Mortality In Preterm Infants Research Articles

Probiotics (Bacillus clausii) for Prevention of Late-onset Sepsis in Preterm Infants (<34 weeks): A Randomised Controlled Trial

Introduction: Late-onset Sepsis (LOS) causes significant morbidity and mortality in preterm infants. Probiotics have been suggested to improve the integrity of mucosal barrier by modifying the enteric microflora and suppress the overgrowth and translocation of pathogens in the gut, thus preventing life- threatening infections. Although probiotics have a definite role in prevention of Necrotising Enterocolitis (NEC) in preterm neonates, their effect on prevention of LOS in preterm neonates is still uncertain. Aim: To evaluate the role of probiotics in reducing incidence of LOS in preterm neonates (<34 weeks). Materials and Methods: A double blinded randomised control trial was conducted in a tertiary care Neonatal Intensive Care Unit (NICU) in Karnataka, India between 1st January 2019 to 31st December 2019. Seventy haemodynamically stable preterm neonates, <34 weeks of Gestational Age (GA), were randomised into ‘Probiotic’ and ‘Placebo’ groups. The probiotic group (n=36) was prophylactically administered Bacillus clausii suspension at a dose of 2.5 mL per-oral (0.4×109 spores in 1 mL) BD with breast milk, from initiation of enteral feeds till seven days, discharge/ death/LOS, whichever was earlier. The placebo group (n=34) received breast milk with sterile water 2.5 mL per- oral BD. All the neonates were investigated and managed as per standard hospital protocol. Primary outcome of the study was to find the incidence of LOS. Student’s t-test, Mann-Whitney U test, Chi-square test and Fisher’s exact test were used for statistical analysis. Results: There was no significant difference between the probiotic vs placebo group, with respect to incidence of LOS (11.11% vs 17.64%; (p>0.05)) and duration of hospital stay (10.86±3.19 vs 11.23±2.98 days; (p>0.05)). However, incidence of feed intolerance in the probiotic group (11.11%) was significantly less than that the other (26%) (p<0.05). Conclusion: Probiotics, prophylactically fed enterally, did not reduce the incidence of LOS but provide a promising strategy to prevent feed intolerance in premature neonates.

Evidence on the Benefits of Probiotics for Preterm Infants

This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature infants. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks’ gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis (NEC), mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher NEC, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment time for preterm infants to achieve the health benefits identified.

THE RISKS OF BEING A PRETERM TWIN

Aim: Twins may have additional clinical problems compared to singletons, but there is insufficient information about whether preterm twins (especially those born before 32 weeks of gestation) are at greater risk than singletons. This study aimed to compare morbidity and mortality in twins and singletons born before 32 weeks of gestation. Materials and Methods: Infants with a gestational age (GA) < 32 weeks who were followed in our unit between July 2019 and December 2020 were examined retrospectively. The demographic and clinical characteristics of the infants were recorded and compared between twins and singletons. Results: A total of 770 preterm infants were included in the study, 584 singletons and 186 twins. The singleton group had higher rates of maternal hypertension and small for GA status, while the rate of cesarean delivery was higher in the twins group (p<0.05). Other demographic characteristics and clinical outcomes were similar in the singleton and twin groups (p<0.05). Conclusion: Preterm morbidity and mortality were similar in the twin and singleton groups in this study. This can be attributed to the similar GA and birth weight (BW) in both groups. Therefore, our results suggest that the main determinants of mortality and morbidity in preterm infants are GA and BW rather than twin pregnancy.

POSC217 Hypertension in Pregnancy, Preeclampsia - Analysis of Complications and Cost of Therapy in Ukraine

Hypertension in pregnancy occurs in approximately 8-10% of all women. Hypertension in pregnancy are a serious complication, leading to premature birth, future disability, maternal and infant mortality.

Contribution of Concurrent Comorbidities to Sepsis-Related Mortality in Preterm Infants ≤32 Weeks of Gestation at an Academic Neonatal Intensive Care Network.

This study sought to identify concurrent major comorbidities in preterm infants ≤32 weeks of gestation that may have contributed to sepsis-related mortality following a diagnosis of bacteremia or blood culture-negative sepsis within the neonatal period (≤28 days of life). This is a retrospective chart review of infants ≤32 weeks of gestation who were admitted to a single academic network of multiple neonatal intensive care units between January 1, 2012, and December 31, 2015, to determine the primary cause(s) and timing of death in those diagnosed with bacteremia or blood culture-negative sepsis. Direct comparisons between early-onset sepsis (EOS; ≤72 hours) and late-onset sepsis (LOS; >72 hours) were made. In our study cohort, of 939 total patients with ≤32 weeks of gestation, 182 infants were diagnosed with 198 episodes of sepsis and 7.7% (14/182) died. Mortality rates did not significantly differ between neonates with bacteremia or blood culture-negative sepsis (7/14 each group), and those diagnosed with EOS compared with LOS (6/14 vs. 8/14). Nearly 80% (11/14) of infants were transitioned to comfort care prior to their death secondary to a coinciding diagnosis of severe grade-3 or -4 intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and/or intestinal perforation. Preexisting comorbidities commonly associated with extreme preterm birth contributed to sepsis-related mortality in our patient cohort. · Concurrent comorbidities contribute to, and may artificially inflate, sepsis-related mortality.. · Absence of a consensus definition for neonatal sepsis complicates the investigation of infection.. · Accurate assessment of the incidence of sepsis in very low birth weight infants is vital for future investigations..

The Role of Dietary Fats in the Development and Prevention of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a significant cause of mortality and morbidity in preterm infants. The pathogenesis of NEC is not completely understood; however, intestinal immaturity and excessive immunoreactivity of intestinal mucosa to intraluminal microbes and nutrients appear to have critical roles. Dietary fats are not only the main source of energy for preterm infants, but also exert potent effects on intestinal development, intestinal microbial colonization, immune function, and inflammatory response. Preterm infants have a relatively low capacity to digest and absorb triglyceride fat. Fat may thereby accumulate in the ileum and contribute to the development of NEC by inducing oxidative stress and inflammation. Some fat components, such as long-chain polyunsaturated fatty acids (LC-PUFAs), also exert immunomodulatory roles during the early postnatal period when the immune system is rapidly developing. LC-PUFAs may have the ability to modulate the inflammatory process of NEC, particularly when the balance between n3 and n6 LC-PUFAs derivatives is maintained. Supplementation with n3 LC-PUFAs alone may have limited effect on NEC prevention. In this review, we describe how various fatty acids play different roles in the pathogenesis of NEC in preterm infants.

Continuous glucose monitoring for the prevention of morbidity and mortality in preterm infants.

Preterm infants are susceptible to hyperglycaemia and hypoglycaemia, which may lead to adverse neurodevelopment. The use of continuous glucose monitoring (CGM) devicesmight help in keeping glucose levels in the normal range, and reduce the need for blood sampling. However, the use of CGM might be associated with harms in the preterm infant. To assess the benefits and harms of CGM versus intermittent modalities to measure glycaemia in preterm infants 1. at risk of hypoglycaemia or hyperglycaemia; 2. with proven hypoglycaemia; or 3. with proven hyperglycaemia. We searched CENTRAL (2021, Issue 4); PubMed; Embase; and CINAHL in April2021. We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. We included RCTs and quasi-RCTs comparing the use of CGM versus intermittent modalities to measure glycaemia in preterm infants at risk of hypoglycaemia or hyperglycaemia; with proven hypoglycaemia; or with proven hyperglycaemia. We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) with 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of the evidence. We included four trials enrolling 300infants in our updated review. We included one new study and excluded another previously included study (because the inclusion criteria of the review have been narrowed). Wecomparedthe use ofCGM to intermittent modalities in preterm infantsat risk of hypoglycaemia or hyperglycaemia; however, one of these trialswas analyzedseparately because CGMwas used as a standalone device, without being coupled to a control algorithm as in the other trials.We identified no studies in preterm infants with provenhypoglycaemia orhyperglycaemia. None of the four included trials reported the neurodevelopmental outcome (i.e. the primary outcome of this review), or seizures. The effect of the use of CGM on mortality during hospitalization is uncertain (RR 0.59,95% CI 0.16 to 2.13; RD -0.02, 95% CI -0.07to 0.03; 230 participants; 2studies; very low-certainty evidence). The certaintyof the evidence was very low for all outcomesbecause of limitations in study design, and imprecision of estimates. One studyisongoing (estimated sample size 60 infants) and planned to be completed in 2022. There is insufficient evidence to determine if CGM affects preterm infant mortality or morbidities. We are very uncertain of the safety of CGM and the available management algorithms, and many morbidities remain unreported. Preterminfants at risk of hypoglycaemia or hyperglycaemiawere enrolled in all four included studies. No studies have been conducted in preterm infants with provenhypoglycaemia orhyperglycaemia. Long-term outcomeswerenot reported.Events of necrotizing enterocolitis,reported in the study published in 2021, were lower in the CGM group. However, the effect of CGM on this outcome remains very uncertain. Clinical trials are required to determine the most effective CGM and glycaemic management regimens in preterm infants before larger studies can be performed to assess the efficacy of CGM for reducing mortality, morbidity, and long-term neurodevelopmental impairments.

HYPOXIC BRAIN DAMAGEIN PREMATURE INFANTS (MORPHOLOGICAL STUDY)

The aim of the study was to investigate the morphological signs of hypoxic damage to the central nervous system (CNS) in premature infants. Material and methods: The autopsy reports of 20 premature infants were analyzed. The mean gestational age was 25.9±3.7 weeks, median birth weight was 650 [535;940] grams, and height was 32.6±5.4 cm. We analyzed clinical assessment of the infant's condition at birth, the course of the neonatal period, blood gases and acid-base status, the mode and parameters of mechanical lung ventilation, as well as the oxygenation index (OI) and oxygen saturation index (OSI). Macroscopic and histological signs of damage to various brain structures were studied during pathological anatomical examination. Cortex, parietal subcortex, hippocampus, striatum, cerebellum, foci of hemorrhage were examined. Results: The main causes of mortality in premature infants were severe asphyxia and its sequelae such as combined ischemic and hemorrhagic brain and spinal cord damage (45%). Severe hypoxia was confirmed by laboratory investigations. Critical lactate and acid-base blood values corresponding to decompensated lactate acidosis were registered in newborns including hyperlactatemia up to 9±3.6 mmol/l, pH 7.01±0.21, BE (-12.3) [-30; -7.9] mmol/l. The OI and OSI, indicating severity of hypoxia, were significantly elevated with their medians being 13.7[9.6;19.8] and 31.8[9.6;16.2], respectively. All infants had central nervous system lesions of varying severity with the underlying morphological immaturity. Pericellular and perivascular cerebral edema, unilateral or bilateral subcortical and subependymal hemorrhages, intraventricular hemorrhages of various degrees, up to tamponade and blood leakage into the cisterna magna, and cerebral leukomalacia were the most frequent findings. In all patients, altered neuronal shape and size as well as hyperchromic nuclei were revealed in the subcortical zone. Changes in all cell structures (cytoplasm, nuclei, and nucleoli), as well as satellitosis and neuronophagy, were characteristic. Conclusion: Polymorphic morphological changes were observed in the brain structures of premature infants who died as a result of perinatal hypoxia. Along with signs of morphological immaturity, irreversible changes in cortical and subcortical neurons were found. The magnitude of changes is associated with the severity of perinatal hypoxia and decompensated lactate acidosis.

Pigs in a Blanket: Evaluation of a Novel Device to Support Premature Neonatal Thermal Regulation

Background: 1.47 million preterm births worldwide tragically end in neonatal death (death within 28 days after birth). Contributing to this is the inability for preterm neonates to thermoregulate. In low-resource areas, access to incubators may be non-existent. Kangaroo Mother Care/Skin-to-Skin care (KMC/STS) is one method used in such situations and involves the caregiver strapping the infant to their chest in a kangaroo-like pouch. This method is effective but does not provide warming when the caregiver needs rest, nor does it allow the infants heart and respiratory rate to be monitored reliably. We created a device that aims to solve these issues in a safe, cost effective, and efficient way.
 Methods: Pilot studies were performed with 3 pigs to develop parameters that will validate the devices efficacy in a pre-clinical trial. Newborn pigs from 0-5 days old were used as the model for these initial trials. Test configurations were designed to demonstrate 1) the pigs could not regulate their core temperature without the device and 2) the heating elements of the device provided better support than a simple blanket. The pig’s core temperature was used as the standard measurement across all trials.
 Results: When exposed to an ambient temperature of 20oC, the pigs were not able to regulate their core temperature, which dropped 0.5oC per hour. After reaching hypothermic temperature (below 36.5oC), pigs placed in the warming device returned to a healthy core temperature (38.6oC) over the course of one hour. Pigs in the device with heating off only recovered partially. No pig had any abrasions or burns.
 Conclusion: These studies prove the devices feasibility and have established the parameters needed to design a larger trial. If the device continues to show similar efficacy in the future tests, it could be used to help lower premature infant mortality in low-resource settings.

Impacts of Enriched Human Milk Cells on Fecal Metabolome and Gut Microbiome of Premature Infants with Stage I Necrotizing Enterocolitis: A Pilot Study.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants, occurring more often in formula-fed infants than in breastfed infants. Recent animal studies have shown that cells in fresh breast milk survive in the newborns' digestive tract. However, no clinical studies have been conducted on the effects of human milk cells, and their biological roles in the infants' intestines remain unexplored. Twenty premature infants are enrolled. Cells from fresh milk of their own mothers are enriched and fed to infants with Bell's Stage I NEC once a day for 7 days since the onset of NEC. Fecal samples are collected at enrollment and 2 weeks later. Fecal sphingolipids are observed to be enriched in NEC patients and positively correlated with calprotectin levels. After intervention with enriched human milk cells, inflammation-associated sphingolipids and microbiome profiles are altered and resembled those of the controls. These preliminary findings reveal the potential impacts of enriched human milk cells on premature infants with Bell's Stage I NEC and provide insight into the roles of fecal sphingolipid metabolism in the neonates' intestinal inflammation. However, the limited sample size of the study indicates the need for further investigation.

Conventional study and discussion on premature infants nursing essentials and feeding methods

Abstract Explore the nursing essentials and feeding methods for premature infants and their clinical effects. We selected 90 premature infants born in the neonatology department of our hospital over the past year, implemented the nursing measures combined with several nursing methods and reasonable and effective feeding methods according to the clinical manifestations of the premature infants, and observed the clinical effects. After a period of careful nursing, among these 90 premature infants, 2 infants died unfortunately, 4 infants abandoned the treatment, the remaining premature infants were discharged in good condition in all respects, could autonomously suck milk and reach the minimum daily suction volume, their weights increased to some extent, and their body temperatures could maintain normal under normal room temperature condition. According to the clinical experience, timely implementing the nursing measures combined with several nursing methods and reasonable and effective feeding methods to the premature infants can effectively reduce the morbidity and mortality of premature infants, and improve the survival rate and living quality of the premature infants, so that it is suitable for clinical promotion.

The effect of daily probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight

Background:Necrotizing enterocolitis remains a leading cause of morbidity and mortality in premature infants. The role of prophylactic probiotics in its prevention is unclear. This study evaluates the effect of routine probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight in the neonatal intensive care unit.Methods:This retrospective cohort study compared infants cared for at a single institution before and after implementation of routine probiotic administration (2014– 2018). Babies born after July 2016 received probiotics containing Bifidobacterium and Lactobacillus daily until 35 weeks corrected gestational age. Baseline characteristics, necrotizing enterocolitis incidence and severity, infections, mortality, and length of stay were compared between groups.Results:Of the 665 infants included in the study, 310 received probiotics and 355 did not. The 2 groups did not differ with regard to gestational age, birth anthropometrics, mode of delivery, comorbidities, and type of enteral feed. The incidence of necrotizing enterocolitis (Bell’s stage 2 of 3) was similar between groups (4% v. 5%, p = 0.35), as was its severity (p = 0.10). In addition, there were no significant differences in mortality and length of stay between the groups. Significantly fewer infants receiving probiotics developed infections (27% v. 34%, p = 0.046), with the rate of urinary tract infections having the largest reduction.Conclusion:The routine use of Bifidobacterium and Lactobacillus probiotics in infants with very low birth weight did not significantly affect the incidence and severity of necrotizing enterocolitis. However, the use of probiotics was associated with fewer overall infections.

Nasal continuous positive airway pressure levels for the prevention of morbidity and mortality in preterm infants.

Nasal continuous positive airway pressure levels for the prevention of morbidity and mortality in preterm infants.

Neonatal Outcomes of Premature Infants Born to Women with the Novel Coronavirus (SARS-CoV-2) Infection: A Case Control Study.

Novel coronavirus disease 2019 (COVID-19) is a disease associated with atypical pneumonia caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The first cases of COVID-19 were reported in Wuhan at the end of 2019. Transmission usually occurs via infected droplets and close personal contact; the possibility of vertical transmission is still under debate. This retrospective study aimed to analyze clinical characteristics of premature infants born to mothers with symptomatic COVID-19 disease. This case control study compared the clinical and laboratory data of 20 premature infants born to mothers infected with SARS-CoV-2 with sex and gestational age-matched historical controls. The median gestational age and birth weight in both groups were similar. Respiratory distress developed in 11 (55.5%) infants in study group and 19 (47.5%) infants in control group. Mechanical ventilation and endotracheal surfactant administration rates were similar. Median duration of hospitalization was 8.5 (2-76) days in study group and 12 days in historical controls. Real-time reverse-transcription polymerase chain reaction tests (RT-PCR) of nasopharyngeal swab samples for SARS-CoV-2 were found to be negative twice, in the first 24 hours and later at 24 to 48 hours of life. No neutropenia or thrombocytopenia was detected in the study group. Patent ductus arteriosus, bronchopulmonary dysplasia, and necrotizing enterocolitis rates were similar between groups. No mortality was observed in both groups. To the best of our knowledge, this is one of the few studies evaluating the clinical outcomes of premature infants born to SARS-CoV-2 infected mothers. There was no evidence of vertical transmission of SARS-CoV-2 from symptomatic SARS-CoV-2-infected women to the neonate in our cohort. The neonatal outcomes also seem to be favorable with no mortality in preterm infants. · SARS-CoV-2 pandemic is a challenge for pregnant women.. · Neonatal outcomes of premature infants born to mothers infected with SARS-CoV-2 not well defined.. · SARS-CoV-2 infection seems to have no adverse effect on mortality and morbidity in premature infants..

The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure

BackgroundBronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in BPD, and its relationship with endoplasmic reticulum stress (ERS) mediated type II alveolar epithelial cell (AECII) apoptosis.MethodsA hyperoxia-induced BPD rat model was constructed and the pathologic changes of lung tissues were evaluated by hematoxylin–eosin staining. Cell apoptosis and protein expression were determined by TUNEL assay and Western blotting, respectively. Further reagent kit with specific fluorescent substrate was utilized to measure the activity of 20 s proteasome. Meanwhile, AECII were cultured in vitro and exposed to hyperoxia. AECII apoptosis were measured by flow cytometry. In contrast, MG132 treatment was induced to explore UPP during hyperoxia exposure on AECII apoptosis and ERS sensors expression.ResultsA significant increase in apoptosis and total ubiquitinated proteins expression were observed in BPD rats and AECII culture, and the change of UPP was associated with ERS. In order to confirm the role of UPP in AECII apoptosis of BPD, AECII cells were treated by MG132 with the concentration of 10 μmol/L under hyperoxia exposure. We found that the proteins expression of glucose-regulated protein 78 (GRP-78), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), as well as AECII apoptosis were increased following MG132 treatment. Furthermore, the relatively up-regulated in the levels of total ubiquitinated proteins expression and 20 s proteasome activity were correlated with increased ERS sensors expression.ConclusionsOur findings indicate that UPP may participate in the ERS-induced AECII apoptosis under hyperoxia condition.

Abstract 14028: N-formyl Peptide Receptor 2 Activation via Annexin A1 Up-Regulates Hematoma Resolution After Germinal Matrix Hemorrhage

Introduction: Germinal matrix hemorrhage (GMH) is one of the leading causes of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, which include cerebral palsy, mental retardation, and post-hemorrhagic hydrocephalus. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are key contributors towards post-hemorrhagic hydrocephalus development. n-formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor, has been associated with the activation of scavenger receptor CD36. CD36, a transmembrane glycoprotein, plays an essential role in microglia phagocytic blood clot clearance after GMH. Currently, FPR2’s role in blood clot clearance after hemorrhagic stroke is unknown. Hypothesis: We hypothesize that FPR2 activation by Annexin A1 will enhance hematoma resolution via upregulation of the CD36 signaling pathway, thereby improving short- and long-term neurological outcomes. Methods: Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in male and female P7 rat pups to induce GMH. Annexin A1 and FPR2 Inhibitor (Boc2) were given at 1-hour post-GMH via intranasal administration. Short-term neurobehavior were assessed using negative geotaxis test. Hematoma volume was assessed using hemoglobin assay. Protein expression was assessed using western blots. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests. Nissl staining was conducted on long-term samples to calculate ventricular dilation. Results: We have demonstrated that Annexin A1 treatment decreased hemoglobin content and improved neurobehavior at 72 hours post-ictus. Annexin A1 attenuated post-hemorrhagic hydrocephalus and neurological deficits 4 weeks post-ictus. Lastly, treatment increased FPR2 and CD36 protein expression. Conclusions: This present study demonstrates that FPR2 agonism via Annexin A1 enhances blood clot clearance, thereby improving outcomes after GMH.

Mortality and morbidity in preterm infants with congenital heart disease.

To compare in-hospital mortality and rates of necrotising enterocolitis (NEC), sepsis, IVH and length of invasive respiratory support in preterm infants <36weeks' gestation with congenital heart disease (CHD) to matched preterm infants without CHD in a single London centre over 13-year period. Single-centre retrospective case-control study over the 13-year period from May 2004 to May 2017. Two hundred forty-seven preterm infants with CHD were matched to 494 infants without CHD. Patients with CHD had a significantly increased risk of in-hospital mortality compared to controls (OR 7.39 (95% CI 4.37-12.5); p<0.001). Preterm infants with CHD had a higher risk of NEC (OR 2.42 (95% CI 1.32-4.45); p=0.005), sepsis (OR 1.68 (95% CI 1.23-2.28); p=0.001) and invasive respiratory support ≥28days (OR 2.34 (95% CI 1.19-4.58); p=0.017). Risk of IVH was lower in preterm infants with CHD (OR 0.22 (95% CI 0.11-0.42); p=0.0001). Preterm birth with CHD is associated with a higher risk of in-hospital mortality, NEC, sepsis and prolonged invasive respiratory support, but a lower risk of IVH compared to matched controls. In-hospital mortality remains high in moderate-to-late preterm infants with CHD.

Identification and design of a multi-epitope subunit vaccine against the opportunistic pathogen Staphylococcus epidermidis: An immunoinformatics approach

Staphylococcus epidermidis is one of the major causes of nosocomial infections around the globe that leads to a high rate of mortality and morbidity in both immunocompromised patients and preterm infants. Despite the alarming increase in multi-drug resistance, no promising vaccines are readily available against this pathogen. Thus, the present study is focused on designing a multi-epitope subunit vaccine using five antigenic proteins of S. epidermidis through an immunoinformatics approach. The final vaccine comprised B-cell, HTL, and CTL binding epitopes followed by Lipoprotein LprA adjuvant added at N-terminal to augment the immunogenicity. Physicochemical assessment of the vaccine reveals the antigenic and non-allergic nature. The vaccine structure was designed, refined, validated, and disulfide engineered to obtain the best model. Molecular docking and dynamics simulation of the proposed vaccine with toll-like receptors (TLR-2 and TLR-4) showed strong and stable interactions. MM-PBSA analysis was implemented as an efficient tool to determine the intermolecular binding free energies of the system. The vaccine was subjected to immune simulation to predict its immunogenic profile. In silico cloning suggested that the proposed vaccine can be expressed efficiently in E.coli. Furthermore, in vivo animal experiment is needed to determine the effectiveness of the in silico designed vaccine. Communicated by Ramaswamy H. Sarma

Antenatal dexamethasone reduces mortality in preterm infants in low-resource countries.

Oladapo, OT, et al. (2020). ‘Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries’ The New England Journal of Medicine. PMID: 33095526. Antenatal corticosteroids (ANC) improve survival and decrease morbidity in premature infants.1, 2 However, their use has been controversial in low-resource countries (LRC) due to the ACT study, which questioned the safety and efficacy of ANC.3. The ACT study had limitations; it did not collect or process the data on the use of co-interventions affecting outcomes, thus confounding the results. They used birthweight percentiles instead of gestational age to define the target subgroup, thus misclassifying some term infants as preterm. To answer the question better, Oladapo et al., the WHO ACTION collaborators, designed a multi-country randomised control blinded study. This study found a significant reduction in neonatal death and stillbirth and death with the use of antenatal dexamethasone without increasing maternal morbidity or mortality. The researchers adhered to stricter inclusion and exclusion criteria. They obtained accurate gestational age ultrasound dating, enrolled women who were at risk of preterm birth within 48 h and delivered in hospitals equipped with essential standard resources to support preterm newborns. The discrepant results of the WHO ACTION and ACT trials highlight an important learning point for high-resource countries (HRC). The WHO ACTION trial assessed ANC efficacy in highly selected populations managed in settings equipped with standard resources, whilst the ACT trial evaluated the consequence of massive implementation of ANC in uncontrolled situations. Indiscriminate administration of interventions such as ANC might be harmful; thus, patients in LRC must be carefully assessed for eligibility before receiving interventions with known benefits in HRC. Previous studies show benefit for premature newborns exposed to ANC in LRC,4, 5 but these studies are not placebo-controlled. Strengths of this study include the size, randomisation, blinding and multinational. The study was designed to identify and recruit patients and foetuses who would potentially receive the most benefit from ANC. Reporting data with and without the use of multiple imputations and using the false-discovery-rate approach amplified the significance of findings. Additionally, because the primary outcome in this study was neonatal death, not respiratory distress syndrome or other morbidities, the crucial impact of ANC on reducing preterm mortality in LRC is apparent. One weakness is the clinical management of the mother-baby dyad varied depending on local resources and guidelines. This may alter outcomes depending on the training and protocols of a particular centre. Data were analysed with and without stratifying for study site. Despite this, there was still benefit to preterm newborns exposed to antenatal dexamethasone demonstrating its favourable impact on mortality and morbidity, which is important as it will be used in many LRC. Prematurity is the leading cause of death in children under age 5 worldwide.6 Low-cost, high-impact preventive interventions are needed to help reduce this burden. This study reaffirms that dexamethasone is safe, efficacious and cost-saving for LRC to reduce their hospital-based stillbirth or neonatal mortality in premature infants. Dexamethasone has the potential to make a major impact on the survival of premature newborns in LRC when used with the appropriate clinical protocolised approach. None. https://ebneo.org/category/reviews/.

Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats

Antenatal corticosteroid therapy is used to reduce neonatal mortality in preterm infants but it is currently unknown whether this intervention affects lipid metabolism at the peripartum. This study aimed to evaluate if antenatal corticosteroid therapy in pregnant rats and women affects lipid metabolism during early lactation. We evaluated women at risk of preterm delivery that received corticosteroid therapy (CASE) and women that were not exposed to corticosteroid and were not at risk of preterm delivery (CONTROL). Samples were collected to measure serum and milk triacylglycerol (TAG) three days after delivery. Rats were treated with dexamethasone (DEX) between the 15th and the 20th days of pregnancy. Samples were collected at different days after delivery (L3, L8 and L14). TAG was measured in serum, liver and mammary gland (MG). TAG appearance rates were measured after tyloxapol injection and gavage with olive oil. We also evaluated the expression of key genes related to lipid metabolism in the liver and in the MG and hepatic phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). CASE volunteers delivered earlier than CONTROL but presented unaltered milk and serum TAG concentrations. Early lactating DEX rats exhibited increased TAG in serum, MG and milk. No changes in CD36 and LPL were detected in the MG and liver. Early lactating DEX rats displayed increased TAG appearance rate and reduced hepatic AMPK/ACC phosphorylation. Our data revealed that antenatal corticosteroid therapy reduces hepatic AMPK/ACC phosphorylation during early lactation that reflects in increased TAG concentration in serum, MG and milk.