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Frontiers in Pediatrics

Frontiers Media SA

All preprints, 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. Older preprints may already have been published elsewhere.

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Widespread annual rhythms in pediatric emergencies

Tachinardi, P.; Witt, R. M.; Wu, G.; Paulose, J. K.; Koritala, B. S. C.; Wong, H. R.; Mendonca, E. A.; Smith, D. F.; Hogenesch, J. F.; Ruben, M. D.

2024-12-20 emergency medicine 10.1101/2024.12.18.24319175 medRxiv
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Assessments of emergency department (ED) utilization for specific medical conditions reveal distinct annual rhythms, providing valuable insights into risk factors and optimal clinical staffing. However, focusing on a single condition in isolation can lack essential context. Such rhythms may (i) depend on co-occurrence with other conditions, (ii) be obscured by systemic factors that influence all conditions similarly, or (iii) offer limited clinical utility without understanding their rhythmic effect sizes relative to other emergencies. Using a unified framework for analysis, we studied the annual variation in incidences of all chief complaints (CCs) from 1.5 million admissions to our pediatric ED and urgent care centers from 2010 to 2021, enabling comparison of seasonality, effect sizes, and interactions across all types of emergencies. Most CCs ([~]80%) had annual rhythms, with a range of phases. Specific patterns, such as spring and fall peaks in neurologic-, injury-, and psychiatric-related CCs, have immediate significance. For example, psychiatric emergencies, which the American Academy of Pediatrics has designated a national crisis, were among the largest rhythmic effect sizes of all CCs. Further evaluation integrating ICD-10 diagnoses identified patient subtypes for psychiatric and other CCs, suggesting distinct annual influences. Using counterpart data from across Brazil, we identified marked global differences in annual patterns of ED utilization, including psychiatric emergencies. Lastly, we identified CCs with large weekday effects, impacting care and staffing needs, especially when combined with annual rhythms.

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Description and comparison of PIMS-TS innate cell signature and immunophenotype with a cohort of healthy children, severe viral and bacterial infections and Kawasaki Disease.

Garcia-Salido, A.; Leoz-Gordillo, I.; Gonzalez Bravin, A.; Garcia-Teresa, M. A.; Martinez-de-Azagra-Garde, A.; Iglesias-Bouzas, M. I.; Cabrero-Hernandez, M.; de - Lama - Caro - Paton, G.; Unzueta - Roch, J. L.; Castillo-Robleda, A.; Ramirez-Orellana, M.; Nieto-Moro, M.

2021-03-29 immunology 10.1101/2021.03.29.437479 medRxiv
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A new clinical syndrome associated to SARS-CoV-2 has been described in children. It has been named as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). This new disease is a main cause of hospital and pediatric intensive care unit (PICU). In this work we describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS. Also, we compare it with healthy controls and children admitted to PICU because bacterial infection, viral infection and Kawasaki disease. We made a prospective-retrospective observational study in a tertiary pediatric hospital. Children admitted to PICU because of PIMS-TS from March 2020 to September 2020 were consecutively included. They were compare with previous cohorts from our center. A total of 247 children were included: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 Kawasaki disease and 13 PIMS-TS. PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p =0,000). At the same time, we describe a differential expression of CD64, CD11a and CD11b. Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression compared to all groups (p = 0,000). Also, proteins involved in leukocyte tissue migration, like CD11a and CD11b were highly expressed compare to other severe viral or bacterial infections (p = 0,000). In PIMS-TS this increased CD11a expression could be a sign of the activation and trafficking of these leukocytes. These findings are congruent with an inflammatory process and the trend of these cells to leave the bloodstream. In conclusion, we compare for the first time the innate cellular response of children with PIMS-TS with other severe forms of viral or bacterial infection and Kawasaki disease. Our findings define a differential cell innate signature. These data should be further studied and may facilitate the diagnosis and management of these patients.

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Serum IL-6 and IL-18 Responses in Pediatric COVID-19: Role of Vitamin D Status in a Cohort from Azerbaijan

Huseynova, I. Y.; Hasanov, A. Q.; Sultanova, N. H.; Mammadova, F. M.; Taghi-zada, T. G.; Gafarov, I. A.; Allahverdiyeva, A. B.

2025-12-05 immunology 10.64898/2025.12.03.692155 medRxiv
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BackgroundThis study investigated the effects of COVID-19 infection and vitamin D status on inflammatory cytokine levels in children during the pandemic. A cohort of 170 children aged 1-17 years with PCR-confirmed SARS-CoV-2 infection was enrolled. Serum levels of IL-6 and IL-18 were analyzed in relation to vitamin D status and COVID-19 diagnosis. Our analysis revealed that children with vitamin D deficiency exhibited a trend toward increased levels of IL-6 and IL-18 compared to those with normal vitamin D levels; however, this association did not reach statistical significance. In contrast, COVID-19 infection was associated with significantly higher cytokine levels relative to healthy controls. These findings suggest a potential modulatory role of vitamin D in pediatric inflammatory responses to SARS-CoV-2, meriting further investigation through prospective studies.

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Predictors of Post intensive care syndrome in paediatrics (PICS-p): A Systematic Review and Meta-Analysis protocol

Ali, S.; Ladak, L. A.; Abbas, Q.; Siddiqui, N. U.- R.; Manning, J. C.

2025-07-17 pediatrics 10.1101/2025.07.17.25331459 medRxiv
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IntroductionPost-Intensive Care Syndrome in Pediatrics (PICS-p) is being increasingly reported and investigated in children after a critical illness. This manifests as physical, cognitive, and mental problems that affect their quality of life. This systematic review aims to explore the risk factors leading to PICS-p to inform prevention and management strategies. Method and AnalysisThis systematic review and Meta-analysis will be carried out in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The inclusion studies were quantitative cohort, case control, cross section and observational. Studies conducted in the last 2.5 decade (January 1, 2000 to January 1, 2025) involving pediatric population starting 1 month to 18 years of age, discharged from PICU. PubMed,Embase, Scopus and CINAHL databases will be used to search for the relevant studies. Boolean operations and Mesh terms will be used to ensure exhaustive literature coverage. ConclusionThe review will provide an opportunity to know the risk factors non-modifiable (Age, sex, pre-existing health conditions and severity of illness) and modifiable (Delirium, sedation practice, PICU environment, Rehabilitation services and family support) that are associated with PICS-p and the findings can be used to make recommendations for targeted interventions to target interventions. Thus, by contributing toward overcoming this problem, the study is meant to improve the outcome for pediatric patients and families while decreasing future burdens due to long-lasting ailments. The outcomes are expected to shape clinical practices and policymaking in the direction of holistic care and recovery among survivors from a PICU. What is already known on this Topic?Despite growing recognition of post intensive care syndrome in pediatrics, there is no systematic review has been made regarding the factors that predispose to PICS-p in children with the age 1 month to 18 years, highlighting a huge knowledge gap. What this study hopes to add?The results of this systematic review identify risk factors linked to PICS-p and offer important new information for the future development of intervention programs for childrens risk factors modifiable and non-modifiable linked to PICS-p. How this study might affect research, practice or policy?This review is intended to present a body of evidence that will be useful in informing clinical practice and preventive efforts on preventive work for at risk children. The review will address how risk factor will help healthcare providers, researcher, policymakers, and caregivers in the long-term health and well-being of pediatric patients who will be discharged from PICUs.

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Frequency of hospitalization of infants with bronchiolitis during 2017 in Puerto Madryn, Argentina

TAIRE, D. L.; PAZOS, B. A.

2021-01-31 respiratory medicine 10.1101/2021.01.28.21250671 medRxiv
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IntroductionBronchiolitis is considered the most frequent disease in infants and still represents an important cause of morbidity and mortality worldwide. Despite its viral etiology, socioeconomic variables could influence the disease outcome. We aimed to determine the frequency of hospital discharge for bronchiolitis in a local Hospital in the city of Puerto Madryn, in the province of Chubut, Patagonia Argentina. Population and methodsWe performed a cross-sectional study that analyzed all hospitalized patients discharged for bronchiolitis in Hospital "Dr. Andres R. Isola" during the year 2017 and based on data provided by the hospital administrative staff. The study variables were the length of stay, readmission rate and place of origin of hospitalized patients. ResultsA total of 120 patients were included. The median age was 4.45 months (3.9-5). The mean length-of-stay (LOS) was 7.30 days (5.52-9.08). Of the total number of patients, 24 (20%) had a LOS [≤]3 days and 96 (80%) a >3 days. One hundred patients (88.33%) had no hospital readmissions and 10 patients (8.33%) had hospital readmissions. The median age of patients with readmissions was 4.2 months (2.69-5.71). The mean LOS during readmission was 17.3 days (5.25-29.35). Of the 120 hospitalized children, 100 infants (83.33%) live in areas identified as having "unsatisfied basic needs" in Puerto Madryn. ConclusionsThe overcrowding as a result of the demographic transformation on the frequency of hospitalization of infants with bronchiolitis was homogeneous within the Puerto Madryn population with "unsatisfied basic needs".

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Multisystem inflammatory syndrome in European White children - study of 274 cases

Ludwikowska, K. M.; Okarska-Napierala, M.; Dudek, N.; Tracewski, P.; Kusa, J.; Piwonski, K.; Afelt, A.; Cysewski, D.; Biela, M.; Werner, B.; Jackowska, T.; Suski, C.; Kursa, M. B.; Kuchar, E.; Szenborn, L.

2021-03-31 pediatrics 10.1101/2021.03.30.21254584 medRxiv
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BackgroundDespite the growing literature on multisystem inflammatory syndrome in children (MIS-C), the data in European White population is limited. Our aim was to capture MIS-C emergence in Poland (central Europe) and to describe its characteristics with a focus on severity determinants. MethodsPatients who met the MIS-C definition (fever, multiorgan failure, inflammation, and proven SARS-CoV-2 infection or contact) were reported retrospectively and prospectively in an online survey. Study definitions fulfilment was automatically evaluated by a dedicated software. For the assessment of univariate relationships, either directed or divided by sex, age, or disease severity, we used the test for two categorical variables and the Kruskal-Wallis test for categorical-continuous variable pairs. FindingsThe analysis involved 274 children, 62.8% boys, median age 8.8 years. Besides one Asian, all were European White. Merely 23 (8.4%) required paediatric intensive care treatment (PICU). They were older (11.2 vs. 8.4 years), and at hospital admission had higher respiratory rate (30 v. 20/minute), lower systolic blood pressure (89 vs. 100 mmHg), prolonged capillary refill time (40% vs. 11%), and decreased consciousness (22% vs. 5%). Teenage boys had more common cardiac involvement (fraction 25.9% vs. 14.7%) and macrophage activation syndrome (31.0% vs. 15.2%) than others. Boys were also more often hospitalised in PICU with age (from median 11.2 years to 9.1). InterpretationThe severity of MIS-C is not as uniform as it seemed, ethnicity and sex may affect MIS-C phenotype. Management might not be universally applicable and should rather be adjusted to the specific population. FundingPSP: 501-D402-20-0006100

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October 2018 - December 2023 time-series analysis of pediatric RSV immunizations and RSV-associated hospitalizations

Cartwright, B. M. G.; Gratzl, S.; Rodriguez, P. J.; Baker, C.; Stucky, N.

2024-01-25 respiratory medicine 10.1101/2024.01.25.24301780 medRxiv
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This study describes two population under age two 1) who received an RSV immunization and 2) experienced RSV-associated hospitalizations since 2018. Results show low uptake of the RSV immunization. RSV-associated hospitalizations exhibited earlier and higher peaks in the 2021/22 and 2022/23 seasons compared to previous years.

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Relationship between national changes in mobility due to non-pharmaceutical interventions and emergency department visits due to pediatric acute respiratory infections during the COVID-19 pandemic.

DIAZ, F.; Carvajal, C.; Gatica, S.; Vasquez-Hoyos, P.; Jabornisky, R.; von Moltke, R.; Jaramillo-Bustamante, J.-C.; Pizarro, F.; Cruces, P.

2022-06-17 pediatrics 10.1101/2022.06.16.22276017 medRxiv
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BackgroundStrong social distancing measures were quickly implemented in Chile during the SARS-CoV-2 outbreak. One of the aims of non-pharmaceutical interventions (NPI) mandates was to decrease overcrowding, thus is usually measured as mobility changes. Methodswe gather data from national health statistics for pediatric emergency (PED) visits for acute respiratory infection (ARI) in children younger than 15. We defined a historical cohort, including data from 2016 to 2019, and compared them with 2020 and 2021 pandemic years. Also, Chiles national mobility reports from the online google database were downloaded. We tested the correlation between changes in mobility and relative reduction in PED-ARI by Spearmans Rank Test. ResultsHistorical data showed a mean of 46863 {+/-} 3071 PED-ARI weekly visits with a high seasonal variation, with two peaks in weeks 20 and 28 and weeks 32 to 36. This transient drop was temporally associated with the mid-winter 2-week holiday of schools. The usual PED visits peaks did not occur in 2020 and 2021. Mobility declined from week 9, reaching lower than historical data from week 12 and a minimum of 43% in week 15 of 2020 (Figure 1). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/22276017v1_fig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1999627org.highwire.dtl.DTLVardef@50ff2aorg.highwire.dtl.DTLVardef@1a0393borg.highwire.dtl.DTLVardef@d69f1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Variables analyzed per epidemiological week. (A) pediatric emergency visits for acute respiratory infections (PED-ARI) in Chile. Historical cohort, 2015-2019 average, and consecutive weeks of pandemic, 2020 and 2021. (B) Variation between historical cohort and consecutive weeks of the pandemic, 2020 and 2021, for PED-ARI; (C) National mobility variation per epidemiological week during 2020 and 2021. (0) First COVID-19 case in Chile; (1) Mandatory School closure (2) Partial quarantines in high incidence counties; (3) National Catastrophic Disaster declaration; (4) total quarantine in major urban areas; (5) DELTA variant identified in Chile; (6) Universal Vaccination for > 16 yo; (7) Vaccination for > 12 yo; (8) Non-mandatory in-person schooling; (9) Sanitary passport for vaccination proof in >17 yo; (10) Vaccination for children 12-17 yo; (11) Vaccination for children 6-11 yo; (12) Sanitary Passport for children (12-17 yo); (13) Omicron first case in Chile; (14) Vaccination for children 3-5 yo. C_FIG The correlation between mobility and PED-ARI visits showed a strong monotonic relationship (quadratic) with a Spearmans rho of 0.80 (95% CI 0.75 to 0.86) (Figure 2). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=53 SRC="FIGDIR/small/22276017v1_fig2.gif" ALT="Figure 2"> View larger version (14K): org.highwire.dtl.DTLVardef@a6546corg.highwire.dtl.DTLVardef@1f08804org.highwire.dtl.DTLVardef@71f2e5org.highwire.dtl.DTLVardef@101a1d8_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO Correlation between national change in mobility (%) and the relative reduction in pediatric emergency department visits for acute respiratory infections (D PED-ARI). Spearmans Rank Test, Spearmans rho of 0.80 (95% CI 0.75 to 0.86). C_FIG ConclusionNPI resulting in a decrease in mobility should be considered a robust public health measure to relieve the winters collapse of the national health system, decreasing morbimortality in children due to PED-ARI. WHATS KNOWN ON THIS SUBJECTA remarkable decrease in pediatric respiratory infections has been described during the pandemic, although the causes are still poorly understood. WHAT THIS STUDY ADDSIn a historical cohort before the pandemic, we observed a temporal association between mid-winter holidays and the gap between the two peaks of acute pediatric respiratory infections. We found a strong correlation between national mobility changes due to non-pharmaceutical interventions and acute pediatric respiratory infections during the pandemic. Therefore, timely implementation of non-pharmaceutical interventions might be considered as a robust public health measure to attenuate the seasonal epidemic of non-COVID viral acute respiratory infections. With these data, we wonder if the time has come to implement non-pharmaceutical interventions to mitigate the stress, and frequently collapse, of national health systems due to the increase in pediatric acute respiratory infection, placing children as a priority, and provide the best care to this vulnerable population.

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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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The magnitude, determinants, and outcome of shock among pediatric patients: A cross-sectional hospital-based study.

Kidanu, M. G.; Tazebe, E.; Birhane, A.; Yemane, M.; Kahsay, M. M.; Tedla, M.

2023-10-28 emergency medicine 10.1101/2023.10.27.23297683 medRxiv
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BackgroundPediatric shock, a potentially fatal illness, develops after a systemic circulatory system failure. It appears to be a common emergency in children and produces substantial morbidity and mortality particularly if there is no early identification and therapy. The extent and causes of shock-induced death among children in Ethiopia have not been sufficiently studied. ObjectiveThis study was conducted to evaluate the severity, determinants, and prognosis of shock in pediatric patients who visited Ayder Comprehensive Specialized Hospital in Tigray, Northern Ethiopia. MethodsFrom October 1st, 2020, to July 30th, 2022, an observational cross-sectional study was carried out at Ayder Comprehensive Specialized Hospital. The study included 132 children from the age of 1 month to 18 years. According to pediatric advanced life support guidelines, shock was diagnosed among patients. To gather information, a pretested questionnaire was employed. To examine the relationship between the independent variables and shock outcome, bivariate logistic regression was performed, and statistical significance was defined as a P-value of 0.05 or lower. ResultThe prevalence of shock was 2.2%. This study revealed 70.4 % decompensated stage of shock. Mortality rate of shock was 45.5% (95% CI: 37.1-53.8). A delayed presentation by more than one week with an adjusted odd ratio(AOR) of 16.9 (95% CI:2.3-123), type of shock other than hypovolemic shock with AOR of 8.3 (95% CI: 1.4-48), stage of shock with AOR of 27.8 (95% CI: 2.8-157), requirement of mechanical ventilation with AOR of 11 (95% CI:2.6-53) and length of hospital stay less than three days with AOR of 9 (95% CI: 1.7-48) were identified as a predictor of mortality by shock in children. ConclusionAccording to this study, shock causes a higher rate of child mortality. Independent predictors of mortality included delayed presentation, shock type, shock stage, need for mechanical ventilation, and brief hospital stay (less than three days).

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Weight-Adjusted Waist Index and Its Association with Pulmonary Function in Children: 6-17 Years: Cross-Sectional Findings

liang, g.; zhai, w.; yang, x.; Cheng, J.; zhou, y.; zhou, j.

2025-06-05 health systems and quality improvement 10.1101/2025.06.03.25328930 medRxiv
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BackgroundExcess adiposity has been linked to compromised lung function and elevated susceptibility to respiratory diseases which may lead to long-term lung deterioration. Conventional indicators of obesity, such as BMI and waist circumference, have limitations due to the so-called "obesity paradox." The Weight-Adjusted Waist Index (WWI) is another way to assess central fat distribution. However, its relationship with lung function in children has not been explored to date. ObjectiveTo explore the correlation between WWI and lung function parameters among children aged 6 to 17. MethodsData from NHANES 2007-2012 were used for cross-sectional analysis. An adjusted multivariate regression framework weighted by the inclusion sample was used to assess the relationship between WWI and pulmonary function indices (FVC, FEV1, FEF25% -75%, PEF, and FEV1/FVC). Possible nonlinear relationship was assessed using curve fitting and split linear regression. Subgroup analyses were performed to assess differences between groups. ResultsThis study involved 3,717 US children. Higher WWI was associated with lower FVC, FEV1, FEV1 25%-75% and PEF ({beta} = -0.28, -0.26, -0.30, -0.30, -0.30, and -0.58). The association between FEV1/FEVC and WWI was nearly significant ({beta} = -0.06, P = 0.054). The breakpoints for nonlinear associations were 10.83, 10.70, 10.70, 11, and 10.79 (P < 0.001). Subgroup analyses showed stronger correlations for boys and L-shaped correlations for boys. ConclusionA nonlinear negative correlation between WWI and respiratory capacity metrics was found in US children, emphasizing the potential relevance of maintaining optimal WWI to respiratory health. Prospective cohort studies are warranted to validate these preliminary observations.

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Sociodemographic predictors of asthma control and exacerbation among children in Central Kenya: A hospital-based cross-sectional study

Robai, L.; Mukala, J.; Bernard, K.; Ogweno, K.; David, K.

2026-02-06 emergency medicine 10.64898/2026.02.05.26345704 medRxiv
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IntroductionChildhood asthma remains a major public health challenge in low- and middle-income countries, where social and economic factors influence disease outcomes. This study examined the sociodemographic determinants of asthma exacerbation among children attending clinic at Thika Level 5 Hospital, Kenya. MethodsThis study employed a hospital-based cross-sectional study involving 108 caregivers- child dyads, each consisting of a child with confirmed asthma and their primary caregiver. The dyads were recruited from the pediatric asthma clinic from 31st March 2025 to 30th April 2025 then follow up was conducted for six months form 1st May to 31st October 2025. Data were collected using structured questionnaires and clinic records. Descriptive statistics summarized sociodemographic characteristics, while chi-square tests and logistic regression assessed associations between caregiver factors and asthma control. ResultsThe mean age of children was 8.1 years (range 3-17), with males comprising 57.4%. Most caregivers were mothers (88%), had secondary education (57.4%), and were in informal employment (75.9%). Household income was low for 59.3% of participants (<KES 30,000/month). Caregiver education (AOR=2.8; 95% CI:1.5-5.2; p=0.001) was the strongest predictor of asthma control, followed by medical insurance ({chi}2=10.41; p=0.001). Formal employment and higher income were significantly associated with controlled asthma ({chi}2=6.45; p=0.04 and {chi}2=9.72; p=0.02 respectively). Urban residence modified the positive effect of education on asthma management (interaction AOR=1.9; p=0.03). ConclusionCaregiver education level, employment, income, and medical insurance significantly influence asthma control among children. Enhancing health literacy and expanding insurance coverage under the Social Health Authority (SHA) can improve asthma outcomes in Kenyan children.

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Maternal cytokine response after SARS-CoV-2 infection during pregnancy

Gigase, F. A. J.; Molenaar, N. M.; Missall, R. D.; Rommel, A.-S.; Lieb, W.; Ibroci, E.; Ohrn, S.; Lynch, J.; Krammer, F.; Brody, R.; Jessel, R. H.; Sperling, R. S.; Lesseur, C.; Callipari, F.; Galang, R. R.; Snead, M. C.; Janevic, T.; Stone, J.; Howell, E. A.; Chen, J.; Pop, V. J. M.; Dolan, S. M.; Bergink, V.; De Witte, L. D.

2022-01-04 immunology 10.1101/2022.01.04.474908 medRxiv
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ObjectiveDysregulation of the immune system during pregnancy is associated with adverse pregnancy outcomes. Recent studies report cytokine changes during the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examine whether there is a lasting association between SARS-CoV-2 infection during pregnancy and peripheral blood cytokine levels. Study designWe conducted a case-control study at the Mount Sinai health system in NYC including 100 SARS-CoV-2 IgG antibody positive people matched to 100 SARS-CoV-2 IgG antibody negative people on age, race/ethnicity, parity, and insurance status. Blood samples were collected at a median gestational age of 34 weeks. Levels of 14 cytokines were measured. ResultsIndividual cytokine levels and cytokine cluster Eigenvalues did not differ significantly between groups, indicating no persisting maternal cytokine changes after SARS-CoV-2 infection during pregnancy. ConclusionOur findings suggest that the acute inflammatory response after SARS-CoV-2 infection may be restored to normal values during pregnancy.

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Admission biomarkers may not have an association with cardiovascular involvement in Latin American patients with Multisystem Inflammatory Syndrome in Children (MIS-C)

Galindo-Hayashi, J. M.; Gonzalez-Moctezuma, K.; Tamez-Rivera, O.; Villarreal-Trevino, A. V.

2023-06-16 cardiovascular medicine 10.1101/2023.06.13.23291351 medRxiv
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ObjectivesThe aim of the study is to determine if there is an association between altered biomarkers and cardiovascular involvement in Latin American patients with MIS-C. DesignThe researchers of this study conducted a retrospective cohort study. SettingSecondary care maternal unit hospital in Monterrey, NL, Mexico. ParticipantsAny register of a Latin-American pediatric patient with MIS-C within the database from March 2019 to February 2022. Primary and secondary outcome measuresCut, mean, odds ratio (OR), relative ratio (RR), 95% confidence interval (CI) and p values of inflammatory markers associated with cardiovascular affection in MIS-C. As a secondary outcome we measure being male as an independent risk factor. ResultsNone of the biomarkers and gender variables taken were significant (Table 1). O_TBL View this table: org.highwire.dtl.DTLVardef@1140c78org.highwire.dtl.DTLVardef@13eb581org.highwire.dtl.DTLVardef@1fe447corg.highwire.dtl.DTLVardef@426569org.highwire.dtl.DTLVardef@10fd4bb_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO C_TBL ConclusionsThe researchers analysis suggests there is no evidence of cause-effect association between admission biomarkers and the presence of cardiovascular affection in MIS-C. Remarkably, neutrophilia and ESR had a high odds ratio and a nearly significant p-value, which makes them ideal for further analysis with a bigger sample. Additionally, gender was included as a risk factor and was analyzed independently, nonetheless, it was not associated with a higher risk of presenting cardiovascular affection. Article summary Strengths and limitations of this studyO_LIFirst study measuring the association of a series of available and economical biomarkers with a higher incidence of cardiovascular involvement in MIS-C in a Latin-American population. C_LIO_LISet ground for further research regarding the current treatment of MIS-C C_LIO_LISample size non-representative. C_LIO_LISince this is an observational study we cant fully control confounding and bias (e.j. reporting bias) C_LI

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Examining the Link Between Emergency Department Arrival Mode, Social Determinants of Health, and Social Service Needs in Pediatric Emergency Medicine: A Cross-Sectional Study

Buted, S. C.; Dillon, M.; Meadows, M. J.; Elston, C.; Mahoney, A. A.; Adelgais, K. M.

2025-09-12 emergency medicine 10.1101/2025.09.10.25335528 medRxiv
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BackgroundUnmet social needs can increase the risk of adverse health outcomes in children. Emergency medical services (EMS) utilization is higher among families facing challenges with certain social determinants of health (SDoH). Understanding service needs among families seeking emergency care may inform interventions designed to support better health outcomes. MethodsWe conducted a cross-sectional survey of caregivers and EMS clinicians presenting to a pediatric emergency department (ED) via EMS or private vehicle (POV). Participants completed a survey reporting access to transportation, food, housing, healthcare, mental healthcare, and financial support. We evaluated differences in self-reported SDoH and service needs by arrival mode and differences in caregiver-reported needs with those perceived by EMS clinicians using Pearsons chi-squared and Fishers exact tests. ResultsA total of 159 caregivers (111 POV, 48 EMS) and 17 EMS clinicians were enrolled. Caregiver demographics were similar between groups. Overall, 67 (42%) caregivers reported at least one service need with few differences between groups. Difficulty seeking healthcare, childcare, and mental health support were most frequently reported. EMS arrivals were more likely to report difficulty seeking child healthcare (p=.02); POV arrivals were more likely to report personal mental health needs (p<.01). There was no difference in requests for child mental health treatment (p>.90). ConclusionsService needs are common in pediatric emergency care. Difficulty accessing child healthcare and mental healthcare were common in our population. Screening pediatric caregivers during emergency care including during EMS activations may identify families in need of support services. KEY MESSAGE STATEMENTSocial Determinants of Health (SDoH) have important health implications in children. In pediatric emergency care, caregivers and children arriving via Emergency Medical Services (EMS) are more likely to have social needs. There is a paucity of research on the specific needs of this population compared to private vehicle arrives and if EMS clinicians are aware of these needs. This study compares the SDoH of caregivers in the ED between arrival type and assesses if EMS clinicians recognize the needs of the people they transport. These results may be useful in improving EMS clinician curricula and addressing SDoH in families with young children.

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Clinical-epidemiological and treatment characteristics of children with COVID-19 in a tertiary referral center in Peru

Chiara-Chilet, C.; Luna-Vilchez, M.; Maquera-Afaray, J.; Salazar-Mesones, B.; Portillo-Alvarez, D.; Priale-Miranda, R.; Mendoza-Torres, F.; Munayco-Perez, A.; Baca-Cama, Y.; Santiago-Abad, M.; Lopez, J. W.; Pediatric COVID-19 Working Group INSN SB,

2020-09-18 pediatrics 10.1101/2020.09.18.20186866 medRxiv
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IntroductionCOVID-19 pandemic represents a big impact on childrens health, this study describes the behavior of the disease in hospitalized pediatric patients in the Instituto Nacional de Salud del Nino San Borja (INSN-SB). MethodsRetrospective study of patients with confirmed COVID-19 diagnostic between March and July 2020. Demographic, clinic, laboratory, radiology and treatment data were collected and for the analysis descriptive statistics were included. ResultsFrom a total of 91 patients. 36.3% (33) were female. The age group who was affected the most were school children with a median age of 4 years old (IQR 1-8). Patients who came from Lima represented 61.5%. Previous contact was determined in 30.8% of the cases. PCR results for SARS CoV-2 were positive in 50.6% of the cases and 49.4% in the quick tests. Comorbidity was present in 53.8% of the cases. Most frequent symptoms were fever (39.6%), general discomfort (23.1%), cough (19.8%) and shortness of breath (14.3%). Presence of MIS-C was confirmed in 6 patients. Use of antibiotics represented 76.9% of the cases. The most frequent radiology pattern was bilateral interstitial (57.7%). Comorbidities were present in 68.2% (15/22) of patients in PICU. From a total of 9 deceased patients, 6 were admitted in PICU and 8 presented associated comorbidities. ConclusionsCOVID-19 in children displays mild and moderate clinical manifestations. A great proportion of patients exhibited comorbidities, especially PICU patients and the ones that died. What is known about the subjectIn pediatric patients, the prevalence and severity of COVID-19 are usually low, however, in the presence of MIS-C, greater severity and probability of admission to the PICU is observed. What this study adds- This study describes the results of complex pediatric patients and the associated comorbidity in LMIC setting that showed greater severity and admission to the ICU. - Microbiological isolates in cultures were low, therefore the initiation of empirical antibiotic therapy is not justified in most cases.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy In China: A Retrospective Cohort Study

Yin, M.; Zhang, L.; Deng, G.; Han, C.; Shen, M.; Sun, H.; Zeng, F.; Zhang, W.; Chen, L.; Luo, Q.; Yao, D.; Wu, M.; Yu, S.; Chen, H.; Baud, D.; Chen, X.

2020-04-11 respiratory medicine 10.1101/2020.04.07.20053744 medRxiv
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BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the cause of the ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19) in China and worldwide. However, there were few studies about the effects of SARS-CoV-2 infection on pregnant women. MethodsIn this retrospective cohort study, we enrolled 31 pregnant women and 35 non-pregnant women from Jan 28 to Feb 28, 2020 to evaluate the effects of SARS-CoV-2 infection during pregnancy. Inflammatory indices were used to assess the severity of COVID-19. Evidence of vertical transmission was determined by laboratory confirmation of SARS-CoV-2 in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. FindingsCompared with non-pregnant women, pregnant women had a significantly lower proportion of fever (54{middle dot}8% vs. 87{middle dot}5%, p= 0.006), a shorter average interval from onset to hospitalization (7{middle dot}80 {+/-}7{middle dot}0d vs. 13{middle dot}2 {+/-} 8{middle dot}2d, p= 0.005), and a higher proportion of severe or critical COVID-19 (32{middle dot}3% vs. 11{middle dot}4%, p=0.039). Neutrophil-to-lymphocyte ratio (NLR) and systematic immune-inflammation-based prognostic index (SII) were significantly higher on admission in severe/critical pneumonia group than moderate pneumonia group. We could not detect the presence of SARS-CoV-2 by RT-PCR in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. InterpretationThe clinical symptoms of COVID-19 in pregnant women were insidious and atypical, compared with those in non-pregnant patients. SII and NLR could be a useful marker to evaluate the severity of COVID-19. There was no evidence of vertical transmission during pregnancy with SARS-CoV-2 infection. FundingNational Natural Science Foundation of China and Research Funds for the Central Universities. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, Embase and Web of science for articles published up to March 1st, 2020, using the keywords ("novel coronavirus" OR "2019 novel coronavirus" OR "2019-nCoV" OR COVID-19 OR SARS-CoV-2) AND (pregnancy OR "maternal infection" OR "fetal infection") AND "Cohort studies". We identified no published cohort studies on pregnant women with the 2019 novel coronavirus disease (COVID-19) infection. Added value of this studyFor this retrospective cohort study, we reviewed clinical records, laboratory findings, and chest CT scans from 31 pregnant women and 35 non-pregnant women from Jan 28 to Feb 28, 2020 to evaluate the effects of SARS-CoV-2 infection during pregnancy. Inflammatory indices were used to assess the severity of COVID-19. Evidence of vertical transmission was determined by laboratory confirmation of SARS-CoV-2 in amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples. Compared with non-pregnant women, pregnant women had a significantly lower proportion of fever (54{middle dot}8% vs. 87{middle dot}5%, p= 0.006), a shorter average interval from onset to hospitalization (7{middle dot}80 {+/-}7{middle dot}0d vs. 13{middle dot}2 {+/-} 8{middle dot}2d, p= 0.005), and a higher proportion of severe or critical COVID-19 (32{middle dot}3% vs. 11{middle dot}4%, p=0.039). Neutrophil-to-lymphocyte ratio (NLR) and systematic immune-inflammation-based prognostic index (SII) were significantly higher on admission in severe/critical pneumonia group than moderate pneumonia group. Amniotic fluid, placenta, neonatal throat and anal swab and breastmilk samples were tested for SARS-CoV-2 by RT-PCR and all results were negative. Implications of all the available evidenceThe clinical symptoms of COVID-19 in pregnant women were insidious and atypical, compared with those in non-pregnant patients. SII and NLR could be a useful marker to evaluate the severity of COVID-19. There was no evidence of vertical transmission during pregnancy with SARS-CoV-2 infection.

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Parental Perception of Children Sleep Pattern Changes During FIFA 2022

Aljamaan, F.; Alhuzaimi, A.; Dasuqi, S. A.; Alharbi, N.; Altamimi, I.; Alageel, R.; Alsulami, H.; Jamal, A.; Alenezi, S.; Alarabi, M.; Saad, K.; Saeed, E.; Alrabiaah, R.; Alhadeed, A.; Alhasan, K.; BaHammam, A. S.; Temsah, M.-H.

2025-12-23 pediatrics 10.64898/2025.12.21.25342765 medRxiv
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IntroductionThe circadian clock is an internal, [~]24-hour biological timer that synchronizes physiology with the day-night cycle. Social jetlag (SJL) describes the misalignment between this internal clock and social schedules, a condition affecting approximately 70% of the population and linked to a spectrum of metabolic, mental, and cognitive health issues. This study examined how the 2022 FIFA World Cup disrupted normal childrens sleep routines and other associated factors from parents prospect. MethodsAn online, cross-sectional survey was distributed to parents (N=848). The questionnaire collected sociodemographic data, childrens habitual sleep habits, and changes perceived during the 2022 FIFA World Cup. SJL was defined as a [&ge;]1-hour delay in bedtime on weekends versus weekdays. Multivariable logistic regression analyses identified factors associated with perceived sleep changes and SJL. ResultsOver half (53.4%) of the children exhibited pre-existing weekend SJL. Children aged 5-11 (OR=1.847, p<0.001), higher socioeconomic status (OR=1.383, p<0.001), international residency (OR=2.845, p<0.001) were significant predictors of baseline weekend SJL. During the tournament, 33% and 17.8% of parents reported their children had delayed sleep ([&ge;]1 hour) on weekdays and weekends due to match watching, respectively. Regression analysis revealed that these parental perceived FIFA impact on their children sleep was significantly associated with weekdays SJL OR= 1.958, p=0.001 and weekends OR= 1.784, p=0.009 during the FIFIA season. DiscussionOur findings indicate that major social events can exacerbate circadian misalignment and SJL, likely driven by social conformation. The high prevalence of baseline SL confirms it is a widespread pediatric health issue. The vulnerability of the 5-11 age group shows SJL is not exclusively an adolescent problem. ConclusionMajor sporting events significantly disrupt childrens sleep schedules, compounding the public health issue of chronic SJL. Proactive guidance for families is needed during such events. More importantly, these findings underscore the urgent need for structural changes to align social schedules with pediatric circadian biology.

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Machine Learning-based Mortality Prediction for Pediatric Fulminant Myocarditis Using Cytokine Profiles

Jing, S.; Suzuki, T.; Nomura, Y.; Kunida, K.; Sakumura, Y.; Uchida, H.; Saito, K.; Ito, R.; Kito, M.; Kawai, S.; Suzuki, K. T.; Floh, A. A.; Yoshimoto, J.; Yoshikawa, T.; Yasuda, K.

2025-05-08 cardiovascular medicine 10.1101/2025.05.07.25327044 medRxiv
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BackgroundFulminant myocarditis (FM) is a rare but life-threatening pediatric condition that rapidly progresses to cardiogenic shock and fatal arrhythmias. Early identification of prognostic biomarkers is vital for timely intervention and better outcomes. Although inflammatory cytokines contribute to FM pathogenesis, their prognostic value remains unclear. This study aimed to identify mortality-associated markers by integrating cytokine profiles and clinical variables through a machine learning approach. MethodsWe retrospectively analyzed 21 pediatric FM cases from two tertiary centers (2012-2022). At admission, 37 cytokines and 14 clinical parameters were assessed. Partial least squares discriminant analysis was employed to identify prognostic features, with variable importance in projection scores quantifying their contribution. Model performance was evaluated using leave-one-out cross-validation. Statistical significance was determined via the Benjamini-Hochberg method at a false discovery rate of 0.05. ResultsOf the 51 features analyzed, 23 emerged as key predictors with variable importance in projection scores above 1.0, including 20 cytokines and three clinical parameters. Six cytokines (TNF-, M-CSF, MIP-1, IL-8, IL-6, and IL-15) were both statistically significant and highly important. Elevated CK-MB and lactate levels and lower pH were also linked to poor outcomes. The model performed robustly, with an AUC of 0.92, 85.7% accuracy, 92.9% sensitivity, and 71.4% specificity. ConclusionsTNF- emerged as a key cytokine linked to mortality in pediatric FM, supporting its role as a prognostic biomarker and potential therapeutic target.

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Children with COVID-19 like symptoms in Italian Pediatric Surgeries: the dark side of the coin

Trapani, G.; Fanos, V.; Bertino, E.; Maiocco, G.; Al Jamal, O.; Fiore, M.; Bembo, V.; Careddu, D.; Barberio, L.; Zanino, L.; Verlato, G.

2020-07-29 pediatrics 10.1101/2020.07.27.20149757 medRxiv
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BackgroundSymptoms of SARS-CoV-2 infection in children are nonspecific and shared with other common acute viral illnesses (fever, respiratory or gastrointestinal symptoms, and cutaneous signs), thus making clinical differential diagnosis tricky. In Italy, first line management of pediatric care is handed over to Primary Care Pediatricians (PCPs), who were not allowed to directly perform diagnostic tests during the recent COVID-19 outbreak. Without a confirmatory diagnosis, PCPs could only collect information on "COVID-19 like symptoms" rather than identify typical COVID-19 symptoms. AimTo evaluate the prevalence of COVID-19 like symptoms in outpatient children, during Italian lockdown. To provide PCPs a risk score to be used in clinical practice during the differential diagnosis process. MethodsA survey was submitted to 50 PCPs (assisting 47,500 children) from 7 different Italian regions between the 4th of March and the 23rd of May 2020 (total and partial lockdown period). COVID-19 like symptoms in the assisted children were recorded, as well as presence of confirmed/suspected cases in childrens families, which was taken as proxy of COVID-19. Multivariable logistic regression was accomplished to estimate the risk of having suspected/confirmed cases in families, considering symptoms as potential determinants. Results2,300 children (4.8% of overall survey population) fell ill with COVID-19 like symptoms, 3.1% and 1.7% during total and partial lockdown period respectively. The concurrent presence of fatigue, cough, and diarrhea in children, in absence of sore throat/earache and abnormal skin signs, represents the maximum risk level of having a suspected/confirmed case of COVID-19 at home. ConclusionsThe percentage of children presenting COVID-19 like symptoms at home has been remarkable also during the total lockdown period. The present study identified a pattern of symptoms which could help, in a cost-effective perspective, PCPs in daily clinical practice to define priorities in addressing children to the proper diagnostic procedure.