The pandemics of obesity, undernutrition, and climate change represent severe threats to child health. They co-occur; interact with each other to produce sequelae at biological, psychological, or social levels; and share common underlying drivers. In this paper, we review the key issues concerning child diet and nutritional status, focusing on the interactions with climate and food systems. Inadequate infant and young child feeding practices, food insecurity, poverty, and limited access to health services are the leading causes of malnutrition across generations. Food system industrialization and globalization lead to a double burden of malnutrition, whereby undernutrition (i.e., stunting, wasting, and deficiencies in micronutrients) coexists with overweight and obesity, as well as to harmful effects on climate. Climate change and the COVID-19 pandemic are worsening child malnutrition, impacting the main underlying causes (i.e., household food security, dietary diversity, nutrient quality, and access to maternal and child health), as well as the social, economic, and political factors determining food security and nutrition (livelihoods, income, infrastructure resources, and political context). Existing interventions have the potential to be further scaled-up to concurrently address undernutrition, overnutrition, and climate change by cross-cutting education, agriculture, food systems, and social safety nets. Several stakeholders must work co-operatively to improve global sustainable nutrition.

Pneumonia remains a leading cause of childhood mortality in sub-Saharan African countries. The World Health Organization (WHO) recommends a combination of ampicillin or benzylpenicillin with gentamicin for severe pneumonia in children aged 2-59 months. Real-world adherence to these guidelines remains limited. We conducted a retrospective observational study at St. Luke Hospital in Woliso, Ethiopia, including all children aged 2-59 months admitted with severe pneumonia between May 2021 and April 2024. Antibiotic prescriptions were evaluated for adherence to WHO guidelines and categorized using the WHO AWaRe classification. Clinical outcomes were analyzed based on adherence status using univariate and multivariate analyses. Among 427 patients, 46.1% received guideline-adherent treatment, based on drug selection alone. Gentamicin and ampicillin were underdosed in 94.5% and 62.4% of cases, respectively. Overall, 43.6% of children received at least one antibiotic from the Watch group. In adjusted analyses, adherence to WHO guidelines was associated with longer duration of oxygen therapy (0.7 days, 95% CI: 0.1-1.3, P = 0.02) but showed no significant association with mortality or treatment failure. Adherence to WHO guidelines was suboptimal, particularly regarding antibiotic dosing. These findings underscore the need for improved antimicrobial stewardship and further evaluation of guideline implementation in Ethiopia.

Background: High-flow nasal cannula (HFNC) therapy is increasingly used for lower respiratory tract infections (LRTIs) in infants and young children, but recommendations vary, and standardised practice is lacking. Objective: To systematically review national or international guidelines on HFNC use in children aged 1–23 months with LRTIs, focusing on initiation, administration, monitoring, discontinuation and feeding. Methods: We searched MEDLINE, EMBASE, CINAHL, Web of Science and professional society websites (2014–2025) for guidelines on HFNC use in this age group. Four reviewers independently screened, extracted data and assessed quality with the AGREE II tool. Interguideline concordance was calculated for all guidelines and separately for those addressing bronchiolitis and for evidence-based versus consensus-based guidelines. Recommendations were synthesised narratively. Results: Fifteen guidelines were included, including nine bronchiolitis guidelines. All addressed HFNC initiation, with low oxygen saturation (73%) and respiratory distress (47%) as common indications. Initial flow recommendations varied; 2 L/kg/min was most frequent (57%), and all bronchiolitis guidelines reporting it advised weight-based settings. Only two guidelines included weaning or discontinuation protocols, and seven addressed failure criteria. Monitoring typically included pulse oximetry and clinical observation; pulse oximetry was endorsed by all bronchiolitis guidelines that reported it (8/9). Enteral feeding was supported by all reporting guidelines (6/15). Guideline quality was moderate to high, though applicability and updating were frequent gaps. Conclusions: HFNC guideline recommendations for young children with LRTIs remain inconsistent, particularly regarding weaning, failure criteria and procedural details. Regular updates and greater standardisation are needed to improve care and optimise resource use. PROSPERO registration number: CRD42024622544.

Background: Primary care paediatricians play a key role in the diagnosis, management, and prevention of bronchiolitis, but data on their clinical practices remain limited. Methods: An online survey was conducted via email by the Lombardy section of the Italian Primary Care Paediatrics Society (SICuPP) between January 1 and April 30, 2025. Primary care paediatricians were invited to participate via email. Associations were assessed using the chi-square or Fisher’s exact test. Multivariable logistic regression identified factors associated with the prescription of antibiotics, corticosteroids, and bronchodilators—three drug categories commonly used in bronchiolitis despite not being recommended by current guidelines. Results: The response rate was 28.8%, yielding 306 valid responses. Most respondents (62.1%) had over 20 years of clinical experience. Diagnostic criteria varied: 42.8% used 12 months as the upper age limit, 42.2% used 24 months, and 5.6% applied no age limit. Diagnostic approaches differed, with 45.1% relying on wheezing/grunting and 36.9% on wet sounds. Pulse oximetry was always used by 39.5%, and 67.9% never used rapid viral tests. Bronchodilators and steroids were recommended by 37.6% and 32.3%, respectively. Antibiotics were prescribed in 30.1% of cases with poor general condition and 18.6% with fever. Nirsevimab prophylaxis was well accepted (96.4%), with high caregiver compliance (97.7%). Paediatricians diagnosing bronchiolitis up to 36 months were less likely to report never prescribing antibiotics (OR 0.13, 95% CI 0.02–0.51), whereas those relying on widespread sounds were more likely than those using grunting or wheezing (OR 2.42, 95% CI 1.23–4.83). Bronchodilator use was lower with diagnosis based on widespread sounds (OR 0.38, 95% CI 0.18–0.77). Steroid use was higher without an age limit (OR 3.09, 95% CI 1.09–9.25) and lower with widespread sounds (OR 0.31, 95% CI 0.13–0.66). Conclusions: This first Italian survey on bronchiolitis management in primary care reveals substantial variability in diagnostic and treatment practices. Diagnostic inconsistency is associated with non-guideline-recommended prescribing. Standardized diagnostic criteria are needed. Nirsevimab prophylaxis was widely accepted, supporting its continued use to reduce the burden of bronchiolitis.

Introduction Immune dysregulation, whether due to deficiency or hyperactivation, results from a complex interplay of genetic, environmental, and infectious factors. Recent progress in genomic diagnostics, newborn screening, and mechanistic studies has dramatically expanded the recognized spectrum of inborn errors of immunity, which now includes more than 550 distinct genetic defects (1–3). Innovations in biologic therapies and advanced monitoring tools such as multiple breath washout (4) and magnetic resonance imaging (5) are transforming how pediatric immunodeficiencies and inflammatory disorders are diagnosed, managed, and prognosed. At the same time, globalization and emerging infections have introduced new challenges. The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted both acute and long-term implications for immune regulation (6). Beyond the emergence of Multisystem Inflammatory Syndrome in Children (MIS-C), children with inborn errors of immunity are at heightened risk for severe coronavirus disease 2019 (COVID-19) and may exhibit suboptimal vaccine responses (1). Reduced exposure to common pathogens during lockdowns raises questions about long-term immune maturation, allergy, and autoimmunity, consistent with the Old Friends hypothesis (7). Integrating genomic insights with post-COVID immunology may allow earlier identification of children at risk for severe or atypical immune responses. This Research Topic brings together contributions that illustrate how genomic medicine and post-COVID immunology are reshaping pediatric immunology. Genetic Advances Common variable immune deficiency (CVID) and X-linked agammaglobulinemia (XLA) remain the most frequent predominantly antibody deficiency disorders. Traditional genetic methods, such as Sanger sequencing of the tumor necrosis factor receptor superfamily, member 13b/transmembrane activator and CAML interactor (TACI/TNFRSF13B) in CVID and Bruton's tyrosine kinase (BTK) in XLA, continue to confirm diagnoses and uncover pathogenic variants. Chakrobortty et al. (8) conducted a cross-sectional study in Bangladesh of 35 children with suspected predominantly antibody deficiencies. They used serum immunoglobulin measurement, immunophenotyping, Polymerase Chain Reaction (PCR), and Sanger sequencing of BTK and TACI. Among 15 confirmed cases, 7 had CVID, 7 had XLA, and 1 had another form of agammaglobulinemia. BTK sequencing identified seven pathogenic or likely pathogenic variants, three of which were novel, while no pathogenic TACI variants were detected. This study demonstrates how implementing genetic testing in countries where it is not routinely available can improve diagnosis and patient care. Zhu et al. (9) used whole-exome sequencing to uncover a novel topoisomerase II beta (TOP2B) variant in an infant with epileptic spasms, B-cell immunodeficiency, and dysmorphic features. This case shows how sequencing technologies can reveal previously unrecognized genotype-phenotype associations and guide targeted therapy. Boyarchuk et al. (10) described two neonates in Ukraine with B-cell lymphopenia identified through newborn screening. Both carried Immunoglobulin lambda-like polypeptide 1 (IGLL1) variants, c.425C>T and c.258del. Although their clinical manifestations were mild and immunoglobulin levels were near normal, early identification enabled close monitoring and timely therapy, preventing severe complications. These cases highlight how newborn screening can reveal underdiagnosed causes of B-cell lymphopenia. Unfortunately, healthcare disruptions in conflict zones limit access to genetic testing and early interventions (11). Together, these studies illustrate how targeted gene analysis, whole-exome sequencing, and newborn screening are expanding the genetic and clinical spectrum of predominantly antibody deficiencies. They also show how early diagnosis can improve management worldwide. Looking ahead, whole genome sequencing, single-cell immune profiling, and gene therapy are expected to further transform care. New Treatment Approaches for Immune Dysregulation Advances in understanding the genetic and immunologic basis of immune dysregulation have enabled more targeted therapies. Immunoglobulin replacement remains the cornerstone for antibody deficiencies and related rare disorders, as demonstrated by Zhu et al. (9), where early intervention prevented severe infections in a child with a novel TOP2B defect. Biologic therapies are also showing promise for complex complications. Xie et al. (12) reported a juvenile patient with chronic graft versus host disease and refractory arthritis who improved markedly after intra-articular tocilizumab injections. This resulted in better joint function and lower interleukin 6 levels, showing how biologics may be repurposed in challenging situations. In the setting of MIS-C, Lin et al. (13) performed a meta-analysis of 4,269 patients. They found that glucocorticoid monotherapy significantly lowered treatment failure and persistent fever, while combination therapy with intravenous immunoglobulin reduced the need for further immunomodulation. These results highlight the importance of evidence-based approaches guided by genetic and immunologic profiling. Additional modalities such as Janus kinase (JAK) and phosphatidylinositol 3-kinase (PI3K) inhibitors, hematopoietic stem cell transplantation, and gene therapy are expanding treatment options for genetically defined inborn errors of immunity (1). Careful application of these strategies, tailored to individual context, will continue to improve outcomes. Global Health and Equity Considerations Scientific advances promise transformative benefits, but healthcare disparities limit their global impact. The experiences from Bangladesh and Ukraine emphasize the importance of equitable access to genomic testing, newborn screening, and biologic therapies (1,14). Strengthening healthcare systems and investing in scalable...