Moratti et al. exemplify how an effective management of IEI-related LPD demands close collaboration among immunologists, hematologists, and pathologists—integrating clinical presentation with serology, histology, immunohistochemistry, clonality assays, EBV status, and genetics. Reliance on histopathology alone risks misclassification, and atypical cases should prompt re-biopsy and multidisciplinary genetic reassessment to avoid overtreatment.

Background/Objectives: Glycogen storage disease type IX (GSD IX) is an inherited metabolic disorder characterized by marked clinical heterogeneity and variable severity. Dietary therapy is considered the cornerstone of management, but evidence on treatment strategies, efficacy, and safety remains limited. This study aimed to systematically synthesize available data on therapeutic approaches and clinical outcomes in GSD IX. Methods: A focused analysis of treatment-related data was conducted from a previously performed PRISMA-based systematic review. Clinical studies reporting treatment and follow-up data in genetically confirmed GSD IX patients were included. Results: Among 400 patients identified in the original review, 129 from 26 studies had treatment and follow-up data available. Dietary management combined with uncooked cornstarch (UCCS) was the most common approach (96.1%), with highly heterogeneous protocols. Hepatic manifestations improved in 59/129 (45.7%) of patients, and hypoglycemia in 45/129 (34.9%). Growth outcomes were variable, with catch-up growth in 14.0% and persistent impairment in 19.4%, although data were often missing. Muscle involvement was rarely assessed. No treatment-related adverse events were reported. However, disease-related complications were described, including liver cirrhosis, neurological involvement, osteopenia/osteoporosis, and two deaths in GSD IXa patients. Conclusions: Dietary therapy combined with UCCS remains the mainstay of treatment in GSD IX and is associated with improvement in key clinical domains. However, evidence is limited, heterogeneous, and largely based on small studies. Data on modified cornstarch formulations, such as Glycosade®, are scarce. Prospective studies and standardized treatment protocols are needed to support evidence-based management.

Importance:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children, imposing a substantial burden on health care systems. Nirsevimab, a long-acting monoclonal antibody, has shown high efficacy in clinical trials, and modeling studies suggest it may be cost-effective; however, real-world evidence on its cost-effectiveness in European health care settings remains limited. Objective:To evaluate the real-world cost-effectiveness of nirsevimab immunization in preventing pediatric hospitalizations due to RSV. Design, Setting, and Participants:This multicenter, observational, real-world cost-effectiveness analysis was conducted between October 1, 2022, and March 31, 2025. Precampaign data were modeled using Poisson regression models to estimate expected hospitalizations in the absence of immunization. Data were gathered from 19 pediatric hospitals distributed across 11 Italian regions, from northern to southern areas. Included were all pediatric hospitalizations with RSV-specific International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnoses recorded at participating hospitals between October 1, 2022, and March 31, 2025. Exposures:Regional nirsevimab immunization campaigns with varying start dates and eligibility criteria, implemented between October 2024 and January 2025. Main Outcomes and Measures:Effectiveness, expressed as hospitalizations averted (ΔE), and incremental costs (ΔC) were estimated from the Italian National Health Service perspective. Cost-effectiveness ratios (CERs = ΔC/ΔE) were calculated for each center. Results:During the 2024 to 2025 season, 5924 RSV-related hospitalizations were recorded in children 18 years and younger across 19 centers. Observed admissions were consistently lower than model-based counterfactual predictions in most centers. Immunization averted between 6 and 151 admissions per center, corresponding to a rate of 83 and 1162 per 100 000 children. Incremental costs were negative in most centers, indicating cost savings ranging from -€10 924 (US $12 562.60) to -€266 954 (US $306 997.10) per center. Corresponding cost-effectiveness ratios were negative (-€1071 [US $1231.65] and -€1682 [(US $1934.30]), reflecting a cost-saving intervention. In 2 centers with late initiation and restricted eligibility, immunization was associated with higher costs relative to the number of hospitalizations prevented, with incremental costs of €19 715 (US $22 672.25) and €81 454 (US $93 672.10). Sensitivity analyses confirmed the robustness of results. Conclusions and Relevance:Results of this Italian multicenter, real-world economic evaluation suggest that nirsevimab immunization was both clinically effective and cost saving from a health system perspective. Timing and eligibility of immunization strongly influenced cost-effectiveness, highlighting the importance of early and broad rollout strategies to maximize clinical and economic benefits.

OBJECTIVE:To evaluate the impact of timing of aggressive joint pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion piperacillin-tazobactam on early clinical response in paediatric hematopoietic stem cell (HSCT) recipients with febrile neutropenia (FN). METHODS:This prospective, monocentric, observational study included paediatric HSCT recipients receiving at least 72 h of therapeutic drug monitoring-guided continuous infusion piperacillin-tazobactam monotherapy for treating FN episodes. Plasma CRP, procalcitonin, and IL-6 levels were assessed at the onset of FN episodes and at day + 1 and + 3 after starting antibiotic therapy, together with steady-state piperacillin-tazobactam concentrations (Css). Aggressive piperacillin-tazobactam joint PK/PD target attainment was calculated at each timepoint. Multivariate logistic regression analyses were performed for identifying independent predictors significantly associated with the attainment of aggressive PK/PD target at each timepoint. RESULTS:Overall, 42 patients who received continuous infusion piperacillin-tazobactam for 49 documented FN episodes were enrolled. The proportion of aggressive joint PK/PD target attainment was 46.7% at day + 1 and increased to 67.3% at day + 3 (P = 0.04). Clinical response at day + 3 was reported in 35 FN episodes (71.4%). Aggressive PK/PD target attainment occurred more frequently in cases having lower baseline creatinine clearance values at day + 1 (OR 1.01; 95% CI 1.00-1.02; P = 0.018) and was an independent predictor of >50% reduction of baseline plasma interleukin-6 levels at day + 3 (OR 4.62; 95% CI 1.22-17.45; P = 0.024). CONCLUSIONS:Attaining aggressive piperacillin-tazobactam joint PK/PD target in pediatric HSCT recipients with FN was significantly associated with reduction >50% in interleukin-6 levels at day + 3, although no significant impact on early clinical response was found.

OBJECTIVES:To describe paediatric RSV-hospitalisation trends over six seasons and changes following regional nirsevimab strategies in Italy. METHODS:A Retrospective study across 19 Italian paediatric units was conducted analysing RSV-related hospitalisations in patients aged <18 years from January 2019 to March 2025. Centres were grouped by regional nirsevimab eligibility criteria (Groups A-G). Group-level ratios of 2024-2025 to pre-immunisation hospitalisations were estimated with a negative-binomial model. Influenza was analysed as a negative control RESULTS: 10,915 RSV hospitalisations were recorded. In 2024-2025 RSV season, hospitalisations decreased 43.6% overall. The largest reductions were in groups with broader eligibility and earlier initiation (Group B: ratio 0.28, 95% CI 0.22-0.36; Group A: 0.40, 95% CI 0.22-0.74) and Group F (0.24; single centre, interval indicative). Groups C, D, and E showed more modest reductions (ratios 0.58-0.70), with Group C spanning unity (0.58, 95% CI 0.27-1.25). Group G showed no clear change once baseline instability was accounted for (1.84, 95% CI 1.15-2.94). CONCLUSIONS:These population-level study describe a temporal association between the 2024-2025 nirsevimab rollout and reduced RSV hospitalisations, particularly with broader eligibility and timely rollout. The study design cannot establish causation or compare the effectiveness of regional strategies.

Background: At the onset of Type 1 Diabetes (T1D), international guidelines recommend initiating subcutaneous insulin therapy within a wide dosage range (0.5-1 IU/kg/day), as insulin requirement (IR) varies greatly based on several factors, including age, pubertal status, and the presence of diabetic ketoacidosis (DKA). In clinical practice, some individuals require higher-than-expected IR, leading to prolonged hospitalization. This study aimed to identify predictive factors for elevated IR at T1D onset. Methods: We conducted a retrospective observational study including 218 children and adolescents diagnosed with T1D between January 2010 and September 2020. Clinical and laboratory parameters were collected. IR was defined as the highest daily subcutaneous insulin dose (IU/kg/day) during hospitalization, after resolution of DKA. Results: As expected, DKA severity and HbA1c levels were associated with increased IR. However, the strongest independent predictor in the multivariate model was serum triglyceride level (β = 0.27, p < 0.001), with an adjusted R2 of 0.37. No evidence of multicollinearity was detected, and ROC analysis yielded an AUC of approximately 0.70. Conclusions: Hypertriglyceridemia at T1D onset is independently associated with higher IR, regardless of DKA severity. Early recognition of this marker could help optimize insulin dosing, improve metabolic stabilization, and potentially shorten hospital stays.

Advances in pediatric oncology have markedly improved survival, shifting attention toward long-term treatment-related morbidity. Targeted agents and immune-based therapies are now widely used across pediatric malignancies and selected non-malignant conditions, often for prolonged periods and during critical windows of growth and development. Because many therapeutic targets regulate physiological pathways involved in growth, pubertal maturation, gonadal function, bone metabolism, and energy homeostasis, clinically relevant endocrine toxicity may emerge during treatment or become apparent only with extended follow-up. This narrative review summarizes pediatric evidence on endocrine and metabolic effects associated with major classes of targeted and immune-based therapies, including tyrosine kinase inhibitors, mTOR inhibitors, MAPK-pathway inhibitors (BRAF/MEK), TRK inhibitors, ALK inhibitors, immune checkpoint inhibitors, and immune effector therapies. Distinct patterns of endocrine vulnerability emerge across drug classes: growth impairment and bone–mineral alterations are most consistently reported with tyrosine kinase inhibitors; weight gain and metabolic changes predominate with MAPK-, TRK-, and ALK-targeted agents; immune checkpoint inhibitors are characterized by early, multi-axis immune-related endocrinopathies with a high likelihood of permanent hormone deficiency once established. In contrast, endocrine abnormalities observed after immune effector therapies largely reflect indirect effects of systemic inflammation, corticosteroid exposure, and prior hematopoietic stem cell transplantation rather than direct endocrine toxicity. Given the limited pediatric-specific data, frequent confounding by multimodal therapy, and the potential for delayed or irreversible endocrine sequelae, structured endocrine monitoring and long-term survivorship care are essential for children exposed to modern anticancer therapies.

This study compares the efficacy and safety of three levothyroxine (LT4) formulations in pediatric patients with congenital hypothyroidism (CH). This is a retrospective-prospective observational monocentric study conducted at the Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy. Patients’ data were collected from diagnostic confirmation following CH positivity on newborn screening (occurring between January 2019 and April 2024) through age 3 years. According to the LT4 pharmaceutical formulation used in routine clinical practice, patients were assigned to one of three specific groups: T (tablets), D (oral drops), or S (oral solution). 82 patients were enrolled (group D, N = 30; group S, N = 25; group T, N = 27). At 7–15 days of follow-up, the median TSH concentration was significantly higher in group S compared with group T (p = 0.020). Accordingly, the proportion of patients with serum TSH concentrations above the reference range was significantly higher in group S compared with group T at this time point (p = 0.005). Another difference was observed at 12 months of follow-up, when the proportion of patients with serum fT4 concentrations below the reference range was higher in group D than in groups S and T (p = 0.011). No treatment-related adverse effects were observed with any formulation. The three LT4 formulations were equally effective in normalizing and maintaining serum TSH and fT4 within reference ranges. However, the clinical relevance of the differences observed at specific time points requires further investigation.

Children with skin color (SOC) are underrepresented in dermatologic research, despite structural and functional differences that shape disease presentation. Atopic dermatitis (AD), one of the most common pediatric dermatoses, often appears differently in SOC than in white children. This study compared dermatologic conditions prompting Pediatric Emergency Department (PED) referral in SOC and white children, and described clinical features of AD in SOC. A retrospective study was performed at IRCCS AOUBO Policlinico di Sant’Orsola, Bologna, Italy, analyzing records and photographs from 2019. Patients presenting with dermatologic conditions and evaluated by a pediatric dermatologist were included. Of 411 patients, 109 (26.5%) had SOC. In SOC, common diagnoses were scabies (22%), AD (17.4%), viral infections (12.8%), burns (9.2%), and contact dermatitis (7.3%). In white children, viral infections (16.9%), burns (14.2%), contact dermatitis (13.9%), AD (12.9%), and insect bites (5.6%) predominated. Scabies and pruritus were significantly more frequent in SOC (p < 0.05). Among 38 SOC patients with AD, lichenoid (31.6%), pityriasis alba (29.0%), prurigo nodularis (26.3%), and classic AD (13.2%) were the most frequent variants. Erythema was often subtle or absent. Dermatologic conditions and AD morphology differ between SOC and white children, highlighting the need for tailored diagnostic approaches and equitable care.

Artificial intelligence (AI) is increasingly recognized as a transformative technology in healthcare, with growing evidence supporting its applicability across time-critical clinical environments. This perspective aims to evaluate the integration of AI and machine learning (ML) into pediatric emergency departments (PEDs) across three core domains: clinical decision support, stakeholder engagement, and medical education. Within clinical decision support, ML architectures have demonstrated high predictive performance across several high-acuity clinical scenarios, including triage stratification, pediatric traumatic brain injury risk classification, early sepsis detection and clinical deterioration prediction, and dermatological assessment. Model interpretability and real-world implementability remain critical prerequisites for clinical adoption, with explainability methods representing fundamental instruments to enhance transparency and stakeholder trust. Regarding stakeholder engagement, the triadic dynamic among clinicians, caregivers, and patients defines a unique communication challenge in PEDs, with large language models (LLMs) showing preliminary utility; however, stakeholder-inclusive model validation and robust data privacy protections for minors remain key challenges, particularly regarding legal ambiguities of LLM deployment in clinical pipelines. In medical education, AI-driven simulation platforms and LLM-generated adaptive curricula represent promising tools for competency-based training across pediatric emergency scenarios. Future directions emphasize the imperative of prospective multicenter validation in pediatric-specific cohorts, rigorous data quality standards addressing conformance, completeness, and plausibility, and the development of pediatric-tailored governance frameworks. Real-world implementation will require the systematic involvement of all stakeholders-including children, caregivers, clinicians, developers, and institutions-as co-designers of equitable, transparent, and safe AI systems for this uniquely vulnerable population.

ABSTRACT Objective Congenital endocrine salt‐wasting syndromes unrelated to 21‐hydroxylase deficiency are rare disorders with overlapping clinical and biochemical features at presentation. This study described the spectrum, early clinical course, and 36‐month outcomes of these conditions in the era of newborn screening, and assessed whether severity at presentation was associated with later treatment requirements and growth. Methods Retrospective single‐center cohort study including infants diagnosed between 1989 and 2023 with endocrine salt‐wasting syndromes unrelated to 21‐hydroxylase deficiency. Clinical presentation, biochemical findings, treatment requirements, genetic data, and longitudinal growth outcomes up to 36 months were analysed. Results Twenty patients were included: eight with aldosterone synthase deficiency, six with renal pseudohypoaldosteronism type 1, four with systemic pseudohypoaldosteronism type 1, and two with congenital adrenal hypoplasia. Systemic pseudohypoaldosteronism type 1 presented earliest and with the most severe biochemical abnormalities, requiring higher sodium supplementation at onset. Aldosterone synthase deficiency and renal pseudohypoaldosteronism type 1 presented later, with less severe, overlapping biochemical profiles. Differences in early management across etiologies were mainly limited to sodium supplementation, whereas time to electrolyte stabilization and mineralocorticoid initiation did not differ significantly. In exploratory analyses, severity at presentation was not associated with later treatment requirements or growth outcomes, whereas growth was largely preserved, with greater auxological vulnerability in systemic pseudohypoaldosteronism type 1. Conclusions Congenital endocrine salt‐wasting syndromes unrelated to 21‐hydroxylase deficiency show substantial overlap at onset, whereas disease‐specific features become more recognizable during follow‐up. Growth outcomes were generally preserved with appropriate management and did not appear to be influenced by clinical severity at presentation.

The authors would like to make the following correction to their published paper [...]

Inborn errors of immunity (IEI) are genetic disorders that not only heighten infection risk but also disrupt immune regulation, frequently leading to lymphoid tissue overgrowth known as lymphoid proliferations (LPD). We retrospectively reviewed 38 patients with genetically or clinically confirmed IEI and persistent LPD, comparing those with nonneoplastic/reactive hyperplasia to those who developed overt lymphoid neoplasm (lymphoma). Overall, 26% developed lymphoma—predominantly classical Hodgkin lymphoma or diffuse large B cell lymphoma—often after earlier IEI onset. Immunophenotyping and principal component analysis revealed that patients with common variable immunodeficiency developing Hodgkin lymphoma shared a distinctive T cell profile, differing from immunocompetent lymphoma cases. Centralized histologic re-evaluation reclassified several presumed lymphoma as nonneoplastic/reactive hyperplasia and identified Castleman-like and germinal center transformation patterns in nonneoplastic/reactive LPD. Notably, elevated blood IgM and circulating T follicular helper cells mirrored IgM deposits and PD-1+ T cells in lymph nodes. These findings highlight the importance of an integrated approach involving clinical, genetic, and pathological reviews to improve IEI diagnosis and avoid overtreatment.

Synthetic data are increasingly proposed as a strategy for addressing data scarcity and representation imbalance in medical AI, particularly for paediatric populations and darker skin tones. However, visually plausible synthetic images may still contain clinically implausible features or fairness-relevant inconsistencies that are not adequately captured by automatic image-quality metrics. In this study, we present and empirically evaluate a clinician-guided framework for validating and selecting synthetic paediatric dermatology images. The framework combines a clinician-facing evaluation platform with structured assessments of visual realism, mask quality, diagnostic plausibility, confidence, and skin-tone relevance. Four clinicians with complementary expertise in paediatrics and dermatology completed 282 assessments of 93 real and synthetic images. Synthetic images were often rated as visually realistic but showed lower inter-rater agreement and weaker mask-quality assessments than real images. Clinician realism and confidence ratings were then used to divide 30 synthetic images into 18 approved and 12 non-approved images. To assess downstream utility, we compared a real-only ResNet50 classifier with classifiers augmented using all synthetic images, clinician-approved synthetic images, or non-approved synthetic images. Across three patient-level experimental splits, the clinician-approved condition achieved the strongest overall classification performance and the largest gains for the under-represented Dark-Skin subgroup. Because the Dark-Skin subgroup contained only seven patients and the synthetic subsets differed in size and disease composition, these fairness results should be interpreted as exploratory. The present study therefore provides evidence for clinician-guided validation and data curation rather than for a completed iterative generator-retraining process. Future work will evaluate whether clinician feedback can also support repeated generative-model refinement in larger, multi-centre datasets.

Background:Common variable immune deficiency (CVID) is the most prevalent inborn error of immunity (IEI), marked by diverse clinical-immunological phenotypes and significant immune-dysregulation, including granulomatous lymphocytic interstitial lung disease (GLILD). GLILD is a severe manifestation of CVID, contributing to reduced life expectancy and a challenging diagnosis due to its insidious and non-specific clinical course. Current management strategies for GLILD rely on expert opinion due to a lack of randomized controlled trials (RCTs). Objectives:This study aims to provide a comprehensive immunophenotypical characterization of CVID patients with and without GLILD, investigate predictive biomarkers for GLILD development, and explore therapeutic strategies, particularly during concomitant SARS-CoV-2 and chronic cytomegalovirus (CMV) infections. Sources:Primary data were collected from a cohort of 25 patients with CVID who underwent high-resolution computed tomography (HRCT), immunophenotyping, and serum immunoglobulin analysis at diagnosis and after immunoglobulin replacement therapy. Existing literature on CVID and GLILD biomarkers, immunological profiles, and therapeutic interventions informed comparative analyses. Content:Patients with GLILD exhibited distinct immunophenotypical features, including reduced regulatory T-cells, CD8+ naïve, central memory T-cells, and B-cell subsets (memory and switched memory), alongside increased CD21low B-cells and naïve B-cells, indicative of chronic inflammation-driven immune activation. IgA and IgG4 concentrations were significantly lower in patients with GLILD at diagnosis. Immunosuppressive therapy, predominantly mycophenolate mofetil (MMF), demonstrated favorable clinical and functional outcomes, though radiological progression persisted in some cases. CMV infection in patients with GLILD on immunosuppressants resulted in favorable outcomes, underscoring the importance of personalized treatment strategies. Implications:This study highlights novel immunological markers and clinical-radiological patterns as potential predictors for GLILD, advocating for their integration into diagnostic and monitoring frameworks to reduce reliance on invasive histopathology. Future research should focus on validating biomarkers and conducting RCTs to establish evidence-based guidelines for GLILD management.

Background/Objectives: Biotinidase deficiency (BD) is a treatable autosomal recessive disorder included in many newborn screening (NBS) programs. The importance of early diagnosis and treatment is now well established. However, recent studies are emerging on the possibility of increased enzyme activity with age, an observation that raises questions about the long-term validity of the initial classification of these patients. This study aimed to assess the incidence, genetic and clinical features, and, notably, the longitudinal enzymatic trajectory of BD in a cohort identified by NBS in Emilia-Romagna, Italy, with implications for diagnostic re-evaluation and therapeutic decisions. Methods: A retrospective and prospective analysis was conducted on 64 infants recalled after NBS for suspected BD between 2016 and 2020. Biochemical, molecular, and clinical data were collected, and biotinidase (BTD) activity was monitored longitudinally. Affected individuals were supplemented with biotin and followed clinically for at least 5 years. Results: Thirty-one patients were diagnosed with BD (30 partial, 1 profound; incidence 1:5448). A significant and sustained increase in BTD activity was observed from diagnosis through early childhood (p < 0.001 up to 60 months), particularly among patients carrying the p.Asp444His variant. This enzymatic trend suggests a potential remodulation of biochemical classification over time. Genotype–phenotype concordance was high (92%), and clinical outcomes were favorable across the cohort. Conclusions: This study provides new evidence that BTD activity in patients with BD increases progressively, supporting the concept of age-dependent enzyme recovery. Our results support the need for systematic re-evaluation of diagnosis and treatment, especially at 12 months of age, and particularly in patients with evidence of partial activity deficiency and the p.Asp444His mutation.

INTRODUCTION:Respiratory syncytial virus (RSV) causes significant morbidity and mortality in young children. For 25 years, palivizumab has been the only effective pharmaceutical RSV preventive. AREAS COVERED:We summarize the development and a quarter-century of real-world evidence with palivizumab. We highlight its positive impact on the burden of RSV in high-risk children. Based on lessons learnt from its implementation, we suggest strategies for effective and equitable deployment of newer RSV preventives. EXPERT OPINION:Following failure of the formalin-inactivated RSV vaccine in 1967, RSV intravenous immunoglobulin was approved in 1996 after three decades' research. Subsequently, palivizumab emerged as the most effective and safe RSV preventive, demonstrated by the IMpact trial, and was licensed in 1998 in the United States. Over the last 25 years, the benefits of palivizumab have been firmly established through a wealth of evidence, predominantly from high-income countries (HICs). To achieve a global impact with the newer RSV preventives, evidenced-based universal guidelines must be developed and endorsed by regulatory authorities and relevant scientific societies. Independent economic evaluations should incorporate all RSV-associated healthcare costs, reduction of long-term respiratory sequelae, and standardized outcomes. Most importantly, equity in product availability and implementation, particularly in low- and middle-income countries (LMICs) is essential.

Background: Expanded Newborn Screening (ENS) allows the early identification of many inherited metabolic diseases (IMDs) for which timely treatment can modify the natural history. For most IMDs, diagnosis by ENS is pre-clinical. However, clinical symptoms may emerge for certain conditions before screening results become available. Methods: We describe six cases of patients with early-onset IMDs born between 2013 and 2023, who were admitted or transferred to Sant’Orsola University Hospital in Bologna (Italy). Results: Over the study period, 379,013 newborns underwent ENS in the Italian region of Emilia-Romagna. Excluding cases of congenital hypothyroidism, pre-clinical diagnoses from ENS were 410. In addition, six cases of IMD presented with early-onset clinical symptomatology, an antecedent to the outcome of newborn screening (incidence over 11 years of 1.58 cases per 100,000 infants). Among these patients, three were diagnosed with Urea Cycle Disorders (UCDs)—two with Citrullinemia type I (CIT1) and one with Argininosuccinic Acidemia (ASA); two were diagnosed with Methylmalonic Acidemia (MMA); and one was found to have Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD). Conclusions: Our 11-year experience with ENS has shown that clinical onset can occur between the second and fourth day of life, though rare. Even if dried blood spot (DBS) collection was performed 24–48 h after birth, the time required for sample transportation and processing would still delay result availability, making early intervention unlikely. Therefore, our experience supports performing ENS at 48–72 h, as currently implemented in Italy, while also highlighting the advantages and limitations of earlier screening.