Complications Of Prematurity Research Articles

Endoplasmic Reticulum Stress in Bronchopulmonary Dysplasia: Contributor or Consequence?

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity. Oxidative stress (OS) and inflammation are the major contributors to BPD. Despite aggressive treatments, BPD prevalence remains unchanged, which underscores the urgent need to explore more potential therapies. The endoplasmic reticulum (ER) plays crucial roles in surfactant and protein synthesis, assisting mitochondrial function, and maintaining metabolic homeostasis. Under OS, disturbed metabolism and protein folding transform the ER structure to refold proteins and help degrade non-essential proteins to resume cell homeostasis. When OS becomes excessive, the endogenous chaperone will leave the three ER stress sensors to allow subsequent changes, including cell death and senescence, impairing the growth potential of organs. The contributing role of ER stress in BPD is confirmed by reproducing the BPD phenotype in rat pups by ER stress inducers. Although chemical chaperones attenuate BPD, ER stress is still associated with cellular senescence. N-acetyl-lysyltyrosylcysteine amide (KYC) is a myeloperoxidase inhibitor that attenuates ER stress and senescence as a systems pharmacology agent. In this review, we describe the role of ER stress in BPD and discuss the therapeutic potentials of chemical chaperones and KYC, highlighting their promising role in future therapeutic interventions.

Necrotizing enterocolitis following spontaneous intestinal perforation in very low birth weight neonates.

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are severe gastrointestinal complications of prematurity. The clinical presentation and treatment of NEC and SIP (peritoneal drain vs laparotomy) can overlap; however, the pathogenesis is distinct. Therefore, a patient initially treated for SIP can subsequently develop NEC. This phenomenon has only been described in case reports, and no risk factor evaluation exists. We evaluate clinical characteristics, risk factors, and outcomes of patients treated for a distinct episode of NEC after SIP. We performed a retrospective review of very low birth weight (<1500 g) neonates who presented with pneumoperitoneum between 07/2004 and 09/2022. Data was obtained from two separate neonatal intensive care units that were part of the same institution. Patients with an initial preoperative, intraoperative, or pathological diagnosis of NEC were excluded. Patients with an intraoperative diagnosis of SIP or preoperative diagnosis of SIP successfully treated with a peritoneal drain (PD) were evaluated. Patients subsequently treated (medically or surgically) for NEC after SIP were then compared to SIP-alone patients. Clinical characteristics included demographics, gestational age (GA), birth weight (BW), perinatal risk factors (chorioamnionitis, steroids, indomethacin), postoperative feeding regimen, and length of stay (LOS) were compared. Of the 278 patients included, 31 (11.2%) patients had NEC after SIP. There was no difference in GA (25 weeks vs 25 weeks, p = 0.933) or BW (760 g vs 735 g, p = 0.370) between NEC after SIP vs SIP alone cohorts, respectively. Twenty (64%) of NEC after-SIP patients were previously treated with LP. NEC after SIP occurred with a median onset of 56 days. Pneumatosis was the most frequent (81%) presenting symptom and 12 (39%) patients had hematochezia. Four (12.9%) patients required LP for NEC and all had NEC intraoperatively and on pathology. A majority (77.4%) of patients were on breast milk (BM) at time of NEC diagnosis. NEC after SIP patients had lower maternal age at delivery (29.0 vs 25.0, p = 0.055) and the incidence of NEC after LP (primary or failed drain) was higher than PD alone (16.7% vs 6.2%, p = 0.007). NEC after SIP patients had longer LOS (135 vs 81, p < 0.001). We report an 11.2% incidence of NEC at a median of 56 days following successful treatment of SIP, resulting in increased LOS. SIP patients are a high-risk cohort and protocols to prevent this phenomenon should be investigated.

Preterm birth is associated with dystonic features and reduced cortical parvalbumin immunoreactivity in mice.

Preterm birth is a common cause of dystonia. Though dystonia is often associated with striatal dysfunction after neonatal brain injury, cortical dysfunction may best predict dystonia following preterm birth. Furthermore, abnormal sensorimotor cortex inhibition is associated with genetic and idiopathic dystonias. To investigate cortical dysfunction and dystonia following preterm birth, we developed a new model of preterm birth in mice. We induced preterm birth in C57BL/6J mice at embryonic day 18.3, ~24 h early. Leg adduction variability and amplitude, metrics we have shown distinguish between dystonia from spasticity during gait in people with CP, were quantified from gait videos of mice. Parvalbumin-positive interneurons, the largest population of cortical inhibitory interneurons, were quantified in the sensorimotor cortex and striatum. Mice born preterm demonstrate increased leg adduction amplitude and variability during gait, suggestive of clinically observed dystonic gait features. Mice born preterm also demonstrate fewer parvalbumin-positive interneurons and reduced parvalbumin immunoreactivity in the sensorimotor cortex, but not the striatum, suggesting dysfunction of cortical inhibition. These data may suggest an association between cortical dysfunction and dystonic gait features following preterm birth. We propose that our novel mouse model of preterm birth can be used to study this association. Mouse models of true preterm birth are valuable for studying clinical complications of prematurity. Mice born preterm demonstrate increased leg adduction amplitude and variability during gait, suggestive of clinically observed dystonic gait features. Mice born preterm demonstrate fewer parvalbumin-positive interneurons and reduced parvalbumin immunoreactivity in the sensorimotor cortex, suggesting dysfunction of cortical inhibition. Mice born preterm do not demonstrate changes in parvalbumin immunoreactivity in the striatum. Cortical dysfunction may be associated with dystonic gait features following preterm birth.

Preterm Infant Enteral Feeding Practices in Saudi Arabia: A Scoping Review.

Preterm infants are at risk of developing nutritional deficiencies, which is further compounded by the fact that providing them with adequate nutrition is often challenging. Enteral feeding (EF) practices vary across neonatal units and can be impacted by the setting and geographical region. There is also a lack of evidence on best practices. To investigate EF practices and related nutrition factors, patterns, and outcomes in preterm infants in Saudi Arabia by examining studies published in this area. A search was conducted for articles on EF practices among preterm infants in Saudi Arabia that were published between January 2010 and May 2024. Searches were carried out across five electronic databases and through searching inward and backward citation and reference lists of relevant papers. Studies that described or assessed EF practices used in preterm infants from any region of Saudi Arabia and were published in English or Arabic were included. The database and manual search resulted in 1905 articles. After removing duplicates and applying the inclusion/exclusion criteria, 14 publications were included: 12 were observational studies, 1 was a conference abstract (with retrospective analysis), and 1 was a commentary. Of these, 7 studies were conducted in the Central Province, 6 in the Western Province, and 1 in the Eastern Province. More than half of the publications (8 of 14) were published between 2021 and 2023. The studies included were categorized to three themes based on their aim: studies describing practices on mother-infant bond to encourage breastfeeding, assessing nutritional status and EF, and assessing EF as a risk factor for developing prematurity complications. While research activity on EF practices in Saudi Arabia has increased very recently, yet there is a paucity of studies, particularly experimental studies that focus on both short- and long-term health outcomes.

Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common lung complication of prematurity. Despite extensive research, our understanding of its pathophysiology remains limited, as reflected by the stable prevalence of BPD. Prematurity is the primary risk factor for BPD, with oxidative stress (OS) and inflammation playing significant roles and being closely linked to premature birth. Understanding the interplay and temporal relationship between OS and inflammation is crucial for developing new treatments for BPD. Animal studies suggest that OS and inflammation can exacerbate each other. Clinical trials focusing solely on antioxidants or anti-inflammatory therapies have been unsuccessful. In contrast, vitamin A and caffeine, with antioxidant and anti-inflammatory properties, have shown some efficacy, reducing BPD by about 10%. However, more than one-third of very preterm infants still suffer from BPD. New therapeutic agents are needed. A novel tripeptide, N-acetyl-lysyltyrosylcysteine amide (KYC), is a reversible myeloperoxidase inhibitor and a systems pharmacology agent. It reduces BPD severity by inhibiting MPO, enhancing antioxidative proteins, and alleviating endoplasmic reticulum stress and cellular senescence in a hyperoxia rat model. KYC represents a promising new approach to BPD treatment.

Sacrococcygeal Teratoma: Tales of the “Tailbone” Tumour in a Newborn

Sacrococcygeal teratoma (SCT) is a rare tumour with a low incidence, but it is the most common extragonadal tumour in the newborn. It occurs at the base of the coccyx (tailbone) and is derived from embryonic germ cell layers. Although the majority are benign in nature, they are associated with significant morbidity and mortality for the mother and the foetus. A multidisciplinary approach is needed where an accurate early diagnosis should be made antenatally, leading to anticipation of complications during intrapartum for the mother and foetus, and ultimately early, complete surgical excision of the tumour. The prognosis for survival is good after resection. We report a case of a newborn delivered at 29 weeks who was diagnosed with SCT at post-partum but unfortunately passed away due to the complications of prematurity before surgery could be performed. This case report highlights the literature review of this pathology, especially the management of SCT, which begins in the antenatal period soon after the diagnosis is made.

The Impact of Oral Maternal Colostrum Administration on the Immune System of Premature Babies

In children under five years of age, premature complications are now the second leading cause of death. Colostrum has important benefits in promoting the maturity of premature infants' organ functions and preventing infections. Preterm infants are recommended to be given colostrum orally and pharyngeally as early as possible after birth to provide immune protective effects for their bodies. However, the sucking and swallowing functions of preterm infants are often not optimal, partly due to comorbidities, which poses a significant challenge. As a result, the immune system of preterm infants is often low. This literature review aimed to evaluate the effect of oropharyngeal colostrum feeding through subgroup analysis based on complications. Descriptive research was conducted in April-June 2024 using the literature review method with PRISMA guidelines for RCTs. Literature sources were obtained from Pubmed (MEDLINE), Science Direct, Google Scholar, and Cochrane with a publication limit of the last ten years (2014-2023). Of the 1,657 results, 13 articles met the criteria. A total of 1,451 preterm infants were included in the 13 RCT studies. Results showed a lower incidence of late-onset sepsis and Necrotizing Enterocolitis (NEC) in the group that received oropharyngeal colostrum. The administration of oropharyngeal colostrum was shown to have a positive impact on the development and defense of the immune system of preterm infants, reduce health problems such as sepsis and NEC, accelerate the recovery of birth weight, and reduce the incidence of mortality.

Umbilical cord management in newborn resuscitation: a systematic review and meta-analysis.

Evidence supporting the benefits of delayed cord clamping is increasing; however, there is no clear recommendation on cord management during newborn resuscitation. This study aimed to investigate the effects of resuscitation initiated with an intact umbilical cord, hypothesizing it is a safe stabilization procedure that improves neonatal outcomes. Systematic search was conducted in MEDLINE, Embase, CENTRAL, and Web of Science from inception to March 1, 2024. Eligible articles compared neonatal outcomes in newborns receiving initial stabilization steps before and after cord clamping. Twelve studies met our inclusion criteria, with six RCTs included in the quantitative analysis. No statistically significant differences were found in delivery room parameters, in-hospital mortality, or neonatal outcomes between the examined groups. However, intact cord resuscitation group showed higher SpO2 at 5 min after birth compared to cord clamping prior to resuscitation group (MD 6.67%, 95% CI [-1.16%, 14.50%]). There were no significant differences in early complications of prematurity (NEC ≥ stage 2: RR 2.05, 95% CI [0.34, 12.30], IVH: RR 1.25,95% CI [0.77, 2.00]). Intact cord management during resuscitation appears to be a safe intervention; its effect on early complications of prematurity remains unclear. Further high-quality RCTs with larger patient numbers are urgently needed. Initiating resuscitation with an intact umbilical cord appears to be a safe intervention for newborns. No statistically significant differences were found in delivery room parameters, in-hospital mortality, and neonatal outcomes between the examined groups. The utilization of specialized resuscitation trolleys appears to be promising to reduce the risk of intraventricular hemorrhage in preterm infants. Further high-quality RCTs with larger sample sizes are urgently needed to refine recommendations.

Social determinants of health and somatic growth in preterm infants and children with chronic lung disease.

Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with impaired lung function and increased morbidity in childhood. These children display heterogeneous somatic growth patterns which may ultimately impact their risk for later respiratory disease. We aim to understand the relationship between socioenvironmental exposures and growth in this population. A retrospective longitudinal cohort study was conducted using participants (n = 616) enrolled in the Johns Hopkins Outpatient BPD Registry. Growth measurements between 0 and 36 months of age were obtained. Somatic growth measurements, both corrected and uncorrected for gestational age, were converted to z-scores using Center for Disease Control and Prevention normative data. Using a participant's residential zip code, we utilized the 2019 Area Deprivation Index (ADI), the Childhood Opportunity Index (COI) 2.0, and neighborhood food insecurity data from the Maryland Food Bank. Linear regression analysis was performed employing individual socioenvironmental measures as independent variables and growth z-scores as dependent variables in univariate analysis. Univariate analysis was repeated adjusting for gestational age, BPD severity, and the presence of a gastrostomy tube (GT). Of the three measures analyzed, national COI (nCOI) showed a significant association with mean weight z-scores, mean ADI showed some association with mean weight z-scores, and the percentage of a community experiencing food insecurity showed no association with mean weight z-scores. After adjusting for gestational age, BPD severity, and presence of a GT, children living in areas of greater opportunity (higher nCOI values), had significantly lower weight z-scores at 12 months corrected and at 24 and 36 months uncorrected CONCLUSIONS: Our findings suggest that the COI 2.0, a multidimensional measure, captures more facets of an individual's social environment, as compared to the singular nature of a measure of food insecurity. There are several potential explanations for the phenomenon seen, and further understanding of this dynamic is crucial for designing effective interventions and policies to better address inequities in outcomes.

Intravenous lipid emulsions designed to meet preterm infant requirements increase plasma and tissue levels of docosahexaenoic acid and arachidonic acid in mice

Intravenous lipid emulsions used in preterm infants contain insufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) to support normal development, resulting in deficiencies that contribute to complications of prematurity and cognitive delay. We sought to investigate the effects of new intravenous lipid emulsions designed to contain sufficient DHA and ARA to meet preterm needs, while avoiding liver toxicity. Three new lipid emulsions (NLE A-C) were laboratory-generated using high pressure homogenization. First, a long-term experiment evaluated the impact on plasma, liver, and frontal cortex fatty acid composition compared to commercially available lipid emulsions. Lipid emulsions were administered via daily orogastric gavage to four-week-old C57Bl/6J mice. Next, liver toxicity was evaluated in a murine model of parenteral nutrition-induced hepatosteatosis. Mice were provided an ad lib fat-free high carbohydrate diet, with intravenous lipid emulsion administration every other day for 19 days. Administration of commercially available lipid emulsions (soybean oil, mixed oil, or fish oil) resulted in decreased plasma and tissue levels of DHA and/or ARA compared to a chow control. The new lipid emulsions demonstrated a dose-response effect in plasma and tissue concentration of DHA and ARA. NLE C (with an approximately even DHA:ARA ratio), compared to chow, maintained similar DHA (19.2±0.3 vs. 19.3±0.3%, P=1.00) and ARA (10.4±0.2 vs. 9.9±0.2% ARA, P=0.75) content in frontal cortex tissue. All three new lipid emulsions prevented biochemical liver injury and pathologist-assessed hepatosteatosis; soybean oil lipid emulsion and mixed oil lipid emulsion treatment resulted in hepatosteatosis in both experiments. Long-term treatment with the new lipid emulsions in juvenile mice resulted in increased plasma and tissue DHA and/or ARA content compared to currently available lipid emulsions. The new lipid emulsions also prevented hepatosteatosis and biochemical liver injury with enteral and parenteral administration.

Use of interleukin-6 receptor antibodies in the second and third trimester of pregnancy: a retrospective cohort study

A paucity of data exists to inform the use of interleukin (IL)-6 receptor antibodies (anti-IL-6) in pregnancy, particularly in the third trimester. This study aimed to describe outcomes of pregnant women and their neonates exposed to these medications given after the first trimester to treat COVID-19. In this retrospective cohort study, we included all women with COVID-19 who were treated with an anti-IL-6 during pregnancy at two tertiary hospitals in London, UK-Guy's and St Thomas' NHS Foundation Trust and Imperial College Healthcare NHS Trust-between March 1, 2020, and Sept 30, 2022. Maternal demographics, clinical data, administered medications, and maternal and neonatal outcomes were assessed for all included women via a review of medical records and through maternal medicine networks. 25 women received an anti-IL-6 for COVID-19 in pregnancy during the study period and were followed up for 12 months. The group described were a population at high risk, with 24 requiring level two or three critical care. 24 women received tocilizumab and one received sarilumab. All women were prescribed at least three concomitant medications. 16 received the anti-IL-6 in the third trimester of pregnancy and nine during the seocnd trimester. There were no women with maternal neutropenia or pancytopenia; increases in liver enzymes in 16 of 20 women with available alanine aminotransferase data were in keeping with the severity of COVID-19 reported and all three women who developed a secondary bacterial infection mounted a C-reactive protein response. There was one maternal death due to COVID-19. All pregnancies resulted in livebirths and there was one twin pregnancy. 16 of 26 babies were born preterm. One baby died at age 6 months due to complications of extreme prematurity. A transient neonatal cytopenia was described in six of 19 babies in whom a full blood count was performed. Although these findings are likely to be in keeping with prematurity alone, we cannot exclude the possibility that transplacental transfer of anti-IL-6 was contributory. We report further data on the use of anti-IL-6 in the second and third trimesters of pregnancy for the management of COVID-19. When extrapolated, our data can inform shared decision making for individuals who would benefit from the use of anti-IL-6 into the third trimester of pregnancy for management of rheumatological disease. None.

Beyond the Question: Reexamining a Parent's Unusual Request.

Pediatricians sometimes think about medical ethics as the field of determining right and wrong in in answering difficult moral questions that occur at the bedside. But an emphasis on rapidly determining right and wrong when faced with ethical dilemmas can lead clinicians to miss important issues underlying both the question and their approach to answering it. We argue that ethical reflection is not merely a process of getting to the right answer but also a way to probe beyond the original question to better understand the stakeholders' perspectives and priorities. In this Ethics Rounds, we present the case of an infant born at 23 weeks' gestation who initially faced numerous complications of prematurity, but has progressed beyond acute critical illness. His father requests a transition to palliative care at a point this option would not typically be offered. The straightforward response to this father's request is "no." However, we reexamine the father's request from the perspective of a neonatologist, a clinical ethicist, and a conflict mediator. Why is the father making this request? Why do clinicians feel rushed to respond? The authors discuss how elements of surprise and implicit biases can push clinicians to hasty answers. We introduce tools used in clinical ethics consultation and conflict mediation that can facilitate alternative responses from the clinical team. Employing the "Ladder of Inference," ascertaining the "View from Everywhere," and differentiating positions from interests can help clinicians explore the context of ethical questions and lead to more fruitful resolutions.

Transcatheter and Surgical Ductus Arteriosus Closure in Very Low Birth Weight Infants: 2018-2022.

The optimal patent ductus arteriosus (PDA) closure method in very low birth weight (VLBW) infants is uncertain. In 2019, the first transcatheter occlusion device was approved in the United States for infants ≥700 g. We described survival and short-term outcomes among VLBW infants who underwent transcatheter or surgical PDA closure (2018-2022). Vermont Oxford Network members submitted data on infants born from 401 to 1500 g or 22 to 29 weeks' gestational age. Adjusted risk ratios (aRR) for survival, length of stay (LOS), prematurity complications, and discharge support were used to compare transcatheter versus surgical closure. Subgroup analyses were conducted for infants with birth weight ≥700 g and born in 2020-2022. Overall, 6410 of 216 267 infants at 726 hospitals received invasive PDA treatment. Transcatheter closure increased from 29.8% in 2018 to 71.7% in 2022. VLBW infants undergoing transcatheter closure had higher survival (adjusted rate ratio [aRR] 1.03; 1.02-1.04) with similar LOS (aRR 1.00; 0.97-1.03), neonatal complications (aRR 1.00; 0.98-1.01), and receipt of discharge support (aRR 0.94; 0.89-1.01). In subgroup analyses, survival (aRR 1.02; 1.00-1.04) and discharge support (aRR 0.90; 0.81-1.01) were similar between groups, whereas selected neonatal complications (aRR 0.95; 0.93-0.98) and LOS (aRR 0.95; 0.90-0.99) were lower after transcatheter closure. Transcatheter PDA closure in VLBW infants was increasingly used after 2018. Selected short-term outcomes for infants receiving transcatheter closure may be more favorable, compared with surgical, and warrants further clinical investigation.

Association of Acute Kidney Injury with Bronchopulmonary Dysplasia in Preterm Infants.

Bronchopulmonary dysplasia (BPD) is among the most common complications of prematurity and is associated with high morbidity and mortality rates. Acute kidney injury (AKI) is also commonly observed in premature infants and significantly increases morbidity and mortality. Studies have shown that systemic changes in AKI may also trigger lung damage. This study aimed to determine the effects of AKI on the development of BPD in preterm infants with a postconceptional age of ≤32 weeks and/or birth weight of ≤1500 grams. The relationship between demographic features and accompanying perinatal and postnatal morbidities among the patients was investigated. The incidence of BPD in infants with AKI was 52.6% (10 of 19 infants) and 38.3% (61 of 140 infants) in infants without AKI. In infants who developed BPD, the rate of AKI did not vary notably between babies born at ≤28 weeks and those born at >28 weeks [n=9, 17.3% (9 of 52 infants) and n= 1, 5.3%, (1 of 19 infants) respectively] of gestation (p>0.05). AKI was associated with a greater need for resuscitation at birth, a greater need for invasive mechanical ventilation, fewer ventilatorfree days, and a higher incidence of sepsis, patent ductus arteriosus, and necrotizing enterocolitis in premature infants. It was also more frequently associated with fluid-electrolyte imbalance, blood pressure, and hemodynamic disorders in the first postnatal week. The rate of BPD development was higher in infants with AKI, but this disparity was not statistically notable (p>0.05).

Early Prediction of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants using Non-invasive Electrical Cardiometry

Abstract Background Prematurity is a term for the broad category of neonates born at less than 37 weeks' gestation following onset of the last menstrual period. Different degrees of prematurity are defined by gestational age (GA) or birth weight (BW). Prematurity is associated with approximately one- third of all infant deaths. Complications of prematurity are the underlying cause of the higher rate of infant mortality and morbidity in preterm infants compared to full term infants. Objective To identify hemodynamic changes during the first 48hrs in life using non-invasive cardiometry and how these changes can predict which infants would develop clinical and echocardiographic criteria for PDA treatment. Patients and Methods This Prospective cohort study was conducted at tertiary care hospital at the neonatal intensive care units of Ain Shams University, Children’s Hospital from October 2021 till April 2022 and performed on preterm neonates who are less than 35 weeks gestational age and admitted to the NICU of pediatric hospital. Results Hemodynamically-significant PDA group had significantly lower systolic, diastolic blood pressure and mean arterial blood pressure than hemodynamically not significant PDA group at each time of follow up and significantly higher heart rate at (12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 45, 48) hours in patients with hemodynamically-significant PDA. There was statistically significant difference between the two studied groups as regards vital data of Oxygen saturation (SpO2) and UOP which were significantly lower in hemodynamically-significant PDA. Conclusion in our prospective cohort study increased heart rate, decreased mean arterial blood pressure predict a clinically significant PDA requiring treatment. Furthermore, vital data seem to be a good non invasive tools to monitor hemodynamic changes in preterms with hemodynamically significant PDA. However, further studies with a higher number of patients are necessary to ground the outcomes of these preliminary considerations.

Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production

Background and AimsNecrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using small intestinal organoids derived from fetal tissue of a gestational age similar to an extremely preterm infant, this study aims to assess the effect of diet on intestinal epithelial growth and differentiation to elucidate the role nutrition type plays in intestinal development and modifies the risk for NEC. MethodsOrganoids were cultured for 5 days in growth media and 5 days in differentiation media supplemented 1:40 with four different diets: parental milk (PM), donor human milk (DHM), standard formula, or extensively hydrolyzed formula. Images were captured daily and organoids were quantified. Organoids were preserved for RNA sequencing and immunofluorescence staining with Ki67, cleaved caspase 3, and chromogranin-A. Media was saved for cytokine/chemokine and growth factor analysis. ResultsHuman milk supplementation improved growth and differentiation of intestinal organoids generating larger organoids during the growth phase and organoids with longer and wider buds during differentiation compared to formula. Ki67 staining confirmed the proliferative nature of milk-supplemented organoids and chromogranin A staining proved that MM-supplemented organoids induced highest enteroendocrine differentiation. Human milk supplementation also upregulated genes involved in Wnt signaling and fatty acid metabolism pathways and promoted a homeostatic immune landscape, including via increased secretion of TNF-related apoptosis inducing ligand (TRAIL) among other cytokines. Conversely, organoids supplemented with formula had a downregulation of cell-cycle-promoting genes and a more inflammatory immune signature, including a reduced levels of leukemia inhibitory factor (LIF). ConclusionsOur results demonstrate that PM, and to a lesser extent DHM, support robust intestinal epithelial proliferation, differentiation, and homeostatic cytokine production, suggesting a critical role for factors enriched in human milk in intestinal epithelial health.

Time, cause of early neonatal death, and its predictors among neonates admitted to neonatal intensive care units at Bahir Dar City public hospitals, northwest Ethiopia: a prospective follow-up study.

Globally, 75% of neonatal deaths occur during the first weeks of life and more than 43% of deaths are covered by sub-Saharan Africa. Health-related policymakers and decision-makers need to use evidence-based treatments to reduce the time to early neonatal death and associated predictors. However, there are limited studies on median survival time, cause, incidence, and predictors in the study area as well as the country. Therefore, the aim of the present study was to assess time, the cause of early neonatal death, and its predictors among neonates admitted to neonatal intensive care units at Bahir Dar City public hospitals in northwest Ethiopia. An institution-based prospective follow-up study design was conducted among 387 early neonates selected by systematic sampling between 22 February and 22 April 2023. Statistical software, Epi Data version 4.6 and Stata version 14, was used for entry and analysis, respectively. Proportional hazard assumption and model fitness were checked by the Schoenfeld residual test and the Cox-Snell residual test, respectively. Descriptive statistics, the Kaplan-Meier curve, and the life table were used to describe variables. The Cox regression analysis model was fitted to identify the predictors of early neonatal death. During the follow-up time, 59 (15.25%) early neonates died, with an incidence of 31.79 per 1,000 early neonate days [95% confidence interval (CI): 0.024-0.041]. The leading causes of early neonatal death were prematurity complications, asphyxia, sepsis, meconium aspiration syndrome, and necrotizing enterocolitis. The mean survival time was 2.72 days. Being born from a multigravida mother [adjusted hazard ratio (AHR) 4.34; 95% CI: 1.63-11.55], a grand multigravida mother (AHR 3.50; 95% CI: 1.12-10.95), respiratory distress syndrome (AHR 2.60; 95% CI: 1.03-6.58), birth asphyxia (AHR 7.51; 95% CI: 2.30-24.51), a small gestational age (AHR 2.05; 95% CI: 1.08-4.92), and being unable to exclusively breastfeed (AHR 3.46; 95% CI: 1.52-7.88) were significantly associated predictors for time to early neonatal death. The incidence of early neonatal death was high, and the mean survival time was 2.72 days. Gravidity, respiratory distress syndrome, birth asphyxia, and being unable to exclusively breastfeed were identified as predictors of early neonatal death. Therefore, future research will consist of long-term prospective follow-up studies at a multicenter, nationwide level.

Assessment of Neonatal Mortality amongst Sick Neonates in the Special Care Baby Unit of a Tertiary Institution in Orlu, Nigeria

Introduction: Neonatal mortality constitutes more than 41% of under 5 mortality in sub-Saharan Africa, despite advancement in technology and concerted effort aimed at decreasing under-five mortality. This study aims at assessing the risk factors and causes of neonatal mortality among sick infants in the special care baby unit (SCBU); focused at identification of possible areas of improvement in care and result. Methods: A retrospective review of medical records of sick neonates admitted into SCBU of Imo State University Teaching Hospital Orlu. Sociodemographic and clinical characteristics of 214 sick neonates that died was obtained out of the 948 admitted/treated over a five year period (2018-2022). Descriptive statistics was used to summarize data, logistic regression at 95% level of significance was used to determine association between independent variables and neonatal death. Values of p &lt; 0.05 were considered significant. Results: A total of 948 sick neonates were admitted into SCBU, with a neonatal mortality rate of 22.6%. Complications of prematurity 78 (36.7%), severe birth asphyxia 63(29.6%) and neonatal sepsis 31(14.6%) are the leading causes of death with majority of death occurring in the first 24 hours of life 130(60.8%). Low birth weight [OR=2.59 (95% CI 1.84-3.54)], prematurity [OR=2.79 (95% CI 2.03-3.83)] and spontaneous vaginal deliveries [OR=1.85 (95% CI 1.32-2.60)] were positively associated with increased mortality. While Caesarean section as mode of delivery [OR=0.54 (95% CI 0.38-0.76)] and birth weight &gt;2.5-4.0kg [OR=0.46 (95% CI 0.34-0.64)] significantly reduced neonatal mortality. Conclusion: Neonatal mortality rate is still unacceptably high, with complications of prematurity, severe birth asphyxia and neonatal sepsis contributing the highest percentage of poor outcome (death). Low birth weight, prematurity, and spontaneous vaginal deliveries were positively associated with increased mortality. Multidisciplinary measures aimed at reduction of neonatal morbidity and mortality such as improving the utilization of antenatal care services, quality of care at delivery, at the neonatal intensive care unit needs be strengthened.

Electroencephalographic Patterns on Follow-Up Visits in Extremely Premature Infants With Periventricular Leukomalacia: An Observational Study

BackgroundPeriventricular leukomalacia (PVL) is a common brain injury in premature infants, and epilepsy remains a significant complication. One concerning electroencephalographic (EEG) pattern found is developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS). This pattern is associated with persistent neuropsychological and motor deficits, even without a diagnosis of epilepsy. The purpose of this study is to identify the relationships between various PVL grades and EEG patterns in this population on follow-up visits, especially the occurrence of DEE-SWAS pattern on EEG. MethodsThis is a retrospective study of <36 weeks gestational age newborns who were followed in the neurodevelopmental clinic at Corewell Health East/Corewell Health Children's Hospital in Royal Oak, Michigan, between 2020 and 2022. Patients' demographics along with prematurity complications, diagnostic head ultrasound (HUS), and EEG studies were reviewed and graded. EEG studies are usually ordered when seizures were suspected. ResultsA total of 155 newborns met the inclusion criteria. Twenty-six patients had PVL. Nine patients had grade 2 to 3 PVL based on HUS review. EEG was performed on 15 patients with PVL at a mean age of 22 months. More severe PVL grades were significantly associated with worse EEG patterns (P = 0.005). Five patients had DEE-SWAS pattern on EEG, all of whom had grade 2 or 3 PVL. Epilepsy was eventually diagnosed in three infants with PVL. ConclusionsEEG can help identify important abnormal electrographic patterns in premature infants with PVL early in life; this might give a window of opportunity to intervene early and improve long-term developmental outcomes in this population.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.