Neonatal Disorders Research Articles

Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia.

Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, in the treatment of PH. Methods: Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy. A control group of pregnant rats received saline instead. The resulting offspring were divided into the following groups: Group 1-intact rats; Group 2-rat pups subjected to prenatal hypoxia (PH) and treated daily with physiological saline; and Groups 3 to 6-rat pups exposed to prenatal hypoxia and treated daily from the 1st to the 30th day after birth. Levels of sEPCR, Tie2 tyrosine kinase, VEGF-B, SOD1/Cu-Zn SOD, GPX4, and GPX1 in the heart's cytosolic homogenate were assessed using ELISA. The expression of VEGF and VEGF-B mRNA was analyzed via real-time polymerase chain reaction, and the nuclear area of myocardial microvessel endothelial cells was evaluated morphometrically. Results: We have shown that only two representatives of this group-Angiolin and Thiotriazoline-are able to exert full effect on the indices of endothelial dysfunction after PH to decrease sEPCR, increase Tie-2, VEGF-B and VEGF-B mRNA, Cu/ZnSOD, and GPX in myocardial cytosol, and increase the area of endotheliocyte nuclei in 1- and 2-month-old rats in comparison with the control. Conclusions: Our results experimentally substantiate the necessity of early postnatal cardio- and endothelioprotection using NO modulators, taking into account the role of NO-dependent mechanisms in the pathogenesis of cardiovascular system disorders in neonates after PH.

First-trimester metabolic profiling of gestational diabetes mellitus: insights into early-onset and late-onset cases compared with healthy controls

IntroductionGestational diabetes mellitus (GDM) is a global health concern with significant short and long-term complications for both mother and baby. Early prediction of GDM, particularly late-onset, is crucial for implementing timely interventions to mitigate adverse outcomes. In this study, we conducted a comprehensive metabolomic analysis to explore potential biomarkers for early GDM prediction.MethodsPlasma samples were collected during the first trimester from 60 women: 20 with early-onset GDM, 20 with late-onset GDM, and 20 with normal glucose tolerance. Using advanced analytical techniques, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS), we profiled over 150 lipid species and central carbon metabolism intermediates.ResultsSignificant metabolic alterations were observed in both early- and late-onset GDM groups compared to healthy controls, with a specific focus on glycerolipids, fatty acids, and glucose metabolism. Key findings revealed a 4.0-fold increase in TG(44:0), TG(46:0), TG(46:1) with p-values <0.001 and TG(46:2) with 4.7-fold increase and p-value <0.0001 as well as changes in several phospholipids as PC(38:3), PC(40:4) with 1.4-fold increase, p < 0.001 and PE(34:1), PE(34:2) and PE(36:2) with 1.5-fold change, p < 0.001 in late-onset GDM.DiscussionObserved lipid changes highlight disruptions in energy metabolism and inflammatory pathways. It is suggested that lipid profiles with distinct fatty acid chain lengths and degrees of unsaturation can serve as early biomarkers of GDM risk. These findings underline the importance of integrating metabolomic insights with clinical data to develop predictive models for GDM. Such models could enable early risk stratification, allowing for timely dietary, lifestyle, or medical interventions aimed at optimizing glucose regulation and preventing complications such as preeclampsia, macrosomia, and neonatal metabolic disorders. By focusing on metabolic disruptions evident in the first trimester, this approach addresses a critical window for improving maternal and fetal outcomes. Our study demonstrates the value of metabolomics in understanding the metabolic perturbations associated with GDM. Future research is needed to validate these biomarkers in larger cohorts and assess their integration into clinical workflows for personalized pregnancy care.

Digenic Inheritance Mode in Congenital Hypothyroidism due to Thyroid Dysgenesis: HYPOTYGEN translational cohort study.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and is chiefly caused by thyroid dysgenesis (CHTD). The inheritance mode of the disease remains complex. Gain insight into the inheritance mode of CHTD. Prospective multicenter nationwide translational study in France. We prospectively included 514 patients with CH diagnosed through systematic newborn screening (HYPOTYGEN cohort). We focused on CHTD cases and studied their clinical and molecular phenotypes. Targeted next-generation sequencing using a 78-gene panel, including genes involved in thyroid development, function, transport, metabolism and action of thyroid hormones. Statistical analysis, familial segregation and in vitro functional studies focusing on cell migration have been performed. We analyzed the clinical phenotypes of 458 patients with CH. Cardiac and renal malformations were present in 7.7%(14/182) and 3.9%(7/178) of patients, respectively. Genetic analysis was performed on 292 patients of the cohort, based on criteria for ethnicity and availability of DNA samples for index cases and their parents. A disease-causing mutation in one of the 10 known genes for CHTD was identified in 20/292 (6.8%) patients. We found a digenic mode of inheritance in 16 (5.5%) patients, each carrying a variant in a thyroid development gene and a variant in the H2O2 generation complex gene DUOX2/DUOXA2. Familial segregation analysis and in vitro functional studies supported this model. This work expands our understanding of the molecular causes of CHTD by demonstrating that digenic inheritance can be implicated, with deleterious variants in thyroid development and DUOX2/DUOXA2 genes. The complexity of this model implies a revision of the genetic landscape of CHTD and specific clinical care of patients during long-term follow-up. NCT01916018.

Ubiquitin-like modifier-activating enzyme 1 interacts with Zika virus NS5 and promotes viral replication in the infected cell.

Translation errors, impaired folding or environmental stressors (e.g. infection) can all lead to an increase in the presence of misfolded proteins. These activate cellular responses to their removal, including intracellular protein degradation activities. Protein ubiquitylation is involved in two major degradation pathways, the ubiquitin-proteasome system and selective autophagy. In humans, the ubiquitin-like modifier-activating enzyme 1 (UBA1) is the primary E1 enzyme in the ubiquitin conjugation cascade. Viruses have evolved to exploit protein degradation pathways to complete their infection cycles. Zika virus (ZIKV) is an emerging orthoflavivirus causing serious neurologic disorders in neonates (congenital microcephaly) and adults (Guillain-Barré syndrome). Non-structural protein 5 (NS5), the largest and most conserved protein in the orthoflaviviruses, catalyses the synthesis and capping of new viral genomes. In addition to viral RNA replication in the cytoplasm, ZIKV NS5 is translocated into the nucleus to interfere with host antiviral responses. Here, we demonstrate that ZIKV NS5 co-immunoprecipitates with cellular UBA1. Immunofluorescence assays suggest that this interaction takes place primarily in the nucleus of an infected cell, although colocalization of both proteins is also detected in the cytosol. RNA interference-mediated depletion of UBA1 leads to reduced virus titres in the infected cells, while transient overexpression of UBA1 favours faster replication kinetics, with higher virus titres and protein levels detected. Moreover, UBA1-targeting drugs cause significant drops in virus infectivity. These results support a proviral role for UBA1 during ZIKV infection and encourage the potential use of inhibitors against this enzyme or its NS5-interacting epitopes as potential therapeutic targets.

Estimates of resource use in the public-sector health-care system and the effect of strengthening health-care services in Malawi during 2015–19: a modelling study (Thanzi La Onse)

In all health-care systems, decisions need to be made regarding allocation of available resources. Evidence is needed for these decisions, especially in low-income countries. We aimed to estimate how health-care resources provided by the public sector were used in Malawi during 2015-19 and to estimate the effects of strengthening health-care services. For this modelling study, we used the Thanzi La Onse model, an individual-based simulation model. The scope of the model was health care provided by the public sector in Malawi during 2015-19. Health-care services were delivered during health-care system interaction (HSI) events, which we characterised as occurring at a particular facility level and requiring a particular number of appointments. We developed mechanistic models for the causes of death and disability that were estimated to account for approximately 81% of deaths and approximately 72% of disability-adjusted life-years (DALYs) in Malawi during 2015-19, according to the Global Burden of Disease (GBD) estimates; we computed DALYs incurred in the population as the sum of years of life lost and years lived with disability. The disease models could interact with one another and with the underlying properties of each person. Each person in the Thanzi La Onse model had specific properties (eg, sex, district of residence, wealth percentile, smoking status, and BMI, among others), for which we measured distribution and evolution over time using demographic and health survey data. We also estimated the effect of different types of health-care system improvement. We estimated that the public-sector health-care system in Malawi averted 41·2 million DALYs (95% UI 38·6-43·8) during 2015-19, approximately half of the 84·3 million DALYs (81·5-86·9) that the population would otherwise have incurred. DALYs averted were heavily skewed to children aged 0-4 years due to services averting DALYs that would be caused by acute lower respiratory tract infection, HIV or AIDS, malaria, or neonatal disorders. DALYs averted among adults were mostly attributed to HIV or AIDS and tuberculosis. Under a scenario whereby each appointment took the time expected and health-care workers did not work for longer than contracted, the health-care system in Malawi during 2015-19 would have averted only 19·1 million DALYs (95% UI 17·1-22·4), suggesting that approximately 21·3 million DALYS (20·0-23·6) of total effect were derived through overwork of health-care workers. If people becoming ill immediately accessed care, all referrals were successfully completed, diagnostic accuracy of health-care workers was as good as possible, and consumables (ie, medicines) were always available, 28·2% (95% UI 25·7-30·9) more DALYS (ie, 12·2 million DALYs [95% UI 10·9-13·8]) could be averted. The health-care system in Malawi provides substantial health gains with scarce resources. Strengthening interventions could potentially increase these gains, so should be a priority for investigation and investment. An individual-based simulation model of health-care service delivery is valuable for health-care system planning and strengthening. The Wellcome Trust, UK Research and Innovation, the UK Medical Research Council, and Community Jameel.

Genetics of biliary atresia: Approaches, pathological insights and challenges.

Biliary atresia (BA) is a severe neonatal cholestatic disorder marked by fibro-obliteration of the extrahepatic and intrahepatic bile ducts. It is the most common cause of pediatric end-stage liver disease and the leading indication for liver transplantation in children. There is significant heterogeneity in the etiology, involving various genetic and environmental factors such as viral infection, immune dysregulation and genetic predisposition to defective hepatobiliary development. In this review, we discuss the strategies to uncover the genetic factors underlying BA and highlight their associated molecular and pathological mechanisms, as well as the challenges faced in this area of research.

A Case Study on Neurological Outcome in Persistent Neonatal Hypoglycemia in Upper Middle-Income Country

In Indonesia, comprehensive management and monitoring of persistent neonatal hypoglycemia, is rarely reported. Despite the fact that there are studies highlighting the risk of neurodevelopmental disorders in neonates with hypoglycemia, there seems to be limited comprehensive case reports detailing both the early diagnosis and the long-term growth and development monitoring in these neonates. A unique case report of a 10-day-old male baby, born at a term weeks gestation via caesarean section, diagnosed with persistent hypoglycemia and suspect of hyperinsulinemia is presented in this study. At birth, the neonate exhibited hypoglycemia with a blood glucose level of 25 mg/dL, accompanied by a one-minute seizure characterized by upward gaze and stiffening of the extremities. The neonate cried after seizure and there was no loss of consciousness and was admitted to the NICU due to worsening respiratory distress. Based on the thoracic X-ray examination, he was diagnosed with transient tachypnea of newborn (TTN). Blood glucose levels were monitored every four hours, and tests for cortisol, thyroid and growth hormone and routine urinalysis were planned. Total parenteral nutrition (TPN) were given with intravenous antibiotics. At 6months of age, the infant was diagnosed with intellectual disability by the growth and development social pediatric unit. At 7 months, the infant began undergoing physiotherapy. This case was followed for 7 months in total and the findings highlight the challenges in managing neonatal persistent hypoglycemia and the potential long-term developmental implications in neonates with early-life hypoglycemia, emphasizing the need for continual growth and development monitoring.

Impact of COVID-19 on Neonatal Outcomes : A Comprehensive Systematic Review

Background: Throughout the COVID-19 pandemic, pregnant women have been classified as a vulnerable population. However, the epidemiological evidence for infection risk during pregnancy on maternal and neonatal outcomes, such as preterm birth, hypertensive disorders in pregnancy, and postpartum hemorrhage of mothers and prematurity, respiratory and neurodevelopmental disorders of neonates, is still undetermined. The aim: The aim of this study to show about the impact of COVID-19 on neonatal outcomes. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. This search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SagePub, and Sciencedirect were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: The intrauterine transmission of SARS-CoV-2 was possible, although rare, with early postnatal transmission through direct contact with infected persons occurring more frequently.

Pulmonary MRI in Newborns and Children.

Lung MRI is an important tool in the assessment and monitoring of pediatric and neonatal lung disorders. MRI can provide both similar and complementary image contrast to computed tomography for imaging the lung macrostructure, and beyond this, a number of techniques have been developed for imaging the key functions of the lungs, namely ventilation, perfusion, and gas exchange, through the use of free-breathing proton and hyperpolarized gas MRI. Here, we review the state-of-the-art in MRI methods that have found utility in pediatric and neonatal lung imaging, the structural and physiological information that can be gleaned from such images, and strategies that have been developed to deal with respiratory (and cardiac) motion, and other technological challenges. The application of lung MRI in neonatal and pediatric lung conditions, in particular bronchopulmonary dysplasia, cystic fibrosis, and asthma, is reviewed, highlighting our collective experiences in the clinical translation of these methods and technology, and the key current and future potential avenues for clinical utility of this methodology. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

The impacts of the COVID-19 pandemic on the burden of maternal and neonatal disorders: A counterfactual modeling based on the global burden of disease study (2021).

During the COVID-19 pandemic, global health systems faced unprecedented challenges, as well as in maternal and neonatal health, thus this study aims to clarify the impacts of COVID-19 on maternal and neonatal disorders (MNDs), regional variations, and the role of economic support. We have developed a counterfactual model integrating Autoregressive Integrated Moving Average and Long Short-Term Memory models to forecast the burden of MNDs from 2020 To et al., 2021, which was compared with the actual burden to quantify the specific impact of the COVID-19 pandemic on MNDs. During the COVID-19 pandemic, the burden of MNDs surpassed predictions, particularly in Russia, where incidence was about 10.20% higher than expected. In Tokelau, neonatal disorders increased by 412.35% in DALYs. The incidence of maternal disorders in Russia has increased by 12.00%, with maternal abortion and miscarriage increasing by 23.08%. The incidence and prevalence of maternal hypertensive disorders, the incidence of hemolytic disease and other neonatal jaundice and neonatal preterm birth accelerated. In low and low-middle Socio-demographic Index countries, mortality rates from maternal abortion and miscarriage, maternal obstructed labor and uterine rupture, neonatal encephalopathy due to birth asphyxia and trauma significantly increased. Similarly, countries with a low economic support index saw higher burden for these conditions, with the burden decreasing as economic support improved. The COVID-19 pandemic has disproportionately increased the burden of MNDs in countries with lower economic support, highlighting the critical need for strengthened global economic support, particularly in low- and middle-income countries.

Cure of Congenital Purpura Fulminans via Expression of Engineered Protein C Through Neonatal Genome Editing in Mice.

PC (protein C) is a plasma anticoagulant encoded by PROC; mutation in both PROC alleles results in neonatal purpura fulminans-a fatal systemic thrombotic disorder. In the present study, we aimed to develop a genome editing treatment to cure congenital PC deficiency. We generated an engineered APC (activated PC) to insert a furin-cleaving peptide sequence between light and heavy chains. The engineered PC was expressed in the liver of mice using an adeno-associated virus vector or CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9)-mediated genome editing using an adeno-associated virus vector in vivo. The engineered PC could be released in its activated form and significantly prolonged the plasma coagulation time independent of the cofactor activity of PS (protein S) in vitro. The adeno-associated virus vector-mediated expression of the engineered PC, but not wild-type PC, prolonged coagulation time owing to the inhibition of activated coagulation FV (factor V) in a dose-dependent manner and abolished pathological thrombus formation in vivo in C57BL/6J mice. The insertion of EGFP (enhanced green fluorescent protein) sequence conjugated with self-cleaving peptide sequence at Alb locus via neonatal in vivo genome editing using adeno-associated virus vector resulted in the expression of EGFP in 7% of liver cells, mainly via homology-directed repair, in mice. Finally, we succeeded in improving the survival of PC-deficient mice by expressing the engineered PC via neonatal genome editing in vivo. These results suggest that the expression of engineered PC via neonatal genome editing is a potential cure for severe congenital PC deficiency.

PD-L1 expression and characterization of its carrier macrophages in placentas with acute and specifically post-SARS-CoV-2 infection.

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, uncertainties about the virus and its dangers during pregnancy caused great uncertainty and fear, especially among pregnant women. New data suggest an increased risk of obstetric complications, including maternal complications, preterm labor, intrauterine growth restriction, hypertensive disorders, stillbirths, gestational diabetes and risk, of neonatal developmental disorders. In addition, preeclampsia (PE)-like syndromes were also induced by severe COVID-19 infection. Therefore, the aim of this study was to investigate the expression of CD68 and CD163 and PD-L1 on placental tissues from acute covid patients, patients who survived a covid-19 infection and normal term controls that are known to be dysregulated in preeclampsia cases.We examined a total of 60 placentas from women that had given birth to female or male offspring in the University Hospital Augsburg. We investigated ten acute COVID-19 females, ten acute COVID-19 males, ten post-COVID-19 females, ten post-COVID-19 males, ten female term controls, and ten male term controls. Immunohistochemical staining against CD68, CD163, and PD-L1 was performed and the expression of the markers was evaluated with an immunoreactive score (percentage score). Identity of CD163- or PD-L1 expressing cells was analyzed by double immune fluorescence analyses. In opposite to PE, CD163 positive maternal macrophages are significantly upregulated in the decidua of male acute COVID-19 placentas. PD-L1 is significantly upregulated on male acute- and post-COVID-19 decidual immune cells and on male post-COVID-19 extravillous trophoblast cells. Surprisingly the observed effects are related to the fetal gender as they were not observed in female offsprings. Further investigation is necessary to analyze especially the imprinting effect of this infection.

Factors Affecting Successful Completion of the Neonatal Hearing Screening Test (Otoacoustic Emission Test) in the First Attempt in Healthy Term Newborns Prior to Discharge from the Hospital

Introduction: Hearing loss is one of the most prevalent congenital disorders in neonates. Infants with untreated hearing loss usually struggle greatly in terms of emotional, social, and verbal development. Early identification via neonatal hearing tests and preventive strategies have been advised in order to lessen the negative impacts of congenital hearing loss on the infant's life.Objectives: To assess the factors affecting the success of performing an otoacoustic emissions(OAE) test in stable term neonates.Methodology: A descriptive type of cross sectional study was carried out at Sri Jayewardenepura Hospital from 01/06/20222 to 01/09/2022. All healthy term neonates were included, and preterm and neonates associated with other medical conditions were excluded. Results: Out of 455 neonates, 422 (92.7%) were able to successfully complete the OAE test. 85.1% (n = 365) had a bedside sound level of 60dB-65 with a mean value of 61.62 dB at the time of OAE testing (p = 0.030). 134 (29.5%) neonates were breastfed (p = 0.281) and the majority of the newborns (n=367, 80.7%) were sleeping (p = 0.460) during the OAE test. Considering the factors affecting the successful outcome of the OAE testing, there is a statistically significant association with crying (p<0.001,OR(95% CI) = 0.026 (0.010- 0.068)), struggling (p = 0.003), OR (95% CI) = 0.194 (0.58 - 0.647), debris in the external ear (p<0.001) with OR (95% CI) = 0.019 (0.005 - 0.75), throat secretions (p <0.001), and OR (95% CI) of 0. 122 (0.034 - 0.442), external ear abnormalities (p = 0.005), and OR (95% CI) = 0.169(0.041 - 0.686).Conclusion: Crying, struggling, debris in the external ear, throat secretions, external ear abnormalities, and the sound level (dB) at the time of the test are the factors that are statistically significantly associated with the success of the OAE test. Thus, to achieve a successful OAE test, it is pivotal to keep the baby in a calm state with an optimal bedside sound level.

Deep learning approaches for automated classification of neonatal lung ultrasound with assessment of human-to-AI interrater agreement

Neonatal respiratory disorders pose significant challenges in clinical settings, often requiring rapid and accurate diagnostic solutions for effective management. Lung ultrasound (LUS) has emerged as a promising tool to evaluate respiratory conditions in neonates. This evaluation is mainly based on the interpretation of visual patterns (horizontal artifacts, vertical artifacts, and consolidations). Automated interpretation of these patterns can assist clinicians in their evaluations. However, developing AI-based solutions for this purpose is challenging, primarily due to the lack of annotated data and inherent subjectivity in expert interpretations. This study aims to propose an automated solution for the reliable interpretation of patterns in LUS videos of newborns. We employed two distinct strategies. The first strategy is a frame-to-video-level approach that computes frame-level predictions from deep learning (DL) models trained from scratch (F2V-TS) along with fine-tuning pre-trained models (F2V-FT) followed by aggregation of those predictions for video-level evaluation. The second strategy is a direct video classification approach (DV) for evaluating LUS data. To evaluate our methods, we used LUS data from 34 neonatal patients comprising of 70 exams with annotations provided by three expert human operators (3HOs). Results show that within the frame-to-video-level approach, F2V-FT achieved the best performance with an accuracy of 77% showing moderate agreement with the 3HOs. while the direct video classification approach resulted in an accuracy of 72%, showing substantial agreement with the 3HOs, our proposed study lays down the foundation for reliable AI-based solutions for newborn LUS data evaluation.

LC-MS-Based Simultaneous Determination of Biomarkers in Dried Urine Spots for the Detection of Cofactor-Dependent Metabolic Disorders in Neonates.

Deficiency of cofactors for various enzymes can lead to inborn errors of metabolism. These conditions frequently occur as seizures, which lead to permanent brain damage. Newborn screening for biomarkers associated with these disorders can help in early detection and treatment. Our objective was to establish a liquid chromatography mass spectrometry technique for quantifying biomarkers in dried urine spots to detect specific vitamin-responsive inborn errors metabolism. Biomarkers were extracted from dried urine spots using a methanol:0.1% v/v formic acid solution (75:25) containing an internal standard mixture. Separation was achieved using a Luna PFP column (150mm×4.6mm, 3µm) under gradient elution conditions. The LC-MS technique was validated as per ICH M10 guidelines. Urine samples from healthy newborns in Udupi district, South India, were analyzed to establish reference values for these biomarkers. The method demonstrated excellent linearity (R2>0.99) with low limits of quantification: 0.1µg/mL for leucine, isoleucine, valine, proline, hydroxyproline, methylmalonic acid, and 3-hydroxyisovaleric acid; 0.01µg/mL for pipecolic acid and α-aminoadipic semialdehyde; and 0.03µg/mL for piperideine-6-carboxylate. Interconvertibility between urine and dried urine spot assays was observed from the results of the regression and Bland-Altman analyses. Reference intervals for these biomarkers in the Udupi neonatal population were established using the validated dried urine spot method.

Time to recovery from necrotizing enterocolitis and its predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar, Ethiopia: A retrospective follow up study, 2022.

Necrotizing enterocolitis is one of the most common, life-threatening, gastrointestinal disorders in neonates. The recovery time for neonates with NEC varies depending on disease severity, prompt diagnosis, and effective treatment. Therefore, this study was intended to assess the time to recover from necrotizing enterocolitis and its' predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar City, Ethiopia. An institution-based retrospective follow-up study design was employed. A sample of 361 medical records of neonates with necrotizing enterocolitis was selected using systematic random sampling. Diagnosis of NEC in this study required clinical, laboratory and radiographic findings. The survival function was described using Kaplan Meier survival curve and log-rank test. Bivariate and multivariate Cox-proportional hazard (Cox-PH) regression models were used for analysis. The median recovery time from necrotizing enterocolitis for neonates in the neonatal intensive care unit was 12 days. The multivariable Cox-PH model showed that neonates classified as Stage III NEC (AHR: 0.42, 95% CI = 0.23-0.77) and those exposed to perinatal asphyxia (AHR: 0.51, 95% CI: 0.35-0.74) had a negative impact on NEC recovery time. However, neonates with a birth weight of 1500-2499gm (AHR: 1.65, 95% CI: 1.05-2.58) and a platelet count greater than 150,000 (AHR: 1.75, 95% CI: 1.24-2.48) had a positive effect on NEC recovery time. The recovery time for neonates in the neonatal intensive care unit with necrotizing enterocolitis was longer. Comorbidities and advanced stage of NEC were associated with prolonged recovery time from NEC. However, neonates with better platelet count and birth weight greater than 1500mg had shorter recovery time from NEC.

Effect of different CPAP levels on ultrasound-assessed lung aeration and gas exchange in neonates

BackgroundRespiratory distress syndrome (RDS) and transient tachypnoea (TTN) are the two commonest neonatal respiratory disorders. The optimal continuous positive airway pressure (CPAP) to treat them is unknown. We aim to clarify the effect of different CPAP levels on lung aeration and gas exchange in patients with RDS and TTN.MethodsProspective, observational, pragmatic, physiological cohort study. CPAP was sequentially increased from 4 to 6 and 8 cmH2O and backwards, with interposed wash-out periods. Lung aeration was assessed with a validated neonatal lung ultrasound score. Gas exchange was non-invasively evaluated with transcutaneous monitoring. Ultrasound score and PtcO2/FiO2 ratio were the co-primary outcomes. PtcCO2 and other oxygenation metrics were the secondary outcomes.Results30 neonates with RDS and 30 with TTN were studied. Each CPAP increment significantly (overall always p < 0.001) improved both lung aeration and oxygenation, but the increase from 6 to 8 cmH2O achieved a small absolute benefit. In RDS patients, the absolute improvements were small and the diagnosis of TTN was significantly associated with greater improvement of lung aeration (β= -1.4 (95%CI: -2.4; -0.3), p = 0.01) and oxygenation (β = 39.6 (95%CI: 4.1; 75.1), p = 0.029). Aeration improved in 16 (53.3%) and 27 (90%) patients in the RDS and TTN groups, respectively (p = 0.034). Lung aeration showed significant hysteresis in TTN patients. Secondary outcomes gave similar results.ConclusionsIncreasing CPAP from 4 to 8 cmH2O improves ultrasound-assessed lung aeration and oxygenation in RDS and TTN. The absolute improvements are small when CPAP is beyond 6 cmH2O or for RDS patients.

The Assessment and Management of Biliary Atresia in Hawai'i, 2009-2023.

Although biliary atresia (BA) is a rare neonatal disorder, it remains the leading cause of pediatric end-stage liver disease. Early diagnosis of BA and treatment with the Kasai procedure can significantly reduce the need for pediatric liver transplant. Current data suggests that performing the Kasai procedure at 30-45 days of life is associated with longer native liver survival rates and reduction of the need for liver transplant. The incidence rate of BA in the state of Hawai'i is nearly double the incidence rate in the continental US. International studies have demonstrated that screening programs for BA reduce the age at diagnosis and treatment. However, there has been no statewide analysis on the ages at diagnosis or at Kasai, nor does a statewide screening program for BA exist. The purpose of this study is to review the age of diagnosis and treatment of BA to determine if the current practice in Hawai'i is in line with the published data. A retrospective chart review of all patients diagnosed with BA at the state's primary children's hospital was performed (2009-2023) and 19 patients who underwent the Kasai procedure were identified. The mean age at diagnosis is 71.4 days (n=19) and the mean age at Kasai procedure is 72.0 days (n=19). Both the average age at diagnosis and treatment for BA in Hawai'i is significantly higher than published data suggesting best outcomes at 30-45 days of life. This review suggests that the implementation of a statewide screening program for BA in Hawai'i is warranted.

Effects of air pollution on global health: evidence from the global burden of disease study in the BRICS countries.

Considering the dynamic influence of environmental, social, economic, and political factors in the emergence and growth of the BRICS countries (Brazil, Russia, India, China, and South Africa) over the years and pre-existing differences, the adverse effects of air pollution on the health and well-being of the people have remained major areas of academic inquiry and policy interventions. The present study examines the global trend of deaths and Disability Adjusted Life Years (DALYs) attributable to air pollution with particular reference to the BRICS countries for the period 1990 to 2019. This study has used the global burden of disease estimates by using different rounds of the Global Burden of Disease (GBD) study report published by the Institute of Health Metrics Evaluation. This study has calculated the cause of death and DALYs due to environmental risk factors (i.e. Air pollution). Data analysis has been done by using the standard formula for the calculation of death (mortality) rate and DALYs rate. Similarly, we calculated the age and gender-wise death and DALYs rate by using the appropriate numerator and denominator. The study discovered a significant shift in disease patterns over this period, as communicable diseases like respiratory infections and tuberculosis were replaced by non-communicable diseases such as ischemic heart disease (17.2 million), chronic obstructive pulmonary disease (14.59 million), and stroke (17.02 million) as the primary causes of air pollution-related deaths in 2019 at the global level. Additionally, the study identified a worrying increase in deaths linked to neonatal disorders and respiratory infections caused by ambient particulate matter pollution in South Africa, India, and Brazil. The impact of air pollution on public health is evident across different age groups and genders, with people aged 50-69 years, those aged 70 and above, and children under 5 years being more vulnerable. Furthermore, the male population is disproportionately affected by communicable and noncommunicable diseases caused by air pollution. The study highlights the need for policymakers to implement evidence-based interventions to tackle this global health problem. The interventions should aim to reduce the emerging crisis of non-communicable diseases related to air pollution, particularly among vulnerable age groups and the male population, ultimately improving public health outcomes.

Clinical application of flexible fiberoptic bronchoscopy in neonatal respiratory diseases

BackgroundRespiratory disease is a predominantly observed problem in neonates. Moreover, the application of flexible bronchoscopy in newborns is gradually increasing. This study aimed to investigate the value of bronchoscopy in neonates respiratory abnormalities and evaluate the safety of bronchoscopy application.MethodsClinical data and outcomes of 56 neonates who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were assessed.ResultsA total of 56 neonates had a minimum weight of 1200 g at the time of bronchoscopy, while the minimum gestational age at birth was 26 + 1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were respiratory distress in 24 (42.9%), stridor in 22 (39.3%), pulmonary atelectasis in 10 (17.6%), feeding difficulty in 10 (17.6%), and difficult weaning from mechanical ventilation in 6 (10.7%) cases. A total of 13 types of abnormalities were detected in the respiratory tract. The most common abnormalities were laryngomalacia in 29 (59.2%), tracheobroncomalacia in 8 (16.3%), and vocal cord paralysis in 6 (12.2%) cases. Bronchoalveolar lavage was performed in 39 cases. Eight cases were diagnosed by bronchoscopy and then treated with surgery in the Thoracic Surgery/Otolaryngology Department; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, of whom none died.ConclusionsFlexible bronchoscopy could play an important role in diagnosing and identifying respiratory disorders in neonates and be safely used with few serious complications.