Immunocompromised pediatric patients, including hematopoietic cell and solid organ transplant recipients, those undergoing chemotherapy for malignancy, and those receiving biologic response modifiers for autoimmune or inflammatory conditions, are at risk for severe disease from vaccine-preventable respiratory viral infections such as influenza, SARS-CoV-2 (COVID-19), and respiratory syncytial virus (RSV). These children face higher rates of hospitalization, intensive care admissions, and mortality, reflecting contributions from an immature immune system, absence of immunologic memory, and/or increased environmental exposures. Immunization recommendations for immunocompromised children are largely extrapolated from studies conducted among healthy children and/or immunocompromised adults due to a paucity of primary data on immunological responses and vaccine efficacy in immunocompromised children. Trends in vaccine hesitancy in the general population, ongoing transmission of respiratory viral infections in the community, and suboptimal vaccination rates among immunocompromised children and their household contacts further compound the risk for this vulnerable population. As the number of children with immunocompromising conditions expands, it is imperative that primary care practitioners and subspecialists who care for immunocompromised children ensure appropriate immunizations are provided to these patients and their household and community contacts. We will review available data supporting the current guidelines regarding vaccine dosing, scheduling, and formulations to prevent influenza, COVID-19, and RSV infections in immunocompromised children. Furthermore, we highlight key knowledge gaps and areas of current investigation aimed at improving respiratory viral vaccine immunogenicity and optimize protection.

Circadian rhythms are intrinsic 24-hour cycles that regulate nearly all aspects of human physiology and play essential roles in brain development, immune regulation, and redox balance. Adult studies have explored the links between circadian rhythms and neurological or metabolic diseases, but research in pediatric populations remains limited. In infants and children, circadian systems undergo rapid maturation, and this developmental window is particularly vulnerable to disruption from maternal, environmental, or endogenous factors. The aim of this review is to examine how circadian mechanisms intersect with inflammatory and oxidative pathways in pediatric neurological disorders, highlighting both mechanistic insights and therapeutic potential. We conducted a narrative review of PubMed/MEDLINE and complementary sources, covering studies published between January 2016 and March 2025, with relevant studies selected for detailed synthesis. Evidence shows that oxidative stress and inflammation are exacerbated by immature circadian control, with glial circadian clocks, clock genes, and cytokine-melatonin interactions playing important roles. Melatonin is frequently identified as a key circadian-regulated mediator in pediatric conditions, including hypoxic-ischaemic encephalopathy, autism spectrum disorder, metabolic encephalopathies, and sepsis. Preclinical and translational studies demonstrate that melatonin reduces oxidative damage, maintains mitochondrial function, and modulates immune responses, while early clinical data indicate that it is safe and holds promise as an adjunctive therapy. The review further emphasizes that circadian regulation of oxidative stress is shaped by maternal signals, melatonin in breast milk, and environmental exposures in neonates, particularly in preterm infants. Despite growing evidence, major gaps remain, including the lack of pediatric-specific chronotherapy trials, standardized dosing protocols, and time-stamped biospecimen studies. We suggest a feasible roadmap for future melatonin-based pediatric chronotherapy trials, linking mechanistic insights to clinical application. Overall, advancing circadian biology, particularly through melatonin, offers a promising avenue for pediatric neuroprotection and opens new directions for chronotherapy in vulnerable populations.

Dilated cardiomyopathy (DCM) is the most prevalent form of cardiomyopathy in children, characterized by left ventricle dilation and impaired systolic function. The etiology critically influences clinical trajectory and prognosis. Mitochondrial disorders represent a rare but increasingly recognized cause of DCM. Herein, we report three pediatric patients, diagnosed with early-onset DCM at ages of 8, 9, and 8, who progressed rapidly to end stage heart failure, resulting in two fatalities and one cardiac transplantation. Whole exome sequencing (WES) analysis identified compound heterozygous TOP3A pathogenic variants in all three cases, accompanied by reduced mitochondrial DNA copy number. Therefore, this report expands the recognized etiologies of childhood DCM and delineates a severe cardiac phenotype within the TOP3A pathogenic variant spectrum. Trial Registration: Registered at Chinese Clinical Trial Registry (ChiCTR2600117173). Registered 20/01/2026. Retrospectively registered.