Pediatric Drugs最新文献

Introduction: β-Blockers are an essential treatment for cardiovascular disease, the incidence of which is rising among women of childbearing age. Several large cohort and registry studies have reported an association between β-blocker exposure in pregnancy and reduced birth weight, but most have included women with hypertension or structural heart disease. Our study's primary objective was to evaluate the impact of these medications on the birth weight of infants born to mothers with morphologically normal hearts, including women with long QT syndrome (LQTS) or Marfan syndrome (MFS). Secondary objectives were to evaluate the influence of β-blocker type on birth weight, diagnoses that fetuses were small for gestational age (SGA) or growth-restricted (FGR) during pregnancy and at birth, uterine Doppler abnormalities, and neonatal adverse effects (bradycardia and hypoglycemia), which are expected effects of in utero β-blocker exposure.

Materials and methods: This retrospective observational single-center study compared pregnancies in patients with LQTS or MFS treated with β-blockers with those of untreated matched control patients. Pregnancies were matched for maternal age, body mass index, parity, gestational age at birth, presence of gestational or pre-existing diabetes, and smoking status.

Results: Fifty-seven pregnancies of 40 mothers exposed to β-blockers were matched with 165 control pregnancies. This study's main finding was that the mean birth weight of infants whose mothers used β-blockers during pregnancy was a significant 442 grams lower (unadjusted 2890 g vs 3285 g; p < 0.001) than that of the control group. SGA/FGR during pregnancy and at birth were diagnosed significantly more often in the treated patients, and their incidence of neonatal bradycardia was higher in the exposed group. Among the uterine Doppler examinations available, no clear differences were observed between groups. Data on neonatal hypoglycemia were inconclusive because of differential screening strategies and a high proportion of missing values, particularly in the control group.

Discussion: To our knowledge, this is the first study specifically focusing on β-blocker use in pregnant women with LQTS or MFS and structurally normal hearts, using matched controls to minimize confounding by underlying cardiac disease. β-Blocker use-mainly nadolol and bisoprolol-was associated with significantly lower birth weight and higher rates of FGR/SGA and neonatal bradycardia. Our findings support the continuation of β-blocker therapy when clinically indicated, combined with careful fetal growth monitoring and targeted neonatal surveillance.

Pediatric myocarditis is a clinically diverse and often under-recognized inflammatory condition of the myocardium, with presentations that range from mild symptoms to acute heart failure. Advances in cardiac imaging, biomarker discovery, and molecular genetics have improved diagnostic precision and individualized care. Genetic studies indicate that 8-10% of pediatric patients with myocarditis carry pathogenic variants in cardiomyopathy-related genes, supporting the "double-hit" hypothesis where genetic predisposition interacts with viral or autoimmune triggers. This paradigm shift has underscored the relevance of precision medicine, emphasizing tailored management based on the underlying etiology and genetic background. While supportive care remains the foundation of therapy, including rest, hemodynamic monitoring, and guideline-directed medical therapy for heart failure, pharmacologic strategies are evolving. Corticosteroids are under investigation for modulating inflammation, with mixed results showing improvements in ventricular function but unclear survival benefits. Immunomodulatory agents, such as intravenous immunoglobulin and other immunosuppressive therapies, offer promise in reducing myocardial fibrosis and injury. Virus-specific therapies are increasingly utilized in confirmed viral myocarditis, improving outcomes in selected cases. Recent studies highlight the potential role of biologic agents targeting inflammatory pathways, such as interferons, interleukin modulators, and micro-RNA-based therapy in refractory cases. Despite limited pediatric-specific trial data, extrapolation from adult myocarditis studies continues to inform treatment direction. Continued translational research and pediatric-focused clinical trials are critical to optimizing treatment of myocarditis and improving long-term cardiac outcomes. Future investigations should focus on refining immunomodulatory strategies, identifying novel therapeutic targets, and enhancing risk stratification to improve individualized care.

Pediatric tinea capitis, a common superficial fungal infection of the scalp, is primarily caused by Trichophyton and Microsporum species. While oral antifungal therapy remains the cornerstone of treatment, clinical outcomes vary considerably owing to differences in dosing practices and the species-specific response of the infecting organism. This narrative review synthesizes the existing literature to emphasize contemporary dosing regimens and species-directed efficacy on four widely used agents: griseofulvin, terbinafine, itraconazole, and fluconazole. Across studies published between 1997 and 2025, griseofulvin consistently demonstrated strong performance for both Trichophyton and Microsporum infections when administered at the recommended 20-25 mg/kg/day, confirming its enduring role in pediatric care. Terbinafine achieved reliable results for Trichophyton but was markedly less effective for Microsporum, with wide variability in reported cure rates. Though less extensively studied in children, itraconazole and fluconazole emerged as effective alternatives, while both warrant careful use owing to potential hepatotoxicity and other adverse effects. The evidence underscores the importance of species identification and optimal dosing in guiding antifungal selection. Empirical treatment without microbiologic confirmation risks reduced cure rates and may contribute to emerging antifungal resistance. Future investigations should prioritize long-term follow-up and the potential role of combination therapy to refine and sustain effective management strategies for pediatric tinea capitis.

Doxecitine and doxribtimine (KYGEVVI^®) are pyrimidine nucleosides developed by UCB for the treatment of thymidine kinase 2 deficiency (TK2d). In November 2025, doxecitine and doxribtimine received its first approval in the USA for the treatment of TK2d in adult and pediatric patients with an age of symptom onset on or before 12 years. This article summarizes the milestones in the development of doxecitine and doxribtimine leading to this first approval for TK2d.

Polyarticular-course juvenile idiopathic arthritis (polyJIA) is a chronic inflammatory arthritis involving > 4 distinct joints over the course of the disease. PolyJIA tends to be more difficult to treat than other forms of nonsystemic JIA, but advances in immunosuppressive therapies over the past 25 years have dramatically reduced patient morbidity. Despite significant advances in treatment options and outcomes, there is little evidence to guide how and when these treatments should be implemented to be most effective. Optimizing the initial timing and choice of these medications may further enhance outcomes and potentially mitigate the need for serial trials of therapy. There are recent data to suggest that earlier and more aggressive initial immunosuppressive therapy may help patients with polyJIA achieve inactive disease more quickly and may improve long-term outcomes. This approach, however, is counterweighted by the risk of overtreatment and the need for improved risk stratification models that can reliably inform individualized treatment strategies. This article explores the main treatment approaches to new-onset polyJIA and current evidence to support which approach may be optimal.

Neurological adverse effects (NAEs) are commonly reported in individuals treated with antipsychotic medications. Children and young people (CYP) may be particularly susceptible to these effects, but few studies have focused on the risk of NAEs in this population. This review provides an overview of the published literature on NAEs in CYP with an emphasis on data from randomised placebo-controlled trials. Most antipsychotics are associated with sedative effects that may impair daily functioning. Akathisia, dystonia and parkinsonism are commonly reported in CYP, although rating scale assessments typically show minimal changes from baseline in short-term randomised studies. Tardive dyskinesia appears to be less common in CYP than in adults, but data are limited. Some antipsychotics, in particular clozapine, are associated with a reduced seizure threshold, but it is unclear whether CYP may be more vulnerable than adults and available studies are subject to various confounding factors. Neuroleptic malignant syndrome, a rare and potentially fatal adverse drug reaction, has been reported in CYP treated with both first-generation and second-generation antipsychotics. Data on risk factors and management strategies for NAEs are largely from studies in adults and may not be relevant to CYP. Future studies should aim to resolve some of the current uncertainties. In particular, within-subject "self-controlled" studies using prospectively collected data from large databases would help to clarify the incidence and risk factors, in particular for less common NAEs, while controlling for possible confounders.

Objective: Our objective was to describe the clinical impact of time to initiation of indomethacin or ibuprofen on patent ductus arteriosus (PDA) closure rates in preterm neonates.

Methods: This was a retrospective cohort study including preterm neonates who received at least one dose of intravenous indomethacin or ibuprofen as their first treatment course for PDA closure. Patients were categorized into the early treatment (ET) cohort if pharmacologic therapy was initiated on day of life (DOL) 0-7 and to the late treatment (LT) cohort if initiated on DOL 8 or later. PDA closure rate was the primary outcome, and data were also evaluated to assess the need for additional medical or surgical interventions for PDA closure, as well as neonatal safety outcomes based on time to initiation of therapy.

Results: A total of 97 patients with a median gestational age of 25 weeks were included for analysis, with 29 in the ET cohort and 68 in the LT cohort. Baseline characteristics were similar between the ET and LT cohorts, with a median DOL of therapy initiation of 5 (interquartile range 4-6) and 11 (interquartile range 10-13.5) days, respectively. Rates of indomethacin as the initial nonsteroidal anti-inflammatory drug choice were similar between the ET and LT cohorts (66% vs 56%, p = 0.5). There was no difference in PDA closure rates following the initial course of pharmacologic therapy between the ET and LT cohorts (45% vs 32%, p = 0.26). Similarly, there was no difference in the incidence of a second pharmacologic treatment course (25% vs 26%, p = 1), surgical ligation, transcatheter closure, or adverse neonatal outcomes between cohorts.

Conclusion: The time to initiation of intravenous indomethacin or ibuprofen did not significantly affect PDA closure rates, the need for subsequent PDA pharmacotherapy, or adverse neonatal outcomes. Overall rates of PDA closure with pharmacologic intervention were low.

Childhood epilepsies comprise a group of heterogeneous conditions associated with diverse aetiologies, seizure severities/types, comorbidities, degrees of impairment and prognoses. Seizures are refractory to antiseizure medications (ASMs) in around one-third of cases. Alternatives to medication, for example surgical resection, are not always feasible, implying that new treatments are needed. In the past decade, new ASMs have been approved for specific childhood-onset epilepsy syndromes, notably cannabidiol for Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) and tuberous sclerosis complex (TSC); fenfluramine for LGS and DS; everolimus for TSC; and ganaxolone for cyclin-dependent kinase-like deficiency disorder. However, seizure freedom with these medications has rarely been achieved in randomised controlled trials. Alongside ASM development, and surgical strategies such as laser interstitial therapy, neurostimulation modalities have evolved towards responsive systems, such as autostimulation vagus nerve stimulation (VNS) and responsive neurostimulation, and non-invasive devices such as transcutaneous VNS and transcranial direct current stimulation; these have achieved similar decreases in seizure frequency to traditional neurostimulation in some studies. However, data for paediatric epilepsy are limited. Focused ultrasound is being developed not only for seizure focus ablation but also for other approaches to seizure control. In parallel with these developments, accumulating research in the areas of genetic testing, including genetic and related therapies designed to correct or compensate for underlying genetic causes of seizures, suggests that these technologies may have the potential to transform epilepsy treatment in the future. This review summarises major recent developments and current research in the treatment of epilepsy in children.

Congenital hyperinsulinism (CHI) is a rare disorder causing persistent hypoglycaemia in infants due to excessive insulin secretion from pancreatic β-cells. It has genetic causes, primarily mutations in ATP-sensitive potassium channel genes (ABCC8, KCNJ11). CHI manifests in three forms-focal, diffuse, and atypical-distinguished by histology and genetics, influencing treatment strategies. Early diagnosis and tailored management are vital to prevent neurological damage. While transient CHI resolves spontaneously, permanent CHI often requires complex medical and/or surgical intervention. Despite advances, long-term neurodisability remains high, highlighting increased need to improve monitoring as well as better therapies with lesser side effects. Acute treatment aims to rapidly normalize glucose levels and long-term treatments include diazoxide (KATP channel agonist) to suppress insulin secretion, though its effectiveness depends on genetic mutation type. Other therapies include somatostatin analogues. Newer emerging therapies include novel glucagon analogues, monoclonal antibodies targeting insulin receptors, GLP-1 receptor antagonist, and selective somatostatin receptor agonist, currently under clinical trials. Along with medical treatment, children may require additional feeding support with carbohydrate supplementation using glucose polymers and special formulas. Continuous glucose monitoring aids detection but has limitations. Surgery is preferred for focal lesions to potentially cure CHI.