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Frontiers in Pediatrics

Frontiers Media SA

Preprints posted in the last 30 days, ranked by how well they match Frontiers in Pediatrics's content profile, based on 29 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Beyond Citations: Identifying Transformational Research in Hypospadias Through Bibliometrics and the Disruption Index

Abbas, T.; Naznine, M.; Mykha, M.; Mancha, M.; Hardas, A.; Raharja, P. A. R.; Chowdhury, M. E. H.

2026-04-20 urology 10.64898/2026.04.18.26351160 medRxiv
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Hypospadias, a common congenital anomaly requiring surgical correction, has seen growing research in surgical techniques and outcomes. However, no comprehensive bibliometric or disruption-based analysis exists to map the fields evolution. This study uses bibliometrics and the Disruption Index (DI) to identify key transformational research in hypospadias. A systematic search of five databases (PubMed, Web of Science, ScienceDirect, Scopus, and Dimensions) from January 1990 to December 2023 was conducted, yielding 7,732 articles. After applying inclusion criteria, 200 studies were analyzed. Citation data and DI scores were calculated using OpenCitations. Spearmans rank test assessed correlations between DI and citation metrics. A subgroup analysis identified trends based on the latest hypospadias research priorities. The mean citation count was 72.3 (SD = 43.1) with a mean DI of 0.011 (SD = 0.17). Five studies, focusing on complications, analgesia, and surgical techniques, had the highest DI (1.0). A moderate positive correlation was found between DI and citation rate ({rho} = 0.405, p < 0.001). Subgroup analysis showed most research focused on surgical techniques (30.5%) and etiology (25.8%), while areas like surgical training (2.6%) and innovation (0%) were underrepresented. This study identifies critical gaps in hypospadias research. The DI reveals influential studies that redirect research trajectories. Future work should focus on innovation and translational research to accelerate advancements in hypospadias care.

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Development and validation of an XGBoost model with SHAP-based interpretability and a web-based calculator for predicting extrauterine growth restriction in preterm infants

Xu, Z.; Yu, C.-L.; Zhang, J.-X.

2026-04-02 pediatrics 10.64898/2026.04.01.26349838 medRxiv
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Background: Extrauterine growth restriction (EUGR) is a common and clinically significant complication among preterm infants, contributing to adverse neurodevelopmental and metabolic outcomes. Early and individualized risk prediction remains challenging. This study aimed to develop and validate an interpretable machine learning model for early prediction of EUGR using routinely available clinical variables, and to implement a user-friendly web-based calculator for clinical use. Methods: We retrospectively analyzed 1,431 preterm infants admitted within 24 hours after birth to our hospital between May 2020 and March 2025. Infants from the Yangpu campus (n=863) formed the training set, and those from the Huangpu campus (n=568) formed the validation set. Early clinical variables available within 48-72 hours were screened using the Boruta algorithm. Logistic regression, XGBoost, random forest, decision tree, and support vector machine models were developed and compared. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, F1 score, and Brier score. SHapley Additive exPlanations (SHAP) were applied to assess global and individual feature contributions, nonlinear effects, and interactions. A web-based calculator was constructed based on the optimal model. Results: Nine variables were identified as important predictors: birth weight, small for gestational age status, gestational age, breastfeeding, multiple gestation, neonatal respiratory distress syndrome, patent ductus arteriosus, maternal hypertension, and maternal group B Streptococcus infection. Among the five models, XGBoost achieved the best performance in the validation set (AUC 0.922, accuracy 0.849, Brier score 0.108). SHAP analysis showed that low birth weight, small for gestational age, maternal group B Streptococcus infection, and patent ductus arteriosus were major risk factors, while breastfeeding was protective. Notable nonlinear and interactive effects were observed, particularly between birth weight and gestational age and between breastfeeding and patent ductus arteriosus. The web-based calculator provides real-time individualized risk estimation and visualized interpretation. Conclusions: An interpretable XGBoost-based model and web calculator were successfully developed and validated for early prediction of EUGR in preterm infants. This tool may support clinicians in identifying high-risk infants and guiding individualized nutritional and clinical management.

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Clinical Characteristics of Term Neonatal Bacterial Meningitis and the Correlation Between Pathogens and Imaging Complications

Ying, C.; Du, Y.; Wu, J.; Zou, P.; Zhang, L.; Li, Y.; Wang, Y. j.

2026-04-22 pediatrics 10.64898/2026.04.21.26351424 medRxiv
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Objective: To describe the clinical characteristics of term neonates with neonatal bacterial meningitis (NBM) and explore the association between different pathogens and imaging complications, providing clinical evidence for early identification and individualized management. Methods: A retrospective study was conducted on 531 term neonates diagnosed with NBM admitted to the Capital Institute of Pediatrics from 2013 to 2025. Demographics, clinical manifestations, laboratory parameters, etiological results, imaging complications and treatment measures were collected. Patients were divided into favorable/adverse discharge outcome groups and pathogen-positive/negative groups. Statistical analyses were performed using appropriate tests, and Cramers V coefficient was used to analyze the association between pathogens and imaging complications. Results: (1) The most common clinical manifestations were abnormal body temperature (79.85%), altered consciousness (55.18%) and jaundice (46.52%). CSF/blood culture was positive in 133 cases (25.05%), with Escherichia coli (27.07%), group B streptococcus (17.29%) and Staphylococcus species (16.54%) as predominant pathogens. The overall incidence of imaging complications was 22.22%, mainly hydrocephalus (5.84%), subdural effusion (4.90%) and encephalomalacia (2.64%). (2) Adverse discharge outcomes occurred in 107 cases (20.15%). Compared with the favorable group, the adverse group had higher incidences of convulsions, altered consciousness, anterior fontanelle bulging, abnormal muscle tone and primitive reflexes (all P<0.001), more obvious laboratory abnormalities (higher CRP, CSF leukocytes and protein, lower CSF glucose, all P<0.05), higher culture positive rates and greater need for adjuvant therapy (all P<0.001). (3) Pathogen-positive patients had higher imaging complication rates. Gram-negative infections were associated with higher hydrocephalus and subdural effusion rates, while Gram-positive infections had higher brain abscess risk. Specifically, Escherichia coli correlated with hydrocephalus and subdural effusion; group B streptococcus with cerebral infarction and encephalomalacia; LM with intracranial hemorrhage and brain abscess; negative cultures correlated with no imaging complications (all P<0.05). Conclusion: Term NBM neonates have non-specific manifestations, mainly abnormal body temperature and altered consciousness. Predominant pathogens are Escherichia coli, group B streptococcus and Staphylococcus species, with hydrocephalus and subdural effusion as common imaging complications. Adverse outcomes are associated with severe symptoms, obvious laboratory abnormalities and higher pathogen positivity. Specific pathogens correlate with distinct imaging complications.

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Risk factors, outcomes, and predictors of therapeutic response in preterm infants with patent ductus arteriosus: A retrospective cohort study

Hamida, H. B.; El Ouaer, M.; Abdelmoula, S.; El Ghali, M.; Bizid, M.; Chamtouri, I.; Monastiri, K.

2026-04-17 pediatrics 10.64898/2026.04.10.26350668 medRxiv
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BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.

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Experiences of family caregivers regarding the health of children with congenital craniofacial anomalies in Colombia

Lafaurie, M. M.; Vargas-Escobar, L. M.; Gonzalez, M. C.; Rengifo, H. A.

2026-04-20 pediatrics 10.64898/2026.04.17.26351082 medRxiv
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Recognizing the challenges faced by primary caregivers regarding the health of children with congenital craniofacial anomalies (CCAs) contributes to strengthening healthcare programs according to patient[s] and families differential needs. This qualitative study presents the experiences of 25 caregivers of children with CCAs from Bogota and Cali, Colombia, identified from care registries and consultation statistics provideed from public high-complexity healthcare institutions. Grounded in Giorgis descriptive phenomenology and employing thematic analysis, this research utilized semi-structured interviews and focus groups to explore the diagnostic process and its impact, experiences with healthcare services, and the caregivers role and daily care activities. Data were analyzed using MAXQDA(R) qualitative software. Findings highlighted the emotional complexity of caring for childre[n]s health. Challenges included late diagnoses, pessimistic views of the children with CCAs condition by healthcare team members; lack of effective support, information, and guidance from health staff; absence of clear care and referral protocols, and limited access to specific adaptations and timely specialized care for children with CCAs. There were also reduced therapeutic services, and a pronounced gendered caregiving burden when responsibilities fall almost exclusively on mothers. System fragmentation, reflected in deficiencies in communication and a lack of clear, coordinated, and timely pathways of care, as well as the absence of adequate psychosocial support for families, emerged as common structural problems in healthcare services in both geographic settings where this research has been conducted. Gender-sensitive strategies focused on alleviating emotional concerns and the burden of caregiving from diagnosis onward within a patient and family-centered care model are decisive. Improving comprehensive CCAs training for healthcare personnel and making adjustments to care pathways are suggested to contribute to the implementation of inclusive health programs that address the diverse needs of children and their families.

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National Norms and Psychometrics for the Pubertal Development Scale

Liu, Y.; Bonny, A. E.; Youngstrom, E. A.

2026-03-27 pediatrics 10.64898/2026.03.25.26349307 medRxiv
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Introduction: The Pubertal Development Scale (PDS) is widely used for puberty assessment, yet its psychometric properties and norms are limited to research data. This study examined the psychometric properties of parent- and self-report PDS and established continuous norms in nationally representative samples. Methods: We analyzed two deidentified survey samples: a parent-report sample of children aged 6-18 (N=2000, Mage=11.37, 47.2% female, 74.9% White), and a youth self-report sample aged 12-18 (N=754, Mage=14.33, 49.6% female, 75.3% White). Both samples were representative of the U.S. population on key demographics, and the self-report sample consisted entirely of children whose parents also participated in the parent sample, thus creating parent-child dyads. Internal consistency was evaluated using Cronbach's alpha and McDonald's Omega. Cross-informant agreement was assessed with Intraclass Correlation Coefficient (ICC; two-way model, absolute agreement, single unit) and Bland-Altman plots. Age-dependent norms of each sex were established with Generalized Additive Models for Location, Scale, and Shape (GAMLSS), with 5th-95th percentile curves and reference tables provided. Results: Parent- and self-report PDS demonstrated acceptable-to-good internal consistency (Cronbach's alpha: 0.78-0.89; McDonald's omega: 0.79-0.90). Among the 754 parent-youth dyads, excellent cross-informant agreement was observed for both sexes (ICC(2,1)=0.88). Parents' and children's PDS total scores did not differ significantly for boys; for girls, parents rated pubertal development on average 0.13 points lower than children's self-report. Regardless of informants, PDS scores increased nonlinearly with age and exhibited sex-specific developmental patterns. Girls showed earlier pubertal onset, faster progression, and greater convergence toward pubertal completion by late adolescence. Discussion: The PDS demonstrated strong psychometrics in national samples, supporting its utility in the general pediatric population. The national norms provide empirical benchmarks for PDS score interpretation, strengthening its value as a broad estimation of pubertal status and a pre-screening tool for identifying early or delayed puberty.

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Time to Discharge and Associated Factors Among Preterm Neonates Admitted to Kiwoko Hospital, Nakaseke District, Uganda: A Competing Risks Analysis

Mutibwa, S.; Wandiembe, S.; Mbonye, K.; Nsimbe, D.

2026-04-15 pediatrics 10.64898/2026.04.13.26350793 medRxiv
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Background: Preterm births contribute to approximately 35% of neonatal deaths globally, with an estimated 13.4 million infants born prematurely each year. Despite this substantial burden, limited evidence exists on time to discharge and its determinants among preterm neonates admitted to Neonatal Intensive Care Units (NICUs), particularly in rural Ugandan settings. This study aimed to investigate time to discharge and associated factors among preterm neonates admitted to Kiwoko Hospital in Nakaseke District, Uganda. Methods: A retrospective cohort study was conducted using secondary data from Kiwoko Hospital on preterm neonates admitted to the Neonatal Intensive Care Unit (NICU) between 2020 and 2021 (n = 847). The cumulative incidence function was used to estimate the probability of discharge within 28 days of admission, accounting for competing events. A Fine and Gray sub-distribution hazard regression model was fitted to identify factors associated with time to discharge. Results: Of the 847 preterm admissions, 70.1% were discharged alive within 28 days. The median time to discharge was 14 days. The cumulative incidence of discharge by 28 days was 68%, accounting for competing events. During follow-up, 165 neonates did not complete the 28-day period, including 88 deaths. Factors significantly associated with time to discharge included place of delivery (SHR: 0.62; 95% CI: 0.53-0.73; p<0.001), maternal residence in other districts (SHR: 0.69; 95% CI: 0.48-0.99; p=0.044), extreme preterm (SHR: 0.05; 95% CI: 0.03-0.09; p<0.001), very preterm (SHR: 0.18; 95% CI: 0.14-0.25; p<0.001), moderate preterm (SHR: 0.59; 95% CI: 0.46-0.76; p<0.001), triplet births (SHR: 0.40; 95% CI: 0.23-0.68; p=0.001), 2-4 ANC visits (SHR: 0.70; 95% CI: 0.56-0.87; p=0.002), <=1 ANC visit (SHR: 0.64; 95% CI: 0.49-0.85; p=0.002), respiratory distress syndrome (SHR: 0.64; 95% CI: 0.48-0.74; p<0.001), and birth trauma (SHR: 2.62; 95% CI: 1.60-4.29; p<0.001). Conclusions: Respiratory distress syndrome, fewer antenatal care visits, out-of-district residence, and higher degrees of prematurity were associated with prolonged time to discharge among preterm neonates. Strengthening antenatal care utilization and improving access to quality neonatal care in underserved areas may enhance discharge outcomes.

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Nourishing Hearts: The Link Between Food Insecurity and Overall Health Status of Children with Congenital Heart Disease in U.S.

Jani, S.; Modi, H.; Nadkarni, M.; Fraser, C.; Tenorio, D. F.

2026-04-05 pediatrics 10.64898/2026.04.03.26350134 medRxiv
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Background: Children with congenital heart disease (CHD) require specialized care and may face worse outcomes if they experience food insecurity (FI). FI is associated with poor nutrition, hospitalizations, and developmental delays, compounding cardiac risks. Limited research evaluated impact of FI on health status among children with CHD. This study examines socioeconomic factors and the relationship between FI and health status in children with CHD. Methods: 2023 National Survey of Children?s Health (NSCH) data were used to compare rates of FI between children ages < 17 years with and without CHD and to assess overall health status of those with CHD. Descriptive, univariate, and multivariable logistic regression were utilized. Results: Among 53,477 children, 1,233(2%) had CHD. FI was reported in 35% of children with CHD vs. 27% without CHD(p=0.005). After adjustment, children with CHD had higher odds of FI (OR 1.49; 95% CI: 1.05?2.12). Hispanic ethnicity, residence in Midwest or South, lower household education, and lower poverty index were significantly associated with FI. Households receiving food assistance had higher FI. Living in grandparent household was associated with lower odds of FI. Within the CHD subgroup, 5% reported fair or poor health. Children with CHD experiencing FI had greater odds of fair or poor health than those without FI (OR 3.91, 95% CI 1.70?9.02; p=0.001). Conclusions: Children with CHD face higher odds of FI, which is strongly associated with worse reported health. Addressing socioeconomic vulnerability and FI may improve outcomes and reduce disparities in this high-risk population through targeted screening and intervention strategies nationwide. Keywords: Congenital Heart Disease, Food Insecurity Screening, National Survey of Children?s Health (NSCH), Health Disparities

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Triage Administration of Ondansetron for Gastroenteritis in children; a randomized controlled trial

Weill, O.; Lucas, N.; Bailey, B.; Marquis, C.; Gravel, J.

2026-04-15 pediatrics 10.64898/2026.04.13.26350796 medRxiv
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Objectives: Acute gastroenteritis is a leading cause of pediatric emergency department (ED) visits. While ondansetron reduces vomiting, intravenous rehydration, and hospital admissions, its efficacy when initiated at triage remains unclear. We aimed to evaluate whether triage nurse-initiated administration of ondansetron in children with suspected gastroenteritis reduces the proportion of patients requiring observation following initial physician assessment. Methods: We conducted a randomized, double-blind, placebo-controlled trial in a tertiary pediatric ED in Canada. Children aged 6 months to 17 years presenting with morae than 3 episodes of vomiting in the preceding 24 hours (including 1 within 2 hours of arrival), were eligible. At triage, we randomized participants to receive liquid ondansetron or a color- and taste-matched placebo. The primary outcome was the proportion of patients requiring observation after the first physician evaluation. Secondary outcomes included post-intervention vomiting, ED length of stay, patient comfort, and 48-hour return visits. The trial was registered at ClinicalTrials.gov (NCT03052361). Results: Recruitment was stopped prematurely due to the COVID-19 pandemic. Ninety-one participants were randomized to ondansetron (n= 44) or placebo (n= 47). Overall, 40 patients (45%) were discharged immediately after the initial physician assessment, with no difference between the ondansetron and placebo groups (44% vs. 45%; absolute difference -1%, 95% CI: -20% to 19%). No significant differences were observed in all secondary outcomes. Conclusion: In this trial, triage nurse-initiated ondansetron administration did not reduce the need for ED observation in children with presumed gastroenteritis. While being underpowered, this study could inform researchers planning larger clinical trials.

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Increased S. epidermidis in the airway-gut microbiome of infants with bronchopulmonary dysplasia

Solomon, Z.; Eno, M.; Thompson, S.; Rager, S.; Jin, J.; Zeng, M.; Keerthy, D.; Worgall, S.; Johnson, E.; Heras, A.

2026-04-04 microbiology 10.64898/2026.04.03.715941 medRxiv
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RationaleBronchopulmonary dysplasia (BPD), the lung disease associated with premature birth, is a significant health problem, often with long-term respiratory consequences. Recent research has highlighted the potential role of the lung and gut microbiome in the development and progression of BPD, yet it is unclear what aspects of the microbiome may contribute to BPD susceptibility. ObjectivesTo comprehensively characterize the lung and gut microbiomes of preterm infants and identify shared microbial taxa that are associated with BPD development. MethodsTracheal aspirate and stool samples were collected from 39 premature infants over the first month of life. To assess the taxonomic microbial composition of the lung and gut, samples were analyzed using shotgun metagenomic sequencing. BPD classification was determined using the National Institute of Child Health and Human Development severity-based definition at 36 weeks postmenstrual age. Measurements and Main ResultsMicrobial communities of the lung and gut were significantly different between infants who went on to develop BPD and those who did not, with an enrichment of skin-associated microbial genera such as Staphylococcus, Corynebacterium, and Cutibacterium in infants who developed BPD. Specifically, Staphylococcus epidermidis was enriched in premature infants who developed BPD and was the most prominent species shared between lung and gut communities. Temporal changes in gut microbial communities co-occurred with feeding practices and antibiotic exposure, suggesting an influence of external factors on microbiome composition. ConclusionsOur findings provide evidence that certain microbial colonization patterns among premature infants are closely associated with the pathogenesis and progression of BPD.

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Pleuroparenchymal fibroelastosis in monogenic DGUOK-associated mitochondriopathy

von Hardenberg, S.; Maier, P.; Christian, L.; Das, A. M.; Neubert, L.; Ruwisch, J.; Peters, K.; Schramm, D.; Griese, M.; Skawran, B.; Eilers, M.; Jonigk, D.; Junge, N.; Haghikia, A.; Hegelmaier, T.; Hofmann, W.; Seeliger, B.; Renz, D. M.; Stalke, A.; Hartmayer, L.; Duscha, A.; Schulze, M.; DiDonato, N.; Prokisch, H.; Auber, B.; Knudsen, L.; Schupp, J. C.; Schwerk, N.

2026-04-11 respiratory medicine 10.64898/2026.04.08.26349275 medRxiv
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BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare, fibrotic lung disease with poor prognosis, usually affecting adults which most commonly occurs idiopathically. Biallelic pathogenic variants in DGUOK cause mitochondrial DNA (mtDNA) depletion syndrome, predominantly affecting infants with severe hepatic and neurological symptoms. Detailed description of pulmonary manifestations with late-onset presentation have not been reported. MethodsWe describe nine patients with PPFE and DGUOK-associated mitochondriopathy. Clinical, radiological, histopathological, and genetic data were systematically collected from all patients. Functional studies, single nucleus RNA sequencing (snRNAseq), immunofluorescence staining, transmission electron microscopy and respiratory chain enzyme activity assays were conducted on patient-derived fibroblasts, muscle or lung tissues. mtDNA content quantification was performed on whole genome sequencing (WGS) data. ResultsAll patients (ages 5-36) presented with progressive dyspnea, weight loss and some with spontaneous pneumothoraces. Chest computed tomography and lung biopsies showed features of PPFE. Biallelic pathogenic DGUOK variants were identified in all patients, seven of them carry an unreported intronic variant leading to mtDNA depletion. snRNAseq of lung tissue from four pediatric patients identified Aberrant Basaloid cells and intermediate cells as their precursor localized at the fibrotic edge. Mitochondrial alterations were identified by electron microscopy. ConclusionPPFE in children and young adults is associated with DGUOK-related mitochondriopathy. For the first time, we demonstrate Aberrant Basaloid cells in pediatric fibrotic lung tissue. Since pulmonary involvement may be underrecognized or misinterpreted and the clinical presentation may not always be typical of a mitochondriopathy, we recommend genetic testing in all patients with PPFE of unknown origin.

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Global Burden, Temporal Trends, and Health Inequalities of Early-Onset Group B Streptococcus Infection in Neonates, 1990-2021: A Systematic Analysis of the Global Burden of Disease Study 2021

Wen, Q.; Wang, X.; Wu, Y.; Jiang, Y.; Xu, Z.

2026-04-04 infectious diseases 10.64898/2026.04.02.26350022 medRxiv
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Objectives: Group B Streptococcus (GBS) is a leading cause of neonatal mortality worldwide. However, the global burden of early-onset GBS disease (EOD-GBS) has not been fully elucidated. We aimed to describe the geographical distribution and epidemiological characteristics of the EOD-GBS burden, and analyze its association with socio-economic development and universal health coverage. Methods: We used data from the Global Burden of Disease Study 2021 and the Universal Health Coverage Service Coverage Index (UHC-SCI) to calculate estimated annual percentage changes (EAPCs) of EOD-GBS mortality. Sex differences were analyzed using the conservative overlap assessment. The geographical distribution of EOD-GBS clinical presentations and mortality was mapped. Health inequality analysis was conducted to evaluate the relationship between the sociodemographic index (SDI), UHC-SCI, and EOD-GBS burden. Results: Global EOD-GBS mortality decreased by nearly 50% from 1990 (693.41 per 100,000) to 2021 (348.80 per 100,000). However, the decline was not uniform: the most significant decrease occurred in high-middle SDI regions (EAPC: -7.17%), and the slowest in low SDI regions (EAPC: -2.23%). Male neonates accounted for the most EOD-GBS deaths, particularly in high SDI regions. Lower respiratory infections were common in Asia and Oceania; meningitis was more prominent in Europe. Inequality analysis revealed a phenomenon of "absolute convergence but relative differentiation": as social development and universal health coverage improves, the absolute mortality gap between countries narrowed, but relative burden concentrated increasingly among the poorest populations. Conclusions: The global burden of EOD-GBS has decreased substantially, but there are marked differences among countries. Continued socioeconomic development and expanded universal health coverage are critical to further reduce neonatal mortality.

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Evaluation of diagnostic performance of the "STANDARD G6PDTM" quantitative point-of-care test in neonates and infants

Gornsawun, G.; Moo, E.; Htoo, K.; Chalermvisutkul, S.; Gilder, M. E.; Moo, P. K.; Archusuksan, L. K.; Prins, T. J.; Hanboonkunupakarn, B.; McGready, R.; Nosten, F.; Bancone, G.

2026-03-28 pediatrics 10.64898/2026.03.26.26349364 medRxiv
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Severe neonatal hyperbilirubinaemia represents a considerable cause of mortality and long term-morbidity in neonates born in low resource settings. Early identification of risk factors, such as glucose-6-phosphate dehydrogenase (G6PD) status, has the potential to prevent severe hyperbilirubinaemia and improve the clinical outcomes. The primary aim of the study was to assess equivalency of cord blood and neonatal capillary blood for diagnosis of G6PD deficiency using the quantitative point-of-care "STANDARD G6PDTM" test (SD Biosensor, Korea). Additional secondary aims were to compare the "STANDARD G6PDTM" with gold standard spectrophotometry and to analyse changes in G6PD activity in the first 4 months of life. A total of 75 neonates born in Shoklo Malaria Research Unit (SMRU) clinics were selected based on their G6PD status assessed through routine cord blood screening using the "STANDARD G6PDTM" test. Using activity thresholds established before in this setting, 25 G6PD deficient, 25 G6PD intermediate and 25 G6PD normal neonates were identified and re-tested on capillary blood collected within 24 hours of life and at day 7. They were also followed-up at 1 and 4 months of age to study haematologic and G6PD activity changes over time. The results showed that the "STANDARD G6PDTM" can be used reliably up to one week of life for testing neonates using the same thresholds established in cord blood. Performance of the point-of-care test as compared to the gold standard spectrophotometry remained excellent at all sampling time-points. Nevertheless, G6PD activity assessed longitudinally in the same participants decreased over time, both at 1 month of age and at 4 months of age, and interpretation of results in female infants with intermediate activity might require different thresholds. The study demonstrated that the "STANDARD G6PDTM" can effectively support clinical care in neonates and infants in populations with prevalent G6PD deficiency at the primary care level and especially in low-resource settings.

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Assessing Swedish Genetic Counselling Outcome Measures for Autism and General Use: Rasch Findings Highlight the Need for Improved Measures

Nordstrand, M.; Fajutrao Falk, S.; Johansson, M.; Pestoff, R.; Tammimies, K.

2026-04-15 genetic and genomic medicine 10.64898/2026.04.13.26350766 medRxiv
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Genetic counselling outcome measures are increasingly adapted for diverse clinical contexts. While the Genetic Counselling Outcome Scale (GCOS-24) is available in Swedish, no autism-specific version has been developed. Therefore, we adapted the Swedish GCOS-24 using the English version of the modified GCOS-24 (mGCSOS-24) to create a Swedish autism-specific mGCOS-24. Thereafter, we evaluated both the Swedish autism mGCOS-24 and the Swedish general GCOS-24 using Rasch analysis to assess their psychometric properties. Both instruments exhibited structural challenges, including multidimensionality, disordered thresholds, local item dependence, and invariance issues. For the Swedish autism mGCOS-24, we were able to identify subscales with acceptable measurement properties. However, applying the same structure to the Swedish general GCOS-24 did not resolve its broader limitations. This study introduces the first Swedish autism-specific mGCOS-24 and represents the first Rasch-based evaluation of any GCOS-24 or mGCOS-24 in Swedish. Our findings highlight important opportunities for measure refinement but also indicate that new or more substantially adapted tools may be needed to capture outcomes of genetic counselling in autistic populations.

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Meal Timing Patterns and Associations with Fat Mass in Adolescents

Decker, J. E.; Morales, K. H.; Chen, P.-W.; Master, L.; Kwon, M.; Jansen, E. C.; Zemel, B. S.; Mitchell, J. A.

2026-04-23 nutrition 10.64898/2026.04.22.26351498 medRxiv
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Background: The timing of energy intake could be important in the development of obesity. However, most observational evidence stems from adults, anthropometric defined obesity outcomes, single meal timing phenotyping, and traditional regression modeling. Objective: We aimed to describe meal timing patterns in adolescents and determine if they associated with fat mass by modeling the median and all other percentiles of the frequency distribution. Methods: We analyzed data from the Sleep and Growth Study 2 (S-Grow2, N=286, 12-13y). Participants completed 3-day 24-hour dietary recalls and time stamped eating occasions were used to define 8 meal timing traits, with aide from self-reported wake and bed timing. Principal component analysis (PCA) identified multi-dimensional meal timing patterns. Fat mass index (FMI) was estimated using dual energy X-ray absorptiometry. Quantile regression assessed if there were associations between meal timing traits and FMI across the entire FMI frequency distribution. Results: The typical first and last eating occasions were 8:00am (40 minutes after waking) and 8:00pm (2.7 hours before sleep), respectively, thus the eating period typically lasted 11.5 hours per day. The typical eating period midpoint was 2:15pm, and the timing when 50% of energy intake was consumed typically occurred at 3:15pm. PCA revealed three meal timing patterns: 1) Delayed Start, Condensed Eating Period (43% of variance; shorter eating period and delayed timing of first eating); 2) Late, Sleep Proximal Eating (30% of variance; later timing of last eating and extended eating period), and 3) Later Energy Intake (10% of variance; delayed energy intake midpoint). Higher scores for the Delayed Start, Condensed Eating Period pattern associated with higher body mass index and FMI at the upper tails of their distributions. Conclusions: Distinct multidimensional meal timing patterns emerged in early adolescence, with the delayed start, condensed eating period pattern potentially associated with higher adiposity.

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Availability and Quality of Anthropometric Data in Swiss Childrens Hospitals: The SwissPedGrowth Project

Leuenberger, L. M.; Shoman, Y.; Romero, F.; Deligianni, X.; Hartung, A.; Mozun, R.; Goebel, N.; Bielicki, J. A.; Burckhardt, M.-A.; Latzin, P.; Saner, C.; Posfay-Barbe, K. M.; Schwitzgebel, V.; Giannoni, E.; Hauschild, M.; Stocker, M.; Righini-Grunder, F.; Lauener, R.; Mueller, P.; Schlapbach, L. J.; Jenni, O. G.; Spycher, B. D.; Kuehni, C. E.; Belle, F. N.; for the SwissPedHealth Consortium,

2026-03-30 health informatics 10.64898/2026.03.27.26349493 medRxiv
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OBJECTIVE: Anthropometric data are critical in paediatric care, routinely assessed during clinical visits, and available in electronic health records (EHRs). We describe the feasibility of extracting anthropometric data from heterogeneous EHR systems of Swiss childrens hospitals, evaluate their availability and quality, and assess the cohorts representativeness of the general population. METHODS: In this multicentre study (SwissPedGrowth), we retrospectively collected EHRs from patients <20 years who visited hospitals in Basel, Bern, Geneva, Lausanne, Luzern, St. Gallen, or Zurich between 2017-2023. Sociodemographic, administrative, and clinical information from EHRs were provided in a standardized way by a paediatric national data stream (SwissPedHealth), including the Swiss Neighbourhood Index of Socioeconomic Position (Swiss-SEP). We counted anthropometric recordings per visit to describe availability and used a self-developed and an existing (growthcleanr) algorithm to investigate data quality. To assess representativeness, we compared sociodemographic characteristics between SwissPedGrowth and the general paediatric population in Switzerland, computed standardized differences (effect size: 0.2 small, 0.5 medium, 0.8 large), and weighted the study population to reduce differences. RESULTS: We included 477,531 patients and 2,171,633 hospital visits; 54% boys, 71% Swiss, mean Swiss-SEP 65 (SD: 11), and median age at visit 6.3 [IQR: 2.3, 11.8] years. Height recordings were available for 20% of the visits, weights for 43%, and head circumferences for 5%, with better availability for inpatient stays than outpatient or emergency visits. Combining the self-developed and existing algorithm, 4% of heights and 3% of weights were flagged as outliers and 29% of heights and 31% of weights as carried forward from previous visits or same day duplicates. Sociodemographic differences between SwissPedGrowth and the general population were small or small-to-medium and disappeared after weighting. CONCLUSION: SwissPedGrowth demonstrates feasibility of extracting high-quality anthropometric data for paediatric growth research, but challenges regarding completeness and harmonization of EHR data across Swiss hospitals remain.

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Sentinel Surveillance for Pediatric Bacterial Meningitis in a Tertiary Level Pediatric Hospital in Colombia, 2016 - 2023

Bautista, A.; Moreno, G. C.; Jerez, D.; Rojas, M. d. P. P.; Moreno, J.; Maldonado, L. Y.; Rodriguez, Y. M. E.; Sanabria, O.; Palacios, J.; Sotelo, J. C. R.; Duarte, M. C.; Sabogal, E.; Jimenez, K.; Duarte, C.

2026-03-27 public and global health 10.64898/2026.03.25.26348800 medRxiv
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Introduction: Bacterial meningitis (BM) is a common bacterial infection of the central nervous system, and its incidence in children varies by age, with the highest rates observed in infants younger than two months old. Objective: To describe the etiology, epidemiology, and clinical presentation of children under 5 years of age with BM at HOMI between 2016 to 2023. Materials and methods: Descriptive study of children under 5 years of age with suspected BM. Probable cases were those with CSF results consistent with BM. Confirmed cases had a positive CSF culture or blood culture for a bacterial pathogen or a positive molecular test for a bacterium in the CSF. Demographic variables, incidence of BM per year, mortality, and sequelae among survivors were analyzed. Results: A total of 527 suspected cases of BM were evaluated. Of these, 22.8% (120/527) were classified as probable cases and 13.1% (69/527) as confirmed cases. Children under 2 years of age accounted for 37.2% of probable cases and 78.2% of confirmed cases. Among confirmed cases, the most frequent symptoms were fever (98.3%), altered consciousness (39.1%), seizures (36.2%), and lethargy (27.5%). The mortality rate was 11.6% (8/69), and the mean hospital stay among patients with BM was 24.5 days. Streptococcus pneumoniae was identified in 26.1% of confirmed cases, with most isolates belonging to serotypes not included in PCV10. Haemophilus influenzae accounted for 17.4% of cases, of which 77.7% were serotype b. Neisseria meningitidis represented 10.1% of cases, and 60% of these were serogroup C. Other pathogens were identified in 49.1% of patients. Conclusion: Sentinel surveillance makes it possible to measure the impact of public health interventions and evaluate the impact of vaccines already used.

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Steroid-Responsiveness in TBX4-Associated Pulmonary Hypertension and Interstitial Lung Disease

Morgan, C.; Calder, A.; Brugha, R.; Quyam, S.; Aurora, P.; McGovern, E.; Bush, A.; Moledina, S.

2026-04-20 respiratory medicine 10.64898/2026.04.19.26350630 medRxiv
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BackgroundTBX4 variants are a recognised cause of paediatric pulmonary hypertension (PH), often associated with interstitial lung disease (ILD). Evidence for ILD-directed therapy in this group is lacking. MethodsWe conducted a retrospective study of children ([&le;]18 years) with TBX4-associated PH at a national centre (2001-2025). ILD was defined using ChILD-EU criteria. Patients treated with pulsed intravenous methylprednisolone were assessed for response using ChILD-EU categories. Secondary outcomes included respiratory severity score (RSS), functional class (FC), echocardiographic measures, and NT-proBNP. ResultsOf 21 children, 11 (52%) had ILD; 9 received corticosteroids. Median age at treatment was 0.8 years. A clear or best response occurred in 7/9 (78%). RSS improved in 6/9 (p=0.02), with all children on respiratory support showing partial or complete weaning. Functional class improved in all with FC III/IV at baseline (p=0.02). Right ventricular function improved (TAPSE z-score +1.65, p=0.04), and elevated NT-proBNP normalised. Key clinical milestones included ECMO weaning, transplant delisting, and discontinuation of prostacyclin therapy. No significant adverse effects were observed. Untreated children showed no early improvement. ConclusionsCorticosteroids were associated with meaningful improvements in respiratory and PH outcomes in TBX4-associated PH with ILD. Prospective evaluation is warranted.

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Greater than the sum of its parts: combining epigenetic clocks to characterize the association of biological age acceleration and adiposity in young Filipino adults

Voloshchuk, R. S.; Zannas, A. S.; Kuzawa, C. W.; Lee, N. R.; Carba, D. B.; Adair, L. S.

2026-03-31 public and global health 10.64898/2026.03.30.26349740 medRxiv
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Background Diverse epigenetic clocks are known to capture health risks associated with increased adiposity, but their estimates have never been combined to represent a holistic estimate of biological age acceleration (BAA). There is also a gap in research using epigenetic clocks to study adiposity in lower-middle income Asian countries. Methods and Findings Data from 1,745 participants (21.7{+/-}0.3 years old, 45% female) of the Cebu (Philippines) Longitudinal Health and Nutrition Survey were analyzed. BAA was calculated using PCHorvath 2, PCHannum, PCPhenoAge, PCGrimAge, PCDNAmTL, and DunedinPACE. After ascertaining suitability for factor analysis (Kaiser-Meyer-Olkin 0.81), factor analysis was used to create PCFactorAge. Analogously, FactorAge was created using Horvath, Hannum, PhenoAge, GrimAge, DNAmTL, and DunedinPACE. BMI, waist circumference (WC), and waist-to-height ratio (WHtR) were used to represent adiposity. Linear regression was used to test the association of each adiposity measure with each BAA measure. BMI, WC, and WHtR were positively associated with both BAA combinations: 5 kg/m2 higher BMI corresponded to 0.097 (p=0.015) standard deviation (SD) increase in FactorAge and 0.099 (p=0.004) SD increase in PCFactorAge; 10 cm increase in WC--with 0.091 (p=0.005) SD increase in FactorAge and 0.094 (p<0.001) SD increase in PCFactorAge; 0.1 increase in WHtR--with 0.164 (p=0.001) SD increase in FactorAge and 0.163 (p<0.001) SD increase in PCFactorAge. Additionally, WHtR was associated with meaningful increases in PhenoAge, PCPhenoAge, PCHorvath 2, PCHannum, PCGrimAge, and DunedinPACE. WC was positively associated with PCHorvath 2, PCHannum, PCPhenoAge, and DunedinPACE. BMI was positively associated with PCHannum, PCPhenoAge, and DunedinPACE. Conclusions Our study presents a novel approach to creating a BAA estimate using multiple epigenetic clocks and shows that adiposity measures predict this factor in a young Filipino cohort.

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Metabolic Drivers of Disease Activity and Complications in Crohns Disease: A Retrospective Cross-Sectional Study

Pan, Y.; Huang, S.; Qin, S.; Liu, Z.; Liang, Y.; Jiang, H.

2026-04-06 immunology 10.64898/2026.04.01.715942 medRxiv
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BackgroundThis study aims to examine the independent relationships between individual components of metabolic syndrome (MetS) and two key clinical outcomes in patients with Crohns disease (CD): disease activity, as quantified by the Crohns Disease Activity Index (CDAI), and the occurrence of complications. MethodsThis retrospective cross-sectional study included 376 adults with newly diagnosed Crohns disease. Multiple linear regression was used to examine associations between metabolic parameters and CDAI scores, while multivariate logistic regression assessed links to complications. Analyses were also based on clinical CDAI cut-offs. Predictive nomograms were developed and internally validated via bootstrap resampling. ResultsMultiple linear regression indicated that higher CDAI scores were independently associated with lower BMI (B = -5.866, P < 0.001), lower HDL-C levels (B = -81.770, P < 0.001), higher triglycerides (B = 15.618, P = 0.001), and lower ESR (B = -0.375, P = 0.03). Multivariate logistic regression established low HDL-C (OR = 0.042, P < 0.001), low BMI (OR = 0.915, P = 0.034), and high triglycerides (OR = 1.792, P = 0.007) as significant independent risk factors for complications. The developed nomograms demonstrated strong predictive performance, with an adjusted R2 of 0.207 for the CDAI model and an AUC of 0.765 for the complication model. For both predictive tasks, the model incorporating separate TG and HDL-C measurements significantly outperformed the TG/HDL-C ratio model. ConclusionMetabolic disturbances demonstrate a significant association with increased disease severity and a higher risk of complication development in Crohns disease. Core tipO_LIDual-outcome study reveals HDL-C and TG differentially link to CD inflammation and complications, pointing to distinct mechanisms. C_LIO_LILow HDL-C is the strongest independent predictor for CD complications, underscoring its protective role beyond cholesterol transport. C_LIO_LIIndividual TG and HDL-C metrics outperform their ratio in prediction, challenging its use and suggesting independent pathways in CD. C_LIO_LILow BMI independently associates with both adverse outcomes, refining the "obesity paradox" and highlighting malnutritions key role. C_LIO_LIA practical, validated nomogram (AUC=0.765) integrates HDL-C, TG, and BMI to stratify complication risk, aiding clinical decision-making. C_LI