in the newborn baby.

Introduction: The present study compares the effects of mother’s own milk (MOM) and donor human milk (DM) on anthropometric indices, incidence of sepsis, necrotizing enterocolitis (NEC), and feeding intolerance (FI) among preterm neonates. Methods: Ninety neonates born at 30-32 weeks and hospitalized in the Neonatal Intensive Care Unit were assigned to 3 groups based on their daily milk intake. The first group received only MOM or < 20% DM, the second group received ≥ 20% to < 80% DM, and the third group received ≥ 80% DM. Results: Weight gain velocity was 1.5 g/kg/day in the group that received ≥ 80% DM and 6.2 g/kg/day in the group that received 80-100% MOM (without a statistically significant p-value). Furthermore, there was no statistically significant difference in height increase among the 3 groups, and no sepsis or NEC were observed in any of the 3 groups either. The incidence of FI was not significantly different among the 3 groups. Conclusion: Based on the results, DM is as effective as MOM in preventing sepsis, NEC, and FI. Every effort should be made to educate mothers on this subject, provide breastfeeding support, and use pasteurized and appropriately fortified DM.

Blood group antigens, present on blood cells, can influence the susceptibility to or severity of various diseases. There are many studies describing such relationships in adults. However, in the case of newborns, there are only a few publications concerning the influence of blood type on diseases in the neonatal period. The present literature review deals with the influence of the ABO blood group system on the incidence and course of necrotizing enterocolitis and sepsis in the neonatal period. The review also concerns the effects of bleeding disorders and other changes in peripheral blood counts. Data presented on the relationship between blood group and the risk of developing or affecting the severity of the disease may be useful in neonatal practice, especially in the case of very small premature babies. There is a potentially faster, more accurate diagnosis, that will allow effective treatment of neonates. [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: Preterm human milk has advantages over preterm formula (PF), but it may compromise some functions after pasteurization. Objective: To explore the effects of preterm donor milk (DM) on growth, feeding tolerance, and severe morbidity in very-low-birth-weight infants. Method: This was a single-center, prospective cohort study that included 304 preterm infants weighing 0.05). Feeding intolerance in the DM group was significantly lower than that in PF group (P < 0.05), and parenteral nutrition time and hospitalization time were also shorter than that in the PF group (P < 0.05). Moreover, the incidence of necrotizing enterocolitis and sepsis was also significantly lower in the DM group (P < 0.05). Conclusion: The study indicated that preterm DM does not affect the growth of very-low-birth-weight infants. Further, it significantly reduces feeding intolerance, helps achieve full enteral feeding early, and has protective effects against necrotizing enterocolitis and sepsis. Thus, compared with formula, preterm DM can lower the rate of infection in preterm infants and is worthy of promotion.

Objectives: To evaluate the effects of oral application of mother's own milk (OMOM) on clinical outcomes in preterm infants of 260/7–306/7 wk gestation. Methods: In this placebo-controlled randomized trial, subjects received either OMOM or sterile water, beginning at 24–72 h of life, until the infant reached 32 wk postmenstrual age or spoon-feeds were initiated, whichever was earlier. The primary outcome was a composite adverse health outcome, defined as the occurrence of either mortality, late-onset sepsis (LOS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP). Antibiotic usage and time to full enteral feed were secondary outcomes. Salivary IgA (sIgA) levels at baseline and after 7 d of application in a subset of infants were also compared. Results: A total of 133 neonates (66 colostrum and 67 placebo) were analyzed for the primary outcome. OMOM group had lower incidence of composite adverse health outcome (43.9% vs. 61.2%, RR: 0.70; 95% CI: 0.50–0.99, p = 0.046) and LOS (22.7% vs. 43.3%, RR: 0.73; 95% CI: 0.57–0.93; p = 0.012). There were no significant differences in mortality, NEC, IVH, BPD, ROP, and time to full feeds. The effects were more pronounced in the 290/7–306/7 wk subgroup, in whom the colostrum group also achieved full feeds earlier. There were no differences in the change of sIgA levels from baseline to the seventh day of the application. No adverse effects related to the OMOM application were found. Conclusions: OMOM decreases the incidence of late-onset sepsis in preterm neonates (260/7–306/7 wk) and is safe. Trial Registration: Clinical Trials Registry-India CTRI/2017/03/008031 [ABSTRACT FROM AUTHOR]

Neonates are highly susceptible to infections owing to their immature cellular and humoral immune functions, as well the need for invasive devices. There is a wide practice variation in the choice and duration of antimicrobial treatment, even for relatively common conditions in the NICU, attributed to the lack of evidence-based guidelines. Early decisive treatment with broad-spectrum antimicrobials is the preferred clinical choice for treating sick infants with possible bacterial infection. Prolonged antimicrobial exposure among infants without clear indications has been associated with adverse neonatal outcomes and increased drug resistance. Herein, we review and summarize the best practices from the existing literature regarding antimicrobial use in commonly encountered conditions in neonates.

Abstract Background Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment. Methods This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight

Probiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late–onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain–specific effects and interactions facilitated by the use of combination species. To compare clinical outcomes of very preterm infants receiving multi or single–species probiotics. Retrospective, single–center, cohort study. Very preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi–species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single–species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation. NEC, LOS, and mortality. The overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi–species and single–species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290). The clinical outcomes of very preterm newborns receiving multi vs. single–species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities. • Very preterm infants are at a higher risk of developing necrotizing enterocolitis. • Late onset sepsis is a common complication of prematurity (<32 weeks' gestation). • Probiotics are recommended to prevent these serious morbidities in preterm newborns. • The collective data are inconclusive on optimal strain or combination of probiotics. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to determine the surgical outcome of ileostomy closure at low body weight (<1500 g) and to find any differences in complications and growth of infants whose ileostomy was reversed early (4–6 weeks) versus late (8–10 weeks). Methods: A prospective comparative study was conducted on patients who underwent ileostomy reversal created for necrotizing enterocolitis from January 2017 to December 2019. The patients were divided into two groups: group 1 (early ileostomy closure) between 4 and 6 weeks and Group 2 (late closure) between 8 and 10 weeks. The primary outcome was expressed as the presence of anastomotic leak, obstruction, perforation, wound infection, sepsis, and death. Results: A cohort of 31 patients with 16 patients in Group 1 and 15 in Group 2 were studied. The mean duration between ostomy creation and reversal was 5.1 ± 0.63 weeks in Group 1 and 8.9 ± 0.66 weeks in Group 2. The mean weight at reversal was 1435.5 ± 163.8 g for patients in Group 1 and 1405 ± 99.93 g for patients in Group 2. Weight gain at 90 days in Group 1 was 895 ± 85.2 g and in Group 2 was 455 ± 34.6 g, which was statistically significant (P < 0.00001). Parenteral nutrition, ability to reach full enteral nutrition, and total ventilator days, mortality rate, and complications were not statistically different between the groups. The overall survival rate was 87.27%. Conclusions: Ileostomy reversal at a lower weight and within 6 weeks was not associated with an increased risk of complications. Early stoma reversal may help in weight gain. [ABSTRACT FROM AUTHOR]

L'entérocolite ulcéro-nécrosante (ECUN) est la plus fréquente des urgences digestives touchant principalement les prématurés. Localement n'ayant aucune étude, il convenait de mener une étude dont l'objectif était de déterminer les facteurs de risque de l'ECUN dans un pays aux ressources limitées. Étude rétrospective cas témoins réalisée à l'hôpital gynéco-obstétrique et pédiatrique de Yaoundé de janvier 2013 à décembre 2018 visant les prématurés ayant une ECUN pendant leur hospitalisation appariés à deux témoins également hospitalisés. Parmi les 2181 admissions, nous retrouvions 35 cas d'ECUN appariés à 70 témoins donnant une prévalence de 1,6 % avec une mortalité de 79,4 %. L'âge moyen de survenue était de 7,7 ± 5,9 jours, 62 % des cas était au stade II, 38 % au stade III. Les principaux signes cliniques étaient l'hypotonie (74,3 %), l'instabilité thermique (45,7 %), la distension abdominale (100 %), les résidus gastriques (94,2 %), les rectorragies (40 %), les vomissements (31,4 %). Les facteurs associés retrouvés étaient : l'âge maternel ≤ 20 ans, paludisme sur grossesse, le transfert postnatal, l'alimentation avec substitut de lait maternel, l'ictère, l'anémie, la transfusion sanguine, le sepsis, et la réanimation néonatale ; Ces deux derniers étaient des facteurs indépendants. Comme facteurs protecteurs, nous avions le début de l'alimentation dans les premières 48 heures de vie avec du lait maternel. Dans notre contexte, l'ECUN pourrait être prévenu en agissant d'une part sur les complications de la prématurité et le bon suivi de grossesse et d'autre part en privilégiant une alimentation précoce et au lait de mère. Necrotizing enterocolitis is the most common digestive emergency affecting mainly preterm infants. As no local studies were available, a study was needed to determine the risk factors for ECUN in a country with limited resources. Retrospective case-control study carried out at the Yaoundé Gynaeco-Obstetric and Pediatric Hospital from January 2013 to December 2018 targeting premature infants with ECUN during their hospitalization matched with two controls also hospitalized. Among the 2181 admissions, we found 35 cases of ECUN matched to 70 controls giving a prevalence of 1.6% with a mortality of 79.4%. The mean age of onset was 7.7 ± 5.9 days, 62% of cases were stage II, 38% stage III. The main clinical signs were hypotonia (74.3%), thermal instability (45.7%), abdominal distension (100%), gastric residue (94.2%), rectorrhagia (40%), vomiting (31.4%). The associated factors found were maternal age ≤ 20 years, malaria in pregnancy, postnatal transfer, feeding with breast milk substitute, jaundice, anemia, blood transfusion, sepsis, and neonatal resuscitation; these last two were independent factors. As protective factors, we had the start of feeding in the first 48 hours of life with breast milk. In our context, ECUN could be prevented by acting on the one hand on the complications of prematurity and good pregnancy follow-up and on the other hand by favoring early feeding with mother's milk. [ABSTRACT FROM AUTHOR]

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high. [ABSTRACT FROM AUTHOR]

Background: Gastric pneumatosis is a rare condition characterized by the presence of intramural gas in the stomach wall. It is uncommon in infants and is usually caused by proximal intestinal obstruction or necrotizing enterocolitis, a serious condition typically seen in preterm babies. Case Presentation: An extremely preterm baby born at 23 weeks of gestation weighing 640 grams, with bronchopulmonary dysplasia and other comorbidities like patent ductus arteriosus, staph aureus sepsis, developed abdominal distension and non-bilious vomiting at 4 months of age. X-ray abdomen revealed gastric pneumatosis. The condition was managed with conservative measures. Conclusion: Gastric pneumatosis secondary to necrotizing enterocolitis is uncommon in infants and needs prompt evaluation and management to prevent further deterioration. [ABSTRACT FROM AUTHOR]

Background Probiotics and prebiotics have strain-specific effects on the host. Synbiotics, a mixture of probiotics and prebiotics, are proposed to have more beneficial effects on the host than either agent has alone. Purpose We performed a randomized controlled trial to investigate the effect of Lactobacillus and Bifidobacterium together with oligosaccharides and lactoferrin on the development of necrotizing enterocolitis (NEC) or sepsis in very low birth weight neonates. Methods Neonates with a gestational age ≤32 weeks and birth weight ≤1,500 g were enrolled. The study group received a combination of synbiotics and lactoferrin, whereas the control group received 1 mL of distilled water as placebo starting with the first feed until discharge. The outcome measures were the incidence of NEC stage ≥2 or late-onset cultureproven sepsis and NEC stage ≥2 or death. Results Mean birth weight and gestational age of the study (n=104) and the control (n=104) groups were 1,197±235 g vs. 1,151±269 g and 29±1.9 vs. 28±2.2 weeks, respectively (P>0.05). Neither the incidence of NEC stage ≥2 or death, nor the incidence of NEC stage ≥2 or late-onset culture-proven sepsis differed between the study and control groups (5.8% vs. 5.9%, P=1; 26% vs. 21.2%, P=0.51). The only significant difference was the incidence of all stages of NEC (1.9% vs. 10.6%, P=0.019). Conclusion The combination of synbiotics and lactoferrin did not reduce NEC severity, sepsis, or mortality.

Objective  Feeding intolerance (FI) is a common presentation of necrotizing enterocolitis (NEC) and sepsis. NEC and sepsis are associated with hematological changes, but these changes alone are not reliable biomarkers for early diagnosis. This study examined whether the combination of hematological indices and FI can be used as an early diagnostic tool for NEC or sepsis. Study Design  This retrospective cohort study included infants born at <1,500 g or <30 weeks who had symptoms of FI. The exclusion criteria were congenital or chromosomal disorders, thrombocytopenia or platelet transfusion before the onset of FI, and history of bowel resection. We compared the hematological indices from infants with pathologic FI (due to NEC or sepsis) to infants with benign FI. Results  During the study period, 211 infants developed FI; 185 met the inclusion criteria. Infants with pathologic FI (n  = 90, 37 cases with NEC and 53 with sepsis) had lower birth gestational age and weight compared with 95 infants with benign FI (n  = 95). Pathologic FI was associated with lower platelet count (median 152 × 10 3 /μL vs. 285 × 10 3 /μL, p  < 0.001) and higher immature-to-total neutrophil (I/T) ratio (median 0.23 vs. 0.04, p  < 0.001) at the onset of FI. Pathologic FI was also associated with a decrease in baseline platelets compared with an increase in benign FI. For diagnosis of pathologic FI, a decrease ≥10% in platelets from baseline had a sensitivity and specificity of 0.64 and 0.73, respectively, I/T ratio ≥0.1 had a sensitivity and specificity of 0.71 and 0.78, respectively, and the combination of both parameters had a sensitivity and specificity of 0.50 and 0.97, respectively. Conclusion  FI caused by NEC or sepsis was associated with a decrease in platelets from baseline, and a lower platelet level and higher I/T ratio at the onset of FI. These findings can help clinicians in the management of preterm infants with FI. Key Points FI is a common presentation of NEC and sepsis in preterm infants. FI due to NEC or sepsis is associated with changes in platelets and I/T ratio. These changes could be useful as early markers for diagnosis. [ABSTRACT FROM AUTHOR]

Intralipid (Fresenius Kabi) was the most commonly used lipid emulsion in parenteral nutrition (PN), with a 100% soybean oil composition, a low vitamin E content, and a ω-6: ω-3 ratio of 7:1. A recent alternative formulation is SMOFlipid (Fresenius Kabi), with a ω-6: ω-3 ratio of 5:2 and higher vitamin E content. A retrospective observational study was conducted to determine neonatal morbidity in very low birth weight (VLBW) premature infants during two periods: P1, when PN was based exclusively on Intralipid, and P2, when only SMOFlipid was supplied. In total, 170 VLBW neonates were analyzed, of whom 103 received PN for more than 6 days, 56 during P1, and 47 during P2. In both periods, the antenatal and neonatal characteristics of the cohort were comparable. In this analysis, the prevalence of associated comorbidities was determined. During P2, there were fewer cases of moderate to severe bronchopulmonary dysplasia (BPD) and of cholestasis, but more cases of late sepsis, mainly Staphylococcus epidermidis . No changes in the prevalence of other neonatal comorbidities were observed. We believe that the SMOFlipid used in PN could discreetly improve the prevalence of cholestasis or BPD. [ABSTRACT FROM AUTHOR]

Background: Parenteral nutrition (PN) is crucial for the improvement of long‐term outcomes in very low birth weight (VLBW) neonates. Lipid injectable emulsions are a key component of PN, as they contain essential fatty acids and provide energy critical for brain growth. Prolonged administration increases risk of intestinal failure‐associated liver disease, including cholestasis, and other complications. Methods: This is a retrospective, quasi‐experimental cohort study of 215 VLBW neonates. The primary outcome was a change in direct bilirubin concentration. Secondary outcomes included change in total bilirubin concentration and incidences of cholestasis and other disease states associated with PN and prematurity. Cholestasis was defined as direct bilirubin ≥ 1.0 mg/dL with total bilirubin < 5.0 mg/dL or direct bilirubin > 20% of total bilirubin with total bilirubin > 5.0 mg/dL. Results: Change in direct bilirubin concentration was not different between groups. Incidence of cholestasis was not different between groups per charted diagnosis or per study definition. Non‐stage‐0 retinopathy of prematurity, bronchopulmonary dysplasia, sepsis, and necrotizing enterocolitis were all lower in the mixed oil lipid emulsion group, which remained significant after adjustment for differences in gestational age, birth weight, and PN duration. Conclusions: Although mixed oil lipid emulsion was not found to be associated with a lower risk of cholestasis, it may decrease risks of other disease states associated with PN therapy. [ABSTRACT FROM AUTHOR]

Patent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known: • Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation. • Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new: • The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery. • Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications. [ABSTRACT FROM AUTHOR]

Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and lateonset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini-review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The hostmicrobiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants. [ABSTRACT FROM AUTHOR]

Introduction: At birth, the gastrointestinal (GI) tract is colonized by a complex community of microorganisms, forming the basis of the gut microbiome. The gut microbiome plays a fundamental role in host health, disorders of which can lead to an array of GI diseases, both short and long term. Pediatric GI diseases are responsible for significant morbidity and mortality, but many remain poorly understood. Recent advancements in high-throughput technologies have enabled deeper profiling of GI morbidities. Technologies, such as metagenomics, transcriptomics, proteomics and metabolomics, have already been used to identify associations with specific pathologies, and highlight an exciting area of research. However, since these diseases are often complex and multifactorial by nature, reliance on a single experimental approach may not capture the true biological complexity. Therefore, multi-omics aims to integrate singular omic data to further enhance our understanding of disease. Areas covered: This review will discuss and provide an overview of the main omic technologies that are used to study complex GI pathologies in early life. Expert opinion: Multi-omic technologies can help to unravel the complexities of several diseases during early life, aiding in biomarker discovery and enabling the development of novel therapeutics and augment predictive models. [ABSTRACT FROM AUTHOR]

Background: Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.Methods: This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.Results: The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score - 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.Conclusions: Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment. [ABSTRACT FROM AUTHOR]

BackgroundSeveral clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta‑analysis with trial sequential analysis (TSA).MethodsWe searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed.ResultsNine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02, P = 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52, P = 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57, P = 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13, P = 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32, P = 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94, P = 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08, P = 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06, P = 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84, P = 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required.ConclusionsLimited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice.

Many functions of the immune system are impaired in neonates, allowing vulnerability to serious bacterial, viral and fungal infections which would otherwise not be pathogenic to mature individuals. This vulnerability is exacerbated in compromised newborns such as premature neonates and those who have undergone surgery or who require care in an intensive care unit. Higher susceptibility of preterm neonates to infections is associated with delayed immune system maturation, with deficiencies present in both the innate and adaptive immune components. Here, we review recent insights into early life immunity, and highlight features associated with compromised newborns, given the challenges of studying neonatal immunity in compromised neonates due to the transient nature of this period of life, and logistical and ethical obstacles posed by undertaking studies newborns and infants. Finally, we highlight how the unique immunological characteristics of the premature host play key roles in the pathogenesis of diseases that are unique to this population, including necrotizing enterocolitis and the associated sequalae of lung and brain injury.

The objective of the present study is to review current evidence from randomized controlled trials (RCTs) of probiotics for preterm infants in India. A systematic review of RCTs of probiotics for preterm infants in India was conducted using Cochrane methodology and PRISMA guidelines. Fixed effects model was used for meta-analysis. Nine RCTs (n = 1514) were included. Meta-analysis showed reduced risk of necrotizing enterocolitis (NEC) ≥ Stage II {Risk ratio (RR): 0.36 [95% confidence interval (CI): 0.20, 0.66], p = 0.0009, (9 RCTs)}, late onset sepsis [RR: 0.56 (95% CI: 0.45, 0.71), p < 0.00001, (7 RCTs)] and mortality [RR: 0.62 (95% CI: 0.41, 0.95, p = 0.03 (8 RCTs)] in the probiotic group. Probiotics also reduced the time to full feeds [Mean difference (MD): −4.09 d (95% CI: −4.52, −3.65), p < 0.00001, 5 RCTs] and duration of hospital stay [Fixed effects model (FEM): MD: −2.00 d (95% CI: −2.46, −1.53), p < 0.00001, 6 RCTs]. Current evidence from RCTs supports probiotic supplementation for optimizing outcomes of preterm infants in India. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis is a devastating disease that affects mostly the intestine of premature infants. The wall of the intestine is damaged by hypoxia, and bacteria are invaded, which cause local inflammation and infection that can ultimately destroy with necrosis the wall of the intestine. Such bowel wall destruction can lead to perforation of the intestine and spillage of stool into the infant's abdomen, which can result in an overwhelming infection and death. The clinical presentation of necrotizing enterocolitis includes variable signs, which are often non-specific for gastrointestinal dysfunction. The clinical diagnosis of necrotizing enterocolitis is currently made based on a combination of clinical, laboratory, and instrumental (ultrasound and radiologic) findings. The preventive multi-modal 3-component necrotizing enterocolitis prophylaxis scheme was implemented for necrotizing enterocolitis treatment in December of 2016 in Neonates Intensive Care Unit of "Muratsan" clinical complex of Yerevan State Medical University resulted in significantly reduced necrotizing enterocolitis-associated morbidity and mortality. Necrotizing enterocolitis is severe disease of gastrointestinal tract, yet its early symptoms are nonspecific, easily interchangeable with sepsis. Therefore, reliable biomarkers for early diagnostics are needed in clinical practice. One of the promising trends in early diagnosis of necrotizing enterocolitis is use of biomarkers. The biomarkers used in prognosis and diagnosis of necrotizing enterocolitis are relative nonspecific as other noninvasive and less invasive methods. Amongst variety of biomarkers molecules, based on literature, one of the most promising for necrotizing enterocolitis seems to be intestinal fatty acid-binding protein. In modern days, biomarkers widely used for diagnose and prediction in many diseases. Necrotizing enterocolitis is one of the most severe acquired diseases affecting preterm neonates. Early diagnosis remains elusive which continues to prompt human subject studies in the search for necrotizing enterocolitisassociated biomarkers that may provide for early diagnosis or the recognition of high-risk subcohorts with sufficient precision to facilitate preventive measures. [ABSTRACT FROM AUTHOR]

Background: Several clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta‑analysis with trial sequential analysis (TSA). Methods: We searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed. Results: Nine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02, P = 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52, P = 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57, P = 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13, P = 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32, P = 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94, P = 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08, P = 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06, P = 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84, P = 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required. Conclusions: Limited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is a pathogenic stress factor in preterm infants. Dynamic thiol/disulphide balance has a critical role in antioxidant defense, detoxification, apoptosis, transcription and cellular signal transport mechanisms. Oxidant/antioxidant balance state is a process beginning before birth and premature infants are especially vulnerable to oxidative stress. Objectives: In this study, we aimed to evaluate dynamic thiol/disulphide homeostasis by umbilical blood gas analysis, compare term and preterm infants, evaluate its relation with Apgar score, perinatal risks with mother and occurrence of NEC (necrotizing enterocolitis), sepsis and ROP (Retinopathy of Prematurity). Methods: A total of 108 (51 female and 57 male) newborn infants were included in this prospective cohort study. Of them, 31 were term and 77 were preterm. Demographic variables, Apgar score, NEC, sepsis and ROP intervention data were collected. Disulfide, native thiol, total thiol, index 1 (disulphide/native thiol x 100), index 2 (disulphide/total thiol x 100) and index 3 (native thiol/total thiol x 100) were calculated. Serum total ischemic modified albumin (IMA) and albumin were measured. Bloodgas analysis was performed within 2 minutes following birth. Results: Preterm infants had lower disulphide levels and index 1 and 2 ratios, but higher index 3 ratios. Acidotic infants, index 1 and 2 and disulphide levels were higher and index 3 was lower than patients with normal pH. Disulphide, index 1 and 2 were lower in patients taken to NICU (Neonatal Intensive Care Unit) compared to ones who were not, whereas index 3 values were higher, twenty one patients (19.4%) with scores < 7 had higher index 3 values at 5th minute. Disulphide levels, index 1 and 2 levels were lower in patients with NEC and index 3 levels were higher. Index 3 ratios were higher in septic infants. Index 3 was higher in patients born from preeclamptic mothers compared to ones without preeclampsia. Albumin levels were higher in patients with maternal placental anomalies. Conclusions: We believe that evaluation of thiol-disulphide homeostasis in preterm and term infants may be demonstrative for oxidant capacity of the newborn, hence the oxidative stress. [ABSTRACT FROM AUTHOR]

Pentoxifylline (PTX) is a candidate adjuvant medication for the treatment of sepsis and necrotizing enterocolitis in preterm infants. There is only limited data on safety and compatibility with other commonly used intravenous medications. This retrospective single-center study of 198 preterm infants (September 2012–September 2018) was performed at a level IV neonatal intensive care unit. Electronic data of all preterm infants who received pentoxifylline for sepsis or necrotizing were extracted from routine databases. We analyzed a total of 1081 PTX treatment days from 217 treatment episodes in 198 preterm infants (mean gestational age 27 weeks; mean birth weight 1060 g). At a mean daily dose of 28 mg/kg, no clinically relevant side effects were observed. PTX therapy was not associated with clinically significant changes of blood biochemistry and hematology parameters. Concomitant infusion of PTX with other common NICU medications was well tolerated, and there was no evidence of incompatibility. Conclusion: Intravenous PTX is compatible with standard NICU drugs and well tolerated in critically ill preterm infants. What is Know: •Currently, there are no evidence-based adjuvant medications available that target the harmful inflammatory host response in neonatal sepsis or necrotizing enterocolitis. •Pentoxifylline (PTX) is a candidate adjuvant medication for the treatment of sepsis and necrotizing enterocolitis in preterm infants; however, safety data are rare and PTX is currently used off-label. What is New: •Here we report on our experience in the pragmatic routine use of PTX as adjuvant therapy in 198 preterm infants with sepsis or NEC. •Concomitant infusion of PTX with other common NICU medications was well tolerated, and there was no evidence of incompatibility. No clinically relevant side effects were observed. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is a gastrointestinal emergency characterized by ischemic necrosis of the intestinal mucosa, leading to bacterial translocation and pneumatosis of the bowel wall. Although there are numerous studies on clinical presentations of preterm NEC, approximately 10-15% of cases occur in full-term neonates. Nearly 10% of all infants with NEC will develop a rapidly progressive and fatal form of the disease called NEC totalis.Case Report: A 24-day-old term male infant presented to the Emergency Department (ED) with emesis. The infant was ill-appearing with a tense abdomen and had significant tachycardia and hypotension. The patient was immediately volume resuscitated and started on empiric antibiotics. Initial radiographs revealed no evidence of bowel obstruction or pneumatosis. Pediatric Surgery was consulted, and upper gastrointestinal and abdominal computed tomography scans were obtained, which were nondiagnostic. The patient was taken to the operating room for an exploratory laparotomy after continued clinical deterioration and was diagnosed with NEC totalis and passed away within 6 days. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates an uncommon presentation of NEC in an otherwise healthy term neonate without any known risk factors. The diagnosis of NEC is challenging because imaging studies may be inconclusive, particularly early in the clinical course. Regardless of the etiology, all infants who present to the ED with signs and symptoms of severe gastrointestinal distress should be treated with basic emergency care, including rapid fluid resuscitation, empiric antibiotics, bowel decompression, and early surgical consultation. [ABSTRACT FROM AUTHOR]

Background: Probiotics and prebiotics have strain-specific effects on the host. Synbiotics, a mixture of probiotics and prebiotics, are proposed to have more beneficial effects on the host than either agent has alone. Purpose: We performed a randomized controlled trial to investigate the effect of Lactobacillus and Bifidobacterium together with oligosaccharides and lactoferrin on the development of necrotizing enterocolitis (NEC) or sepsis in very low birth weight neonates. Methods: Neonates with a gestational age ≤32 weeks and birth weight ≤1,500 g were enrolled. The study group received a combination of synbiotics and lactoferrin, whereas the control group received 1 mL of distilled water as placebo starting with the first feed until discharge. The outcome measures were the incidence of NEC stage ≥2 or late-onset cultureproven sepsis and NEC stage ≥2 or death. Results: Mean birth weight and gestational age of the study (n=104) and the control (n=104) groups were 1,197±235 g vs. 1,151±269 g and 29±1.9 vs. 28±2.2 weeks, respectively (P>0.05). Neither the incidence of NEC stage ≥2 or death, nor the incidence of NEC stage ≥2 or late-onset culture-proven sepsis differed between the study and control groups (5.8% vs. 5.9%, P=1; 26% vs. 21.2%, P=0.51). The only significant difference was the incidence of all stages of NEC (1.9% vs. 10.6%, P=0.019). Conclusion: The combination of synbiotics and lactoferrin did not reduce NEC severity, sepsis, or mortality. [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]

Many functions of the immune system are impaired in neonates, allowing vulnerability to serious bacterial, viral and fungal infections which would otherwise not be pathogenic to mature individuals. This vulnerability is exacerbated in compromised newborns such as premature neonates and those who have undergone surgery or who require care in an intensive care unit. Higher susceptibility of preterm neonates to infections is associated with delayed immune system maturation, with deficiencies present in both the innate and adaptive immune components. Here, we review recent insights into early life immunity, and highlight features associated with compromised newborns, given the challenges of studying neonatal immunity in compromised neonates due to the transient nature of this period of life, and logistical and ethical obstacles posed by undertaking studies newborns and infants. Finally, we highlight how the unique immunological characteristics of the premature host play key roles in the pathogenesis of diseases that are unique to this population, including necrotizing enterocolitis and the associated sequalae of lung and brain injury. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the safety and efficacy of Lactobacillus for preventing necrotizing enterocolitis (NEC) in preterm infants.Methods: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases from inception to September 2019. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare outcomes. We also performed a subgroup analysis of the incidence of NEC. Moreover, a sensitivity analysis was performed to examine the stability of the results. A Begg funnel plot was generated to detect publication bias. Two reviewers assessed trial quality and extracted data independently. This work has been reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and the Assessing the Methodological Quality of Systematic Reviews guidelines. Statistical analysis was performed using standard procedures in Review Manager 5.2 software.Results: Twenty-three randomized, placebo-controlled studies (N = 4686 participants) were included in this analysis. Comparing the Lactobacillus and control groups, a significant reduction was found in the incidence of NEC (RR 0.34, 95% CI 0.25-0.46; P < 0.00001) and death (RR 0.48, 95% CI 0.36-0.64; P < 0.00001). No significant difference in the incidence of sepsis was found between the Lactobacillus and placebo groups (RR 0.90, 95% CI 0.72-1.12; P = 0.34).Conclusions: Lactobacillus is safe and can prevent necrotizing enterocolitis in preterm infants. [ABSTRACT FROM AUTHOR]

There is an increasing evidence that the intestinal microbiota plays a pivotal role in the maturation of the immune system and in the prevention of diseases occurring during the neonatal period, childhood, and adulthood. A number of nonphysiological conditions during the perinatal period (i.e. caesarean section, prolonged hospitalization, formula feeding, low gestational age) may negatively affect the normal development of the microbiota, leading to decreased amounts of lactobacilli and bifidobacteria and increased amounts of Clostridia. In addition, perinatal antibiotics can cause intestinal dysbiosis that has been associated with short- and long-term diseases. For example, prolonged early empiric antibiotics increase the risk of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm neonates, whereas the administration of intrapartum antibiotic prophylaxis (IAP) has been associated with inflammatory bowel diseases, obesity, and atopic conditions, such as eczema and wheezing. Promoting breastfeeding, reducing the length of hospital stay, and reducing unnecessary antibiotic therapies are useful strategies to counterbalance unintended effects of these conditions. [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]

Background: Prematurity is accompanied with various complications including sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and apnea. In current study, we assessed the effects of oral vitamin E on incidence of prematurity complications in premature neonates. Methods: This was a clinical trial study on 76 neonates in Alzahra hospital, Isfahan, Iran, during 2015-2017. Neonates were randomly divided in two age- and sex-matched group. 38 neonates of case group were treated with 10 units of vitamin E through orogastric tube for three days. Control group were treated with distilled water through orogastric tube. Patients in two groups were evaluated in terms of sepsis, NEC and IVH. Findings: In this study, 48.7% of patients were boys. Mean neonates' age and weight was 28.49 ± 1.46 weeks and 1183.02 ± 167.97 g, respectively. Incidence of sepsis (P = 0.77), NEC (P = 0.53), hypotension (P = 0.31), death (P = 0.45), and IVH in 4th (P = 0.30) and 7th (P = 0.20) day of birth was not significantly different between the two groups. Conclusion: Using oral vitamin E did not have statistically significant effect on prevention of sepsis, necrotizing enterocolitis, and intraventricular hemorrhage. Due to more controllable bioavailability of oral vitamin E in comparison to intramuscular and intravenous use of it, and increased risk of sepsis and necrotizing enterocolitis by using high doses of vitamin E in other reports, further studies with different doses of oral vitamin E are recommended.

Background: The University of Virginia neonatal intensive care unit is a 51-bed unit with approximately 600 to 700 admissions per year. Despite evidenced-based clinical care, necrotizing enterocolitis (NEC) and feeding intolerance remained problematic.Purpose: In September 2016, the neonatal intensive care unit implemented an exclusive human milk diet (EHMD) for infants born 1250 g or less with the goal of reducing NEC, feeding intolerance, parenteral nutrition use, and late-onset sepsis. Length of stay, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity were also evaluated.Methods: A work group developed systems for charging and documenting products used in an EHMD. Outcomes were compared with a control group of similar infants born prior to the availability of the EHMD.Results: Infants who received an EHMD had significantly fewer late-onset sepsis evaluations (P = .0027) and less BPD (P = .018). While not statistically significant, less surgical NEC was also demonstrated (4 cases vs 1 case, which was 57% of total NEC cases vs 14.3%) while maintaining desirable weight gain and meeting financial goals.Implications For Practice: A multidisciplinary team that implements financial and documentation systems can provide a sustainable clinical practice that improves patient outcomes. Ongoing evaluations of clinical and financial data provide valuable information to guide future clinical practices related to the EHMD.Implications For Research: Future research on the anti-inflammatory effect of an EHMD is needed to provide direction regarding a potential dose-dependent response for reduced BPD rates and severity. The role of human milk and prevention or mitigation of sepsis is not fully understood, but the reduction of the number of late-onset sepsis evaluations may support the relationship between an EHMD and infection protection. Exploring clinical and financial outcomes for implementing the EHMD in infants born more than 1250 g remains a key area for research. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare probiotics with placebo for necrotizing enterocolitis in preterm infants and to evaluate the safety and effect and strict effect of specific probiotic genera.Methods: Data recorded until January 2019 were searched, and relevant academic articles from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were selected by two independent reviewers. Two reviewers independently included randomized controlled trials that compared probiotics and placebo in preterm infants. The outcomes included more than one of the following outcomes: incidence of necrotizing enterocolitis, necrotizing enterocolitis-related mortality, incidence of sepsis, and all-cause mortality. Two reviewers independently extracted data and assessed the risk of bias and quality of evidence.Results: We identified 34 eligible studies of 9161 participants. This meta-analysis showed an overall advantage of probiotics to prevent the incidence of necrotizing enterocolitis (3.54%) and gut-associated sepsis (15.59%), and decrease mortality (5.23%) in preterm infants. A probiotic mixture showed a huge advantage and vitality in preventing necrotizing enterocolitis (2.48%) and gut-associated sepsis (18.39%), and in reducing mortality (5.57%) in preterm infants.Conclusion: The probiotic mixture showed advantages over the single strains to decrease the incidences of necrotizing enterocolitis and gut-associated sepsis, and mortality in preterm infants. [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]