Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
Pediatric diseases and thus their medications are described as rarely occurring, moderately occurring, and frequently occurring. The purpose of this study is to identify the most frequently prescribed categories of pediatric medications by pediatric specialists in the city of Mosul. 100 medical prescriptions written by pediatric specialists in their private clinics from various locations in the city of Mosul. Upon receiving a prescription from one of these doctors, the research member would copy the prescription and keep it. When 100 prescriptions were collected, each prescription was examined, and the prescribed medications were classified into groups according to their pharmacological effect. The highest frequency of prescribed drug categories by pediatric specialists in Mosul was antibiotics, with a usage rate of 27.77%, followed by gastrointestinal drugs at 22.22%, then analgesics and antipyretics at 18.88%, then antihistamines at 14.44%, followed by vitamins and nutritional supplements at 8.88%, and lastly respiratory system drugs at 7.77%. The results of the current study show that the most prescribed drug class by pediatricians in Mosul city are the antibiotics. Also, the types of antibiotics prescribed differ significantly in all three countries, and this depends on the protocol of treatment in each country. Other classes of drugs in the other studies show some similarity, as in Mosul City and sometimes show significant differences from Mosul City, and this depends on different factors and on different climates.
Anesthetic management of pediatric patients with rare diseases presents substantial perioperative challenges and risks. This study evaluated the clinical competency and specific educational needs of anesthesia practitioners in China regarding the perioperative management of this vulnerable patient population. A cross-sectional survey was conducted from May 2024 and March 2025, involving 2127 anesthesia practitioners across China. Data were collected via a validated anonymous questionnaire and analyzed through descriptive statistics and chi-square tests. Among the 2,127 participants, 93.5% were anesthesiologists and 6.5% were nurse anesthetists. Of these, 43.2% (919/2127) reported previous experience in administering anesthesia to children with rare diseases. Despite this exposure, self-assessed competency levels were notably insufficient. Only 9.0% (191/2127) of respondents reported comprehensive knowledge of pediatric rare diseases, and 15.0% (318/2127) expressed adequate confidence in perioperative management protocols. Objective assessment of specific knowledge domains revealed considerable deficiencies: 14.9% (317/2127) of respondents correctly identified contraindications in muscular dystrophy, 6.6% (141/2127) demonstrated adequate understanding of difficult airway indicators, and merely 3.9% (82/2127) accurately recognized depolarizing agent risks. Comparative analysis between self-rated high-familiarity and low-familiarity groups revealed that direct clinical exposure was significantly associated with practitioners' understanding of pediatric rare diseases. Regarding the development of future anesthesia support systems for pediatric rare diseases, practitioners identified two primary requirements: comprehensive diagnostic information (58.6%, 1246/2127) and detailed anesthesia contraindications (57.0%, 1212/2127). Additionally, 50.1% (1065/2127) of respondents emphasized the importance of real-time knowledge base updates to ensure access to current clinical guidelines and safety protocols. This study highlights substantial knowledge gaps and insufficient confidence among anesthesia practitioners in the perioperative management of children with rare diseases, underscoring an urgent need for enhanced training and robust support systems in this specialized area.
Management of the pediatric airway is a challenging procedure in prehospital emergency medicine. This retrospective study evaluates prehospital airway management in 920 pediatric patients in a German helicopter emergency medical service (HEMS) system from 2012 to 2021. Prehospital pediatric intubation was a rare event (0.2% of all missions). Good visualization of the glottis (Cormack-Lehane I or II) was possible in 96.3% of the intubations. The first-pass intubation success was 86.6%; all children could finally be intubated successfully. The use of muscle relaxants significantly improved first-pass success in prehospital emergency anesthesia (90.1% vs. 83.1%; P = .002). We recognized a low rate of the use of aids such as stylet, bougie, or video laryngoscopy. The use of video laryngoscopy increased over the years, but did not translate into a higher first-attempt success rate. When taking over children with an already managed airway, HEMS teams found tube malplacement in 8.4% of the cases in primary missions. In the analyzed data, pediatric airway management was on a comparable level with adult airway management. Nevertheless, room for improvement and a need for further studies were identified.
Dental emergencies are common during childhood and typically occur due to trauma or infection. The current evidence on managing dental injuries is from a dental perspective, with limited information on treating pediatric dental injuries in medical settings. Proper treatment of infection, correct storage, prompt repositioning, and replantation are essential for successful outcomes, as supported by the latest evidence-based guidelines. Pediatric patients have a better prognosis when proper treatment is provided without delay. Understanding potential issues enables providers to assess the severity of the condition, offer initial guidance and management, and recommend appropriate follow-up dental care. This continuing education activity aims to educate providers on how to care for children with low-acuity dental injuries and infections using an evidence-based approach.
Previously, young children had limited respiratory support options during interfacility transport. Recently, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) have become available for pediatric transport. We hypothesized that the implementation of HFNC and NIV on interfacility transport decreases the rate of intubation in infants and toddlers before and after transport to a tertiary-care pediatric intensive care unit (PICU). We conducted a retrospective chart review of children aged 30 days to < 36 months transported to a tertiary-care PICU from a referring hospital with respiratory distress from 2014 to 2019. Groups were analyzed before (2014-2017) and after the implementation (2017-2019) of HFNC and NIV during transport. NIV was defined as positive pressure ventilation delivered through nasal cannula. The primary outcome was to compare the pre- and postimplementation groups with regard to the rate of intubation before transport and within 48 hours of PICU admission. Secondary outcomes were the association between intubation rate and comorbidities and the comparison of length of respiratory support and hospital length of stay between the pre- and postimplementation groups. A total of 262 patients met criteria, 133 before and 129 after the intervention. The rate of intubation before PICU admission was 44% in the preintervention group versus 36% in patients transported after the implementation of HFNC and NIV, a trend that was not statistically significant (P = .19). The rate of intubation within 48 hours of PICU admission was 8% (before) and 11% (after) with no statistical significance (P = .48). Comorbidities were not associated with an increased rate of intubation before transport (P = .09) or within 48 hours of admission (P = .45). Hospital length of stay and length of respiratory support were not different between pre- and postintervention groups (P = .18 and P = .3, respectively). The availability of HFNC/NIV was associated with a significant decrease in the proportion of patients who received oxygen via nasal cannula or face mask during transport (46% before vs. 13% after the intervention; P < .01). After the introduction of HFNC/NIV during transport to a large tertiary-care hospital in a major metropolitan area, fewer nasal cannula/face masks were used during transport in favor of HFNC/NIV but no significant change in intubation rates was found.
This study reviewed pediatric cases managed by the Aeromedical Evacuation Squadron (AMES) of the Japan Air Self-Defense Force and analyzed patient characteristics. Pediatric transportation cases (n = 34) between 2006 and 2023 were reviewed. Data on patient age, main disease, transportation purpose and distance, and use of mechanical ventilators or extracorporeal membrane oxygenation (ECMO) were obtained by referring to the records. The average (standard deviation) patient age was 5.7 (5.8) years (range: 0-16 years), and 17 patients (50%) were younger than 1 year of age. Furthermore, 10 (58.8%) of these 17 children were younger than 7 months of age and 1 child was under 1 month of age. The most common diseases in the overall patient population were cardiovascular diseases (CVDs, n = 18) and respiratory diseases (RDs, n = 14). The purposes of transportation in cases of 17 patients with CVDs and 3 patients with RDs were the implantation of a ventricular assist device and lung transplantation, respectively. The average transportation distance was 453.7 (218.6) (range: 176.9-962.8) miles or 730.2 (351.8) (range: 284.7-1,549.5) km, and in 8 cases, the transportation distance was > 600 miles. Of the patients, 29 (85.3%) were fitted with a ventilator, of whom 8 received ECMO (6 with CVDs and 2 with RDs). In all cases, physicians from the transporting hospitals were on board. There were no cases of cardiac arrest during the transportation. AMES plays an important role, especially in the long-distance transportation of critically ill children.
This contemporary review examines health care disparities that pediatric patients may experience throughout the perioperative period, focusing on the ambulatory surgery setting. Existing literature focused on outcomes during inpatient procedures; however, disparities may manifest preoperatively, intraoperatively and postoperatively in the outpatient setting. Inequities related to race/ethnicity, geographic location, language barriers, insurance status, and utilization of perioperative services are highlighted. Strategies to mitigate these disparities in the ambulatory setting include selecting patients carefully, encouraging accreditation of facilities, and increasing the number of fellowship-trained pediatric anesthesiologists. Future opportunities include system-level changes to promote more equitable perioperative care in the ambulatory setting.
Ambulatory surgical centers (ASCs) are projected to increase in numbers for a myriad of reasons. They provide a cost effective, efficient way to render medical care in a setting that is often also more convenient for patients and families. As a result of this growth, several questions arise for the ideal pediatric patient candidate for this setting. This review highlights selection criteria such as patient age, cardiopulmonary status, and preoperative comorbidities to further elucidate appropriate selection criteria for pediatric patients in ASCs.
Pediatric femoral neck fractures require stable fixation to avoid complications. It remains unclear whether fixation with the Proximal Humeral Internal Locking System (PHILOS) can serve as an alternative to cannulated screw fixation. The purpose of this study was to compare the biomechanical properties of PHILOS and cannulated screws for stabilizing unstable pediatric femoral neck fractures using a synthetic bone model. Twelve fourth-generation synthetic composite femurs were randomly assigned to screw fixation (Group S) or PHILOS fixation (Group P) (n = 6 each). A standardized vertically oriented Delbet type II osteotomy was created in all specimens. Group S was fixed with three 6.5-mm cannulated screws, whereas Group P received a PHILOS plate with 3.5-mm locking screws. Each specimen underwent a standardized loading protocol using a universal testing machine. Axial stiffness, cyclic displacement, ultimate failure load, and failure modes were recorded and statistically compared between groups. No statistically significant difference was found in axial stiffness between Group P (746 ± 300 N/mm) and Group S (753 ± 256 N/mm) (p = 1.000). Displacement after cyclic loading was significantly greater in Group P (1.42 ± 0.3 mm) compared with Group S (0.57 ± 0.2 mm) (p = 0.004). The ultimate failure load was higher in Group S (2378 ± 513 N) than it was in Group P (1652 ± 206 N) (p = 0.025). Upon reaching ultimate load, all specimens in both groups failed at the femoral head region due to femoral head broken. The adult PHILOS plate with 3.5-mm locking screws demonstrated inferior biomechanical stability compared with three 6.5-mm cannulated screws in this synthetic composite femur model. Controlled laboratory study.
This review synthesizes best practices for ambulatory pediatric tonsillectomy with or without adenoidectomy in ambulatory surgery centers. It emphasizes rigorous patient selection-particularly for severe obstructive sleep apnea, age, obesity, and complex comorbidities-along with individualized anesthetic plans (induction and airway choice), multimodal opioid-sparing analgesia, and robust post-operative nausea and vomiting prophylaxis. Standardized post-anesthesia care unit monitoring, discharge criteria, caregiver education, and escalation pathways address common complications (airway events, hemorrhage, pain, dehydration). Preparedness-pediatric advanced life support-certified staff, emergency equipment, and transfer agreements-underpins safety. Quality-improvement initiatives and emerging tools offer avenues to further reduce morbidity and unplanned admissions.
A 3-year-old male passenger developed acute respiratory distress approximately 30 minutes after takeoff during an international flight from the United States to Addis Ababa. Despite multiple rounds of nebulized albuterol and escalating oxygen therapy, his respiratory status progressively deteriorated. A multidisciplinary team of onboard physicians administered epinephrine and hydrocortisone from the emergency medical kit while coordinating with ground medical control. The aircraft was subsequently diverted to Athens, Greece, where the child was handed over to emergency services and later stabilized. This case highlights the challenges of managing pediatric respiratory distress in-flight and the critical importance of prompt coordination, adequate medical supplies, and crew preparedness.
The goal of this study was to identify symptoms that occur in children post-SARS-CoV-2 infection, their trajectory over the first-year post-enrollment, and relationship to age. Longitudinal comparison of infected and uninfected cohorts. Participants (0-21 years) with laboratory-confirmed SARS-CoV-2 infection were enrolled as infected. The uninfected cohort was individuals without laboratory evidence of SARS-CoV-2 infection. Primary outcome was presence or absence of symptoms. 852 participants (705 infected, 147 uninfected) completed baseline visits. Of those, 558 infected subjects completed a 12-month post-enrollment visit. Twenty symptoms were identified as more common in infected participants compared to uninfected, at either baseline or 12-months, with symptoms varying by age. Some symptoms in the infected were more frequent at baseline (e.g. fever, weight loss), whereas many symptoms persisted through 12-months. Several symptoms were more frequent at 12-months (e.g. dysmenorrhea, persistent headache). Presence of symptoms at 12-months was not significantly associated with the wave of circulating virus at original infection. Interim analysis at one-year post-enrollment identifies 20 symptoms that infected participants were more likely to report post SARS-CoV-2 infection compared to uninfected, at either visit. Type of symptoms varies by age. Ongoing longitudinal data up to 3-years post-enrollment will increase understanding of long-term symptoms of SARS-CoV-2 infection in children and their trajectory. NCT04830852. Although most children recover fully from SARS-CoV-2 infection, some children experience a variety of prolonged symptoms following infection. Many studies attempting to characterize these symptoms and trajectory are not prospective nor longitudinal and lack comparison to uninfected controls. This longitudinal analysis identifies and characterizes post-COVID symptoms in children and adolescents and their trajectory through the first-year post enrollment compared to an uninfected cohort. 20 post-infection symptoms were identified as occurring more frequently in the infected as compared to uninfected cohort. Age played a critical role in the type and frequency of symptoms after SARS-CoV-2 infection. Gastrointestinal symptoms were prominent.
Intranasal dexmedetomidine is widely used in pediatric procedural sedation; however, its dose-related effect on delayed awakening remains insufficiently characterized. This single-center retrospective cohort study included pediatric patients who received oral midazolam combined with intranasal dexmedetomidine for procedural sedation at the Sedation Center of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital between March 2022 and March 2024. The exposure was the intranasal dexmedetomidine dose (μg/kg). The primary outcome was delayed awakening, defined as a time of ≥ 90 min from the last sedative administration (including rescue/secondary sedatives when applicable) to full awakening documented by the anesthesiologist on duty using routinely recorded standardized criteria (Modified Aldrete score ≥ 9). Firth penalized multivariable logistic regression models were applied to evaluate the association between dexmedetomidine dose and delayed awakening, adjusting for age group, sex, weight, fasting duration, procedure type, and midazolam dose. Dose-response relationships and subgroup analyses restricted to baseline/procedural characteristics were also conducted. A total of 2,116 children were included, with an overall delayed awakening incidence of 2.6%. When stratified by tertiles of dexmedetomidine dose, the incidence of delayed awakening increased from 1.1% in the low-dose group to 2.9% in the medium-dose group and 4.1% in the high-dose group (P = 0.004). In multivariable analyses, each 1 μg/kg increase in intranasal dexmedetomidine dose was associated with a significantly higher risk of delayed awakening (adjusted odds ratio [OR] 3.665, 95% confidence interval [CI] 2.091-6.636; P < 0.001). Dose-response analysis demonstrated a positive linear association (no evidence of nonlinearity, P = 0.451) between dexmedetomidine dose and delayed awakening. This corresponds to an aOR of 1.91 per 0.5 μg/kg increase (and 1.99 per IQR increase); adjusted predicted probabilities were 0.96% at 2 μg/kg, 3.37% at 3 μg/kg, and 10.70% at 4 μg/kg. In pediatric procedural sedation, higher intranasal dexmedetomidine dose is associated with delayed awakening and demonstrates a positive dose-response relationship. Younger children appear to be more susceptible to this adverse outcome. Clinically, dexmedetomidine dosing should be carefully individualized-particularly in younger patients-to balance effective sedation with recovery efficiency.
Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking. We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin. This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that imposes significant personal and societal burdens. Traditional diagnostic approaches, which rely on behavioral assessments, are susceptible to subjectivity and variability, underscoring the need for objective and automated diagnostic tools. This study develops an ADHD-specific, biologically informed multi-stream deep learning framework for pediatric brain MRI classification, in which a Vision Transformer (ViT) and an Enhanced Convolutional Neural Network (ECNN) are integrated with Raw MRI, Phase Spectrum Transform (PST), and Quantile Histogram Equalization with Denoising (QHED) representations to capture complementary global and local neuroanatomical characteristics. The architecture leverages complementary modeling capacities by combining global contextual representations from ViT with localized discriminative features extracted by ECNN across a biologically informed multi-stream preprocessing strategy, including Raw MRI to preserve global anatomy, Phase Spectrum Transform (PST) to highlight cortical boundary irregularities, and Quantile Histogram Equalization with Denoising (QHED) to enhance subtle gray-white matter contrasts. Experimental evaluations conducted on a stratified pediatric MRI dataset demonstrated that the proposed ViT+ECNN model achieved a classification accuracy of 99.4%, precision of 99.3%, recall of 99.5%, and an F1-score of 0.99, substantially outperforming standalone ViT and ECNN configurations. These findings indicate that hybrid transformer-convolutional models can substantially enhance diagnostic accuracy and offer a promising approach for supporting early identification and intervention in ADHD.
Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes (T1DM) and a leading cause of pediatric mortality. Prevention depends on caregivers' ability to recognize early signs and initiate proper sick-day management. However, data on DKA awareness among Iranian parents remains limited. This study aimed to evaluate both subjective self-ratings and objective calculated knowledge regarding DKA among parents of children with T1DM. This cross-sectional study was conducted among 217 parents at a pediatric diabetes clinic in Shiraz, Iran. A validated questionnaire (Cronbach's alpha = 0.8), adapted through forward-backward translation, assessed demographics, disease duration, HbA1c, and DKA knowledge. Data were analyzed using descriptive statistics, Kruskal-Wallis tests, and Spearman's correlations (rs) to identify predictors of awareness. Most participants were mothers (80.6%), and 38.7% reported DKA as the initial presentation at diagnosis. Subjective knowledge scores (0-10) were 1.86 ± 3.07 for mothers and 0.89 ± 2.16 for fathers (P = 0.06). Mothers demonstrated significantly higher calculated objective awareness than fathers (P = 0.007). Higher objective knowledge significantly correlated with higher education levels (rs=0.280, P = 0.01), longer disease duration (P = 0.01), and prior DKA admission (P = 0.02). Awareness showed no significant relationship with the child's most recent HbA1c levels (P = 0.98). Parental DKA knowledge is critically inadequate. As DKA mortality is preventable through early detection, targeted educational interventions and accessible resources are urgently needed to empower parents and improve clinical outcomes for children with T1DM.
Achondroplasia (ACH) is the most common skeletal dysplasia characterized by disproportionate short stature due to impaired endochondral ossification. One of the most critical and potentially fatal complications of ACH is foramen magnum and upper cervical canal stenosis. Compression at the cervicomedullary junction may lead to myelopathy, hypotonia, developmental delay, and central sleep apnea. Early detection and timely surgical intervention are essential to prevent permanent neurological injury. This retrospective study evaluated 15 pediatric patients with ACH (9 girls, 6 boys; age range 3-42 months, mean 17.2 months) who underwent foramen magnum decompression and C1 laminectomy at Marmara University Neurosurgery Department between 2016 and 2025. All patients underwent comprehensive neurological and radiological evaluation, including MRI and 3D CT of the craniovertebral junction, and were classified by the Achondroplasia Foramen Magnum Score (AFMS). Nine patients had AFMS level 4 stenosis and six had level 3. The anteroposterior diameter of the foramen magnum ranged from 4.03 to 11.03 mm, with an area between 17.40 and 105.16 mm2. Presenting symptoms included motor delay (n = 4), respiratory disturbances or central apnea (n = 4), and macrocephaly (n = 3). Postoperative imaging confirmed adequate decompression in all patients. Neurological and respiratory improvement occurred in all patients except one with persistent hypotonia. One patient died early postoperatively due to recurrent pneumonia and sepsis. Complications were minimal. Foramen magnum decompression with C1 laminectomy is a safe and effective procedure for infants and children with achondroplasia presenting with cervicomedullary compression. Early radiological and neurological evaluation, particularly with AFMS, facilitates accurate surgical decision-making and improves outcomes.
Cross-study inconsistencies in autism spectrum disorder (ASD) blood microRNA biomarker studies suggest that methodological heterogeneity may substantially limit reproducibility. We conducted an exploratory meta-analysis of publicly available ASD blood miRNA datasets from the Gene Expression Omnibus, applying rigorous inclusion criteria and standardized analytical protocols. Three datasets were included (GSE89596, GSE67979, GSE222046) comprising 614 miRNAs across 90 participants (45 ASD, 45 controls). Random-effects meta-analysis was performed using Hedges' g effect sizes, with comprehensive heterogeneity assessment and leave-one-dataset-out cross-validation. No miRNAs survived multiple testing correction (Benjamini-Hochberg FDR < 0.05), though seven candidate signals showed consistent evidence with unadjusted p < 0.01 and large effect sizes. These candidates demonstrated near-zero between-study heterogeneity and consistent directionality across validation analyses. Potential age-related and platform-related differences were observed, with near-zero correlation between adult and pediatric effect sizes (Kendall's τ = -0.022); however, these two sources of variability were fully confounded in the available data and could not be separated. Some miRNAs exhibited extreme between-study variability (I² > 80%), indicating substantial methodological differences. Cross-validation revealed that excluding the single adult dataset reduced sign consistency from 89.9% to 68.9%. Our findings suggest that age-related and methodological factors, including technical platform differences, may contribute to limited reproducibility in ASD blood miRNA research, and that blood-derived signals should be interpreted as potentially reflecting peripheral physiological states rather than central disease mechanisms. A supplementary cross-tissue analysis using post-mortem prefrontal cortex data (GSE59286; n = 45) provided direct empirical support for this interpretation: the majority of blood candidate miRNAs showed no corresponding expression in brain tissue, with only hsa-miR-29c-5p demonstrating directional concordance across both tissues. These findings suggest that age stratification, platform harmonization, and cross-tissue validation should be considered essential prerequisites for reliable ASD miRNA biomarker discovery, rather than optional refinements.