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Tantaleán Da Fieno J, León Paredes R, Palomo Luck P, Del Águila Villar C, Rizo Patrón E. Down syndrome and outcomes in critically ill pediatric patients. Front Pediatr 2025; 12:1483944. [PMID: 39925460 PMCID: PMC11802518 DOI: 10.3389/fped.2024.1483944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 02/11/2025] Open
Abstract
Introduction Information regarding children with Down syndrome (DS) in the Pediatric Intensive Care Unit (PICU) is limited and conflicting. We aimed to investigate the association between DS and clinical outcomes in pediatric patients admitted to the PICU at the Instituto Nacional de Salud del Niño (National Institute for Child Health, INSN for the acronym in Spanish) and to assess nutritional status within the study cohort. Methods This study involved the secondary analysis of a database. We included patients consecutively admitted to INSN, a tertiary care children's hospital in Lima, Peru. We collected demographic data, clinical characteristics, and nutritional status using standardized tables. The outcomes assessed included mortality, length of stay, duration of mechanical ventilation (DMV), ventilator-free days (VFD), and healthcare-associated infections (HAI). We applied Cox regression and Poisson regression analyses to explore the relationship between Down syndrome and clinical outcomes, providing both crude and adjusted results. Results A total of 525 children (average age 71.3 months, range 1-218 months) were analyzed. Children with DS were younger and had a higher prevalence of comorbidities, congenital heart disease, and underweight. Both crude bivariate and multivariate analyses demonstrated that children with DS had higher mortality rates, increased frequency of HAIs, longer DMV, longer PICU stay, and fewer VFD. Adjusted multivariate analysis revealed that children with DS had a significantly higher risk of developing HAIs (RR 2.95; 95% CI 1.10, 7.87) and longer DMV (RR 1.43; 95% CI 1.24, 1.65). Among the 525 children, underweight was associated with increased risk of mechanical ventilation (MV) use and longer DMV. Discussion Critically ill children with DS are at increased risk of developing HAIs and longer DMV. In all 525 children, underweight is associated with higher risk of MV use and longer duration of MV.
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Affiliation(s)
| | - Rosa León Paredes
- Intensive Care Unit, Instituto Nacional de Salud del Niño, Lima, Peru
| | - Patricia Palomo Luck
- Nutrition Services, Instituto Nacional de Salud del Niño; Department of Nutrition, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Carlos Del Águila Villar
- Department of Physiology, Faculty of Human Medicine, Universidad Nacional Federico Villarreal; Endocrinology Services, Instituto Nacional de Salud del Niño, Lima, Peru
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Takita SY, Sé ABS, Hoffmann GM, Bunduki W, Carvalho LR, Fonseca CRB. Causes of Hospitalization in Children with Down Syndrome. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1480. [PMID: 39336521 PMCID: PMC11433946 DOI: 10.3390/medicina60091480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/04/2024] [Accepted: 08/15/2024] [Indexed: 09/30/2024]
Abstract
Background and Objectives: Down syndrome (DS) is the most common chromosomal disorder in the world. It is caused by the imbalance of the chromosomal constitution of 21 by free trisomy, translocation or mosaicism. Children and adolescents with Down syndrome have immune dysregulation and are more susceptible to infections. This study aims to evaluate hospitalizations of children and adolescents with DS in the pediatric ward of Botucatu Clinics Hospital (HCFMB) and to classify the population of children included in the study according to age, diagnosis, outpatient follow-up, length of stay and need for the intensive care unit (ICU). Thus, it will be possible to improve care for these children, aiming to reduce these hospitalizations. Materials and Methods: This study was an observational, cross-sectional study, with retrospective data collected from the last nine years of hospitalization, from January 2013 to December 2021, from children and adolescents with DS in the pediatric ward, emergency room, and the ICU of HCFMB. Children hospitalized in this period in the pediatric ward and ICU, in the age range of 30 days to 15 years, were included in this study. The evaluation of comorbidities that culminated in the need for hospitalization in this population can be the focus of actions to improve the diagnoses and conducts for this population, which can prevent worsening illness and hospitalizations in future populations. Results: In this analysis, 80 children with DS were evaluated, with a total of 283 hospitalizations. The most prevalent age group was 1 to 3 years, and the main cause was due to problems in the respiratory system (99 cases). Among the respiratory causes, the main cause of hospitalization was due to pneumonia in 50% of cases, followed by acute respiratory failure in 14%. The average hospitalization time was 8 days, and in 49 hospitalizations, the children required the ICU. The main cause of hospitalization in the ICU was due to respiratory causes (36%), followed by cardiac malformations (14%). During the ICU hospitalizations, there were 13 deaths, and we observed a higher prevalence of heart conditions and, in some cases, positive urine cultures in these children. Conclusions: The Hospital serves as a reference for pediatric hospitalizations within its region and beyond, owing to its specialized capabilities. The main causes of hospitalization were those related to the respiratory system and cardiac malformations. Roughly one-third of the children required admission to the intensive care unit.
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Affiliation(s)
- Stefanie Yaemi Takita
- Department of Pediatrics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-000, São Paulo, Brazil
| | - Ana Beatriz Silva Sé
- Department of Pediatrics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-000, São Paulo, Brazil
| | - Giovanna Michelin Hoffmann
- Department of Pediatrics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-000, São Paulo, Brazil
| | - William Bunduki
- Department of Pediatrics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-000, São Paulo, Brazil
| | - Lidia Raquel Carvalho
- Department of Biostatistics, Institute of Biosciences, São Paulo University (UNESP), Botucatu 18618-000, São Paulo, Brazil
| | - Cátia Regina Branco Fonseca
- Department of Pediatrics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-000, São Paulo, Brazil
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DeBoer EM, Wolter-Warmerdam K, Deterding RR, Marmolejo J, Blumenthal T, Espinosa JM, Hickey F, Wagner BD. Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome. Clin Pediatr (Phila) 2024; 63:474-481. [PMID: 37306037 PMCID: PMC11060669 DOI: 10.1177/00099228231179453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether pulmonary diagnoses in children with DS are common and occur independently of cardiac disease and pulmonary hypertension (PH) is unknown. Cardiopulmonary phenotypes were examined in a cohort of 1248 children with DS. Aptamer-based proteomic analysis of blood was performed in a subset (n = 120) of these children. By the age of 10 years, half of the patients in this cohort (n = 634, 50.8%) had co-occurring pulmonary diagnoses. That proteins and related pathways were distinct between children with pulmonary diagnoses and those with cardiac disease and/or PH may indicate that pulmonary diagnoses appear to occur independently of cardiac disease and PH. Heparin sulfate-glycosaminoglycandegradation, nicotinate metabolism, and elastic fiber formation were ranked highest in the group with pulmonary diagnoses.
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Affiliation(s)
- Emily M. DeBoer
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
- Children’s Hospital Colorado, Aurora, CO, USA
- Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Aurora, CO, USA
| | | | - Robin R. Deterding
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
- Children’s Hospital Colorado, Aurora, CO, USA
| | | | - Tom Blumenthal
- Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Aurora, CO, USA
| | - Joaquin M. Espinosa
- Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Aurora, CO, USA
| | - Francis Hickey
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
- Children’s Hospital Colorado, Aurora, CO, USA
| | - Brandie D. Wagner
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
- Children’s Hospital Colorado, Aurora, CO, USA
- Department of Biostatistics & Informatics, University of Colorado School of Public Health, Aurora, CO, USA
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Bloom JL, Furniss A, Suresh K, Fuhlbrigge RC, Lamb MM, Rosenberg S, Edwards A, O’Leary ST. The Impact of Altitude at Birth on Perinatal Respiratory Support for Neonates with Trisomy 21. Am J Perinatol 2023; 40:1515-1520. [PMID: 34674211 PMCID: PMC10766162 DOI: 10.1055/s-0041-1736594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Both high altitude and trisomy 21 (T21) status can negatively impact respiratory outcomes. The objective of this study was to examine the association between altitude and perinatal respiratory support in neonates with T21 compared with those without T21. STUDY DESIGN This retrospective cohort study used the United States all-county natality files that included live, singleton, in-hospital births from 2015 to 2019. Descriptive statistics for neonates with and without the primary outcome of sustained assisted ventilation (>6 hours) were compared using t-tests and Chi-squared analyses. Multivariable logistic regression was used to determine the association between respiratory support and the presence of T21, and included an interaction term to determine whether the association between respiratory support and the presence of T21 was modified by elevation at delivery. RESULTS A total of 17,939,006 neonates, 4,059 (0.02%) with T21 and 17,934,947 (99.98%) without, were included in the study. The odds of requiring sustained respiratory support following delivery were 5.95 (95% confidence interval [CI]: 5.31, 6.66), 4.06 (95% CI: 2.39, 6.89), 2.36 (95% CI: 1.64, 3.40), and 5.04 (95% CI: 1.54, 16.54) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevations, respectively. The odds of requiring immediate ventilation support following delivery were 5.01 (95% CI: 4.59, 5.46), 5.90 (95% CI: 4.16, 8.36), 2.86 (95% CI: 2.15, 3.80), and 12.08 (95% CI: 6.78, 21.51) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevation, respectively. CONCLUSION Neonates with T21 have increased odds of requiring respiratory support following delivery when compared with neonates without T21 at all categories of altitude. However, the odds ratios did not increase monotonically with altitude which indicates additional research is critical in understanding the effects of altitude on neonates with T21. KEY POINTS · Neonates with T21 have an increased need for perinatal respiratory support at all altitudes.. · The odds of needing perinatal respiratory support did not increase monotonically with elevation.. · Additional research is critical to understanding the effects of altitude on neonates with T21..
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Affiliation(s)
- Jessica L. Bloom
- Department of Pediatrics, Section of Pediatric Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Anna Furniss
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Krithika Suresh
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado
| | - Robert C. Fuhlbrigge
- Department of Pediatrics, Section of Pediatric Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Molly M. Lamb
- Department of Epidemiology and Center for Global Health, Colorado School of Public Health, Aurora, Colorado
| | - Sophie Rosenberg
- Department of Community and Behavioral Health, Colorado School of Public Health, Aurora, Colorado
| | - Anastasia Edwards
- Colorado Department of Public Health and Environment, Denver, Colorado
| | - Sean T. O’Leary
- Department of Pediatrics, Section of Infectious Disease, Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Pathobiology, Severity, and Risk Stratification of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 2023; 24:S12-S27. [PMID: 36661433 DOI: 10.1097/pcc.0000000000003156] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To review the literature for studies published in children on the pathobiology, severity, and risk stratification of pediatric acute respiratory distress syndrome (PARDS) with the intent of guiding current medical practice and identifying important areas for future research related to severity and risk stratification. DATA SOURCES Electronic searches of PubMed and Embase were conducted from 2013 to March 2022 by using a combination of medical subject heading terms and text words to capture the pathobiology, severity, and comorbidities of PARDS. STUDY SELECTION We included studies of critically ill patients with PARDS that related to the severity and risk stratification of PARDS using characteristics other than the oxygenation defect. Studies using animal models, adult only, and studies with 10 or fewer children were excluded from our review. DATA EXTRACTION Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations for clinical practice. There were 192 studies identified for full-text extraction to address the relevant Patient/Intervention/Comparator/Outcome questions. One clinical recommendation was generated related to the use of dead space fraction for risk stratification. In addition, six research statements were generated about the impact of age on acute respiratory distress syndrome pathobiology and outcomes, addressing PARDS heterogeneity using biomarkers to identify subphenotypes and endotypes, and use of standardized ventilator, physiologic, and nonpulmonary organ failure measurements for future research. CONCLUSIONS Based on an extensive literature review, we propose clinical management and research recommendations related to characterization and risk stratification of PARDS severity.
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Bineth N, Barel N, Bdolah-Abram T, Levin P, Einav S. Intellectually disabled patients' intensive care admission characteristics, weaning from mechanical ventilation, and sedative drug use: a single-center retrospective case-control study. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE (ONLINE) 2022; 2:52. [PMID: 37386609 DOI: 10.1186/s44158-022-00081-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 12/01/2022] [Indexed: 07/01/2023]
Abstract
BACKGROUND Intellectually disabled (ID) patients present unique therapeutic challenges. We aimed to describe the characteristics of ID patients admitted to a general intensive care unit (ICU). RESULTS We conducted a retrospective cohort study comparing critically ill adult ID patients to matched patients without ID (1:2 ratio) in a single ICU (2010-2020). The main outcome measure was mortality. Secondary outcomes included complications during admission and characteristics of weaning from mechanical ventilation. The study and control groups were randomly selected based on similar age and sex. ID patients nonetheless had an average APACHE score of 18.5 ± 8.7 vs. 13.4 ± 8.5 in controls (p < 0.001). ID patients had more hematological (p = 0.04), endocrinological (p < 0.001) and neurological (p = 0.004) comorbidities and used more psychiatric medication before admission. No difference was found in mortality rates. Differences were found as there were more secondary complications, such as pulmonary and sepsis (p < 0.03), frequent requirement of vasopressors (p = 0.001), significantly higher intubation rates with more weaning attempts, tracheostomies and longer ICU and hospital admissions (p < 0.019). CONCLUSIONS Critically ill adult ID may have more comorbidities and be sicker at the time of admission compared to their age- and sex-matched counterparts. They require more supportive treatment and their weaning from mechanical ventilation may be more challenging.
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Affiliation(s)
- Noa Bineth
- Department of Military Medicine and "Tzameret", Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
| | - Nevo Barel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Tali Bdolah-Abram
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Philip Levin
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- General Intensive Care Unit, Shaare Zedek Medical Center and Hebrew University Faculty of Medicine, Jerusalem, Israel
| | - Sharon Einav
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- General Intensive Care Unit, Shaare Zedek Medical Center and Hebrew University Faculty of Medicine, Jerusalem, Israel
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Griffiths M, Yang J, Vaidya D, Nies M, Brandal S, Ivy DD, Hickey F, Wolter-Warmerdam K, Austin ED, Mullen M, Pauciulo MW, Lutz KA, Rosenzweig EB, Hirsch R, Yung D, Nichols WC, Everett AD. Biomarkers of Pulmonary Hypertension Are Altered in Children with Down Syndrome and Pulmonary Hypertension. J Pediatr 2022; 241:68-76.e3. [PMID: 34687693 PMCID: PMC9092284 DOI: 10.1016/j.jpeds.2021.10.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 10/05/2021] [Accepted: 10/15/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To evaluate the performance of pulmonary hypertension (PH) biomarkers in children with Down syndrome, an independent risk factor for PH, in whom biomarker performance may differ compared with other populations. STUDY DESIGN Serum endostatin, interleukin (IL)-1 receptor 1 (ST2), galectin-3, N-terminal pro hormone B-natriuretic peptide (NT-proBNP), IL-6, and hepatoma-derived growth factor (HDGF) were measured in subjects with Down syndrome and PH (n = 29), subjects with Down syndrome and resolved PH (n = 13), subjects with Down syndrome without PH (n = 49), and subjects without Down syndrome with World Symposium on Pulmonary Hypertension group I pulmonary arterial hypertension (no Down syndrome PH group; n = 173). Each biomarker was assessed to discriminate PH in Down syndrome. A classification tree was created to distinguish PH from resolved PH and no PH in children with Down syndrome. RESULTS Endostatin, galectin-3, HDGF, and ST2 were elevated in subjects with Down syndrome regardless of PH status. Not all markers differed between subjects with Down syndrome and PH and subjects with Down syndrome and resolved PH. NT-proBNP and IL-6 levels were similar in the Down syndrome with PH group and the no Down syndrome PH group. A classification tree identified NT-proBNP and galectin-3 as the best markers for sequentially distinguishing PH, resolved PH, and no PH in subjects with Down syndrome. CONCLUSIONS Proteomic markers are used to improve the diagnosis and prognosis of PH but, as demonstrated here, can be altered in genetically unique populations such as individuals with Down syndrome. This further suggests that clinical biomarkers should be evaluated in unique groups with the development of population-specific nomograms.
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Affiliation(s)
- Megan Griffiths
- Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD; Department of Internal Medicine, Johns Hopkins University, Baltimore, MD
| | - Jun Yang
- Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD
| | - Dhananjay Vaidya
- Division of Pediatric Cardiology, Children's Hospital Colorado, Aurora, CO
| | - Melanie Nies
- Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD
| | - Stephanie Brandal
- Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD
| | - D Dunbar Ivy
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Francis Hickey
- Sie Center for Down Syndrome, Children's Hospital Colorado, Aurora, CO
| | - Kristine Wolter-Warmerdam
- Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
| | - Eric D Austin
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Mary Mullen
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Michael W Pauciulo
- Division of Pediatric Cardiology; Department of Pediatrics, Columbia University, New York, NY
| | - Katie A Lutz
- Division of Pediatric Cardiology; Department of Pediatrics, Columbia University, New York, NY
| | - Erika B Rosenzweig
- Department of Internal Medicine, Johns Hopkins University, Baltimore, MD
| | - Russel Hirsch
- Division of Pediatric Cardiology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Delphine Yung
- Division of Pediatric Cardiology, Department of Pediatrics, University of Washington, Seattle, WA
| | - William C Nichols
- Division of Pediatric Cardiology; Department of Pediatrics, Columbia University, New York, NY
| | - Allen D Everett
- Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD.
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Zakharchenko L, EL-Khuffash A, Hurley T, Kelly L, Melo A, Padden M, Franklin O, Molloy EJ. Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses. Pediatr Res 2022; 92:1716-1723. [PMID: 35352006 PMCID: PMC9771806 DOI: 10.1038/s41390-022-02000-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 12/03/2021] [Accepted: 02/15/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Infants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively. METHODS Infants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-β; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1β, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO). RESULTS Ninety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1β, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05). CONCLUSIONS Children with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children. IMPACT This study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively. These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population. Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.
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Affiliation(s)
- Lyudmyla Zakharchenko
- grid.417322.10000 0004 0516 3853Paediatric Cardiology, Children’s Health Ireland at Crumlin & Tallaght, Dublin, Ireland ,grid.452722.4National Children’s Research Centre, Crumlin, Dublin, Ireland
| | - Afif EL-Khuffash
- grid.452722.4National Children’s Research Centre, Crumlin, Dublin, Ireland ,grid.416068.d0000 0004 0617 7587Department of Neonatology, Rotunda Hospital, Dublin, Ireland ,grid.4912.e0000 0004 0488 7120Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland ,grid.8217.c0000 0004 1936 9705Paediatrics, Trinity College, The University of Dublin, Trinity Research in Childhood Centre (TRiCC) & Trinity Translational Medicine Institute (TTMI), Dublin, Ireland
| | - Tim Hurley
- grid.8217.c0000 0004 1936 9705Paediatrics, Trinity College, The University of Dublin, Trinity Research in Childhood Centre (TRiCC) & Trinity Translational Medicine Institute (TTMI), Dublin, Ireland
| | - Lynne Kelly
- grid.8217.c0000 0004 1936 9705Paediatrics, Trinity College, The University of Dublin, Trinity Research in Childhood Centre (TRiCC) & Trinity Translational Medicine Institute (TTMI), Dublin, Ireland
| | - Ashanti Melo
- grid.8217.c0000 0004 1936 9705Paediatrics, Trinity College, The University of Dublin, Trinity Research in Childhood Centre (TRiCC) & Trinity Translational Medicine Institute (TTMI), Dublin, Ireland
| | - Maureen Padden
- grid.452722.4National Children’s Research Centre, Crumlin, Dublin, Ireland
| | - Orla Franklin
- grid.417322.10000 0004 0516 3853Paediatric Cardiology, Children’s Health Ireland at Crumlin & Tallaght, Dublin, Ireland ,grid.452722.4National Children’s Research Centre, Crumlin, Dublin, Ireland ,grid.8217.c0000 0004 1936 9705Paediatrics, Trinity College, The University of Dublin, Trinity Research in Childhood Centre (TRiCC) & Trinity Translational Medicine Institute (TTMI), Dublin, Ireland ,grid.411886.20000 0004 0488 4333Paediatrics, Coombe Women and Infants University Hospital, Dublin, Ireland
| | - Eleanor J. Molloy
- grid.452722.4National Children’s Research Centre, Crumlin, Dublin, Ireland ,grid.4912.e0000 0004 0488 7120Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland ,grid.8217.c0000 0004 1936 9705Paediatrics, Trinity College, The University of Dublin, Trinity Research in Childhood Centre (TRiCC) & Trinity Translational Medicine Institute (TTMI), Dublin, Ireland ,grid.411886.20000 0004 0488 4333Paediatrics, Coombe Women and Infants University Hospital, Dublin, Ireland ,grid.417322.10000 0004 0516 3853Neonatology, Children’s Health Ireland at Crumlin & Tallaght, Dublin, Ireland
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De Lausnay M, Ides K, Wojciechowski M, Boudewyns A, Verhulst S, Van Hoorenbeeck K. Pulmonary complications in children with Down syndrome: A scoping review. Paediatr Respir Rev 2021; 40:65-72. [PMID: 34148805 DOI: 10.1016/j.prrv.2021.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/20/2021] [Accepted: 04/23/2021] [Indexed: 10/21/2022]
Abstract
CONTEXT Down syndrome (DS) is a prevalent chromosomal disorder associated with a wide range of congenital anomalies and other health problems. OBJECTIVES To give a scoping overview of encountered lower airway problems (both infectious and non-infectious) in DS children. DATA SOURCES We systematically searched the MEDLINE and PubMed databases for relevant publications. STUDY SELECTION Studies were eligible if they were original studies about pediatric airway problems in DS and were evaluated by the PRISMA guidelines. DATA EXTRACTION Data concerning patient characteristics, study methods and outcomes were critically reviewed. RESULTS Sixty papers were included. These were reviewed and summarized by topic, i.e. airway anomalies, dysphagia and aspiration, lower respiratory tract infections (and bronchiolitis in particular), pulmonary hypertension and other. Respiratory problems are proven to be a frequent and a major health burden in DS children. Airway anomalies (both single and multiple) are more prevalent and require a specific approach. A large proportion of DS children have (often silent) aspiration, resulting in protracted and difficult-to-treat symptoms. Respiratory tract infections are usually more severe and associated with an increased need for (prolonged) hospitalization. Pulmonary hypertension, wheeze and some other rare conditions are more commonly encountered in DS. LIMITATIONS Large number of studies and high levels of study heterogeneity. CONCLUSIONS Several lower airway problems are more frequent and more complex in children with DS. These findings emphasize the need for a multidisciplinary approach by an experienced team allowing for a prompt diagnosis, proper management and improved long term outcome.
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Affiliation(s)
- Mariska De Lausnay
- Department of Pediatrics, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium; Laboratory of Experimental Medicine and Pediatrics (LEMP), Antwerp University, Belgium.
| | - Kris Ides
- Department of Pediatrics, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium; Laboratory of Experimental Medicine and Pediatrics (LEMP), Antwerp University, Belgium; Cosys Lab, Flanders Make, Antwerp University, Belgium
| | - Mark Wojciechowski
- Department of Pediatrics, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
| | - An Boudewyns
- Department of Otorhinolaryngology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
| | - Stijn Verhulst
- Department of Pediatrics, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium; Laboratory of Experimental Medicine and Pediatrics (LEMP), Antwerp University, Belgium
| | - Kim Van Hoorenbeeck
- Department of Pediatrics, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium; Laboratory of Experimental Medicine and Pediatrics (LEMP), Antwerp University, Belgium
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10
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Taksande A, Pujari D, Jameel PZ, Taksande B, Meshram R. Prevalence of pulmonary hypertension among children with Down syndrome: A systematic review and meta-analysis. World J Clin Pediatr 2021; 10:177-191. [PMID: 34868894 PMCID: PMC8603643 DOI: 10.5409/wjcp.v10.i6.177] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 05/13/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pulmonary hypertension (PH) has serious short- and long-term consequences. PH is gaining increasing importance in high risk groups such as Down syndrome (DS) as it influences their overall survival and prognosis. Hence, there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.
AIM To determine the prevalence of PH in children with DS.
METHODS The authors individually conducted a search of electronic databases manually (Cochrane library, PubMed, EMBASE, Scopus, Web of Science). Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion. The words used in the literature search were “pulmonary hypertension” and “pulmonary arterial hypertension”; “Down syndrome” and “trisomy 21” and “prevalence”. The data were analyzed by Comprehensive Meta-Analysis Software Version 2. Risk of bias assessment and STROBE checklist were used for quality assessment.
RESULTS Of 1578 articles identified, 17 were selected for final analysis. The pooled prevalence of PH in these studies was 25.5%. Subgroup analysis was carried out for age, gender, region, year of publication, risk of bias and etiology of PH.
CONCLUSION This review highlights the increasing prevalence of PH in children with DS. It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management. Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.
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Affiliation(s)
- Amar Taksande
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
| | - Divya Pujari
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
| | - Patel Zeeshan Jameel
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
| | - Bharati Taksande
- Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Wardha 442102, Maharashtra, India
| | - Revat Meshram
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
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11
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Bloom JL, Frank B, Weinman JP, Galambos C, O'Leary ST, Liptzin DR, Fuhlbrigge RC. Diffuse alveolar hemorrhage in children with trisomy 21. Pediatr Rheumatol Online J 2021; 19:114. [PMID: 34273981 PMCID: PMC8285855 DOI: 10.1186/s12969-021-00592-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 05/04/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Respiratory conditions are the leading cause of hospitalization and death in children with Trisomy 21 (T21). Diffuse alveolar hemorrhage (DAH) occurs at higher frequency in children with T21; yet, it is not widely studied nor is there a standardized approach to diagnosis or management. The objective of this study was to identify children with T21 and DAH in order to understand contributing factors and identify opportunities to improve outcomes. We identified 5 children with T21 at a single institution with histology-proven DAH over 10 years and discuss their presentation, evaluation, management, and outcomes. We also reviewed the cases in the literature. CASE PRESENTATION Patient 1 died at age seven due to secondary hemophagocytic lymphohistiocytosis. DAH was seen on autopsy. Patient 2 was a three-year-old with systemic-onset juvenile idiopathic arthritis diagnosed with DAH after presenting for hypoxia. Patient 3 was diagnosed with DAH at age nine after presenting with recurrent suspected pneumonia and aspiration. Patient 4 was diagnosed with DAH at age eight after presenting with pallor and fatigue. She had additional ICU admissions for DAH with infections. Patient 5 developed hemoptysis at age three and had recurrent DAH for 10 years. Four patients responded positively to immune-modulation such as intravenous immunoglobulin, glucocorticoids, and rituximab. Of the 19 patients identified in the literature, only one was from the United States. The majority had anemia, respiratory distress, autoantibodies, and recurrences. Very few patients had hemoptysis. Idiopathic pulmonary hemosiderosis was the most common diagnosis. Almost all received glucocorticoids with or without additional immunosuppression. The majority of our patients and those in the literature had positive auto-antibodies such as anti-neutrophil cytoplasmic antibodies and anti-nuclear antigen antibodies. Diagnostic clues included respiratory distress, hypoxia, anemia, recurrent pneumonia, and/or ground glass opacities on imaging. We identified four contributors to DAH: structural lung abnormalities, pulmonary arterial hypertension, infection/aspiration, and autoimmune disease/immune dysregulation. CONCLUSION These cases demonstrate the need for an increased index of suspicion for DAH in children with T21, particularly given the low frequency of hemoptysis at presentation, enrich the understanding of risk factors, and highlight the favorable response to immunosuppressive therapies in this vulnerable population.
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Affiliation(s)
- Jessica L Bloom
- Department of Pediatrics, Section of Pediatric Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
| | - Benjamin Frank
- Department of Pediatrics, Section of Pediatric Cardiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Jason P Weinman
- Department of Radiology, |University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Csaba Galambos
- Department of Pathology and Laboratory Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sean T O'Leary
- Department of Pediatrics, Section of Infectious Disease, Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Deborah R Liptzin
- Department of Pediatrics, Section of Pediatric Pulmonology and Sleep Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Robert C Fuhlbrigge
- Department of Pediatrics, Section of Pediatric Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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12
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Blake JM, Estrada Gomez D, Skotko BG, Torres A, Santoro SL. Pneumonia and respiratory infection in Down syndrome: A 10-year cohort analysis of inpatient and outpatient encounters across the lifespan. Am J Med Genet A 2021; 185:2878-2887. [PMID: 34056836 DOI: 10.1002/ajmg.a.62355] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 04/29/2021] [Accepted: 05/04/2021] [Indexed: 11/10/2022]
Abstract
Respiratory illnesses are a significant contributor of morbidity and mortality among persons with Down syndrome (DS). Reviews have described respiratory illnesses of DS in childhood, but few have looked across the lifespan. Retrospective chart review of patients in our DS program with clinical encounters for respiratory illnesses from 2011 to 2020 was completed. Eighteen percent of clinical encounters were due to respiratory illnesses. Of these, 120 were seen in the emergency department, 88 were admitted, and 21 were seen in urgent care. Common comorbidities included congenital heart disease, asthma, and dysphagia. Admission was common for children under the age of 5 years and adults over the age of 45 years. Admitted patients were more likely to have history of pneumonia and chronic lung disease. Of admitted patients, 77% required supplemental oxygen and 46% required intensive care unit admission. Our findings highlight that respiratory illnesses are a common cause of healthcare utilization among patients with DS, particularly early in childhood and later in life. Patients were seen predominately in outpatient settings; when an inpatient setting was needed, they frequently required higher levels of care. With our findings, clinicians can stratify patients most at risk for respiratory infections and provide targeted monitoring.
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Affiliation(s)
- Jasmine M Blake
- Departments of Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.,University of Maryland School of Medicine, Baltimore, Maryland, USA
| | | | - Brian G Skotko
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.,Down Syndrome Program, Division of Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Amy Torres
- Down Syndrome Program, Division of Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Stephanie L Santoro
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.,Down Syndrome Program, Division of Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA
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13
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Uggeri S, Gilioli F, Cosenza R, Nasi F, Moreali S, Guicciardi N. COVID-19 pneumonia: a tailor-made dress for a Down syndrome patient. ITALIAN JOURNAL OF MEDICINE 2021. [DOI: 10.4081/itjm.2021.1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
We report here a case of coronavirus disease 2019 pneumonia in a 40-year-old Caucasian woman with Down syndrome admitted to the Internal Medicine Unit. She was initially treated with hydroxychloroquine and azithromycin. When respiratory conditions dramatically worsened, she was not admitted to the intensive care unit because of impaired cognitive function. Thus helmet-based continuous positive airway pressure was started. The respiratory conditions progressively improved, reaching spontaneous breathing.
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14
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Smith A, Molloy E, Miletin J, Curley A, Balfe J, Franklin O, El-Khuffash A. Longitudinal assessment of cardiac function in infants with Down's syndrome using novel echocardiography techniques - project protocol. HRB Open Res 2020; 3:77. [PMID: 34095748 PMCID: PMC8145226 DOI: 10.12688/hrbopenres.13168.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2020] [Indexed: 11/21/2022] Open
Abstract
Background: Down’s syndrome (DS) is the most common chromosomal abnormality globally. Ireland has one of the highest rates of DS in the western world with an incidence of 1:444 live births. Congenital heart disease (CHD) and pulmonary hypertension (PH) are the commonest morbidities affecting the cardiovascular system in DS. PH is associated with significant morbidity and an increase risk of mortality. The impact of the diagnosis of DS, the presence of CHD and the associated PH on myocardial function during transition and over the first 2 years of age in this population is not well defined and warrants further study. In particular, serial measurements of pulmonary pressures in this population over the first week of age are lacking. This study aims to characterise myocardial function and pulmonary haemodynamics in infants with Down syndrome during the transitional period (over the first week of age) and throughout the first two years of age. Methods: A prospective, observational study utilising novel echocardiography techniques to assess myocardial function and pulmonary haemodynamics over the first two years of age in infants with Down Syndrome. A population of healthy infants without CHD or a diagnosis of DS will be recruited as controls. This study will be conducted across the three Dublin maternity units. Discussion: In total, 70 babies with DS have been enrolled into this study with 292 echocardiograms performed to date. Further evaluation of cardiac performance in DS infants with and without CHD may yield more insight into the pathophysiology of cardiac dysfunction and pulmonary hypertension that are recognised features in these patients. This could aid in our ability to monitor and treat patients, as well as improve our ability to predict outcomes.
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Affiliation(s)
- Aisling Smith
- Department of Neonatology, The Rotunda Hospital, Dublin, Dublin, D01P5W9, Ireland
| | - Eleanor Molloy
- Department of Paediatrics and Child Health, Trinity College Dublin, Dublin, Dublin, D02PN40, Ireland.,Department of Neonatology, Coombe Women and Infants University Hospital, Dublin, Dublin, D08XW7X, Ireland
| | - Jan Miletin
- Department of Neonatology, Coombe Women and Infants University Hospital, Dublin, Dublin, D08XW7X, Ireland
| | - Anna Curley
- Department of Neonatology, The National Maternity Hospital, Dublin, Dublin, D02YH21, Ireland
| | - Joanne Balfe
- Department of Paediatrics, Tallaght University Hospital, Dublin, Dublin, D24NR0A, Ireland
| | - Orla Franklin
- Department of Paediatric Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin, Dublin, D12N512, Ireland
| | - Afif El-Khuffash
- Department of Neonatology, The Rotunda Hospital, Dublin, Dublin, D01P5W9, Ireland.,School of Medicine, Royal College of Surgeons in Ireland, Dublin, Dublin, D02P796, Ireland
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15
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Langkamp DL, Dusseau A, Brown MF. Vaccine Hesitancy and Low Immunization Rates in Children with Down Syndrome. J Pediatr 2020; 223:64-67.e2. [PMID: 32418813 DOI: 10.1016/j.jpeds.2020.03.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 03/11/2020] [Accepted: 03/12/2020] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To determine the prevalence of vaccine hesitancy and refusal among parents of children with Down syndrome and to determine how well the Parent Attitudes about Childhood Vaccines Survey (PACV) is associated with vaccine receipt among children with Down syndrome. STUDY DESIGN We mailed the PACV to parents of children with Down syndrome who attend the Down Syndrome Clinic at Akron Children's Hospital and examined associations between PACV scores and immunization status at 19 months of age. RESULTS Of 120 surveys sent, 63 parents completed the PACV (52% response rate) of which 60 were linked to vaccination records. Of these 60 respondents, 55 children were ≥19 months old. PACV scores were significantly correlated with days of underimmunization at 19 months of age. All parents who refused all vaccines had PACV scores of ≥50. Only 58% of children were up to date for the combined 7 vaccine series at 19 months of age. CONCLUSIONS The PACV may be a valuable tool to identify vaccine hesitancy among parents of young children with Down syndrome. Special emphasis is needed to increase adherence with on-time vaccine recommendations for children with Down syndrome to optimize their health and to potentially avoid hospitalizations.
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Affiliation(s)
- Diane L Langkamp
- NeuroDevelopmental Science Center, Akron Children's Hospital, Akron, OH
| | - Anna Dusseau
- NeuroDevelopmental Science Center, Akron Children's Hospital, Akron, OH
| | - Miraides F Brown
- Considine Research Institute, Akron Children's Hospital, Akron, OH
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16
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Verstegen RHJ, Chang KJJ, Kusters MAA. Clinical implications of immune-mediated diseases in children with Down syndrome. Pediatr Allergy Immunol 2020; 31:117-123. [PMID: 31599041 DOI: 10.1111/pai.13133] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 09/27/2019] [Accepted: 09/30/2019] [Indexed: 12/18/2022]
Abstract
Children with Down syndrome have changes in their innate and adaptive immunity, which contribute to increased rates of infections, autoimmune diseases, and haematological malignancies. While improved care for congenital heart disease has decreased mortality and morbidity, complications related to immune-mediated diseases continue to limit the life expectancy in Down syndrome. Infectious diseases are common and have a significant effect on development, behaviour and quality of life. Infection frequency and severity are influenced by various anatomical and physiological alterations in addition to immunological changes in Down syndrome. Thus, prevention of respiratory tract infections requires a multifactorial approach. This could include additional active and/or passive immunizations, prophylactic antibiotics, immunoglobulin replacement and ear, nose and throat surgical interventions. Autoimmune conditions like coeliac disease, type I diabetes mellitus and thyroid disease are classically mentioned in the context of Down syndrome. However, autoinflammatory conditions are more prevalent as well. Screening for autoimmune diseases is required and immunosuppression has to be used with caution. Future studies should address optimal screening programmes for immune-mediated diseases in individuals with Down syndrome, as well as the effect of immune modulation, to further decrease morbidity and mortality, and improve the quality of life of individuals with Down syndrome.
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Affiliation(s)
- Ruud H J Verstegen
- Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.,Division of Rheumatology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada
| | - Krystal J J Chang
- Faculty of Social and Applied Human Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Maaike A A Kusters
- Department of Immunology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.,University College London Great Ormond Street Institute of Child Health, London, UK
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17
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Cardiac mechanics in infants with Down syndrome in the early neonatal period. J Perinatol 2019; 39:626-633. [PMID: 30911081 DOI: 10.1038/s41372-019-0354-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 02/09/2019] [Accepted: 02/13/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The objective of this study is to test whether myocardial performance is impaired over the first week of age in infants with Down syndrome (DS) without congenital heart disease (CHD). STUDY DESIGN A prospective cohort study of 20 infants with DS without CHD and 17 healthy term infants comparing echocardiographic measures of left (LV) and right (RV) ventricular function and pulmonary hypertension (PH) on days 1, 2, and 5-7. RESULTS Indices of PH were higher in the DS group over the study period. Infants with DS had larger RV and smaller LV dimensions. Fractional area change and RV longitudinal strain values were lower in the DS group. LV shear strain values were lower in infants with DS driven by a lack of basal rotation. CONCLUSION Infants with DS without CHD and echocardiographic evidence of PH during the early neonatal period demonstrate reduced RV systolic function with impaired LV rotational mechanics, reflective of the ventricular interdependence.
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18
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Bush D, Galambos C, Ivy DD, Abman SH, Wolter-Warmerdam K, Hickey F. Clinical Characteristics and Risk Factors for Developing Pulmonary Hypertension in Children with Down Syndrome. J Pediatr 2018; 202:212-219.e2. [PMID: 30025669 DOI: 10.1016/j.jpeds.2018.06.031] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 04/24/2018] [Accepted: 06/12/2018] [Indexed: 01/02/2023]
Abstract
OBJECTIVES To determine the incidence, characteristics of, and risk factors contributing to the development of pulmonary hypertension in children with Down syndrome. STUDY DESIGN This retrospective, review of a large cohort (n = 1242) of children with Down syndrome receiving care at a specialized referral center evaluated clinical data and serial echocardiograms from a clinic database and electronic medical records. Pulmonary hypertension characteristics and comorbidities were reviewed. Pulmonary hypertension was considered transient if echocardiographic evidence of pulmonary hypertension resolved without recurrence, persistent if no resolution, and recurrent if evidence of pulmonary hypertension returned after a period of resolution. RESULTS The incidence of pulmonary hypertension in children with Down syndrome was 28% (n = 346). Median age at initial diagnosis was 5 days (range: 0-7067 days). Pulmonary hypertension was differentiated into transient (70%), persistent (15%), and recurrent (15%) disease. Median duration of transient pulmonary hypertension was 8 months (range: 0.1-130.2 months). Median age at recurrence was 2.5 years (range 0.2-11.5 years). Initial pulmonary hypertension diagnosis was classified as World Health Organization group I disease in 82%, with 45% associated with congenital heart disease (CHD), and 38% persistent pulmonary hypertension of the newborn (PPHN). The pulmonary hypertension recurrence rate was significant and similar for both those with initial PPHN (12%) and non-PPHN (16%). A majority (87%) of patients with recurrent pulmonary hypertension were classified as World Health Organization group III. Frequently identified comorbid conditions included CHD, obstructive sleep apnea, intermittent hypoxia, and recurrent pneumonia. CONCLUSIONS Pulmonary hypertension is common in children with Down syndrome, is typically transient, and related to CHD or PPHN but can recur in the setting of respiratory disease such as obstructive sleep apnea, intermittent hypoxia, and recurrent pneumonia.
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Affiliation(s)
- Douglas Bush
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
| | - Csaba Galambos
- Department of Pathology, University of Colorado School of Medicine, Aurora, CO; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - D Dunbar Ivy
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Steven H Abman
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | | | - Francis Hickey
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
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19
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Interleukin 6 and 10 Serum Levels and Genetic Polymorphisms in Children with Down Syndrome. Mediators Inflamm 2018; 2018:6539548. [PMID: 30186038 PMCID: PMC6116409 DOI: 10.1155/2018/6539548] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 07/29/2018] [Indexed: 12/17/2022] Open
Abstract
Immunological impairment is a condition that is often observed in individuals with Down syndrome (DS). The immune response is modulated by pro- and anti-inflammatory cytokines whose expressions could be influenced by genetic polymorphisms. The present study was aimed at evaluating the frequencies of -174G>C, -572G>C, and -597G>A polymorphisms in the interleukin 6 (IL-6) gene and -592C>A, -1082A>G, and -819C>T polymorphisms in the IL-10 gene and the IL-6 and IL-10 serum levels in healthy individuals with and without DS. The authors also aimed to investigate the impact of the genotypes on the interleukin concentrations. The genetic polymorphisms were investigated in 200 DS individuals and 200 controls without DS. The serum measurement of IL-6 and IL-10 was performed in a subgroup (54 cases and 54 controls) by enzyme-linked immunosorbent assay (ELISA). The frequencies of the polymorphisms and haplotypes evaluated were not different between individuals with and without DS. IL-10 concentration was higher in DS children but was not influenced by IL-10 gene polymorphisms. IL-6 genotypes had no influence on IL-6 serum levels. The IL-10 serum levels are increased in DS individuals, but IL-10 polymorphisms are not the main factors that influence the IL-10 expression in DS.
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20
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Martin T, Smith A, Breatnach CR, Kent E, Shanahan I, Boyle M, Levy PT, Franklin O, El-Khuffash A. Infants Born with Down Syndrome: Burden of Disease in the Early Neonatal Period. J Pediatr 2018; 193:21-26. [PMID: 29174996 DOI: 10.1016/j.jpeds.2017.09.046] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 07/28/2017] [Accepted: 09/19/2017] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To evaluate the incidence of direct admission of infants with Down syndrome to the postnatal ward (well newborn nursery) vs the neonatal intensive care unit (NICU), and to describe the incidence of congenital heart disease (CHD) and pulmonary hypertension (PH). STUDY DESIGN This retrospective cohort study of Down syndrome used the maternal/infant database (2011-2016) at the Rotunda Hospital in Dublin, Ireland. Admission location, early neonatal morbidities, outcomes, and duration of stay were evaluated and regression analyses were conducted to identify risk factors associated with morbidity and mortality. RESULTS Of the 121 infants with Down syndrome, 54 (45%) were initially admitted to the postnatal ward, but 38 (70%) were later admitted to the NICU. Low oxygen saturation profile was the most common cause for the initial and subsequent admission to the NICU. Sixty-six percent of the infants (80/121) had CHD, 34% (41/121) had PH, and 6% died. Risk factors independently associated with primary NICU admission included antenatal diagnosis of Down syndrome, presence of CHD, PH, and the need for ventilation. CONCLUSIONS Infants with Down syndrome initially admitted to the postnatal ward have a high likelihood of requiring NICU admission. Overall, high rates of neonatal morbidity were noted, including rates of PH that were higher than previously reported. Proper screening of all infants with Down syndrome for CHD and PH is recommended to facilitate timely diagnoses and potentially shorten the duration of the hospital stay.
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Affiliation(s)
- Therese Martin
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Aisling Smith
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Colm R Breatnach
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Etaoin Kent
- Department of Obstetrics and Gynecology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ita Shanahan
- Department of Obstetrics and Gynecology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Michael Boyle
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Phillip T Levy
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO; Goryeb Children's Hospital, Atlantic Health System, Morristown, NJ
| | - Orla Franklin
- Department of Pediatric Cardiology, Our Lady's Children's Hospital, Dublin, Ireland
| | - Afif El-Khuffash
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland; School of Medicine (Department of Pediatrics), Royal College of Surgeons in Ireland, Dublin, Ireland.
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21
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Valentini D, Bianchi S, Di Camillo C, Vittucci AC, Gonfiantini MV, De Vito R, Villani A. Fatal varicella pneumonia in an unvaccinated child with Down Syndrome: a case report. Ital J Pediatr 2016; 42:99. [PMID: 27855688 PMCID: PMC5114766 DOI: 10.1186/s13052-016-0312-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 11/11/2016] [Indexed: 11/10/2022] Open
Abstract
Background Varicella is an acute infectious disease common during childhood. It has mostly an uncomplicated course in early childhood. Neverthless, it may result in severe complications, especially in particular age groups and clinical conditions. Down Syndrome represents a risk factor for developing complications, because of the frequent comorbidities and their immunodeficiency. Case presentation A 2-year-old white Caucasian female affected by Down Syndrome was referred to our hospital for cardiac arrest in course of varicella disease. After cardiopulmonary resuscitation and stabilization, her clinical conditions didn’t improve and she developed a massive pulmonary hemorrage, which led her to exitus. Conclusions Mortality due to varicella infection is rare, but it is more common in subjects with immune deficit or chronic pathologies, and in particular age-groups. The importance of the vaccine for preventable infectious diseases is stressed in this paper, in which we present a case of death in an unvaccinated cardiopathic child with Down Syndrome affected by varicella.
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Affiliation(s)
- Diletta Valentini
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
| | - Simona Bianchi
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Chiara Di Camillo
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Anna Chiara Vittucci
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | | | - Rita De Vito
- Pathology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Alberto Villani
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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