Clinical Characteristics and Hospital Course of Children with Down Syndrome Hospitalized with Pneumonia: A Three-Group Comparative Study

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Alharbi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8528636/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Children with Down syndrome (DS) are recognized as a high-risk population for respiratory infections; however, direct comparisons of pneumonia outcomes between children with DS, previously healthy children, and children with other chronic underlying conditions remain limited. Methods We conducted a retrospective, cross-sectional study of children hospitalized with pneumonia at King Saud University Medical City between May 2015 and March 2020. Patients were categorized into three groups: previously healthy children, children with Down syndrome, and children with other chronic underlying conditions. Demographic characteristics, markers of disease severity, and hospital course were compared. Continuous variables were analyzed using non-parametric tests and reported as median (IQR). Categorical variables were compared using chi-square or Fisher’s exact tests. Pairwise comparisons focused on Down syndrome. Results A total of 456 children were included: 233 (51.1%) previously healthy, 26 (5.7%) with Down syndrome, and 197 (43.2%) with other chronic conditions. Oxygen supplementation was required more frequently in children with Down syndrome compared with previously healthy children (88.5% vs 60.5%, p = 0.005). No significant differences were observed between children with Down syndrome and those with other chronic conditions in severe disease (30.8% vs 40.6%, p = 0.397), mechanical ventilation (23.1% vs 29.1%, p = 0.760), or length of hospital stay (median 6 vs 7 days, p = 0.148). Overall, three-group comparisons demonstrated significant differences in oxygen requirement (p < 0.001) and length of stay (p < 0.001). Conclusion Children with Down syndrome hospitalized with pneumonia require oxygen supplementation more frequently than previously healthy children; however, their overall clinical course closely resembles that of children with other chronic underlying conditions. These findings suggest that medical complexity, rather than Down syndrome alone, is a key determinant of pneumonia outcomes. Pneumonia Down syndrome Underlying Conditions Figures Figure 1 Figure 2 Background Pneumonia remains a critical global health challenge, representing the single greatest infectious cause of pediatric mortality worldwide ( 1 ). It accounts for approximately one-fifth of all deaths in children under five years of age, resulting in nearly one million deaths annually ( 2 , 3 ). In developed nations such as the United States, pneumonia is one of the top three reasons for pediatric hospitalization, with roughly 20% to 25% of emergency department visits for the condition resulting in inpatient admission ( 4 ). Consequently, community-acquired pneumonia (CAP) poses a significant burden and an increasing challenge to healthcare resources ( 2 ). The presence of underlying chronic conditions substantially increases the risk of a severe clinical course and heightened healthcare utilization ( 2 ). Comorbidities such as chronic pulmonary disease, congenital heart defects, genetic syndromes, and neuromuscular disorders predispose children to more serious disease courses and may be worsened by the infection itself ( 1 , 2 ). In resource limited settings, factors such as malnutrition and young age are significant independent predictors of oral antibiotic failure and mortality ( 3 ). Because these populations are at higher risk, clinical management guidelines for CAP often emphasize the need for objective risk-stratification tools to guide decisions and treatment intensity ( 4 ). Down syndrome (DS), the most common chromosomal abnormality, represents a distinct high-risk pediatric population characterized by a significant susceptibility to respiratory tract infections ( 5 , 6 ). Respiratory illnesses are the leading cause of hospital admission for children with DS, with lower respiratory tract infections accounting for up to 40% of their total hospitalizations ( 6 ). This vulnerability is driven by a combination of anatomic and immunologic factors. Anatomically, children with DS often present with a shorter midface, a narrow nasopharynx, and relative macroglossia, all of which interfere with secretion clearance and increase the risk of aspiration ( 7 – 9 ). Furthermore, structural abnormalities such as tracheomalacia, laryngomalacia, and hypoplastic lungs with reduced alveolar numbers decrease the functional reserve and complicate the disease course ( 6 , 9 ). Immunologically, the extent of dysregulation in DS is substantial, spanning both the innate and adaptive systems ( 7 , 8 , 10 ). Innate immune defects include significantly impaired neutrophil chemotaxis and a reduction in classical scavenging monocytes alongside an increase in non-classical pro-inflammatory monocyte subpopulations ( 6 , 11 ). Adaptive immune responses are characterized by significantly reduced B and T cell numbers, smaller hypocellular thymus glands, and suboptimal antibody production following vaccination ( 6 , 7 , 11 ). Additionally, the triplication of chromosome 21 leads to the over-expression of interferon receptors, resulting in chronic interferon hyperactivity and heightened inflammatory responses that can worsen outcomes during acute infection ( 11 ). Summarizing current evidence, it is established that children with DS face a significantly higher relative risk for severe pneumonia outcomes, including longer hospital stays, increased requirements for mechanical ventilation, and higher mortality compared to unaffected peers ( 12 , 13 ). However, a clear knowledge gap exists because most existing literature focuses either on previously healthy children or focuses exclusively on children with DS in isolation. While DS is recognized as an independent risk factor for severe disease in specific contexts, such as respiratory syncytial virus (RSV) and COVID-19, direct comparisons between previously healthy children, children with DS, and children with other chronic underlying conditions hospitalized with pneumonia are limited ( 12 , 14 ). The rationale for a three-group comparison with Down syndrome as the focus is to determine whether the clinical trajectory and healthcare resource use in DS is unique or merely reflective of the general burden associated with chronic medical complexity. Understanding these differences is essential for refining risk stratification and informing personalized management strategies for this vulnerable population. To compare demographic characteristics, disease severity, and hospital courses among children hospitalized with pneumonia, with a specific focus on Down syndrome, compared with previously healthy children and those with other chronic underlying conditions. Methods Study Design This was a retrospective, cross-sectional study analyzing clinical and demographic data from pediatric patients hospitalized with community-acquired pneumonia. Setting The study was conducted in the pediatric inpatient facilities at King Saud University Medical City, a tertiary academic hospital in Riyadh, Saudi Arabia. Study Population All children younger than 15 years of age who were hospitalized with a diagnosis of community acquired pneumonia between May 2015 and March 2020 were eligible for inclusion. Pneumonia was diagnosed based on compatible clinical features such as fever, cough, tachypnea, or signs of respiratory distress, together with radiological evidence of pulmonary infiltrates on chest radiography. Patients were excluded if they had hospital-acquired pneumonia, defined as pneumonia developing 48 hours or more after hospital admission, or if they had additional primary diagnoses that could independently influence hospitalization outcomes, including acute surgical conditions or other severe systemic illnesses unrelated to pneumonia. For analysis, patients were categorized into three groups based on underlying health status: Previously healthy children Children with Down syndrome Children with other chronic underlying conditions Data Collection The data used in this analysis were obtained from a previously collected dataset that had been used in an earlier study led by the author. No new data was collected for the purposes of the current analysis. Clinical and demographic data were originally extracted from electronic medical records using standardized data collection forms. Variables included patient age at admission, sex, presence of underlying chronic medical conditions (including but not limited to chromosomal abnormalities, congenital heart disease, chronic lung disease, immunodeficiency disorders, neurological disorders, and metabolic conditions), pneumonia severity score, presence of hypoxia (defined as oxygen saturation <93%), requirement for respiratory support (including non-invasive and invasive mechanical ventilation), development of pneumonia-related complications (such as pleural effusion, empyema, pneumothorax, or lung abscess), bacteremia status, and total length of hospital stay calculated from admission to discharge. Severity Assessment Disease severity was assessed using a pneumonia severity score adapted from the Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of community-acquired pneumonia in infants and children older than three months. Guideline-defined major and minor criteria were applied to classify disease severity at presentation (1). Statistical Analysis Continuous variables were assessed as non-normally distributed and are presented as median with interquartile range (IQR). Comparisons of continuous variables across the three study groups were performed using non-parametric tests, including the Mann-Whitney test and Kruskal–Wallis test. Categorical variables are presented as counts and percentages and were compared using chi-square tests or Fisher’s exact tests, as appropriate. Overall, three groups comparisons were performed first, followed by predefined pairwise comparisons focusing on: Children with Down syndrome versus previously healthy children Children with Down syndrome versus children with other chronic underlying conditions A p-value < 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics. Results A total of 456 children hospitalized with pneumonia were included in the study, of whom 233 (51.1%) were previously healthy, 26 (5.7%) had Down syndrome, and 197 (43.2%) had other chronic underlying conditions. Male sex was observed in 55.8% of previously healthy children, 61.5% of children with Down syndrome, and 47.7% of children with other chronic conditions (p = 0.159). The median age was 2.0 years across all three groups, with no significant difference observed (p = 0.694). Severe disease occurred in 31.3% of previously healthy children, 30.8% of children with Down syndrome, and 40.6% of children with other chronic conditions (p = 0.118). Oxygen supplementation was required in 60.5% of previously healthy children, 88.5% of children with Down syndrome, and 79.7% of children with other chronic conditions (p < 0.001). Mechanical ventilation was required in 12.9% of previously healthy children, 23.1% of children with Down syndrome, and 29.1% of children with other chronic conditions (p = 0.003). Bacteremia was identified in 3.9%, 11.5%, and 6.6% of patients in the respective groups (p = 0.174). Complicated pneumonia occurred in 7.9% of previously healthy children, 0% of children with Down syndrome, and 3.2% of children with other chronic conditions (p = 0.126). The median length of hospital stay was 5 days for previously healthy children, 6 days for children with Down syndrome, and 7 days for children with other chronic conditions (p < 0.001). In pairwise analysis, children with Down syndrome required oxygen supplementation more frequently than previously healthy children (88.5% vs 60.5%, p = 0.005). No significant differences were observed between children with Down syndrome and those with other chronic conditions in severe disease (p = 0.397), mechanical ventilation (p = 0.760), or length of hospital stay (p = 0.148). See Table 1, Table 2 and Table 3. Discussion In this study of children hospitalized with pneumonia, Down syndrome was associated with a more complex clinical course when compared with previously healthy children, as reflected by a significantly higher requirement for oxygen supplementation. However, when children with Down syndrome were compared with those with other chronic underlying conditions, no significant differences were observed in markers of disease severity, need for ventilation support, or length of hospital stay. These findings suggest that while children with Down syndrome are more vulnerable than previously healthy peers, their in-hospital clinical trajectory largely resembles that of children with other forms of chronic medical complexity rather than representing a distinctly more severe phenotype. The finding that children with Down syndrome (DS) required oxygen supplementation more frequently than previously healthy children is consistent with established literature identifying DS as a high-risk population for severe respiratory tract infections ( 6 , 7 , 11 ). Previous studies have demonstrated that children with DS hospitalized for conditions such as bronchiolitis and pneumonia experience more severe clinical courses and a greater likelihood of requiring supportive interventions compared to their healthy peers ( 7 , 12 , 13 ). This observation is consistent with existing research showing that lower respiratory tract infections are the leading cause of hospital admission among individuals with Down syndrome, frequently associated with an increased need for respiratory support ( 6 , 12 , 15 ). However, the lack of significant differences in disease severity, need for mechanical ventilation, or hospital length of stay between children with Down syndrome and those with other chronic underlying conditions suggests that medical complexity in general is a primary driver of pneumonia outcomes ( 6 , 13 , 16 ). While some evidence proposes that DS represents an independent risk factor for severe lower respiratory tract infection, our observation that clinical trajectory in hospitalized children parallels that of other complex pediatric populations is supported by existing research ( 2 , 12 , 13 ). Previous studies have established that various comorbidities, including cardiopulmonary disease, genetic syndromes, and neurological disorders, predispose children to more serious disease courses and require similar levels of inpatient management ( 1 , 2 , 6 ). The biological plausibility for the increased vulnerability and oxygen requirements of children with Down syndrome is rooted in distinct anatomical and immunological factors ( 6 , 7 , 9 ). Anatomically, physical features such as midface hypoplasia, a narrow nasopharynx, and relative macroglossia contribute to upper airway crowding and interfere with the effective clearance of secretions ( 6 , 7 , 9 ). Additionally, structural lung abnormalities common in DS, including reduced alveolar numbers and hypoplastic lung architecture, decrease functional reserve and exacerbate respiratory distress during acute infection ( 9 ). Immunologically, the population is characterized by substantial dysregulation affecting both the innate and adaptive systems, including impaired neutrophil chemotaxis and reduced circulating B and T cell counts, which can compromise the resolution of respiratory pathogens ( 6 , 7 , 11 ). These findings have significant clinical and health-system implications, underscoring the need for Down syndrome to be recognized alongside other medically complex conditions as a trigger for elevated clinical concern ( 5 , 14 ). Current guidelines emphasize the importance of identifying risk factors associated with severe pneumonia and our results suggest that children with DS consistently represent a high-risk group specifically regarding oxygen requirements ( 1 ). From a health-system perspective, the comparable outcomes between DS and other complex chronic conditions support the implementation of standardized management protocols for all complex pediatric populations to ensure equitable resource allocation ( 9 ). Furthermore, given their susceptibility to severe clinical courses, prioritizing this population for preventive strategies such as annual influenza and pneumococcal vaccinations remains a critical public health objective ( 2 , 6 , 9 ). This study has several important strengths. First, it includes a well-defined cohort of children hospitalized with pneumonia, allowing focused assessment of in-hospital disease severity and clinical course. Second, the use of a three-group comparative design enabled direct evaluation of children with Down syndrome relative to both previously healthy children and those with other chronic underlying conditions, addressing a key gap in the existing literature. Third, the analysis focused on clinically meaningful outcomes, including oxygen requirement, mechanical ventilation, and length of hospital stay, which are directly relevant to patient management and healthcare resource utilization. Several limitations should be considered when interpreting these findings. The sample size of children with Down syndrome was relatively small, which may have limited statistical power to detect differences in less frequent outcomes. The study was observational in nature and conducted within a single healthcare setting, which may limit generalizability to other populations or healthcare systems. In addition, detailed information on pneumonia etiology, vaccination status, and outpatient disease severity prior to hospitalization was not available, potentially contributing to unmeasured confounding factors. Finally, long-term outcomes following hospital discharge were not assessed. Conclusion Future studies should aim to include larger, multicenter cohorts to better characterize pneumonia outcomes in children with Down syndrome and improve statistical power for subgroup analyses. Incorporation of etiologic data, immunization history, and standardized severity scores may further refine risk stratification. Longitudinal studies examining post-discharge outcomes and recurrent respiratory morbidity would also provide valuable insight into the broader impact of pneumonia in this population. Such efforts may help inform tailored clinical pathways and optimize resource allocation for children with Down syndrome hospitalized with pneumonia. Declarations Ethics approval and consent to participate This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Institutional Review Board of King Saud University Medical City (IRB approval number: E-16-2153). Patient confidentiality was strictly maintained, and all data were anonymized prior to analysis. Due to the retrospective nature of the study, the requirement for informed consent from parents or legal guardians was waived by the Institutional Review Board. Consent for publication Not applicable. This study involved secondary analysis of anonymized data, and no identifiable individual participant data are included. Data Availability Statement The datasets generated and analyzed during the current study are not publicly available due to institutional and patient confidentiality restrictions but are available from the corresponding author upon reasonable request. Conflict of Interest The author declares no conflicts of interest related to this study. Funding This research was supported by the Deanship of Scientific Research at King Saud University. Author Contributions The author solely conceived the research question, designed the analytical strategy, performed all statistical analyses, interpreted the findings, and wrote the manuscript. The dataset used in this study was collected as part of an earlier research project led by the author. No other individuals meet authorship criteria for the present work. Acknowledgments The author acknowledges the contributions of the original research team involved in data collection during the initial study phase. Their efforts are gratefully recognized; however, they were not involved in the conception, analysis, interpretation, or writing of the current manuscript and therefore do not meet authorship criteria. The author also acknowledges the use of artificial intelligence–assisted tools (including ChatGPT 5.2) for language refinement and clarity. These tools were used solely to improve readability and did not influence study design, data analysis, or interpretation, The author is fully responsible of the integrity of this research. References Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clinical infectious diseases. 2011;53(7):e25-e76. Kinimi I, Shinde SS, Rao NM, Mahalingam A. Management of Children with Community-acquired Pneumonia: A Review of Literature. Pediatric Infectious Disease. 2020;2(3):99-106. McCollum ED, King C, Hollowell R, Zhou J, Colbourn T, Nambiar B, et al. Predictors of treatment failure for non-severe childhood pneumonia in developing countries–systematic literature review and expert survey–the first step towards a community focused mHealth risk-assessment tool? BMC pediatrics. 2015;15(1):74. Williams DJ, Zhu Y, Grijalva CG, Self WH, Harrell Jr FE, Reed C, et al. Predicting severe pneumonia outcomes in children. Pediatrics. 2016;138(4):e20161019. Pérez JH, Guerra JH. Community-acquired pneumonia in adults with Down syndrome. Three clinical cases and a review of the literature. International Medical Review on Down Syndrome. 2010;14(2):25-30. Ghezzi M, Garancini N, De Santis R, Gianolio L, Zirpoli S, Mandelli A, et al. Recurrent respiratory infections in children with Down syndrome: A review. Children. 2024;11(2):246. Beckhaus AA, Castro-Rodriguez JA. Down syndrome and the risk of severe RSV infection: a meta-analysis. Pediatrics. 2018;142(3):e20180225. Huggard D, Doherty DG, Molloy EJ. Immune dysregulation in children with Down syndrome. Frontiers in pediatrics. 2020;8:73. Craven V, Daw W, Wan J, Elphick HE. Respiratory and airway disorders in children with Down Syndrome: a review of the clinical challenges and management. Frontiers in Pediatrics. 2025;13:1553984. Huggard D, Mahon M, McGrane F, Lagan N, Purcell C, Balfe J, et al. G88 (P) Immunodeficiency in children with down syndrome. BMJ Publishing Group Ltd; 2018. Illouz T, Biragyn A, Iulita MF, Flores-Aguilar L, Dierssen M, De Toma I, et al. Immune dysregulation and the increased risk of complications and mortality following respiratory tract infections in adults with down syndrome. Frontiers in immunology. 2021;12:621440. Chan M, Park JJ, Shi T, Martinón–Torres F, Bont L, Nair H, et al. The burden of respiratory syncytial virus (RSV) associated acute lower respiratory infections in children with Down syndrome: A systematic review and meta–analysis. Journal of global health. 2017;7(2):020413. Ting TW, Chan HY, Wong PPC, Testoni D, Lee JH. Down syndrome increases Hospital length of stay in children with bronchiolitis. Proceedings of Singapore Healthcare. 2016;25(1):64-7. Emes D, Hüls A, Baumer N, Dierssen M, Puri S, Russell L, et al. COVID-19 in children with Down syndrome: data from the Trisomy 21 Research Society Survey. Journal of clinical medicine. 2021;10(21):5125. Manikam L, Lakhanpaul M, Schilder AG, Littlejohns P, Cupp MA, Alexander EC, et al. Effect of antibiotics in preventing hospitalizations from respiratory tract infections in children with Down syndrome. Pediatric Pulmonology. 2021;56(1):171-8. Real de Asua D, Mayer MA, Ortega MdC, Borrel JM, Bermejo TdJ, González-Lamuño D, et al. Comparison of COVID-19 and non-COVID-19 pneumonia in Down syndrome. Journal of clinical medicine. 2021;10(16):3748. Tables Table 1. Comparison Between Healthy Children, Down Syndrome, and Other Underlying Conditions Variable Previously Healthy (n = 233) Down Syndrome (n = 26) Other Chronic Conditions (n = 197) Overall p-value Male sex, n (%) 130 (55.8%) 16 (61.5%) 94 (47.7%) 0.159 Age, years, median (IQR) 2.0 (0–4) 2.0 (1–3) 2.0 (0–4) 0.694 Severe disease, n (%) 73 (31.3%) 8 (30.8%) 80 (40.6%) 0.118 Oxygen supply, n (%) 141 (60.5%) 23 (88.5%) 157 (79.7%) <0.001 Mechanical ventilation, n (%) 18 (12.9%) 3 (23.1%) 46 (29.1%) 0.003 Bacteremia, n (%) 9 (3.9%) 3 (11.5%) 13 (6.6%) 0.174 Complicated pneumonia, n (%) 11 (7.9%) 0 (0.0%) 5 (3.2%) 0.12 Length of stay, days, median (IQR) 5 (3–7) 6 (4–8) 7 (4–13) <0.001 Table 2. Comparison between children with down syndrome and previously healthy children hospitalized with pneumonia Variable Down Syndrome (n = 26) Previously Healthy (n = 233) p-value Male sex, n (%) 16 (61.5%) 130 (55.8%) 0.678 Age, years, median (IQR) 2.0 (1–3) 2.0 (0–4) 0.707 Severe disease, n (%) 8 (30.8%) 73 (31.3%) 1.000 Oxygen supply, n (%) 23 (88.5%) 141 (60.5%) 0.005 Mechanical ventilation, n (%) 3 (23.1%) 18 (12.9%) 0.392 Bacteremia, n (%) 3 (11.5%) 9 (3.9%) 0.107 Complicated pneumonia, n (%) 0 (0.0%) 11 (7.9%) 0.600 Length of stay, days, median (IQR) 6 (4–8) 5 (3–7) 0.110 Table 3. Comparison between children with down syndrome and other chronic conditions hospitalized with Pneumonia Variable Down Syndrome (n = 26) Other Chronic Conditions (n = 197) p-value Male sex, n (%) 16 (61.5%) 94 (47.7%) 0.214 Age, years, median (IQR) 2.0 (1–3) 2.0 (0–4) 0.532 Severe disease, n (%) 8 (30.8%) 80 (40.6%) 0.397 Oxygen supply, n (%) 23 (88.5%) 157 (79.7%) 0.428 Mechanical ventilation, n (%) 3 (23.1%) 46 (29.1%) 0.760 Bacteremia, n (%) 3 (11.5%) 13 (6.6%) 0.409 Complicated pneumonia, n (%) 0 (0.0%) 5 (3.2%) 1.000 Length of stay, days, median (IQR) 6 (4–8) 7 (4–13) 0.148 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers invited by journal 13 Feb, 2026 Editor assigned by journal 29 Jan, 2026 Editor invited by journal 22 Jan, 2026 Submission checks completed at journal 21 Jan, 2026 First submitted to journal 21 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8528636","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":593426052,"identity":"fe025e2d-fe46-4993-b56d-7b03cb446a93","order_by":0,"name":"Nasser S. 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It accounts for approximately one-fifth of all deaths in children under five years of age, resulting in nearly one million deaths annually (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In developed nations such as the United States, pneumonia is one of the top three reasons for pediatric hospitalization, with roughly 20% to 25% of emergency department visits for the condition resulting in inpatient admission (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Consequently, community-acquired pneumonia (CAP) poses a significant burden and an increasing challenge to healthcare resources (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe presence of underlying chronic conditions substantially increases the risk of a severe clinical course and heightened healthcare utilization (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Comorbidities such as chronic pulmonary disease, congenital heart defects, genetic syndromes, and neuromuscular disorders predispose children to more serious disease courses and may be worsened by the infection itself (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In resource limited settings, factors such as malnutrition and young age are significant independent predictors of oral antibiotic failure and mortality (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Because these populations are at higher risk, clinical management guidelines for CAP often emphasize the need for objective risk-stratification tools to guide decisions and treatment intensity (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDown syndrome (DS), the most common chromosomal abnormality, represents a distinct high-risk pediatric population characterized by a significant susceptibility to respiratory tract infections (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Respiratory illnesses are the leading cause of hospital admission for children with DS, with lower respiratory tract infections accounting for up to 40% of their total hospitalizations (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This vulnerability is driven by a combination of anatomic and immunologic factors. Anatomically, children with DS often present with a shorter midface, a narrow nasopharynx, and relative macroglossia, all of which interfere with secretion clearance and increase the risk of aspiration (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Furthermore, structural abnormalities such as tracheomalacia, laryngomalacia, and hypoplastic lungs with reduced alveolar numbers decrease the functional reserve and complicate the disease course (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eImmunologically, the extent of dysregulation in DS is substantial, spanning both the innate and adaptive systems (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Innate immune defects include significantly impaired neutrophil chemotaxis and a reduction in classical scavenging monocytes alongside an increase in non-classical pro-inflammatory monocyte subpopulations (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Adaptive immune responses are characterized by significantly reduced B and T cell numbers, smaller hypocellular thymus glands, and suboptimal antibody production following vaccination (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Additionally, the triplication of chromosome 21 leads to the over-expression of interferon receptors, resulting in chronic interferon hyperactivity and heightened inflammatory responses that can worsen outcomes during acute infection (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSummarizing current evidence, it is established that children with DS face a significantly higher relative risk for severe pneumonia outcomes, including longer hospital stays, increased requirements for mechanical ventilation, and higher mortality compared to unaffected peers (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, a clear knowledge gap exists because most existing literature focuses either on previously healthy children or focuses exclusively on children with DS in isolation. While DS is recognized as an independent risk factor for severe disease in specific contexts, such as respiratory syncytial virus (RSV) and COVID-19, direct comparisons between previously healthy children, children with DS, and children with other chronic underlying conditions hospitalized with pneumonia are limited (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe rationale for a three-group comparison with Down syndrome as the focus is to determine whether the clinical trajectory and healthcare resource use in DS is unique or merely reflective of the general burden associated with chronic medical complexity. Understanding these differences is essential for refining risk stratification and informing personalized management strategies for this vulnerable population.\u003c/p\u003e \u003cp\u003eTo compare demographic characteristics, disease severity, and hospital courses among children hospitalized with pneumonia, with a specific focus on Down syndrome, compared with previously healthy children and those with other chronic underlying conditions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective, cross-sectional study analyzing clinical and demographic data from pediatric patients hospitalized with community-acquired pneumonia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in the pediatric inpatient facilities at King Saud University Medical City, a tertiary academic hospital in Riyadh, Saudi Arabia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll children younger than 15 years of age who were hospitalized with a diagnosis of community acquired pneumonia between May 2015 and March 2020 were eligible for inclusion. Pneumonia was diagnosed based on compatible clinical features such as fever, cough, tachypnea, or signs of respiratory distress, together with radiological evidence of pulmonary infiltrates on chest radiography.\u003c/p\u003e\n\u003cp\u003ePatients were excluded if they had hospital-acquired pneumonia, defined as pneumonia developing 48 hours or more after hospital admission, or if they had additional primary diagnoses that could independently influence hospitalization outcomes, including acute surgical conditions or other severe systemic illnesses unrelated to pneumonia.\u003c/p\u003e\n\u003cp\u003eFor analysis, patients were categorized into three groups based on underlying health status:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003ePreviously healthy children\u003c/li\u003e\n \u003cli\u003eChildren with Down syndrome\u003c/li\u003e\n \u003cli\u003eChildren with other chronic underlying conditions\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used in this analysis were obtained from a previously collected dataset that had been used in an earlier study led by the author. No new data was collected for the purposes of the current analysis.\u003c/p\u003e\n\u003cp\u003eClinical and demographic data were originally extracted from electronic medical records using standardized data collection forms. Variables included patient age at admission, sex, presence of underlying chronic medical conditions (including but not limited to chromosomal abnormalities, congenital heart disease, chronic lung disease, immunodeficiency disorders, neurological disorders, and metabolic conditions), pneumonia severity score, presence of hypoxia (defined as oxygen saturation \u0026lt;93%), requirement for respiratory support (including non-invasive and invasive mechanical ventilation), development of pneumonia-related complications (such as pleural effusion, empyema, pneumothorax, or lung abscess), bacteremia status, and total length of hospital stay calculated from admission to discharge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSeverity Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDisease severity was assessed using a pneumonia severity score adapted from the Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of community-acquired pneumonia in infants and children older than three months. Guideline-defined major and minor criteria were applied to classify disease severity at presentation (1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables were assessed as non-normally distributed and are presented as median with interquartile range (IQR). Comparisons of continuous variables across the three study groups were performed using non-parametric tests, including the Mann-Whitney test and Kruskal\u0026ndash;Wallis test.\u003c/p\u003e\n\u003cp\u003eCategorical variables are presented as counts and percentages and were compared using chi-square tests or Fisher\u0026rsquo;s exact tests, as appropriate.\u003c/p\u003e\n\u003cp\u003eOverall, three groups comparisons were performed first, followed by predefined pairwise comparisons focusing on:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eChildren with Down syndrome versus previously healthy children\u003c/li\u003e\n \u003cli\u003eChildren with Down syndrome versus children with other chronic underlying conditions\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eA p-value \u0026lt; 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 456 children hospitalized with pneumonia were included in the study, of whom 233 (51.1%) were previously healthy, 26 (5.7%) had Down syndrome, and 197 (43.2%) had other chronic underlying conditions. Male sex was observed in 55.8% of previously healthy children, 61.5% of children with Down syndrome, and 47.7% of children with other chronic conditions (p = 0.159). The median age was 2.0 years across all three groups, with no significant difference observed (p = 0.694).\u003c/p\u003e\n\u003cp\u003eSevere disease occurred in 31.3% of previously healthy children, 30.8% of children with Down syndrome, and 40.6% of children with other chronic conditions (p = 0.118). Oxygen supplementation was required in 60.5% of previously healthy children, 88.5% of children with Down syndrome, and 79.7% of children with other chronic conditions (p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eMechanical ventilation was required in 12.9% of previously healthy children, 23.1% of children with Down syndrome, and 29.1% of children with other chronic conditions (p = 0.003). Bacteremia was identified in 3.9%, 11.5%, and 6.6% of patients in the respective groups (p = 0.174). Complicated pneumonia occurred in 7.9% of previously healthy children, 0% of children with Down syndrome, and 3.2% of children with other chronic conditions (p = 0.126).\u003c/p\u003e\n\u003cp\u003eThe median length of hospital stay was 5 days for previously healthy children, 6 days for children with Down syndrome, and 7 days for children with other chronic conditions (p \u0026lt; 0.001). In pairwise analysis, children with Down syndrome required oxygen supplementation more frequently than previously healthy children (88.5% vs 60.5%, p = 0.005). No significant differences were observed between children with Down syndrome and those with other chronic conditions in severe disease (p = 0.397), mechanical ventilation (p = 0.760), or length of hospital stay (p = 0.148). See Table 1, Table 2 and Table 3.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study of children hospitalized with pneumonia, Down syndrome was associated with a more complex clinical course when compared with previously healthy children, as reflected by a significantly higher requirement for oxygen supplementation. However, when children with Down syndrome were compared with those with other chronic underlying conditions, no significant differences were observed in markers of disease severity, need for ventilation support, or length of hospital stay. These findings suggest that while children with Down syndrome are more vulnerable than previously healthy peers, their in-hospital clinical trajectory largely resembles that of children with other forms of chronic medical complexity rather than representing a distinctly more severe phenotype.\u003c/p\u003e \u003cp\u003eThe finding that children with Down syndrome (DS) required oxygen supplementation more frequently than previously healthy children is consistent with established literature identifying DS as a high-risk population for severe respiratory tract infections (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Previous studies have demonstrated that children with DS hospitalized for conditions such as bronchiolitis and pneumonia experience more severe clinical courses and a greater likelihood of requiring supportive interventions compared to their healthy peers (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This observation is consistent with existing research showing that lower respiratory tract infections are the leading cause of hospital admission among individuals with Down syndrome, frequently associated with an increased need for respiratory support (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, the lack of significant differences in disease severity, need for mechanical ventilation, or hospital length of stay between children with Down syndrome and those with other chronic underlying conditions suggests that medical complexity in general is a primary driver of pneumonia outcomes (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). While some evidence proposes that DS represents an independent risk factor for severe lower respiratory tract infection, our observation that clinical trajectory in hospitalized children parallels that of other complex pediatric populations is supported by existing research (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Previous studies have established that various comorbidities, including cardiopulmonary disease, genetic syndromes, and neurological disorders, predispose children to more serious disease courses and require similar levels of inpatient management (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe biological plausibility for the increased vulnerability and oxygen requirements of children with Down syndrome is rooted in distinct anatomical and immunological factors (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Anatomically, physical features such as midface hypoplasia, a narrow nasopharynx, and relative macroglossia contribute to upper airway crowding and interfere with the effective clearance of secretions (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Additionally, structural lung abnormalities common in DS, including reduced alveolar numbers and hypoplastic lung architecture, decrease functional reserve and exacerbate respiratory distress during acute infection (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Immunologically, the population is characterized by substantial dysregulation affecting both the innate and adaptive systems, including impaired neutrophil chemotaxis and reduced circulating B and T cell counts, which can compromise the resolution of respiratory pathogens (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThese findings have significant clinical and health-system implications, underscoring the need for Down syndrome to be recognized alongside other medically complex conditions as a trigger for elevated clinical concern (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Current guidelines emphasize the importance of identifying risk factors associated with severe pneumonia and our results suggest that children with DS consistently represent a high-risk group specifically regarding oxygen requirements (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). From a health-system perspective, the comparable outcomes between DS and other complex chronic conditions support the implementation of standardized management protocols for all complex pediatric populations to ensure equitable resource allocation (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Furthermore, given their susceptibility to severe clinical courses, prioritizing this population for preventive strategies such as annual influenza and pneumococcal vaccinations remains a critical public health objective (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study has several important strengths. First, it includes a well-defined cohort of children hospitalized with pneumonia, allowing focused assessment of in-hospital disease severity and clinical course. Second, the use of a three-group comparative design enabled direct evaluation of children with Down syndrome relative to both previously healthy children and those with other chronic underlying conditions, addressing a key gap in the existing literature. Third, the analysis focused on clinically meaningful outcomes, including oxygen requirement, mechanical ventilation, and length of hospital stay, which are directly relevant to patient management and healthcare resource utilization.\u003c/p\u003e \u003cp\u003eSeveral limitations should be considered when interpreting these findings. The sample size of children with Down syndrome was relatively small, which may have limited statistical power to detect differences in less frequent outcomes. The study was observational in nature and conducted within a single healthcare setting, which may limit generalizability to other populations or healthcare systems. In addition, detailed information on pneumonia etiology, vaccination status, and outpatient disease severity prior to hospitalization was not available, potentially contributing to unmeasured confounding factors. Finally, long-term outcomes following hospital discharge were not assessed.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFuture studies should aim to include larger, multicenter cohorts to better characterize pneumonia outcomes in children with Down syndrome and improve statistical power for subgroup analyses. Incorporation of etiologic data, immunization history, and standardized severity scores may further refine risk stratification. Longitudinal studies examining post-discharge outcomes and recurrent respiratory morbidity would also provide valuable insight into the broader impact of pneumonia in this population. Such efforts may help inform tailored clinical pathways and optimize resource allocation for children with Down syndrome hospitalized with pneumonia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Institutional Review Board of King Saud University Medical City (IRB approval number: E-16-2153). Patient confidentiality was strictly maintained, and all data were anonymized prior to analysis. Due to the retrospective nature of the study, the requirement for informed consent from parents or legal guardians was waived by the Institutional Review Board.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study involved secondary analysis of anonymized data, and no identifiable individual participant data are included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003cbr\u003e\u003c/strong\u003eThe datasets generated and analyzed during the current study are not publicly available due to institutional and patient confidentiality restrictions but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares no conflicts of interest related to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the Deanship of Scientific Research at King Saud University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author solely conceived the research question, designed the analytical strategy, performed all statistical analyses, interpreted the findings, and wrote the manuscript.\u003c/p\u003e\n\u003cp\u003eThe dataset used in this study was collected as part of an earlier research project led by the author. No other individuals meet authorship criteria for the present work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author acknowledges the contributions of the original research team involved in data collection during the initial study phase. Their efforts are gratefully recognized; however, they were not involved in the conception, analysis, interpretation, or writing of the current manuscript and therefore do not meet authorship criteria.\u003c/p\u003e\n\u003cp\u003eThe author also acknowledges the use of artificial intelligence\u0026ndash;assisted tools (including ChatGPT 5.2) for language refinement and clarity. These tools were used solely to improve readability and did not influence study design, data analysis, or interpretation, The author is fully responsible of the integrity of this research.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clinical infectious diseases. 2011;53(7):e25-e76.\u003c/li\u003e\n\u003cli\u003eKinimi I, Shinde SS, Rao NM, Mahalingam A. Management of Children with Community-acquired Pneumonia: A Review of Literature. Pediatric Infectious Disease. 2020;2(3):99-106.\u003c/li\u003e\n\u003cli\u003eMcCollum ED, King C, Hollowell R, Zhou J, Colbourn T, Nambiar B, et al. Predictors of treatment failure for non-severe childhood pneumonia in developing countries\u0026ndash;systematic literature review and expert survey\u0026ndash;the first step towards a community focused mHealth risk-assessment tool? BMC pediatrics. 2015;15(1):74.\u003c/li\u003e\n\u003cli\u003eWilliams DJ, Zhu Y, Grijalva CG, Self WH, Harrell Jr FE, Reed C, et al. Predicting severe pneumonia outcomes in children. Pediatrics. 2016;138(4):e20161019.\u003c/li\u003e\n\u003cli\u003eP\u0026eacute;rez JH, Guerra JH. Community-acquired pneumonia in adults with Down syndrome. Three clinical cases and a review of the literature. International Medical Review on Down Syndrome. 2010;14(2):25-30.\u003c/li\u003e\n\u003cli\u003eGhezzi M, Garancini N, De Santis R, Gianolio L, Zirpoli S, Mandelli A, et al. Recurrent respiratory infections in children with Down syndrome: A review. Children. 2024;11(2):246.\u003c/li\u003e\n\u003cli\u003eBeckhaus AA, Castro-Rodriguez JA. Down syndrome and the risk of severe RSV infection: a meta-analysis. Pediatrics. 2018;142(3):e20180225.\u003c/li\u003e\n\u003cli\u003eHuggard D, Doherty DG, Molloy EJ. Immune dysregulation in children with Down syndrome. Frontiers in pediatrics. 2020;8:73.\u003c/li\u003e\n\u003cli\u003eCraven V, Daw W, Wan J, Elphick HE. Respiratory and airway disorders in children with Down Syndrome: a review of the clinical challenges and management. Frontiers in Pediatrics. 2025;13:1553984.\u003c/li\u003e\n\u003cli\u003eHuggard D, Mahon M, McGrane F, Lagan N, Purcell C, Balfe J, et al. G88 (P) Immunodeficiency in children with down syndrome. BMJ Publishing Group Ltd; 2018.\u003c/li\u003e\n\u003cli\u003eIllouz T, Biragyn A, Iulita MF, Flores-Aguilar L, Dierssen M, De Toma I, et al. Immune dysregulation and the increased risk of complications and mortality following respiratory tract infections in adults with down syndrome. Frontiers in immunology. 2021;12:621440.\u003c/li\u003e\n\u003cli\u003eChan M, Park JJ, Shi T, Martin\u0026oacute;n\u0026ndash;Torres F, Bont L, Nair H, et al. The burden of respiratory syncytial virus (RSV) associated acute lower respiratory infections in children with Down syndrome: A systematic review and meta\u0026ndash;analysis. Journal of global health. 2017;7(2):020413.\u003c/li\u003e\n\u003cli\u003eTing TW, Chan HY, Wong PPC, Testoni D, Lee JH. Down syndrome increases Hospital length of stay in children with bronchiolitis. Proceedings of Singapore Healthcare. 2016;25(1):64-7.\u003c/li\u003e\n\u003cli\u003eEmes D, H\u0026uuml;ls A, Baumer N, Dierssen M, Puri S, Russell L, et al. COVID-19 in children with Down syndrome: data from the Trisomy 21 Research Society Survey. Journal of clinical medicine. 2021;10(21):5125.\u003c/li\u003e\n\u003cli\u003eManikam L, Lakhanpaul M, Schilder AG, Littlejohns P, Cupp MA, Alexander EC, et al. Effect of antibiotics in preventing hospitalizations from respiratory tract infections in children with Down syndrome. Pediatric Pulmonology. 2021;56(1):171-8.\u003c/li\u003e\n\u003cli\u003eReal de Asua D, Mayer MA, Ortega MdC, Borrel JM, Bermejo TdJ, Gonz\u0026aacute;lez-Lamu\u0026ntilde;o D, et al. Comparison of COVID-19 and non-COVID-19 pneumonia in Down syndrome. Journal of clinical medicine. 2021;10(16):3748.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Comparison Between Healthy Children, Down Syndrome, and Other Underlying Conditions\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreviously Healthy (n = 233)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDown Syndrome (n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther Chronic Conditions (n = 197)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall p-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e130 (55.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e16 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e94 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.159\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eAge, years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e2.0 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e2.0 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e2.0 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.694\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eSevere disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e73 (31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e8 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e80 (40.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eOxygen supply, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e141 (60.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e23 (88.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e157 (79.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eMechanical ventilation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e18 (12.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e3 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e46 (29.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eBacteremia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e9 (3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e3 (11.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e13 (6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eComplicated pneumonia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e11 (7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e5 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eLength of stay, days, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e5 (3\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e6 (4\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e7 (4\u0026ndash;13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Comparison between children with down syndrome and previously healthy children hospitalized with pneumonia\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eDown Syndrome (n = 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003ePreviously Healthy (n = 233)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e16 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e130 (55.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eAge, years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e2.0 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e2.0 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.707\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eSevere disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e8 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e73 (31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eOxygen supply, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e23 (88.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e141 (60.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eMechanical ventilation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e3 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e18 (12.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.392\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eBacteremia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e3 (11.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e9 (3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eComplicated pneumonia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e11 (7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eLength of stay, days, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e6 (4\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e5 (3\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Comparison between children with down syndrome and other chronic conditions hospitalized with Pneumonia\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eDown Syndrome (n = 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eOther Chronic Conditions (n = 197)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e16 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e94 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.214\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eAge, years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e2.0 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e2.0 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eSevere disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e8 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e80 (40.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.397\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eOxygen supply, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e23 (88.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e157 (79.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.428\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eMechanical ventilation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e3 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e46 (29.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eBacteremia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e3 (11.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e13 (6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.409\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eComplicated pneumonia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e5 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eLength of stay, days, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e6 (4\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e7 (4\u0026ndash;13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e0.148\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pneumonia, Down syndrome, Underlying Conditions","lastPublishedDoi":"10.21203/rs.3.rs-8528636/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8528636/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChildren with Down syndrome (DS) are recognized as a high-risk population for respiratory infections; however, direct comparisons of pneumonia outcomes between children with DS, previously healthy children, and children with other chronic underlying conditions remain limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective, cross-sectional study of children hospitalized with pneumonia at King Saud University Medical City between May 2015 and March 2020. Patients were categorized into three groups: previously healthy children, children with Down syndrome, and children with other chronic underlying conditions. Demographic characteristics, markers of disease severity, and hospital course were compared. Continuous variables were analyzed using non-parametric tests and reported as median (IQR). Categorical variables were compared using chi-square or Fisher\u0026rsquo;s exact tests. Pairwise comparisons focused on Down syndrome.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 456 children were included: 233 (51.1%) previously healthy, 26 (5.7%) with Down syndrome, and 197 (43.2%) with other chronic conditions. Oxygen supplementation was required more frequently in children with Down syndrome compared with previously healthy children (88.5% vs 60.5%, p\u0026thinsp;=\u0026thinsp;0.005). No significant differences were observed between children with Down syndrome and those with other chronic conditions in severe disease (30.8% vs 40.6%, p\u0026thinsp;=\u0026thinsp;0.397), mechanical ventilation (23.1% vs 29.1%, p\u0026thinsp;=\u0026thinsp;0.760), or length of hospital stay (median 6 vs 7 days, p\u0026thinsp;=\u0026thinsp;0.148). Overall, three-group comparisons demonstrated significant differences in oxygen requirement (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and length of stay (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eChildren with Down syndrome hospitalized with pneumonia require oxygen supplementation more frequently than previously healthy children; however, their overall clinical course closely resembles that of children with other chronic underlying conditions. These findings suggest that medical complexity, rather than Down syndrome alone, is a key determinant of pneumonia outcomes.\u003c/p\u003e","manuscriptTitle":"Clinical Characteristics and Hospital Course of Children with Down Syndrome Hospitalized with Pneumonia: A Three-Group Comparative Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-19 11:35:04","doi":"10.21203/rs.3.rs-8528636/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-24T03:32:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53776418338046948735982912453243306522","date":"2026-02-13T12:21:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-13T10:29:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-29T15:26:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-22T05:47:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-21T10:16:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-21T09:54:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6557375a-b047-4d2e-b068-b5679f4601ff","owner":[],"postedDate":"February 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-19T11:35:04+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-19 11:35:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8528636","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8528636","identity":"rs-8528636","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}