Neonatal Disease Research Articles

Severity-adjusted evaluation of initial dialysis on short-term health outcomes in urea cycle disorders

ObjectiveIn individuals with urea cycle disorders (UCDs) and neonatal disease onset, extracorporeal detoxification by continuous kidney replacement therapy is considered the therapeutic method of choice in addition to metabolic emergency treatment to resolve hyperammonemic decompensation. However, the indications for the initiation of dialysis are heterogeneously implemented transnationally, thereby hampering our understanding of (optimal) short-term health outcomes. MethodsWe performed a retrospective comparative analysis evaluating the therapeutic effects of initial dialysis on survival as well as neurocognitive outcome parameters in individuals with UCDs in comparison to a severity-adjusted non-dialyzed control cohort. Overall, 108 individuals with a severe phenotype of male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) were investigated by stratification based on a recently established and validated genotype-specific disease prediction model. ResultsMortality is associated with the height of initial peak plasma ammonium concentration, but appears to be independent from treatment with initial dialysis in mOTC-D. However, improved survival after initial dialysis was observed in CTLN1, while there was a trend towards improved survival in ASA. In survivors, annual frequency of (subsequent) metabolic decompensations did not differ between the dialyzed and non-dialyzed cohorts. Moreover, treatment with initial dialysis was not associated with improved neurocognitive outcomes. InterpretationThe present severity-adjusted comparative analysis reveals that general practice of initial dialysis is neither associated with improved survival in individuals with mOTC-D nor does it differ with regard to the neurocognitive outcome for the investigated UCD subtypes. However, initial dialysis might potentially prove beneficial for survival in CTLN1 and ASA.Clinical trial registration: The UCDC database is recorded at the US National Library of Medicine (https://clinicaltrials.gov).

Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit

IntroductionChronic respiratory morbidity from bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth and has consequences for later respiratory, cardiovascular and neurodevelopmental outcomes. The early phases of respiratory...

Combining artificial intelligence and conventional statistics to predict bronchopulmonary dysplasia in very preterm infants using routinely collected clinical variables.

Prematurity is the strongest predictor of bronchopulmonary dysplasia (BPD). Most previous studies investigated additional risk factors by conventional statistics, while the few studies applying artificial intelligence, and specifically machine learning (ML), for this purpose were mainly targeted to the predictive ability of specific interventions. This study aimed to apply ML to identify, among routinely collected data, variables predictive of BPD, and to compare these variables with those identified through conventional statistics. Very preterm infants were recruited; antenatal, perinatal, and postnatal clinical data were collected. A BPD prediction model was built using conventional statistics, and nine supervised ML algorithms were applied for the same purpose: the results of the best-performing model were described and compared with those of conventional statistics. Both conventional statistics and ML identified the degree of immaturity (low gestational age and/or birth weight), need for mechanical ventilation, and absent or reversed end diastolic flow (AREDF) in the umbilical arteries as risk factors for BPD. Each of the two approaches also identified additional potentially predictive clinical variables. ML algorithms might be useful to integrate conventional statistics in identifying novel risk factors, in addition to prematurity, for the development of BPD in very preterm infants. Specifically, the identification of AREDF status as an independent risk factor for BPD by both conventional statistics and ML highlights the opportunity to include detailed antenatal information in clinical predictive models for neonatal diseases.

Butyrate protects the intestinal barrier by upregulating Fut2 expression via MEK4-JNK signaling pathway activation.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates. Fucosyltransferase 2 (Fut2) regulates intestinal epithelial cell fucosylation. In this study, we aimed to investigate butyrate-mediated upregulation of Fut2 expression and the underlying mechanisms. In vivo and in vitro models were established. SP600125 was used to inhibit the MEK4-JNK pathway, and anisomycin was used to activate the MEK4-JNK pathway. Fut2, occludin, and ZO-1 expressions were assessed. Furthermore, intestinal permeability was analyzed by FITC-Dextran. The expression of proteins in the MEK-4-JNK pathway was examined by western blotting. In vivo, the addition of exogenous butyrate notably upregulated Fut2, occludin, and ZO-1 expressions and reduced intestinal permeability in mice with NEC. Butyrate may increase the phosphorylation of MEK4, JNK, and c-jun, which are key components of the MEK4-JNK pathway. Additionally, SP600125 inhibited their phosphorylation, which was reversed by anisomycin treatment. In vitro, butyrate substantially increased occludin and ZO-1 expressions. Butyrate considerably increased Fut2 expression and markedly upregulated p-MEK4, p-JNK, and p-c-jun expressions. SP600125 administration decreased their expressions, while anisomycin administration increased their expressions. Butyrate upregulated Fut2 expression via activation of the MEK4-JNK pathway, improved intestinal barrier integrity, and protected neonatal mice from NEC. We found that exogenous butyrate could improve intestinal barrier integrity and protect against NEC in neonatal mice. Our data showed that exogenous butyrate supplementation upregulated Fut2 expression by activating the MEK4-JNK pathway. Our study provides novel insights into the pathogenesis of NEC, thereby laying an experimental foundation for future clinical research on the use of butyrate in NEC treatment.

Urinary Tract Infection Due to Streptococcus agalactiae - A Missed Clinical Entity: A Study from a Tertiary Care Center in Southern India

: Streptococcus agalactiae (group B Streptococcus or GBS) commonly causes various urinary tract infections (UTIs), including asymptomatic bacteriuria, cystitis, pyelonephritis, urethritis, and urosepsis. While GBS neonatal disease has decreased, its prevalence in non-pregnant adults has risen. However, its role in UTIs among males and non-pregnant women is less documented. This study aims to investigate the prevalence, clinical presentation, antibiotic susceptibility, and risk factors of GBS UTIs. Over 16 months, a prospective study included all patients diagnosed with GBS UTIs. Among 6305 urine specimens tested, 2.1% (N = 134, 95% CI: 0.68% - 4.8%) were positive for GBS, with a notably higher prevalence among pregnant women (73%, N = 79). This prevalence rate significantly exceeded regional reports, as indicated by a z-score exceeding the critical value. Additionally, 50% of positive isolates were from antenatal patients, indicating pregnancy as a significant risk factor (P < 0.0001). All 134 GBS isolates exhibited sensitivity to penicillin, cefotaxime, ofloxacin, and vancomycin. Sensitivity to cotrimoxazole, erythromycin, and clindamycin was 80%, 95%, and 97%, respectively. Treatment varied by case severity. Uncomplicated cases (41.7% antenatal; 33.5% non-pregnant women and adults) received 3rd or 4th generation cephalosporins, while complicated cases (24.6%, N = 33) required intravenous vancomycin due to comorbidities like chronic kidney disease (CKD), renal calculi, diabetes, and obstetric complications. In conclusion, GBS UTIs predominantly affect females, particularly pregnant women, followed by those with chronic conditions like CKD and diabetes mellitus. Routine GBS culture and susceptibility testing are crucial in laboratories to ensure effective UTI management.

RISK FACTORS FOR THE DEVELOPMENT OF PLACENTAL DYSFUNCTION ON THE BACKGROUND OF PREGNANT WOMEN GENITAL INFECTIONS

The progress of perinatology revealed new problems related to the gestational process and antenatal protection of the fetus. Among indicators of perinatal morbidity in modern conditions, one of the leading places occupied by placental dysfunction, the frequency of which, according to the data of domestic and foreign scientists ranges from 36% to 60%. It is known that among the many factors that affect the complicated course of pregnancy and perinatal morbidity, infectious factors in modern conditions occupy one of the leading places. Despite certain achievements in elucidating the etiological factors and pathogenesis of the development of placental dysfunction (PD), the issues of diagnosis and treatment of this pathology in pregnant women need further improvement. Thus, the study of links in the pathogenesis of manifestations of placental dysfunction, which develops during pregnancy in the early stages of gestation against the background of genital infections, is relevant and promising.The purpose. To assess the risk factors for the development of placental dysfunction in pregnant women with genital infections.Material and methods. The retrospective comparative study included 55 women who gave birth after involuntary childbirth according to the regional perinatal center of Chernivtsi, who had signs of placental dysfunction and genital infections during pregnancy during the period 2021-2022.Research results. One of the most important factors affecting the fetoplacental system, which leads to the development of chronic PD (CPD), are infections of the TORCH group. Infections during pregnancy, depending on the gestational period, lead to miscarriage, abortion, stillbirth, malformations of the child, cerebral defects, as well as to acute and chronic neonatal diseases. We conducted a retrospective analysis of risk factors, the frequency and structure of obstetric complications based on the data of 55 birth stories of the regional perinatal center in Chernivtsi for 2021-2022. Manifestations of placental dysfunction against the background of genital infections were studied at different gestational periods. Placental dysfunction occurs at different gestational periods in women of different ages. However, in young people (up to 18 years old) it occurs less often at all stages of gestation, compared to other age categories. A significant number of pregnant women with manifestations of placental dysfunction suffered from infectious diseases in childhood (measles, chicken pox, acute respiratory and viral infections, angina, various disorders of menstrual function (hyperpolymenorrhea, hypomenstrual syndrome, algodysmenorrhea) were quite often observed in pregnant women with manifestations of placental insufficiency. More often, placental dysfunction develops during first births than during repeated births. Cases of stillbirth, spontaneous miscarriages, artificial abortions and ectopic pregnancies often occur in the anamnesis. A number of authors [41] indicate that pregnant women with manifestations of placental insufficiency often experience various complications of the current pregnancy. Modern scientific studies show that almost 80% of pregnant women with genital infections show significant changes in the immune, endocrine and coagulation systems, which lead to a violation of the formation of the fetoplacental complex and a violation of adaptation mechanisms in the mother-placenta-fetus system.Conclusion. Clinical and statistical analysis shows the negative impact of manifestations of genital infections in different gestational periods on the course of pregnancy and the state of the fetus and newborn. The conducted studies on this issue give reason to talk about the need to review the system of obstetric tactics for these pregnant women, and further improvement of medical measures for antenatal protection of the fetus with this complication of pregnancy.

Lung Ultrasound and Ultrasound Score: A Useful Tool in Neonatal Intensive Care Units for the Diagnosis and Therapeutic Management of Newborns With Respiratory Pathology.

Pulmonary ultrasound has become a fundamental tool for the early detection and management of major neonatal lung diseases in neonatal intensive care units (NICUs). The advantages of this imaging investigation include its rapid execution and information acquisition, non-invasive nature, early diagnosis establishment, dynamic monitoring, and usefulness in therapeutic management. Regarding therapeutic management, the lung ultrasound (LUS) score is used as a basic tool for indicating surfactant administration. Performing and interpreting pulmonary ultrasounds requires an experienced clinician capable of recognizing anatomical structures, understanding the limitations of the technique, and correlating the obtained data with the patient's clinical picture. A series of diagnostic characteristics of pulmonary ultrasonography for neonatal lung pathologies have been described, making pulmonary ultrasound a useful tool in establishing differential diagnoses. This study evaluates the effectiveness of ultrasonography in determining the severity of lung pathologies in newborns and its impact on therapeutic decision-making, including surfactant administration and continuous positive airway pressure (CPAP) support. Newborns admitted to the NICUwith various respiratory conditions underwent LUS scoring. The study analyzed the relationship between LUS scoring and the severity of conditions such as pneumonia, respiratory distress syndrome, meconium aspiration syndrome, transient tachypnea of the newborn, and pneumothorax. The correlation between LUS scoring, surfactant administration, and CPAP requirements was also examined.

Viewpoint of multi-omics potential in tuberculosis research: identifying biomarkers for biomanufacturing of efficient control tools

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC), remains a global health burden, claiming millions of lives annually. Despite the availability of a vaccine (the Bacillus Calmette-Guérin; BCG), diagnostics (smear microscopy and DNA-based diagnostics) and drugs for treatment, challenges like drug resistance, lower diagnostic sensitivity such as microscopy, instrumentation and high-level operational expertise requirement and poor vaccine efficacy pose a greater hinderance to TB monitoring and control. The inability of the BCG vaccine to protect against TB other than disseminated disease in neonates call for innovative approaches to provide improved interventions. This review highlights the potential of multi-omics as a powerful emerging tool offering a holistic insight into the intricate interplay between pathogens and the host immune response. It discusses the potential of multi-omics for discovering biomarkers as targets for rational drug design, production of more effective vaccines and as stable targets for production of universally applicable rapid diagnostics for early and accurate TB detection as well as monitoring treatment.

Application of blood parameters for the early diagnosis of natural ascending placentitis in pregnant mares

Placental infection is an important cause of late-term pregnancy loss and neonatal diseases in horses. Detection of changes in blood parameters especially during early placentitis could improve the diagnostic accuracy, treatment decision, and potential outcomes. The objectives of this 2-part study were to identify differences in circulating immunological, inflammatory, and hormonal parameters between mares with natural ascending placentitis and control mares; evaluate each and combination of parameters as predictors of placentitis; and determine how these parameters indicate severity of placentitis. Reproductive examination and blood sampling were prospectively performed on pregnant mares in a natural setting. Study 1 enrolled mares diagnosed with early stage of ascending placentitis based on ultrasonographic findings (n = 12), and gestationally age-matched mares with healthy pregnancies as controls (n = 12). Blood samples were classified as pre-onset (before) and early onset (at the time of ultrasonographic changes) of placentitis. There were no detected statistically significant differences between groups and timepoints in immunological and inflammatory parameters, including peripheral lymphocyte subpopulations, cytokine, and serum amyloid A concentrations. The placentitis group showed a reduced (P = 0.01) DHP/20α-DHP ratio when compared to the control group at the early onset timepoint. Plasma estradiol-17β concentration <359 pg/mL predicted ascending placentitis with acceptable accuracy (area under the curve, AUC = 0.71). Combined albumin <3.7 g/dL, estradiol-17β < 499 ng/mL, and DHP <33 ng/mL predicted 100 % of cases of ascending placentitis. In study 2, samples were classified according to the presence and severity of the abnormal ultrasonographic findings as mild (n = 11) and moderate-severe (n = 23), and gestationally age-matched with samples from control mares (n = 34). Mares with moderate-severe ascending placentitis had increased (P = 0.03) plasma 20α-DHP concentration and reduced (P = 0.03) DHP/20α-DHP ratio when compared to control mares. Our results suggest that the early events of ascending placentitis detected by ultrasonographic findings include hormonal alterations of feto-placental metabolism measurable in the mare's circulation, yet without obvious systemic immunological and inflammatory changes. Additional studies are warranted to further assess how hormonal markers and cutoff values could guide decisions for timely therapeutic intervention.

Group B Streptococcus and Intraamniotic Inflammation and Infection.

Intraamniotic inflammation and infection complicate 2% to 5% of term deliveries. Group B Streptococcus (GBS) is a common cause of intraamniotic infection associated with invasive neonatal disease and maternal morbidity. Universal vaginal-rectal screening for GBS colonization is recommended between 36 and 37 weeks. Intrapartum antibiotic prophylaxis is recommended for individuals with positive GBS screens and other risk factors. Intravenous penicillin is the preferred antimicrobial agent. Individuals with penicillin allergies may receive cefazolin for low-risk allergies and either clindamycin or vancomycin for high-risk allergies, depending on their antimicrobial susceptibilities. Clinical trials are underway to evaluate the safety and immunogenicity of maternal anti-GBS vaccine candidates.

Neurodevelopmental impairment associated with neonatal invasive group B Streptococcus disease: Are animal models on track in understanding the mechanisms at play?

Invasive Group B Streptococcus (iGBS) disease is a prominent cause of neurodevelopmental impairment (NDI) in neonates. While the clinical manifestation of iGBS disease in neonates may include pneumonia and meningitis, generalised sepsis without focus is the most frequent manifestation of iGBS disease in neonates. Though recent human based studies highlighted meningitis as an important manifestation in infants with NDI following iGBS disease, they also noted that ∼18% of neonates present with NDI following iGBS related sepsis. Thus, it is important to not only understand the long-term pathophysiological changes associated with NDI in iGBS meningitis survivors, but so too for iGBS sepsis survivors. Since the late 1970's animal models have been used to unravel the pathophysiology of neonatal iGBS disease. These studies have inoculated neonatal or pregnant animals with GBS via various peripheral or central routes. The greatest challenge with using animal models to study NDI associated with neonatal iGBS disease, is effectively mimicking the clinical presentations of pneumonia, sepsis, and meningitis, while inducing relevant pathophysiological changes and ensuring animals survival, so as to test the neurodevelopment of the animals. This review aims to evaluate the validity of neonatal rodent models, specifically in studying NDI associated with neonatal iGBS disease and explore possible future avenues of research in addressing long-term NDI in the clinical setting.

N-Acetylcysteine Alleviates Necrotizing Enterocolitis by Depressing SESN2 Expression to Inhibit Ferroptosis in Intestinal Epithelial Cells.

Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.

Bioinformatics in Neonatal/Pediatric Medicine-A Literature Review.

Bioinformatics is a scientific field that uses computer technology to gather, store, analyze, and share biological data and information. DNA sequences of genes or entire genomes, protein amino acid sequences, nucleic acid, and protein-nucleic acid complex structures are examples of traditional bioinformatics data. Moreover, proteomics, the distribution of proteins in cells, interactomics, the patterns of interactions between proteins and nucleic acids, and metabolomics, the types and patterns of small-molecule transformations by the biochemical pathways in cells, are further data streams. Currently, the objectives of bioinformatics are integrative, focusing on how various data combinations might be utilized to comprehend organisms and diseases. Bioinformatic techniques have become popular as novel instruments for examining the fundamental mechanisms behind neonatal diseases. In the first few weeks of newborn life, these methods can be utilized in conjunction with clinical data to identify the most vulnerable neonates and to gain a better understanding of certain mortalities, including respiratory distress, bronchopulmonary dysplasia, sepsis, or inborn errors of metabolism. In the current study, we performed a literature review to summarize the current application of bioinformatics in neonatal medicine. Our aim was to provide evidence that could supply novel insights into the underlying mechanism of neonatal pathophysiology and could be used as an early diagnostic tool in neonatal care.

Host-derived protein profiles of human neonatal meconium across gestational ages

Meconium, a non-invasive biomaterial reflecting prenatal substance accumulation, could provide valuable insights into neonatal health. However, the comprehensive protein profile of meconium across gestational ages remains unclear. Here, we conducted an extensive proteomic analysis of first meconium from 259 newborns across varied gestational ages to delineate protein composition and elucidate its relevance to neonatal diseases. The first meconium samples were collected, with the majority obtained before feeding, and the mean time for the first meconium passage from the anus was 11.9 ± 9.47 h. Our analysis revealed 5370 host-derived meconium proteins, which varied depending on sex and gestational age. Specifically, meconium from preterm infants exhibited elevated concentrations of proteins associated with the extracellular matrix. Additionally, the protein profiles of meconium also exhibited unique variations depending on both specific diseases, including gastrointestinal diseases, congenital heart diseases, and maternal conditions. Furthermore, we developed a machine learning model to predict gestational ages using meconium proteins. Our model suggests that newborns with gastrointestinal diseases and congenital heart diseases may have immature gastrointestinal systems. These findings highlight the intricate relationship between clinical parameters and meconium protein composition, offering potential for a novel approach to assess neonatal gastrointestinal health.

Noninvasive microvascular imaging in newborn rats using high-frequency ultrafast ultrasound

Ultrasound imaging stands as the predominant modality for neonatal health assessment, with recent advancements in ultrafast Doppler (μDoppler) technology offering significant promise in fields such as neonatal brain imaging. Combining μDoppler with high-frequency ultrasound (HF-μDoppler) presents a potential efficient avenue to enhance in vivo microvascular imaging in small animals, notably newborn rats, a crucial preclinical animal model for neonatal disease and development research. It is necessary to verify the imaging performance of HF-μDoppler in preclinical trials. This study investigates the microvascular imaging capabilities of HF-μDoppler using a 30 MHz high-frequency linear array probe in newborn rats. Results demonstrate the clarity of cerebral microvascular imaging in rats aged 1 to 7 postnatal days, extending to whole-body microvascular imaging, encompassing the central nervous system, including the brain and spinal cord. In conclusion, HF-μDoppler technology emerges as a reliable imaging tool, offering a new perspective for preclinical investigations into neonatal diseases and development.

Genetic markers associated with host status and clonal expansion of Group B Streptococcus in the Netherlands.

Certain Group B Streptococcus (GBS) genotypes are associated with invasive disease in neonates. We conducted a comparative genomic analysis of GBS isolates from neonatal disease and maternal carriage in the Netherlands to determine distribution of genetic markers between the two host groups. Whole genome sequencing was used to characterise 685 neonatal invasive isolates (2006-2021) and 733 maternal carriage isolates (2017-2021) collected in the Netherlands. Clonal complex (CC) 17 and serotype III were significantly more common in disease while carriage isolates were associated with serotypes II, IV, V as well as CC1. Previously reported CC17-A1 sub-lineage was dominant among disease isolates and significantly less common in carriage. The phiStag1 phage, previously associated with expansion of invasive CC17 isolates in the Netherlands, was more common among disease isolates compared to carriage isolates overall, however it was equally distributed between CC17 isolates from carriage and disease. Prevalence of antimicrobial resistance genes was overall lower in disease compared to carriage isolates, but increased significantly over time, mediated by rise in prevalence of a multidrug resistance element ICESag37 among disease isolates. There is a stable association between certain GBS genotypes and invasive disease, which suggests opportunities for developing more precise disease prevention strategies based on GBS targeted screening. In contrast, GBS mobile genetic elements appear less likely to be correlated with carriage or disease, and instead are associated with clonal expansion events across the GBS population.

Retrospective analysis of reference intervals for dried blood spot based ms/ms newborn screening programs in Chinese preterm neonates: a nationwide study

ObjectivesAlthough recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age.Design and methodsThe NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach.ResultsIncreasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates.ConclusionThe current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.

Geographical validation of the Smart Triage Model by age group.

Infectious diseases in neonates account for half of the under-five mortality in low- and middle-income countries. Data-driven algorithms such as clinical prediction models can be used to efficiently detect critically ill children in order to optimize care and reduce mortality. Thus far, only a handful of prediction models have been externally validated and are limited to neonatal in-hospital mortality. The aim of this study is to externally validate a previously derived clinical prediction model (Smart Triage) using a combined prospective baseline cohort from Uganda and Kenya with a composite endpoint of hospital admission, mortality, and readmission. We evaluated model discrimination using area under the receiver-operator curve (AUROC) and visualized calibration plots with age subsets (< 30 days, ≤ 2 months, ≤ 6 months, and < 5 years). Due to reduced performance in neonates (< 1 month), we re-estimated the intercept and coefficients and selected new thresholds to maximize sensitivity and specificity. 11595 participants under the age of five (under-5) were included in the analysis. The proportion with an endpoint ranged from 8.9% in all children under-5 (including neonates) to 26% in the neonatal subset alone. The model achieved good discrimination for children under-5 with AUROC of 0.81 (95% CI: 0.79-0.82) but poor discrimination for neonates with AUROC of 0.62 (95% CI: 0.55-0.70). Sensitivity at the low-risk thresholds (CI) were 85% (83%-87%) and 68% (58%-76%) for children under-5 and neonates, respectively. After model revision for neonates, we achieved an AUROC of 0.83 (95% CI: 0.79-0.87) with 13% and 41% as the low- and high-risk thresholds, respectively. The updated Smart Triage performs well in its predictive ability across different age groups and can be incorporated into current triage guidelines at local healthcare facilities. Additional validation of the model is indicated, especially for the neonatal model.

Beyond Bronchopulmonary Dysplasia: A Comprehensive Review of Chronic Lung Diseases in Neonates.

In neonates, pulmonary diseases such as bronchopulmonary dysplasia and other chronic lung diseases (CLDs) pose significant challenges due to their complexity and high degree of morbidity and mortality. This review discusses the etiology, pathophysiology, clinical presentation, and diagnostic criteria for these conditions, as well as current management strategies. The review also highlights recent advancements in understanding the pathophysiology of these diseases and evolving strategies for their management, including gene therapy and stem cell treatments. We emphasize how supportive care is useful in managing these diseases and underscore the importance of a multidisciplinary approach. Notably, we discuss the emerging role of personalized medicine, enabled by advances in genomics and precision therapeutics, in tailoring therapy according to an individual's genetic, biochemical, and lifestyle factors. We conclude with a discussion on future directions in research and treatment, emphasizing the importance of furthering our understanding of these conditions, improving diagnostic criteria, and exploring targeted treatment modalities. The review underscores the need for multicentric and longitudinal studies to improve preventative strategies and better understand long-term outcomes. Ultimately, a comprehensive, innovative, and patient-centered approach can enhance the quality of care and outcomes for neonates with CLDs.

Maternal Graves Disease and Neonatal Thyroid Disease.

Maternal Graves Disease and Neonatal Thyroid Disease.