Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

Incidence and predictors of mortality among neonates admitted with birth asphyxia to neonatal intensive care unit of West Shewa Zone Public Hospitals, Central Ethiopia.

BACKGROUND: Birth asphyxia is still one of the primary causes of newborn mortality worldwide. Similarly, the risk of newborn asphyxia in Ethiopia remains unacceptably high. Thus, studies on the incidence and predictors of mortality among newborns admitted with birth asphyxia are crucial to addressing this problem. As a result, the purpose of this study was to assess the incidence and predictors of mortality among neonates admitted with birth asphyxia to the neonatal intensive care units (NICUs) of West Shewa Zone Public Hospitals in Central Ethiopia. METHODS: An institution-based retrospective cohort study was conducted among 760 asphyxiated neonates admitted to the NICUs of West Shewa Zone Public Hospitals between 30 March 2021 and 30 April 2023. The data were collected using CSEntry and analysed bu using Stata V.17. Bivariate and multivariate Cox proportional hazard regression analyses were carried out, and significant predictors were found using a 95% CI and a p<0.05. RESULTS: A total of 760 asphyxiated neonates were followed for a total of 6880 neonatal days. At the end of follow-up, 263 (34.6%) of the neonates died (95% CI 31.3% to 38.1%), which resulted in a mortality incidence of 10.6/100 person-days of observation. Chewing khat (adjusted HR, AHR 2.21; 95% CI 1.13 to 4.31), home delivery (AHR 1.45, 95% CI 1.1 to 1.9), lack of antenatal care follow-up (AHR 1.44, 95% CI 1.08 to 1.89), hypothermia (AHR 1.56, 95% CI 1.12 to 2.17), hypoglycaemia (AHR 2.23, 95% CI 1.91 to 2.25) and obstructed labour (AHR 1.4, 95% CI 1.02 to 1.91) were found to be the significant predictors of neonatal mortality among asphyxiated neonates at a p≤0.05. CONCLUSION AND RECOMMENDATION: The magnitude of neonatal mortality among asphyxiated neonates in the study area was high. Therefore, in order to significantly reduce the risks of birth asphyxia and subsequent newborn death, all interested stakeholders should take these predictors into consideration.

Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

BACKGROUND: Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia. METHODS: Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553). RESULTS: Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes. CONCLUSION: We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.

Predictors of neonatal mortality among neonates admitted to the neonatal intensive care unit at Hawassa University Comprehensive Specialized Hospital, Sidama regional state, Ethiopia.

BACKGROUND: Despite promising efforts, substantial deaths occurred during the neonatal period. According to estimates from the World Health Organization (WHO), Ethiopia is among the top 10 nations with the highest number of neonatal deaths in 2020 alone. This staggering amount makes it difficult to achieve the SDG (Sustainable Development Goals) target that calls for all nations to work hard to meet a neonatal mortality rate target of ≤ 12 deaths per 1,000 live births by 2030. We evaluated neonatal mortality and it's contributing factors among newborns admitted to the Neonatal Intensive Care Unit (NICU) at Hawassa University Comprehensive Specialized Hospital (HUCSH). METHODS: A hospital-based retrospective cross-sectional study on neonates admitted to the NICU from May 2021 to April 2022 was carried out at Hawassa University Comprehensive Specialized Hospital. From the admitted 1044 cases over the study period, 225 babies were sampled using a systematic random sampling procedure. The relationship between variables was determined using bivariate and multivariable analyses, and statistically significant relations were indicated at p-values less than 0.05. RESULTS: The magnitude of neonatal death was 14.2% (95% CI: 0.099-0.195). The most common causes of neonatal death were prematurity 14 (43.8%), sepsis 9 (28.1%), Perinatal asphyxia 6 (18.8%), and congenital malformations 3 (9.4%). The overall neonatal mortality rate was 28 per 1000 neonate days. Neonates who had birth asphyxia were 7.28 times more probable (AOR = 7.28; 95% CI: 2.367, 9.02) to die. Newborns who encountered infection within the NICU were 8.17 times more likely (AOR = 8.17; 95% CI: 1.84, 36.23) to die. CONCLUSION: The prevalence of newborn death is excessively high. The most common causes of mortality identified were prematurity, sepsis, perinatal asphyxia and congenital anomalies. To avert these causes, we demand that antenatal care services be implemented appropriately, delivery care quality be improved, and appropriate neonatal care and treatment be made available.

A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections.

Preterm birth is currently the leading cause of neonatal morbidity and mortality. Genetic, immunological and infectious causes are suspected. Preterm infants have a higher risk of severe bacterial neonatal infections, most of which are caused by Escherichia coli an in particular E. coli K1strains. Women with history of preterm delivery have a high risk of recurrence and therefore constitute a target population for the development of vaccine against E. coli neonatal infections. Here, we characterize the immunological, microbiological and protective properties of a live attenuated vaccine candidate in adult female mice and their pups against after a challenge by K1 and non-K1 strains of E. coli. Our results show that the E. coli K1 E11 ∆aroA vaccine induces strong immunity, driven by polyclonal bactericidal antibodies. In our model of meningitis, mothers immunized prior to mating transfer maternal antibodies to pups, which protect newborn mice against various K1 and non-K1 strains of E. coli. Given the very high mortality rate and the neurological sequalae associated with neonatal E. coli K1 meningitis, our results constitute preclinical proof of concept for the development of a live attenuated vaccine against severe E. coli infections in women at risk of preterm delivery.

Enterocolitis necrotizante experimental con lipopolisacárido oral y función protectora de la lechematerna / Experimental necrotizing enterocolitis using oral lipopolysaccharide and protective role of breastmilk

Introducción: La enterocolitis necrotizante (ECN) es una enfermedad potencialmente mortal que afecta a los neonatos, y frente a laque la leche materna ha demostrado tener un papel protector. Administrando lipopolisacáridos (LPS) por vía oral en ratas recién nacidas(RRN), hemos desarrollado un modelo experimental para inducir undaño intestinal similar al que provoca la ECN con objeto de evaluarel aspecto macroscópico y microscópico del intestino, y de ese modo,analizar la presencia de ECN y estudiar el papel que desempeña laleche materna (LM). Material y métodos: Las RRN se dividieron en tres grupos: el grupoA (control, n= 10) permaneció con su madre; el grupo B (LPS, n=25)fue aislado tras el nacimiento, alimentado por sonda con una fórmulaespecial para ratas y LPS oral, y sometido a estrés (hipoxia tras sonda);y el grupo C (LM, n= 12) fue alimentado con leche materna tras elnacimiento y posteriormente aislado y sometido a estrés al igual que elgrupo B. El día 4 se sacrificó a las RRN y se recuperaron sus intestinospara su posterior evaluación. Resultados: En el grupo de control, no se observó ECN ni macroscópica ni histológicamente, mientras que los dos grupos sometidos aestrés (B y C) presentaron una incidencia global de la ECN del 73%.La mayoría de los sujetos del grupo B desarrollaron signos histológi-cos de ECN (85%), y los del grupo C registraron una incidencia de laECN estadísticamente menor (50%, p= 0,04), lo que significa que laLM desempeña una función protectora frente a la ECN (OR= 0,19; IC95%: 0,40-0,904). Conclusión: Nuestro modelo reveló una incidencia significativa dela ECN en RRN (73%), desempeñando la LM la misma función protectora que en el caso de los humanos recién nacidos, lo que significa que estemodelo experimental de ECN es fiable y reproducible. Gracias a dichologro, podremos investigar nuevos y potenciales objetivos terapéuticospara una peligrosa enfermedad que, a día de hoy, carece de tratamiento.(AU)

Introduction: Necrotizing enterocolitis (NEC) is a life-threateningcondition that afflicts neonates. Breastfeeding has demonstrated to playa protective role against it. By administering lipopolysaccharides (LPS)orally in newborn rats (NBR), we have developed an experimental modelto induce NEC-like gut damage. Our aim was to assess the macroscopicand microscopic appearance of the gut, to evaluate the presence of NECand study the role of breast milk (BM). Material and methods: NBR were divided into 3 groups: GroupA (control, n= 10) remained with the mother, group B (LPS, n= 25)was isolated after birth, gavage-fed with special rat formula and oralLPS, then submitted to stress (hypoxia after gavage) and group c (BM,n= 12) was breastfed once after birth, then isolated, and submitted tostress like group B. On day 4, NBR were sacrificed, and intestine washarvested and assessed. Results: In the control group NEC was not present either macroscopically or histologically. Both groups submitted to stress (B and C)presented a global incidence of NEC of 73%. Most of group B developedhistologic signs of NEC (85%) and group C showed a statistically lowerincidence of NEC (50%, p= 0.04), playing the BM a protective roleagainst NEC (OR= 0.19; 95% CI: 0.40- 0.904)Conclusion: Our model showed a significant incidence of NEC inNBR (73%) with the same protective role of BM as in newborn humans,achieving a reliable and reproducible experimental NEC model. This willallow us to investigate new potential therapeutic targets for a devastatingdisease that currently lacks treatment.(AU)

Cuidados postoperatorios en el hipospadias. Prácticas habituales y evidencia disponible / Postoperative care in hypospadias: common practices and evidence available

Introducción: Existen numerosas alternativas en lo que respecta alos cuidados postoperatorios en la cirugía de hipospadias. El objetivo deeste estudio es evaluar la situación actual de estos cuidados en nuestromedio y revisar la evidencia existente al respecto para cirujanos pediátricos que realizan este tipo de intervenciones. Material y métodos: Hemos elaborado y distribuido una encuestaque recoge los principales puntos en el cuidado postoperatorio del hipospadias dirigida a cirujanos pediátricos. Se ha realizado revisión dela evidencia actual publicada al respecto en la especialidad.Resultados: Hemos obtenido un total de 46 respuestas. El 100% delos cirujanos dejan algún tipo de sonda o stent y más del 80% están deacuerdo en retirarlo tras 5 o 7 días. El 87,8% de los encuestados utilizael doble pañal, pero solo el 65,2% da alta precoz en el postoperatorio.Un 60,9% pauta profilaxis antibiótica mientras dure el sondaje y un34,8% antibioterapia a dosis plenas. Discusión: Existe consenso general respecto a la tutorización de lauretroplastia y el uso de apósito compresivo entre los cirujanos pediátricos encuestados. Se detectan más discrepancias en el uso de antibioterapia y el alta precoz. La evidencia actual y la práctica a nivel internacional apunta hacia el uso de la sonda a doble pañal con alta precozy la limitación del uso de antibióticos postoperatorios. En ausencia declara evidencia que favorezca un tipo de cuidado u otro, la experienciadel paciente podría ser utilizada para elegir el mejor protocolo postoperatorio individualizado.(AU)

Introduction: There are many alternatives available regarding postoperative care in hypospadias surgery. The objective of this study wasto assess the current care situation in our environment and to review theevidence available for pediatric surgeons who conduct this procedure. Materials and methods. A survey regarding the main aspects ofhypospadias postoperative care was created and distributed to pediatricsurgeons. In addition, the evidence currently published in this field wasreviewed. Results: A total of 46 replies were achieved. 100% of the surgeonsleave in place a probe or stent, and more than 80% remove it after 5 or7 days. 87.8% of the respondents use a double diaper, but only 65.2%discharge patients early in the postoperative period. 60.9% prescribeantibiotic prophylaxis for as long as the probe remains in place, and34.8% use full-dose antibiotic therapy. Discussion: There was a general consensus regarding urethroplastyguiding and the use of compression dressings among the pediatric surgeons surveyed. However, more discrepancies were found in the use ofantibiotic therapy and early discharge. The currently available evidenceand international practice suggest using a probe with double diaperand early discharge, with postoperative antibiotics being limited. Inthe absence of clear evidence for a specific care type, the patient’sexperience could be used to choose the best postoperative protocol onan individual basis.(AU)

Enfermedad de Hirschsprung no sindrómica por variante en el gen RET / Non-syndromic Hirschsprung’s disease as a result of a RET gene variant

Introducción: La enfermedad de Hirschsprung (EH) se caracterizapor la ausencia de células ganglionares en los plexos submucoso y mientérico del intestino grueso, resultante de deficiencias en la migracióny diferenciación de las células de la cresta neural entérica durante laembriogénesis. Es una condición multifactorial, con más de 11 genesidentificados en su patogénesis, incluyendo el protooncogén RET.Caso clínico: Se presenta el caso de dos hermanos con EH de colontotal, cuyo padre también padeció la enfermedad, y en quien se encontróuna variante potencialmente patogénica en el gen RET.Comentarios: El diagnóstico prenatal mediante pruebas genéticaspermite decisiones informadas y la planificación de cuidados para elneonato afectado, reduciendo demoras en el diagnóstico y tratamiento,y minimizando las complicaciones a largo plazo. La identificación demutaciones como la variante en el gen RET destaca la importancia delenfoque genético en la comprensión y manejo de la EH.(AU)

Introduction: Hirschsprung’s disease (HD) is characterized by theabsence of ganglion cells in the submucosal and myenteric plexuses ofthe colon as a result of disorders in the migration and differentiationof enteric neural crest cells during embryogenesis. It is a cross-factorcondition, with more than 11 genes identified in its pathogenesis, including the RET proto-onco gene.Case report: We present the case of two siblings with total colonHD where a potentially pathogenic variant of the RET gene was found.Their father also had this condition.Discussion: Prenatal diagnosis through genetic testing allows forinformed decisions and care planning for the newborn, thus reducin delayed diagnosis and treatment, and minimizing long-term complications. Mutations such as the RET gene variant highlight the importanceof the genetic approach in understanding and managing HD.(AU)

Oxygenation saturation index in neonatal hypoxemic respiratory failure.

BACKGROUND: This study aimed to assess the validity of the oxygenation saturation index (OSI) and the ratio of oxygen saturation to the fraction of inspired oxygen (FIO2) (S/F ratio) with percutaneous oxygen saturation (OSISpO2 and the Sp/F ratio) and to evaluate the correlation between these values and the oxygen index (OI). It also determined their cut-off values for predicting OI in accordance with neonatal hypoxic respiratory failure severity. METHODS: We reviewed the data of 77 neonates (gestational age 31.7 ± 6.1 weeks; birthweight, 1768 ± 983 g) requiring invasive mechanical ventilation between 2013 and 2020, 1233 arterial blood gas samples in total. We calculated the OI, OSISpO2, OSI with arterial oxygen saturation (SaO2) (OSISaO2), Sp/F ratio, and the ratio of SaO2 to FIO2 (Sa/F ratio). RESULTS: The regression and Bland-Altman analysis showed good agreement between OSISpO2 or the Sp/F ratio and OSISaO2 or the Sa/F ratio. Although a significant positive correlation was found between OSISpO2 and OI, OSISpO2 was overestimated in SpO2 > 98% with a higher slope of the fitted regression line than that below 98% of SpO2. Furthermore, receiver-operating characteristic curve analysis using only SpO2 ≤ 98% samples showed that the optimal cut-off points of OSISpO2 and the Sp/F ratio for predicting OI were: OI 5, 3.0 and 332; OI 10, 5.3 and 231; OI 15, 7.7 and 108; OI 20, 11.0 and 149; and OI 25, 17.1 and 103, respectively. CONCLUSION: The cut-off OSISpO2 and Sp/F ratio values could allow continuous monitoring for oxygenation changes in neonates with the potential for wider clinical applications.

Exploring gestational age, and birth weight assessment in Thatta district, Sindh, Pakistan: Healthcare providers' knowledge, practices, perceived barriers, and the potential of a mobile app for identifying preterm and low birth weight.

INTRODUCTION: Reliable methods for identifying prematurity and low birth weight (LBW) are crucial to ending preventable deaths in newborns. This study explored healthcare providers' (HCPs) knowledge, practice, perceived barriers in assessing gestational age and birth weight and their referral methods for preterm and LBW infants. The study additionally assessed the potential of using a mobile app for the identification and referral decision of preterm and LBW. METHODS: This qualitative descriptive study was conducted in Thatta District, Sindh, Pakistan. Participants, including doctors, nurses, lady health visitors, and midwives, were purposefully selected from a district headquarter hospital, and private providers in the catchment area of Global Network's Maternal and Newborn Health Registry (MNHR). Interviews were conducted using an interview guide after obtaining written informed consent. Audio recordings of the interviews were transcribed and analyzed using NVIVO® software with an inductive approach. RESULTS: The HCPs had extensive knowledge about antenatal and postnatal methods for assessing gestational age. They expressed a preference for antenatal ultrasound due to the perceived accuracy, though accept practical barriers including workload, machine malfunctions, and cost. Postnatal assessment using the Ballard score was only undertaken sparingly due to insufficient training and subjectivity. All HCPs preferred electronic weighing scales for birth weight Barriers encountered included weighing scale calibration and battery issues. There was variation in the definition of prematurity and LBW, leading to delays in referral. Limited resources, inadequate education, and negative parent past experiences were barriers to referral. Foot length measurements were not currently being used. While mobile apps are felt to have potential, unreliable electricity supply and internet connectivity are barriers. CONCLUSION: The HCPs in this study were knowledgeable in terms of potential tools, but acknowledged the logistical and parental barriers to implementation.

Neonatal mortalities without detected risk factors before birth at Mtendeli hospital, Tanzania: a cross-sectional study.

Introduction: neonatal mortality rate (NMR) is defined as the probability of dying during the first 28 days of life expressed per 1,000 live births. The death of neonates without risk factors at the end of pregnancy could be an indicator of sub-optimal quality care during labor and care of sick neonates. Therefore, this study aimed to determine the factors associated with neonatal deaths happening without detected risks during prenatal period. Methods: a cross-sectional study was conducted from 2017 to 2021.The recruited pregnant women were those who had a live, term, single-intrauterine pregnancy without detectable fetal abnormality at the time of starting labor. The data were collected through open data kit (ODK) forms that were customized in kobo tool in the tablets. The data analysis was performed using STATA statistical software. The factors associated with neonatal mortality were analyzed in a multiple logistic regression and considered significant if p < 0.05. Results: among the 4401 enrolled mothers, neonatal deaths were 361 (8.2%). The factors associated with death of neonates without risk factors during prenatal period were low Apgar score [AOR = 4.38: 95%CI (2.33-7.72)], male sex [AOR=2.25: 95%CI (1.12-3.81)], gestational age above 40 weeks [AOR=4.79: (2.50-7.61)] and assisted vaginal delivery [AOR = 2.55: 95%CI (1.12-4.96)]. Conclusion: the increased number of neonatal deaths are associated with sex of neonates, low Apgar score, post maturity and assisted vaginal delivery. The hospital-based studies should be done to address the preventable neonatal deaths with no detected risk factors before birth.

THE ROLE OF RADIODIAGNOSIS OF NECROTIZING ENTEROCOLITIS IN PREMATURE INFANTS.

Necrotizing enterocolitis (NEC) is the most often encountered pathology of newborns and always requires an emerging surgery in cases of perforation. An active study of more important diagnostic factors at early stages of a disease is one of the first aims of neonatologists and pediatric surgeons. This study was therefore designed to examine the state of diagnostic problems in patients presenting with Necrotizing enterocolitis, identification of possible ways of the improvement of a patient's diagnosis suffering from Necrotizing enterocolitis and patients with perforated enterocolitis, definition of the possibilities of roentgenologic methods for the determination of a disease stage of Necrotizing enterocolitis. 69 infants aged one day to 1.5 months admitted at surgical department of K.Y. Farajeva Research Institute of Pediatrics between 2016 and 2021 inclusive were treated and evaluated. The capabilities of plain radiography and using radiocontrast methods of study to reveal NEC stages have been evaluated. The use of CSM has advantages: simplicity and accessibility in use, high diagnostic informativeness, identification of objective signs of NEC in 2-3 hours of research, allows assessing the severity of the patient's condition at an early date and timely correct treatment.

Incidence and development of validated mortality prediction model among asphyxiated neonates admitted to neonatal intensive care unit at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2021: retrospective follow-up study.

INTRODUCTION: Perinatal asphyxia is failure to maintain normal breathing at birth. World Health Organization indicates that perinatal asphyxia is the third major cause of neonatal mortality in developing countries accounting for 23% of neonatal deaths every year. At global and national level efforts have done to reduce neonatal mortality, however fatalities from asphyxia remains high in Ethiopia (24%). And there are no sufficient studies to show incidence and prediction of mortality among asphyxiated neonates. Developing validated risk prediction model is one of the crucial strategies to improve neonatal outcomes with asphyxia. Therefore, this study will help to screen asphyxiated neonate at high-risk for mortality during admission by easily accessible predictors. This study aimed to determine the incidence and develop validated Mortality Prediction model among asphyxiated neonates admitted to the Neonatal Intensive Care Unit at Felege-Hiwot Comprehensive Specialized Hospital, Bahir Dar, Ethiopia. METHOD: Retrospective follow-up study was conducted at Felege-Hiwot Comprehensive Specialized Hospital from September 1, 2017, to March 31, 2021. Simple random sampling was used to select 774 neonates, and 738 were reviewed. Since was data Secondary, it was collected by checklist. After the description of the data by table and graph, Univariable with p-value < 0.25, and stepwise multivariable analysis with p-value < 0.05 were done to develop final reduced prediction model by likelihood ratio test. To improve clinical utility, we developed a simplified risk score to classify asphyxiated neonates at high or low-risk of mortality. The accuracy of the model was evaluated using area under curve, and calibration plot. To measures all accuracy internal validation using bootstrapping technique were assessed. We evaluated the clinical impact of the model using a decision curve analysis across various threshold probabilities. RESULT: Incidence of neonatal mortality with asphyxia was 27.2% (95% CI: 24.1, 30.6). Rural residence, bad obstetric history, amniotic fluid status, multiple pregnancy, birth weight (< 2500 g), hypoxic-ischemic encephalopathy (stage II and III), and failure to suck were identified in the final risk prediction score. The area under the curve for mortality using 7 predictors was 0.78 (95% CI 0.74 to 0.82). With ≥ 7 cutoffs the sensitivity and specificity of risk prediction score were 0.64 and 0.82 respectively. CONCLUSION AND RECOMMENDATION: Incidence of neonatal mortality with asphyxia was high. The risk prediction score had good discrimination power built by rural residence, bad obstetric history, stained amniotic fluid, multiple pregnancy, birth weight (< 2500 g), hypoxic-ischemic encephalopathy (stage II and III), and failure to suck. Thus, using this score chart and improve neonatal and maternal service reduce mortality among asphyxiated neonates.

Plant-Derived Substances for Prevention of Necrotising Enterocolitis: A Systematic Review of Animal Studies.

Inflammation, oxidative injury, and gut dysbiosis play an important role in the pathogenesis of necrotising enterocolitis (NEC). Plant-derived substances have historically been used as therapeutic agents due to their anti-inflammatory, antioxidant, and antimicrobial properties. We aimed to review pre-clinical evidence for plant-derived substances in the prevention and treatment of NEC. A systematic review was conducted using the following databases: PubMed, EMBASE, EMCARE, MEDLINE and Cochrane Library (PROSPERO CRD42022365477). Randomized controlled trials (RCTs) and quasi-RCTs that evaluated a plant-derived substance as an intervention for NEC in an animal model of the illness and compared pre-stated outcomes (e.g., clinical severity, severity of intestinal injury, mortality, laboratory markers of inflammation and oxidative injury) were included. Sixteen studies (n = 610) were included in the systematic review. Ten of the sixteen included RCTs (Preterm rat pups: 15, Mice: 1) reported mortality and all reported NEC-related histology. Meta-analysis showed decreased mortality [12/134 vs. 27/135; RR: 0.48 (95% CI: 0.26 to 0.87); p = 0.02, 10 RCTs] and decreased NEC in the experimental group [24/126 vs. 55/79; RR: 0.34 (95% CI: 0.22 to 0.52); p < 0.001, 6 RCTs]. Markers of inflammation (n = 11) and oxidative stress (n = 13) improved in all the studies that have reported this outcome. There was no significant publication bias for the outcome of mortality. Plant-derived substances have the potential to reduce the incidence and severity of histologically diagnosed NEC and mortality in rodent models. These findings are helpful in guiding further pre-clinical studies towards developing a food supplement for the prevention of NEC in preterm infants.

Values of serum intestinal fatty acid-binding protein, fecal calprotectin, and fecal human ß-defensin 2 for predicting necrotizing enterocolitis.

BACKGROUND: This study aimed to assess the diagnostic potential of serum intestinal fatty acid-binding protein (I-FABP), fecal calprotectin (FC), and fecal human ß-defensin 2 (hBD2) in predicting necrotizing enterocolitis (NEC) in preterm infants. METHODS: A prospective cohort of neonates with a gestational age < 32 weeks, suspected of NEC, was enrolled between June 2021 and December 2022. Serum I-FABP, FC, and fecal hBD2 levels were measured upon NEC suspicion, and diagnosis was confirmed through radiological examination or surgical intervention. Diagnostic precision of serum I-FABP, FC, and fecal hBD2 was assessed using a logistic regression model with multiple variables. RESULTS: The study included 70 neonates (45 males, 25 females), with 30 developing NEC (40% Stage III, n = 12; 60% Stage II, n = 18) and 40 in the control group. NEC patients exhibited significantly higher serum I-FABP and FC levels (4.76 ng/mL and 521.56 µg/g feces, respectively) than those with other diagnoses (1.38 ng/mL and 213.34 µg/g feces, respectively; p ˂ 0.05 for both biomarkers). Stage II NEC neonates showed elevated fecal hBD2 levels (376.44 ng/g feces) than Stage III NEC neonates and controls (336.87 ng/g and 339.86 ng/g feces, respectively; p ˂ 0.05). No such increase was observed in infants progressing to Stage III NEC. Using a serum I-FABP threshold of > 2.54 ng/mL yielded 76.7% sensitivity, 87.5% specificity, 82.1% positive predictive value (PPV), and 83.3% negative predictive value (NPV). For FC (cutoff > 428.99 µg/g feces), corresponding values were 76.7% sensitivity, 67.5% specificity, 63.9% PPV, and 79.4% NPV. CONCLUSION: Serum I-FABP and FC levels are valuable for early NEC detection and provide insights into disease severity. Low fecal hBD2 levels suggest an inadequate response to luminal bacteria, potentially rendering these infants more susceptible to NEC development or exacerbation.

Factors affecting neurodevelopmental outcome following surgical necrotising enterocolitis: a systematic review.

Surgically treated necrotising enterocolitis (sNEC) is associated with significantly worse neurodevelopmental outcomes than that seen in premature infants without NEC. We aim to review the association between factors involved in the surgical treatment of NEC and subsequent neurodevelopmental outcomes to identify potential areas for improvement. The PubMed and Embase databases were interrogated for articles reporting neurodevelopmental outcomes in babies treated surgically for NEC using key terms including: "Infant", "Necrotising enterocolitis", "Surgical", "Neurodevelopmental" and "Outcomes". The search strategy yielded 1170 articles and after applying inclusion and exclusion criteria 22 studies remained and formed the review. A diverse range of neurodevelopmental outcomes were reported. Extreme prematurity and lower birth weight were associated with worse neurodevelopmental outcomes. The use of peritoneal drains and enterostomies were associated with worse outcomes. Modifications to surgical strategies in NEC may improve neurodevelopmental outcomes but the effect of confounding factors remains unclear. Further large scale studies are required to define the optimum strategies for treating NEC surgically and to develop a core outcome set for research into NEC.

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic.

Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic-ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.