Search Results (227)

Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently develop coagulation abnormalities and bleeding complications, yet data on transfusion burden and its clinical correlates in this population remain limited. Materials and Methods: We performed a secondary analysis of a retrospective single-center cohort of neonates with HIE treated with TH between 2014 and 2022. Transfusion burden was defined as receipt of at least one blood component and coagulation/plasma products during hospitalization and the total number of transfusion episodes. Demographic, perinatal, biochemical, and clinical severity variables were collected. Univariable and multivariable logistic regression analyses were used to identify factors independently associated with transfusion exposure. Brain magnetic resonance imaging (MRI) findings were compared between transfused and non-transfused infants. Results: Among 142 included neonates, 74 (52.1%) received at least one blood product. The median number of transfusion episodes among transfused infants was 2 (IQR 1–3). Fresh frozen plasma and prothrombin complex concentrate were the most frequently administered products. Transfused infants showed higher markers of illness severity. In multivariable analysis, clinically visible bleeding (adjusted odds ratio [aOR] 12.95, 95% CI 1.34–124.97) and need for respiratory support (aOR 2.98, 95% CI 1.19–7.45) remained independently associated with transfusion exposure. Pathological brain MRI findings, including intracranial bleeding and hypoxic–ischemic injury, were more frequent among transfused infants. Conclusions: blood components and coagulation/plasma-derived products transfusions are common in neonates with HIE undergoing TH and appear to primarily reflect underlying disease severity. These findings highlight the need for optimized, evidence-based transfusion strategies in this vulnerable population. Full article

Neonatal hypoxic–ischemic encephalopathy (HIE) remains one of the leading causes of neonatal mortality and long-term neurodevelopmental disability despite therapeutic hypothermia, which provides only partial neuroprotection. Among adjunctive therapies, magnesium sulfate (MgSO₄) has emerged as one of the most biologically plausible neuroprotective agents because of its ability to modulate glutamate-mediated excitotoxicity, intracellular calcium influx, oxidative stress, neuroinflammation, and apoptotic pathways. Nevertheless, encouraging molecular and preclinical findings have not translated into consistent clinical benefit. This narrative review critically examines the translational gap between the molecular mechanisms of magnesium sulfate and its clinical performance in neonatal HIE. Evidence from experimental models, clinical studies and recent meta-analyses was integrated to identify the biological and methodological factors potentially responsible for this discrepancy. We discuss the evolving pathophysiology of HIE across the primary, latent, secondary and tertiary phases of brain injury and analyze how the timing of intervention, lesion heterogeneity and inadequate biological stratification may influence therapeutic responsiveness. Current clinical research has largely evaluated broad neurological outcomes, particularly cerebral palsy, despite the heterogeneous neuropathological substrates underlying neonatal brain injury. We argue that this strategy may dilute genuine treatment effects by grouping together distinct lesion phenotypes with different biological mechanisms. Accordingly, we propose the “Neuroprotection per Effective Therapy (NET)” framework, a conceptual translational model integrating molecular targets, experimental evidence, MRI-defined lesion phenotypes, methodological quality, and advanced statistical approaches to improve patient stratification and outcome selection. Rather than questioning the biological efficacy of magnesium sulfate itself, this review suggests that future progress will depend on aligning molecular mechanisms with clinically meaningful phenotypes. Precision-based translational strategies may ultimately allow magnesium sulfate and other neuroprotective therapies to better reveal their therapeutic effects in biologically appropriate patient subgroups. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE) remains a leading cause of neonatal death and long-term neurodisability. Cardiovascular dysfunction commonly accompanies HIE and influences neurological recovery, yet it is difficult to recognize because conventional clinical signs correlate poorly with the myocardial function. This review summarizes the current evidence on cardiac dysfunction in neonates with HIE, with particular attention to the diagnostic tools used to evaluate cardiovascular function and the clinical outcomes associated with myocardial injury. Methods: We conducted a narrative review informed by a systematic, reproducible search of four databases (PubMed, Embase, Cochrane Library, and Web of Science) from 2000 to 2026, using a Population–Concept–Context framework to identify studies of term and near-term neonates (≥35 weeks gestation) with HIE or perinatal asphyxia reporting a measure of cardiac dysfunction (electrocardiographic, biomarker, echocardiographic, or clinical hemodynamic). Records were screened and selected using Covidence systematic review software; eligible studies were original, primary-data reports with a minimum sample size of 20 neonates. Findings were synthesized narratively and grouped thematically by diagnostic modality and clinical outcome. Results: Eighty-one studies met the pre-specified eligibility criteria following a systematic multi-database search and structured screening process. As a subset of included studies are secondary analyses or overlapping cohorts, an aggregate patient count is not reported. Reported prevalence of cardiac dysfunction varied widely with the definition applied, reaching 70–90% when multimodal assessment was used. Blood pressure, heart rate, urine output, and lactate were inconsistently reliable indicators of myocardial function, and ejection fraction and fractional shortening often remained normal despite injury. Tissue Doppler imaging and speckle-tracking strain appeared to be more sensitive, with impaired left ventricular global longitudinal strain associated with brain injury. The right ventricle was more commonly and severely affected, with reduced TAPSE, RV fractional area change, and RV strain associated with death or MRI-defined injury. Each additional 24 h of inotropic support was associated with increased odds of adverse short- and long-term outcomes by 14% and 12%, respectively. Conclusions: Cardiac dysfunction is common and prognostically important but remains underrecognized by the routine clinical assessment and cardiovascular monitoring. Multimodal monitoring centered on TnECHO, near infra-red spectroscopy, and specific biomarkers may enable earlier, physiology-based management. Full article

Hemorrhagic shock is a leading cause of preventable death following multiple trauma, driven by a cascade of interacting cellular and molecular disturbances that extend well beyond simple volume loss. Acute blood loss initiates tissue hypoperfusion and cellular hypoxia, setting in motion the lethal triad of hypothermia, acidosis, and coagulopathy through several converging pathways: complement activation with excessive C3a and C5a production; neutrophil-mediated tissue injury; NADPH-oxidase-driven reactive oxygen species (ROS) overproduction that overwhelms superoxide dismutase defenses; mitochondrial respiratory chain impairment; dysregulation of the pro-inflammatory cytokine network; and endothelial apoptosis with degradation of the endothelial glycocalyx and disruption of interendothelial junctions, with consequent vascular hyperpermeability. These mechanisms provide the biological rationale for the resuscitation strategy. Each class of fluid acts on these pathways in a distinct way: crystalloids modulate acid–base homeostasis, chloride-mediated renal vasoconstriction, and coagulation factor activity; colloids influence oncotic pressure, endothelial integrity, and microvascular perfusion; and blood products, particularly plasma and whole blood, actively modulate mitochondrial metabolism, endothelial permeability, and pro-apoptotic signaling beyond their volume-expanding role. Translating this biology to the bedside requires a multimodal monitoring framework that converts molecular endpoints into real-time therapeutic targets, integrating lactate and base excess as markers of cellular oxygen debt, dynamic preload indices such as pulse pressure and stroke volume variation, advanced hemodynamic platforms, point-of-care ultrasonography, viscoelastic coagulation testing, and near-infrared spectroscopy of tissue oxygenation. This review synthesizes the biological basis of hemorrhagic shock and its translation into an individualized, goal-directed resuscitation strategy for the critically ill polytrauma patient. Full article

Background/Objectives: Neuron-specific enolase (NSE) is one of the most extensively investigated biomarkers for neurological prognostication after cardiac arrest. However, uncertainty remains regarding the influence of targeted temperature management (TTM) on NSE kinetics, optimal prognostic thresholds, and predictive accuracy. This systematic review and meta-analysis aimed to evaluate the prognostic performance of NSE and assess the impact of TTM on its clinical utility in contemporary post-resuscitation care. Methods: A systematic search of PubMed/MEDLINE, Embase, and Scopus was conducted to identify studies published between January 2000 and April 2026. Literature screening, data extraction, and quality assessment were performed in accordance with the PRISMA 2020 statement. Methodological quality was assessed using the Newcastle–Ottawa Scale and the Cochrane Risk of Bias tool, when applicable. Quantitative synthesis was performed for studies reporting sufficiently homogeneous area under the receiver operating characteristic curve (AUC) data. Results: Twenty-one studies met the eligibility criteria and were included in the qualitative synthesis, of which seven were eligible for quantitative analysis. NSE demonstrated good overall prognostic performance for predicting neurological outcome after cardiac arrest, with a pooled AUC of 0.868 (95% CI: 0.849–0.885) and no significant between-study heterogeneity (I² = 0%). Prognostic performance was generally highest when NSE was measured between 48 and 72 h after return of spontaneous circulation. Considerable variability was observed in reported prognostic thresholds, particularly across different TTM strategies. Serial NSE measurements and multimodal neuroprognostication approaches consistently improved predictive performance. Conclusions: NSE provides good prognostic accuracy for neurological outcome prediction after cardiac arrest and remains clinically valuable in patients managed with TTM. Serial measurements obtained between 48 and 72 h after return of spontaneous circulation appear to provide the greatest prognostic value. NSE should be interpreted as part of a multimodal neuroprognostication strategy rather than as a standalone predictor. Full article

Background/Objectives: Selecting appropriate doses for pediatric patients remains one of the most complex challenges in drug development because developmental changes in physiology, metabolism, organ function, and pharmacodynamics substantially influence drug exposure and response. This review summarizes current evidence-based approaches to pediatric dose selection across the developmental continuum and evaluates contemporary model-informed strategies for individualized dosing. Methods: A narrative review of the literature was conducted focusing on pediatric dose-scaling methodologies, developmental pharmacology, physiologically based pharmacokinetic (PBPK) modeling, population pharmacokinetic (PopPK) approaches, exposure–response analysis, therapeutic drug monitoring, and regulatory extrapolation frameworks. Special populations and clinical scenarios relevant to pediatric dose optimization were also evaluated. Results: Simple body weight-based scaling from adult doses inadequately accounts for developmental changes in drug disposition and response. Allometric scaling combined with maturation functions provides improved dose prediction in neonates and infants, while PBPK and PopPK modeling support mechanistic and data-driven dose optimization across pediatric age groups. Fat-free-mass (FFM)-based scaling is preferred over total body weight for many drugs in children with obesity. Additional considerations including obesity, biologics, formulation and excipient safety, pharmacogenomics, critical illness, therapeutic hypothermia, extracorporeal support, therapeutic drug monitoring, and drug–drug interactions substantially influence pediatric dosing strategies. Regulatory frameworks including ICH E11A increasingly support model-informed pediatric extrapolation and precision dosing approaches. Conclusions: Pediatric dose selection has evolved from empirical weight-based dosing toward integrated model-informed strategies incorporating developmental physiology, pharmacometrics, and regulatory science. Allometry, maturation functions, FFM-based scaling, PBPK, PopPK, and therapeutic drug monitoring provide complementary tools for rational pediatric dose optimization, although drug- and pathway-specific validation remains essential, particularly in neonates and critically ill children. Full article

Background/Objectives: Neonatal hypoxic–ischemic encephalopathy (HIE) is a major cause of neurodevelopmental diseases. In a previous retrospective study, we revealed that the levels of the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) are linked to HIE severity. We conducted a prospective investigation to evaluate the association between sLOX-1 levels and HIE severity using the Sarnat staging system, as well as a multicenter study to assess neurodevelopmental sequelae in the short term. Methods: A total of 193 infants were enrolled in the study between April 2018 and March 2021. We divided the infants into groups as follows: infants without HIE were assigned to a normal control group, and those with HIE to mild, moderate, and severe HIE groups. We measured 191 samples, excluding three participants. The distribution of 191 participants was as follows: 88 normal samples of 50 umbilical cord (UC) arteries and 38 venous blood samples (control; CTL), as well as 103 HIE samples of 34 mild, 55 moderate, and 14 severe HIE samples. All the plasma samples were collected until 6 h after birth. Results: The mean sLOX-1 value in the CTL group was 613 pg/mL (IQR: 474–925 pg/mL) and that in the UC group was 497 pg/mL (IQR: 337–693 pg/mL), with no significant difference (p = 0.136). The mean sLOX-1 value in the mild HIE group was 1030 pg/mL (IQR: 658–1547 pg/mL), 1026 pg/mL (IQR: 710–2051 pg/mL) in the moderate HIE group, and 1444 pg/mL (IQR: 766–3927 pg/mL) in the severe HIE group. There were significant differences between the CTL and HIE groups (p = 0.006) and between the CTL and mild HIE groups (p < 0.05), but not between the mild HIE and the moderate and severe HIE groups (p = 0.088). The other blood markers exhibited no correlation with Sarnat severity. Interestingly, blood sLOX-1 levels increased with Sarnat severity. Conclusions: The results of this study indicated that sLOX-1 level was correlated with Sarnat severity. Moreover, early assessment of sLOX-1 level may be useful for deciding whether to induce therapeutic hypothermia and/or other treatments, and sLOX-1 may serve as a short-term outcome biomarker of HIE. Full article

Cold seawater immersion is a critical lethal risk in maritime accidents and military operations, frequently inducing fatal myocardial dysfunction. However, the mechanisms underlying this seawater immersion hypothermia-induced cardiac injury remain poorly defined. This study aimed to elucidate the pathological progression and underlying mechanisms of myocardial injury induced by cold seawater immersion. A male SD rat model was immersed in 15 °C seawater for 2 h. Echocardiography, transmission electron microscopy, transcriptomics, and Western blot were performed to assess cardiac function, mitochondrial ultrastructure, and molecular mechanisms. Cold stress triggered progressive bradycardia (~480 to ~100 bpm) with initial Frank–Starling compensation, followed by decompensation with reduced cardiac output and impaired diastolic function. Mitochondrial ultrastructural damage preceded histological lesions and was accompanied by elevated cardiac injury markers (cTnT, CK-MB, BNP). Cardiac tissue exhibited upregulated TNF-α, IL-1β, and IL-6, while transcriptomic analysis revealed enrichment of inflammatory pathways (TNF, NF-κB) and coordinated upregulation of pattern recognition receptors including scavenger receptor, Toll-like receptor, and NOD-like receptor families. The Western blot confirmed NF-κB activation, NLRP3 inflammasome assembly, and the N-terminal fragment of gasdermin D (GSDMD-NT) accumulation, indicating pyroptotic cell death. These findings demonstrate that cold seawater stress disrupts mitochondrial homeostasis and activates the NF-κB/NLRP3/pyroptosis cascade, contributing to inflammatory cardiomyocyte death and cardiac decompensation. This mechanistic insight may inform therapeutic strategies for seawater immersion hypothermia. Full article

Background and Objectives: Traumatic hemorrhage remains the leading cause of preventable death following major injury, with most hemorrhage-related fatalities occurring within the first hours after trauma. During this early phase, trauma-induced coagulopathy (TIC) frequently develops as an independent pathophysiological response, affecting up to one-third of severely injured patients and being strongly associated with increased morbidity and mortality. Over the past two decades, TIC has been recognized as a complex endogenous process rather than a simple consequence of dilution, hypothermia, or acidosis, prompting a paradigm shift in early trauma resuscitation. Materials and Methods: This narrative review analyzes the current literature on the pathophysiology of TIC and the evolution of hemostatic resuscitation strategies. Key topics include the mechanisms underlying early coagulopathy, its clinical impact, and the evidence supporting contemporary therapeutic approaches. Published data on balanced transfusion strategies, whole blood transfusion, fibrinogen replacement, cryoprecipitate, prothrombin complex concentrates, tranexamic acid and viscoelastic-guided resuscitation were reviewed, along with relevant international guidelines. Results: Emerging evidence supports early, balanced, and targeted hemostatic resuscitation to mitigate the effects of TIC and improve outcomes in bleeding trauma patients. Balanced transfusion ratios, prompt correction of fibrinogen deficiency, early antifibrinolytic therapy and selective use of coagulation factor concentrates have been associated with reduced transfusion requirements and improved survival. Viscoelastic testing enables rapid, individualized assessment of coagulation abnormalities, although its availability and implementation remain inconsistent across trauma systems. Conclusions: Early recognition and aggressive, structured management of trauma-induced coagulopathy are essential to reduce preventable deaths from traumatic hemorrhage. While advances in hemostatic resuscitation have improved outcomes, significant challenges remain in standardizing treatment protocols and expanding access to viscoelastic diagnostics. Ongoing research and system-level optimization are needed to further refine and disseminate evidence-based strategies for the management of TIC. Full article

Background: Following a stroke, body and brain temperatures are closely linked. Elevated temperature may reflect the severity of brain injury rather than infection. The significance of admission temperature remains unclear, and hypothermia treatment lacks proven efficacy and safety. Administering paracetamol (acetaminophen) above 36.5 °C is considered safe, though its clinical benefit is modest. This study aimed to examine how admission temperature, peak temperature in the first 24 h, and temperature fluctuations affect three-month functional outcomes. Methods: We conducted a retrospective study using data from a prospective stroke registry, including 5883 patients (4830 with ischemic stroke [IS] and 1053 with hemorrhagic stroke [HS]). Temperature at admission, maximum temperature within the first 24 h, and the temperature increase during the first day were assessed. Patients with a temperature ≥ 37.5 °C received 3 g of paracetamol per day until normothermia was achieved. Results: Baseline temperature was not associated with 3-month functional outcomes. In IS patients, an increasing temperature during the first 24 h was associated with a 10-fold higher risk of poor functional outcome (sensitivity 81%, specificity 64%); whereas in HS, the risk increased sevenfold (sensitivity 88%, specificity 53%). The most reliable predictor of therapeutic response was the temperature increase on the first day, with sensitivities of 89% and 83%, and specificities of 84% and 71%, for IS and HS, respectively. Conclusions: An increase in temperature during the first 24 h, rather than a single measurement, is the most reliable temperature-based biomarker for predicting poor functional outcomes and guiding the initiation of antihyperthermic treatment. Full article

Neonatal hypoxic–ischemic encephalopathy (HIE) remains a critical neurological emergency resulting from perinatal asphyxia, often leading to lifelong neurodevelopmental disabilities or mortality. The accurate and timely grading of HIE severity is paramount for initiating therapeutic interventions such as therapeutic hypothermia. This work proposes a diagnostic framework that uses long-duration electroencephalogram (EEG) recordings through a hierarchical classification strategy and advanced sequence modeling. A Hybrid Mamba-inspired architecture was developed to effectively capture long-range temporal dependencies in multi-channel neonatal EEG while maintaining computational efficiency. In order to enhance clinical consistency and initialize the models appropriately, a Self-Supervised Learning step based on Masked Signal Modeling is implemented with a mask ratio of 30%. The model structure takes into consideration clinically verified biomarkers, including the suppression ratio, Delta–Alpha Ratio, Spectral Edge Frequency, and Rhythmicity Index, extracted from signals at a microvolt level prior to normalization for physiological interpretability purposes. These features are combined with waveforms using feature gating. In an experiment conducted on a dataset of 169 records using 5-fold subject-wise cross-validation, the designed Hybrid Mamba-based model achieves significant stability and generalizability, achieving an accuracy score of 90%, with an average accuracy of 88.45% ± 6.8% per hierarchical level. Full article

Background/Objectives: Shenfu Decoction (SFD) is a traditional Chinese herbal formula composed of Panax ginseng and Aconitum carmichaelii that can revive and counteract shock. However, how SFD can mitigate hypothermia caused by seawater immersion is poorly understood. Methods: Three commonly used ratios of SFD (Panax ginseng:Aconitum carmichaelii = 1:1, 1:2, 2:1) were prepared, and their chemical properties were analyzed with UPLC-Q-TOF-MS. A rat model of hypothermia caused by seawater immersion at 15 °C was utilized. Survival analysis was used to evaluate the prophylactic effect of single intragastric administration of SFD with different ratios and doses on the survival time of rats, and to identify the optimal intervention conditions. Network pharmacology analysis based on the absorbed constituents of SFD was performed to preliminarily predict the underlying mechanisms, which were subsequently validated using RT-PCR, Western blotting, ELISA, and H&E staining. Results: SFD contained 54 compounds, including ginsenosides and aconitine alkaloids, whose relative concentrations varied across different ratios of SFD. Animal studies showed that pretreatment of SFD (1:1) administered at a dose of 1.35 g/kg was very effective in increasing rats’ survival time in hypothermia and slowed down core body temperature decline. Based on the 28 plasma-absorbed compounds of SFD, network pharmacology identified 503 targets, enriched in cAMP and MAPK signaling pathways. SFD (1:1, 1.35 g/kg) resulted in larger lipid droplets in brown adipose tissue (BAT) and enhanced the respiratory metabolic rate in seawater-immersion-induced hypothermia rats. Furthermore, its thermogenic effect is likely associated with the upregulation of uncoupling protein 1 (UCP1) via activating p38 MAPK/PGC1α/PPARγ and NE-(β3-AR)-cAMP-PKA pathways. Conclusions: The results of this study demonstrate that a single prophylactic administration of the traditional Chinese medicine formula SFD prior to cold seawater exposure significantly prolongs the survival time of rats. This effect is associated with the upregulation of UCP1 and the subsequent enhancement of thermogenesis in BAT. These findings highlight the great potential of SFD as a promising intervention for the management of hypothermia. Full article

Introduction: This study explored how illness severity scores correspond to hypoxic-ischemic brain injury (HIBI) after cardiac arrest. Methods: This study included cardiac arrest survivors with sufficient data to calculate the Pittsburgh Cardiac Arrest Category (PCAC) and revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST) scores who underwent brain magnetic resonance imaging and cerebrospinal fluid neuron–specific enolase (CSF-NSE) measurement within 6 h after return of spontaneous circulation. The primary outcome was the association of PCAC and rCAST with quantitative brain injury markers assessed using whole brain mean apparent diffusion coefficient (mean ADC), low ADC volume fractions (PV600, 650, and 700), and CSF-NSE. Results: In total, 81 patients were included. PCAC was not significantly associated with CSF-NSE, mean ADC, or PVs. The rCAST score was significantly associated with higher CSF-NSE, lower mean ADC, and higher PV700. The neurologic sub-score of PCAC was independently associated with all evaluated brain injury markers, whereas the systemic sub-score was not. Of the individual rCAST components, anoxic time was independently associated with CSF-NSE, whereas no other single component was associated with these markers. Conclusions: rCAST was significantly associated with degree of HIBI, whereas PCAC was not. The neurologic sub-score of PCAC showed independent associations with HIBI. Full article

We examined neocortical pathology and interneuron degeneration in neonatal hypoxia-ischemic encephalopathy (HIE). Piglets in two age groups (2–3 or 7–10 days old, n = 4–12/group) underwent global cerebral hypoxia–ischemia (HI) or sham treatment. Piglets (2–3 days old) had epidural electrodes for continuous electroencephalography (cEEG) and were treated with hypothermia (HT) or remained at normothermia (NT). Older piglets, all NT, had scalp EEG. Piglets at both ages had seizures and survived for 1–7 days. Cortical damage was assessed by hematoxylin & eosin staining and immunohistochemistry; calretinin (CR), parvalbumin (PV), and vasoactive intestinal peptide (VIP) interneurons (INs) were counted. Cell injury was assessed by DNA fragmentation and protein nitration. TAR DNA binding protein-43 (TDP43) and the DNA repair scaffold protein X-ray repair cross complementing-1 (XRCC1) were examined for degeneration mechanisms. Cortical layers 3 and 4 showed high vulnerability; damage emerged as isolated cells, focal and laminar, and distributed as panlaminar throughout different cortical regions that correlated with seizure burden. HT protected strongly against cortical damage. CR- and PV-INs were severely depleted in HI-NT piglets compared to sham. VIP INs appeared invulnerable. HT partially rescued the loss of INs. CR and PV formed nuclear and cytoplasmic inclusions that colocalized with TDP43 and XRCC1; co-immunoprecipitation identified interactions among these proteins, and tyrosine nitration of CR. CR and PV INs accumulated DNA single- and double-strand breaks and appeared as attritional apoptosis variants with proteinopathy. This cell death is identified as aggreosis. IN loss correlated with seizure presence. Postmortem human neonatal HIE cases had a similar loss of CR and PV INs and nuclear depletion of TDP43 in the neocortex. Thus, neonatal HIE causes the loss of neocortical inhibitory IN subtypes with vulnerabilities instructed by their intrinsic calcium-binding protein signature and by mechanisms consistent with toxic sequestration and the nuclear depletion of XRCC1 and TDP43 underlying DNA damage accumulation. Early inhibitory IN deletion could drive seizure evolution in HIE; TDP43 and XRCC1 could be therapeutic targets for neonatal HIE. Full article

Objectives: The purpose of this study was to compare the incidence of hearing loss at three months of age in a cohort of newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) with that reported in the literature. We also evaluated potential risk factors associated with audiological impairment and changes in hearing threshold during follow-up. Methods: This retrospective observational cohort study was conducted at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario A. Gemelli, IRCCS in Rome, Italy, between January 2017 and December 2023. Infants underwent audiological screening and a full diagnostic evaluation at three months of age and were followed during the first year of life. Results: A total of 149 infants were enrolled, and hearing loss was identified in six (4.0%) at three months of age. Two of these six infants showed an improvement in their hearing threshold, resulting in a prevalence of permanent bilateral sensorineural hearing loss (SNHL) of four out of 149 infants (2.7%), with no cases of late-onset hearing loss detected. Gestational age was identified as an independent protective factor against SNHL (OR 0.49; 95% CI 0.22–0.91). Conclusions: The audiological screening program demonstrates effectiveness in early intervention for diagnosing and treating hearing loss. Infants with HIE are at high risk for hearing disorders and require increased attention in neonatological and audiological management. Management should be individualized based on specific risk factors. The association between gestational age and susceptibility to cochlear damage should be confirmed by further studies. Full article