BACKGROUND:Congenital hypothyroidism (CH) is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality. The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology. Here, we explored the etiological relationship between CH, heart failure, and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease. CASE SUMMARY:A 33-day-old extremely premature female infant presented with tachypnea, respiratory distress, recurrent infections, and abdominal distension postnatal. On admission to our facility, she had cardiomegaly, hepatomegaly, and lactic acidosis (revealed on blood gas analysis), with lactate progressively rising to 25 mmol/L. Chest radiographs showed pulmonary congestion, while echocardiography revealed cardiac enlargement, left ventricular wall thickening, and pericardial effusion. Initial management aimed at correcting acidosis and treating heart failure proved ineffective. After reassessment, thyroid function tests showed significantly decreased triiodothyronine, free triiodothyronine, thyroxine, and free thyroxine levels, with a significantly increased thyroid-stimulating hormone level, confirming a CH diagnosis. Levothyroxine was administered, resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms, culminating in full recovery and discharge. We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association. CONCLUSION:This case links CH-induced heart failure with refractory lactic acidosis, urging prompt thyroid screening in affected neonates to reduce mortality.

Objective: To investigate how the high-altitude environment modifies severe pertussis in young infants and analyze its pathophysiological mechanisms and clinical management implications. Methods: Clinical data of two young infants with severe pertussis residing at 3650 m were retrospectively analyzed, including presentation, laboratory findings, pathogen detection, treatment, and outcomes. A literature review explored synergistic interactions between high-altitude factors and pertussis pathophysiology. Results: Case 1 had macrolide-resistant Bordetella pertussis (MRBP, 23S rRNA A2047G) with peak WBC 52.25 × 109/L, and received cefoperazone-sulbactam, piperacillin-tazobactam and azithromycin, and was successfully treated with trimethoprim-sulfamethoxazole combined with exchange transfusion. Case 2 had Bordetella pertussis confirmed by PCR with peak WBC 36.55 × 109/L, receiving cefoperazone-sulbactam and azithromycin, and recovered. Both developed respiratory failure requiring non-invasive ventilation and survived without pulmonary hypertension. High-altitude stressors—hypoxia, enhanced pulmonary vascular reactivity, and hypercoagulability—synergize with pertussis-induced hyperleukocytosis as a “dual hit,” accelerating cardiopulmonary deterioration and elevating thrombotic risks. Conclusions: High altitude is an independent risk modifier in infantile pertussis, demanding heightened vigilance and proactive interventions: early non-invasive ventilation, prophylactic anticoagulation, and timely exchange transfusion before pulmonary hypertension develops. This is the first high-altitude case series that provides essential insights for clinicians in similar environments globally, guiding early recognition and proactive management strategies to improve outcomes in this vulnerable population.

ObjectiveTo evaluate the necessity of routine fluconazole prophylaxis in very preterm infants/very low birth weight (VLBW) infants in neonatal intensive care units (NICUs) with a very low incidence of late-onset invasive fungal infection (IFI), and to inform clinical practice.MethodsA retrospective cohort study using propensity score matching was conducted including eligible very preterm infants/VLBW infants admitted to the NICUs of West China Second Hospital, Sichuan University and Sichuan Provincial Children's Hospital from January 2018 to December 2023. Infants were categorized into fluconazole and non-fluconazole groups according whether they received fluconazole prophylaxis. The primary outcome was the incidence of late-onset IFI.ResultsA total of 1 961 infants were enrolled, with an overall late-onset IFI incidence of 0.25% (5/1 961). After propensity score matching, 442 infants were included in each group. No statistically significant differences were observed between the fluconazole and non-fluconazole groups in the incidence of late-onset IFI (0.45% vs 0.23%), mortality (2.04% vs 0.90%), retinopathy of prematurity requiring surgery (6.11% vs 4.98%), intraventricular hemorrhage grade ≥2 (9.28% vs 6.56%), necrotizing enterocolitis stage ≥2 (10.18% vs 8.14%), or bronchopulmonary dysplasia (36.20% vs 36.88%), nor in length of hospital stay (48.5 days vs 50.5 days) (all P>0.05).ConclusionsIn NICUs with a very low incidence of late-onset IFI, routine fluconazole prophylaxis is not recommended for very preterm infants/VLBW infants.

Very low birth weight infants (VLBWI) are at high risk of mortality and severe neurodevelopmental impairment, including cerebral palsy, yet reliable discharge-time prognostic stratification remains challenging in high-dimensional and data-limited clinical settings. To address this problem, we propose QDSP, an interpretable structured learning framework that integrates Quota-guided Subspace Sampling (QSS) and Differentiable-decision-guided Structure Perception (DSP). The QSS module constructs stability-aware and low-redundancy feature subspaces through bootstrap-based feature consistency estimation, whereas the DSP module employs differentiable soft oblique decision structures to model nonlinear clinical interactions while preserving traceable decision evidence. The proposed framework was evaluated on a real-world VLBWI cohort comprising 51 infants and further validated on three public medical tabular datasets. On the primary cohort, QDSP achieved an accuracy of 0.9200 and an AUC of 0.9714, outperforming representative machine learning and deep tabular learning baselines, including XGBoost, TabNet, and TabPFN. Across external datasets, QDSP maintained competitive discrimination and calibration under varying sample sizes and clinical distributions. In addition, SHAP-based analyses and differentiable decision-path tracing identified clinically relevant predictors, including cystic periventricular leukomalacia (cPVL) and birth weight, consistent with established neonatal pathophysiological evidence. These results suggest that QDSP provides an interpretable and robust framework for discharge-time risk stratification in VLBWI and may support early individualized clinical decision-making in neonatal intensive care settings.

Background:Hearing loss (HL) impairs sound perception and includes sensorineural, conductive, and mixed subtypes. Compared with healthy newborns, infants admitted to the neonatal intensive care unit (NICU) are at substantially increased risk of congenital anomalies and exposure to HL-related risk factors. However, the specific determinants of neonatal HL remain controversial. Objective:This systematic review and meta-analysis seeks to identify risk factors linked to HL in neonates admitted to the NICU. Methods:PubMed, the Cochrane Library, Embase, and Web of Science were systematically searched from March 26, 1996, to February 25, 2025. Eligible studies were English-language retrospective studies employing multivariate logistic regression to evaluate potential risk factors for HL in NICU neonates. Meta-analyses were conducted using STATA, and pooled estimates were reported as odds ratios or relative risks (OR/RR) with 95% confidence intervals (CI). Results:This study included 21 retrospective studies with a total of 21,143 participants. Meta-analysis indicated that very low birth weight (<1,500 g), exposure to ototoxic drugs (aminoglycosides, loop diuretics), history of the surgical ligation of patent ductus arteriosus (PDA), craniofacial anomalies, family history of HL, and TORCH infections were significantly associated with HL in NICU neonates (all P ≤ 0.05). In contrast, low Apgar score, prematurity, low birth weight (1,500-2,500 g), duration of vancomycin exposure, sex, and sepsis were not significantly correlated. The findings were robust, and no evident publication bias was detected. Conclusion:Statistically significant risk factors for HL included craniofacial anomalies, family history of HL, TORCH infections, and surgical ligation of PDA, as well as hyperbilirubinemia, exposure to loop diuretics and other ototoxic drugs, mechanical ventilation, and very low birth weight (<1,500 g) (all P ≤ 0.05). In contrast, low Apgar score, preterm birth, and sepsis were not significantly linked to HL. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/search, PROSPERO CRD420250653476.

BACKGROUND:Delivering bad news in the Neonatal Intensive Care Unit (NICU) constitutes a profound ethical and emotional challenge. In China, this complexity is intensified by a defensive medical culture and strained physician-family dynamics. This study explores the lived experiences of Chinese neonatologists navigating these high-stakes interactions to uncover the phenomenon's essential structure. METHODS:A descriptive phenomenological study was conducted. Using a purposive sampling strategy, 19 neonatologists from a tertiary NICU in Western China were recruited. Data were collected through individual face-to-face, semi-structured in-depth interviews and analyzed using Colaizzi's seven-step method, with rigorous adherence to the COREQ guidelines to ensure trustworthiness. RESULTS:Five interconnected themes emerged: (1) The defensive paradox-strategic communication in a low-trust arena; (2) "Pushing the child off the cliff"-the burden of proxy decision-making; (3) Embodied moral distress-the somatic and emotional toll; (4) From technical anxiety to phronesis-identity reconstruction through virtue ethics; and (5) Systemic solitude-structural deficits and the training-practice gap. The findings reveal a trajectory from defensive adaptation and the moral burden of proxy agency to embodied suffering, mitigated by indigenous cultural meaning-making (xiuxing), yet constrained by systemic solitude. CONCLUSIONS:Delivering bad news in the Chinese context transcends information transmission, representing a form of moral practice that leaves indelible somatic marks on physicians. While practitioners cultivate individual resilience through professional wisdom and spiritual reframing, this "weight" is compounded by institutional voids. Addressing these challenges requires shifting from individual adaptation to multilevel systemic support, including culturally-adapted training, organizational support structures, and clinical ethics consultation services.

Objective To evaluate the efficacy and safety of azithromycin in eradicating Ureaplasma and preventing bronchopulmonary dysplasia (BPD) in preterm infants.Design Six literature databases and three clinical trial registration platforms were searched for studies up to 22 July 2024. The meta-analysis was performed using RevMan V.5.3.Results A total of 1723 preterm infants from 10 randomised controlled trials and 3 case series were included. In all preterm infants, azithromycin significantly improved Ureaplasma clearance (relative risk (RR)=1.47, 95% CI 1.17 to 1.85) and reduced the duration of mechanical ventilation (mean difference (MD)=-2.16, 95% CI -2.65 to -1.68), duration of supplemental oxygen (MD=-5.46, 95% CI -6.65 to -4.37) and length of stay (MD=-4.98, 95% CI -7.19 to -2.76) compared with placebo; however, there was no significant reduction in BPD, BPD-death or mortality, with low quality of evidence. In Ureaplasma-positive preterm infants, azithromycin significantly reduced BPD-death (RR=0.83, 95% CI 0.70 to 0.99) and mechanical ventilation (MD=-2.20, 95% CI -2.72 to -1.69), compared with placebo, and significantly increased Ureaplasma clearance rate. Additionally, compared with erythromycin, azithromycin reduced BPD, without a statistically significant difference. Compared with placebo, azithromycin showed no statistically significant differences in the incidence of necrotising enterocolitis, retinopathy, intraventricular haemorrhage, etc.Conclusions Low-quality evidence indicated prophylactic use of azithromycin could reduce the incidence of BPD-death and the duration of mechanical ventilation in Ureaplasma-positive preterm infants. However, such benefits were not observed in all preterm infants. Meanwhile, azithromycin was found to be safe for administration in preterm infants.PROSPERO registration number CRD42024585836.

Telomerase reverse transcriptase (TERT) exhibits non-canonical neuroprotective functions; its overexpression protects against hypoxic-ischemic brain injury and preserves mitochondrial function. Here, we identified a novel phenomenon in an in vitro model in which oxygen-glucose deprivation/reoxygenation induced a phase-dependent redistribution of endogenous TERT in HT22 neuronal cells, characterized by early mitochondrial accumulation followed by predominant nuclear localization. We aimed to determine whether subcellular localization of TERT dictates its functional specificity in regulating the copy number of mitochondrial DNA-encoded genes in neurons. HT22 cells expressing TERT, targeted to either the mitochondria (mito-TERT) or nucleus (nuc-TERT), were generated using adenoviral transfection. Subcellular localization was confirmed using western blotting. Mitochondrial DNA copy number was assessed using quantitative polymerase chain reaction (qPCR), and direct mito-TERT binding was assessed using chromatin immunoprecipitation (ChIP)-qPCR; ND1 and ND2 mRNA levels were measured using qRT-PCR. Both nuc-TERT and mito-TERT models were successfully established. qPCR analysis showed that mito-TERT specifically upregulated the copy number of mitochondrial complex I genes (nicotinamide adenine dinucleotide-hydrogen dehydrogenase subunit [ND]1/2), whereas nuc-TERT broadly upregulated genes across complexes I, III, IV, and V. A regulation specificity index showed that mito-TERT selectively enhanced ND1 copy number. ChIP-qPCR confirmed mito-TERT enrichment at the ND1 and ND2 promoters. Together, these findings demonstrate that TERT regulates mitochondrial DNA copy number through distinct, compartment-dependent mechanisms. Mito-TERT exhibited gene-specific regulation via direct promoter binding, whereas nuc-TERT displayed broader effects. The stress-induced redistribution of TERT and these mechanistic insights reveal a novel paradigm for multiphasic TERT-mediated neuroprotection in brain injury.

[This corrects the article DOI: 10.3389/fped.2026.1729458.].

Introduction Intraventricular haemorrhage (IVH) remains a major contributor to mortality and long-term neurodevelopmental impairment among preterm infants, particularly those born extremely preterm or extremely low birth weight. Although extensive research has investigated various facets of IVH, including prevention, therapeutic interventions, underlying pathophysiology and long-term outcomes, the heterogeneity in selection, measurement and reporting across studies significantly impairs data synthesis through meta-analysis and limits the translation of evidence into clinical practice. To address this issue, we propose the development of a Core Outcome Set (COS) for IVH research in preterm infants.Methods and analysis This study will follow established guidance from the Core Outcome Measures in Effectiveness Trials Initiative and COS-Standards for Development. The sequential phases include: (1) a systematic review to comprehensively identify outcomes previously reported in IVH research involving preterm infants; (2) qualitative interviews with diverse stakeholders (clinicians, researchers and caregivers) to explore perspectives and identify additional relevant outcomes; (3) a multiround Delphi survey to achieve consensus on core outcomes; and (4) a consensus meeting to finalise the COS.Ethics and dissemination The entire project has been approved by the Ethics Committee of West China Second University Hospital (No. 2022-069). Written informed consent will be obtained from all participants prior to participation. Study findings will be disseminated through conferences and publications in peer-reviewed journals.

Background: Neuroblastoma (NB) is one of the most common malignant tumors in children. Despite intensive multimodal treatments, patients with high-risk NB still have a poor prognosis; therefore, early identification of high-risk patients based on reliable NB biomarkers is essential. Endoplasmic reticulum (ER) stress has been demonstrated to play a vital role in cancer biology; however, it is unclear whether ER stress-related genes are involved in NB and should be further explored as new potential diagnostic and prognostic targets. Methods: We searched publicly available datasets with the aim to identify ER stress-related genes with a role in NB and establish a predictive model using ER stress-related signatures based on clinical information. Results: Seventy-three ER stress-related genes were differentially expressed in NB cells; most of them were involved in biological processes such as intrinsic apoptotic signaling pathways and cellular responses to abiotic stimuli. Protein-protein interaction (PPI) analysis revealed hub genes, among which FN1 and MAPK8 were associated with the prognosis for patients with NB. A risk prediction model established based on 10 differentially expressed ER stress-related genes, including MAP2, PRKCD, MAPK8IP1, JPH1, TPP1, BCL2, EDN1, THBS1, MAPK8, and SERPINA3, could reliably identify patients with NB who had a high risk of poor prognosis. Conclusions: Among the 73 ER stress-related genes differentially expressed in NB, the 2 hub and 10 risk prediction-related genes could potentially serve as therapeutic biomarkers and prognostic indicators for patients with NB.

Background Neonatal intestinal diseases often have an insidious onset and can lead to poor outcomes if not identified early. Early assessment of abnormal bowel function is critical for timely intervention and improving prognosis, underscoring the clinical importance of reducing mortality related to these conditions through rapid diagnosis and treatment. Bowel sounds (BSs), produced by intestinal contractions, are a key physiological indicator reflecting intestinal function. However, manual clinical assessment of BSs has limitations in terms of consistency and interpretative accuracy, which restricts its clinical application. This study aims to develop an machine learning-based diagnostic model for neonatal intestinal diseases using BS analysis and to compare its diagnostic accuracy with that of manual clinical assessment.Methods and analysis This diagnostic study employs a cross-sectional design. The case group includes neonates diagnosed with intestinal diseases (using clinical diagnosis as the gold standard), such as neonatal necrotising enterocolitis (NEC), food protein-induced allergic proctocolitis, and other intestinal conditions (eg, intestinal obstruction, midgut volvulus, congenital megacolon). The control group will be established using frequency matching, stratified by gestational age and postnatal age. Based on the distribution of each stratum in the case group, neonates without intestinal diseases who were hospitalised during the same period will be randomly selected in proportion from the corresponding strata. BSs will be collected using a 3M stethoscope (Littmann 3200). The study will occur in two phases. In the first phase (July 2024 to July 2025), participants from West China Second University Hospital will be randomly divided into a training cohort (for model development with 10-fold cross-validation) and an internal validation cohort in a 7:3 ratio. The second phase (July 2025 to July 2026) will involve external validation, with patients from Sichuan Provincial Children’s Hospital and Shenzhen Children’s Hospital. Clinical diagnosis will serve as the gold standard, and diagnostic outcomes between the machine learning-based model and manual clinical assessment by physicians of varying experience levels will be compared.Ethics and dissemination Ethical approval has been obtained from the Medical Ethics Committee of West China Second University Hospital (Registration No.: 2023SCHH0021), Sichuan Provincial Children’s Hospital (Registration No.: 2021YFC2701704) and the Shenzhen Children’s Hospital (Registration No.: 2021015). Written informed consent will be collected from all participants prior to BS collection. Study findings will be disseminated through conferences and publications in peer-reviewed journals.Trial registration number ChiCTR2400086713.

OBJECTIVES:Neonatal septic shock is a critical condition requiring immediate and individualised intervention. Despite extensive research, there is a significant heterogeneity in outcome reporting across studies which may lead to incomparability of study results and limit evidence synthesis. The aim of this systematic review was to identify and analyse outcomes reported in studies focussing on interventions for neonatal septic shock to inform the development of a core outcome set to standardise outcome reporting for future research and practice. METHODS:We conducted this systematic review following the Core Outcome Measures in Effectiveness Trials initiative framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched PubMed, Embase (Ovid), and the Cochrane Library, covering all records until September 2024. Four independent reviewers performed literature screening and data extraction, with disagreements resolved by consensus among two additional reviewers. Extracted outcomes and their definitions were standardised and categorised into core areas and domains using a 38-item standardised taxonomy. RESULTS:From 7139 records, 25 studies involving 4957 neonates were included, yielding 136 outcomes. After consolidation, 66 unique outcomes were identified and classified into four core areas based on the established taxonomy. The most frequently reported area was physiological/clinical outcomes (72%, 18 of 25 studies), encompassing 32 outcomes. This was followed by death (68%, 17/25), resource use (48%, 12/25), and adverse events (36%, 9/25). In addition, outcomes related to life impact were not measured in the included studies. CONCLUSIONS:This review demonstrates considerable heterogeneity in outcome reporting across neonatal septic shock studies and highlights the absence of life impact measures. These findings support the need for developing a standardised core outcome set to enhance outcome reporting consistency and clinical relevance.

ETHNOPHARMACOLOGICAL RELEVANCE:Astragalus membranaceus is one of the most widely applied traditional Chinese herbal medicines. TA-65 is an extract of Astragalus membranaceus; however, the protective effects of TA-65 in brain damage during development remain unclear. AIM OF THE STUDY:To investigate the neuroprotective effects of TA-65 in a neonatal hypoxic-ischemic brain damage (HIBD) mouse model, focusing on the role of telomerase reverse transcriptase (TERT). MATERIALS AND METHODS:In vivo and in vitro HIBD models were established and treated with TA-65. Nuclear and mitochondrial TERT expressions were measured by western blotting and immunofluorescence. Brain injury was evaluated through the measurement of brain infarction areas and neuronal apoptosis. The neurological function of mice was assessed. TA-65 safety was evaluated by measuring mouse body weight, random blood glucose level, blood cell count, liver and kidney function, and immune function, as well as detecting tumor occurrence in vital organs. RESULTS:TA-65 administration upregulated mitochondrial TERT expression after HIBD both in vivo and in vitro, but did not influence nuclear TERT expression. TA-65 reduced neuronal apoptosis and brain infarction areas, and improved neurological function in mice after HIBD. TA-65 did not change telomere length in the brain or affect body weight, random blood glucose levels, blood cell counts, liver and kidney function, or immune function in mice after HIBD. TA-65 administration did not cause tumor occurrence in the vital organs of mice. CONCLUSIONS:TA-65 exerts neuroprotective effects in neonatal HIBD without significant side effects or tumorigenicity. The possible mechanism may involve enhanced mitochondrial TERT expression.

BACKGROUND:Although cisplatin (Cis) is a foundational chemotherapeutic agent, its dose-limiting nephrotoxicity lacks clinically effective drugs. Curcumol (CUR), a bioactive sesquiterpenoid derived from Curcuma zedoariae rhizome, exhibits multi-organ protective effects. However, its therapeutic potential and molecular targets in Cis-provoked acute kidney injury (AKI) remain unexplored. PURPOSE:This study systematically investigated the nephroprotection and underlying mechanism of CUR in Cis-induced nephrotoxicity. METHODS:C57BL/6 mice received intraperitoneal administration of 20 mg/kg Cis to induce AKI. Dual-concentration CUR (40/80 mg/kg) was administered pre- and post-treatment in Cis-challenged mice, with longitudinal monitoring of renal function. Human tubular epithelial cells (HK-2 cells) were used to evaluate CUR's nephroprotection in vitro. RNA-sequencing transcriptomics identified pathway-level mechanisms, while structure-based molecular docking (MOD) prioritized target proteins. RESULTS:CUR exhibited dose-responsive nephroprotection, reducing apoptosis, oxidative stress, and inflammation more effectively than N-acetylcysteine in pre- and post-Cis treatment regimens. Mechanistically, we revealed that nephroprotection of CUR primarily involves suppression of phosphorylation-mediated MAPK/NF-κB pathway activation, thereby mitigating the inflammatory response. Notably, MOD and Cellular thermal shift assay (CETSA) data suggested a direct interaction between CUR and TAK1. Functional validation experiments demonstrated that TAK1 silencing attenuated cisplatin-induced tubular cell injury, and TAK1 activity was essential for CUR's protective effects. CONCLUSION:CUR ameliorated Cis-triggered AKI by targeting TAK1 and inhibiting MAPK and NF-κB pathways. These findings suggest that CUR may serve as a promising adjuvant to overcome the primary limitation of Cis.

BACKGROUND:This study aimed to assess the necessity of adding heparin to parenteral nutrition for continuous infusion through a peripherally inserted central catheter in very preterm infants. METHODS:This retrospective cohort study was conducted between January 1, 2019, and January 1, 2023. Preterm infants with gestational age <32 weeks requiring a peripherally inserted central catheter for parenteral nutrition were included. The heparin group received parenteral nutrition with 0.5 IU/ml heparin added for infusion through a peripherally inserted central catheter, whereas the nonheparin group did not receive heparin. Propensity score matching was used to balance baseline variables between the two groups. The primary outcome was the incidence of catheter-related complications. A noninferiority margin of 10% was chosen. Nonelective catheter removal, heparin-related side effects, and catheter dwell time were compared between the two groups. RESULTS:A total of 1089 very preterm infants were included. After propensity score matching, 432 infants from each group were analyzed. The incidence of catheter-related complications was 22.9% in the heparin group and 21.8% in the nonheparin group, with an absolute difference of -1.16% (95% CI: -6.71% to 4.40%). The upper bound was below 10% (P for noninferiority < 0.001), confirming noninferiority. In addition, no significant difference was found between the two groups in the incidence of nonelective catheter removal or heparin-related side effects. CONCLUSION:Parenteral nutrition without heparin was noninferior to the addition of heparin during infusion through peripherally inserted central catheter on the risk of catheter-related complications in very preterm infants.

BACKGROUND:The aim of this analysis was to evaluate the impact of different platelet transfusion thresholds on short-term and long-term outcomes in preterm infants, and to inform evidence-based, individualized transfusion strategies. MATERIALS AND METHODS:PubMed, Embase, and the Cochrane Library (database initiation until December 2024) were searched. Comparative studies of restrictive transfusion strategies vs liberal transfusion strategies in thrombocytopenic neonates were included. The review protocol was prospectively registered (CRD42020169262). RESULTS:Of 4,102 reports screened, three randomized controlled trials and two cohort studies were included (1,851 patients). Restrictive transfusion strategies did not increase short-term adverse events and may potentially reduce the incidence of mortality and severe neurodevelopmental impairment at 2 years corrected age. DISCUSSION:Restrictive platelet transfusion thresholds (25×109/L, or even 20×109/L) appear to be safe and may improve long-term prognosis. These findings support a shift toward more individualized, evidence-based transfusion practices in neonatal care.

Neonatal septic shock represents a critical and life-threatening condition that necessitates immediate and personalized interventions. Prior research endeavors have been undertaken to inform the optimization of neonatal septic shock management, yet substantial heterogeneity prevails in the selection, measurement, and reporting of outcomes across relevant studies. The heterogeneity in outcome selections and measures impedes the comparability of results and the synthesis of evidence, thus contributing to suboptimal utilization of research findings. This protocol presents the methodology for identifying and developing a Core Outcome Set for Neonatal Septic Shock Management (COS-NSS), intended for use in both research and routine clinical practice. A rigorous four-stage approach will be employed to develop the COS-NSS. In Stage 1, a scoping review will be conducted to compile a list of currently reported outcomes for neonatal septic shock management. Stage 2 will involve an expert stakeholder meeting using a semi-structured discussion approach to elucidate all identified outcomes and outcome domains, as well as to gather any additional outcomes. Moving to Stage 3, a two-round e-Delphi survey involving a wide variety of stakeholders will be undertaken to elicit diverse perspectives on the level of importance assigned to each proposed outcome. Finally, in Stage 4, the results of the Delphi study will be discussed in a consensus meeting to determine and agree on the final list of outcomes that will constitute the COS-NSS. The stagewise approach integrates research evidence with multi-stakeholder perspectives to establish standardized outcomes that would improve consistency across neonatal septic shock trials. The development and uptake of the COS-NSS will facilitate effective comparison of studies, allowing for study synthesis and generation of high-quality evidence, thus ultimately fostering enhanced medical care for neonates suffering from septic shock. Core Outcome Measures in Effectiveness Trials (COMET) Initiative database registration: 2766 . Registered on July 19th, 2023.

ObjectiveIn this study, we investigated the characteristics of the intestinal microbiota of preterm infants, and then analyzed the effects of probiotics supplementation on intestinal microbiota in preterm infants.MethodsThis study enrolled 64 infants born between 26 and 32 weeks gestational age (GA) and 22 full-term infants. 34 premature infants received oral probiotic supplementation for 28 days. Stool samples were obtained on the first day (D1) and the 28th day (D28) after birth for each infant. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System, specifically targeting the V3-V4 hyper-variable regions of the 16S rDNA gene. The sequencing results were then used to compare and analyze the composition and diversity index of the intestinal microbiota.ResultsThere was no significant difference in meconium bacterial colonization rate between premature and full-term infants after birth (p > 0.05). At D1, the relative abundance of Bifidobacterium, Bacteroides, and Lactobacillus in the stool of preterm infants was lower than that of full-term infants, and the relative abundance of Acinetobacter was higher than that of full-term infants. The Shannon index and Chao1 index of intestinal microbiota in preterm infants are lower than those in full-term infants (p < 0.05). Supplementation of probiotics can increase the relative abundance of Enterococcus and Enterobacter, and reduce the relative abundance of Escherichia and Clostridium in premature infants. The Chao1 index of intestinal microbiota decreased in preterm infants after probiotic supplementation (p < 0.05).ConclusionThe characteristics of intestinal microbiota in preterm infants differ from those in full-term infants. Probiotic supplementation can reduce the relative abundance of potential pathogenic bacteria and increase the abundance of beneficial microbiota in premature infants.

Introduction Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the most frequently used. Due to the potential risk of high osmolality-induced harm to the intestinal mucosa, diluted glycerine enema solutions are commonly used in clinical practice. The challenge lies in the current lack of knowledge regarding the safest and most effective concentration of glycerine enema. This research aims to ascertain the safety of different concentrations of glycerine enema solution in preterm infants.Methods and analysis This study protocol is for a single-centre, two-arm, parallel-group, double-blind and non-inferiority randomised controlled trial. Participants will be recruited from a NICU in a teriary class A hospital in China, and eligible infants will be randomly allocated to either the glycerine (mL): saline (mL) group in a 3:7 ratio or the 1:9 ratio group. The enema procedure will adhere to the standardised operational protocols. Primary outcomes encompass necrotising enterocolitis and rectal bleeding, while secondary outcomes encompass feeding parameters, meconium passage outcomes and splanchnic regional oxygen saturation. Analyses will compare the two trial arms based on an intention-to-treat allocation.Ethics and dissemination This trial is approved by the ethics committee of the Medical Ethics Committee of West China Second University Hospital of Sichuan University. The results will be published in a peer-reviewed journal.Trial registration number ChiCTR2300079199.