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Tsao M, Yanko F, Cheon E. Perioperative Complications in Children with Down Syndrome: A Single Center Retrospective Analysis-Original Clinical Research Report. J Clin Med 2025; 14:2900. [PMID: 40363932 PMCID: PMC12072385 DOI: 10.3390/jcm14092900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/08/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: Down syndrome (DS) is the most common chromosomal abnormality in live births in the United States. Children with DS often require anesthesia for surgery or diagnostic imaging in their lives. These children present a unique perioperative risk profile due to a combination of anatomic and physiological alterations, along with associated comorbid conditions. There are limited studies on the perioperative outcomes of children with DS. This retrospective study assesses perioperative complications in pediatric patients with DS undergoing non-cardiac surgery or diagnostic imaging under anesthesia at a single tertiary pediatric hospital. Methods: The electronic medical record at a tertiary pediatric hospital was queried for children with DS who received anesthesia for non-cardiac surgery or diagnostic imaging from May 2016 to April 2021. The primary outcomes were complications defined as readmission, reoperation, or unexpected respiratory, cardiovascular, neurologic, surgical, or gastrointestinal issues. Exclusion criteria were cardiac surgery, age > 18 years, and records with incomplete or missing data. Results: A total of 1713 anesthetic records from 711 unique patients over five years were included in the final analysis. The study found a low overall complication rate (2.98%), with respiratory events being the most common (43.1%). While most complications are short term and resolved with treatment and time; there were also several severe, life-threatening complications. Increased procedural complexity, multiple procedures, and increased procedure duration were associated with higher complication rates, whereas patient age, sex, weight, and case urgency were not associated with higher complication rates. Conclusions: Children with DS often have comorbid conditions and require multiple life-improving surgeries. Our study found the perioperative complication rate for children with Down syndrome receiving anesthesia for non-cardiac surgery or diagnostic imaging is low, comparable to the general pediatric population. The findings indicate that anesthesia is well tolerated by children with DS. However, given patients' unique anatomic and physiological differences, careful perioperative risk assessment and planning is essential. Clinical Implications: (a) What is already known about the topic: Pediatric patients with DS often require anesthesia for surgical procedures or medical imaging. They have anatomic and physiological alterations and comorbid conditions that may influence perioperative risk. (b) What new information this study adds: In a retrospective study at a tertiary pediatric hospital, patients with DS were found to have a low overall complication rate after anesthesia for non-cardiac surgery or diagnostic imaging. Increased procedural complexity, multiple procedures, and increased procedure duration were associated with higher complication rates.
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Affiliation(s)
- Michelle Tsao
- Department of Pediatric Anesthesiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; (F.Y.); (E.C.)
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Mat Bah MN, Zahari N, Abdullah NA, Sapian MH, Alias EY. Survival and Risk Factor for Mortality of Infants with Trisomy-21 and Pulmonary Hypertension: A Population-Based Study from a Middle-Income Country. Pediatr Cardiol 2024:10.1007/s00246-024-03732-1. [PMID: 39661153 DOI: 10.1007/s00246-024-03732-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 12/05/2024] [Indexed: 12/12/2024]
Abstract
Limited studies are available on the outcome of infants with trisomy-21 and pulmonary hypertension (PHT) in lower- and middle-income countries. This population-based cohort study aims to determine the outcome and survival from birth to 5 years of infants with trisomy-21 and PHT born between 2016 and 2021. The mortality rate and Kaplan-Meier survival analysis were calculated to assess survival rates at 1 and 5 years. Multivariate Cox regression analysis was used to examine mortality-related factors. A total of 488 trisomy-21 infants were identified, with 176 (36%) having PHT and 245 (50%) having congenital heart disease (CHD). Of 176 PHT, 74 (42%) had moderate to severe PHT, and 115 (65%) patients had their PHT resolved at a median age of 7 weeks (Interquartile range [IQR]: 3 to 16.8 weeks), and 48 (27%) died at a median age of 3.6 months (IQR: 0.6 to 7.1 months). The survival at 1 and 5 years was 74% and 71%, respectively. The independent factors for mortality were infants with birth weight less than 2.5 kg (adjusted Hazard Ratio [aHR] 2.1 95% confidence interval [CI] 1.1-4.2, p = .02), symptomatic infants (aHR 3.3 95% CI 1.4-7.6, p = .006), late-onset PHT (aHR 3.8 95% CI 1.6-8.9, p = .002), with CHD (aHR 2.1 95% CI 1.1-4.2, p = .03) and those with Persistent Pulmonary Hypertension of Newborn [PPHN] (aHR 2.1 95% CI 1.0-4.3, p = .047). One-third of infants with trisomy-21 experienced PHT, with seven out of ten surviving until age five. Those with low birth weight, symptomatic infants, CHD, late-onset PHT, and PPHN were associated with low survival rates.
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Affiliation(s)
- Mohd Nizam Mat Bah
- Department of Pediatrics, Ministry of Health Malaysia, Hospital Sultanah Aminah, Persiaran Abu Bakar Sultan, 80100, Johor Bahru, Johor DT, Malaysia.
| | - Norazah Zahari
- Department of Pediatrics, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia
| | - Noor Adibah Abdullah
- Department of Pediatrics, Ministry of Health Malaysia, Hospital Sultanah Aminah, Persiaran Abu Bakar Sultan, 80100, Johor Bahru, Johor DT, Malaysia
| | - Mohd Hanafi Sapian
- Department of Pediatrics, Ministry of Health Malaysia, Hospital Sultanah Aminah, Persiaran Abu Bakar Sultan, 80100, Johor Bahru, Johor DT, Malaysia
| | - Emieliyuza Yusnita Alias
- Department of Pediatrics, Ministry of Health Malaysia, Hospital Sultanah Aminah, Persiaran Abu Bakar Sultan, 80100, Johor Bahru, Johor DT, Malaysia
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Thomas AS, Spector LG, McCracken C, Oster ME, Kochilas LK. Cancer mortality in children surviving congenital heart interventions: A study from the Pediatric Cardiac Care Consortium. Pediatr Blood Cancer 2024; 71:e31271. [PMID: 39138600 PMCID: PMC11499021 DOI: 10.1002/pbc.31271] [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] [Received: 04/04/2024] [Revised: 07/26/2024] [Accepted: 08/01/2024] [Indexed: 08/15/2024]
Abstract
INTRODUCTION Children with congenital heart defects (CHD) have shorter life expectancy than the general population. Previous studies also suggest that patients with CHD have higher risk of cancer. This study aims to describe cancer-related mortality among patients with a history of CHD interventions using the Pediatric Cardiac Care Consortium (PCCC), a large US cohort of such patients. METHODS We performed a retrospective cohort study of individuals (<21 years) who underwent interventions for CHD in the PCCC from 1982 to 2003. Patients surviving their first intervention were linked to the National Death Index through 2020. Multivariable models assessed risk of cancer-related death, adjusting for age, sex, race, and ethnicity. Patients with/without genetic abnormalities (mostly Down syndrome [DS]) were considered separately, due to expected differential risk in cancer. RESULTS Among the 57,601 eligible patients in this study, cancer was the underlying or contributing cause of death for 208; with 20% among those with DS. Significantly increased risk of cancer-related death was apparent among patients with DS compared to the non-genetic group (aHR: 3.63, 95% confidence interval [CI]: 2.52-5.24, p < .001). For the group with non-genetic abnormalities, the highest association with cancer-related death compared to those with mild CHD was found among those with more severe CHD (severe two-ventricle aHR: 1.82, 95% CI: 1.04-3.20, p = .036, single-ventricle aHR: 4.68, 95% CI: 2.77-7.91, p < .001). CONCLUSIONS Patients with more severe forms of CHD are at increased risk for cancer-related death. Despite our findings, we are unable to distinguish whether having CHD raises the risk of cancer or reduces survival.
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Affiliation(s)
- Amanda S. Thomas
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA
- Minnesota Population Center, University of Minnesota, Minneapolis, Minnesota, USA
| | - Logan G. Spector
- Division of Epidemiology and Clinical Research, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Courtney McCracken
- Center for Research and Evaluation, Kaiser Permanente of Georgia, Atlanta, Georgia, USA
| | - Matthew E. Oster
- Division of Cardiology, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
- Department of Pediatrics, Emory University, Atlanta, Georgia, USA
| | - Lazaros K. Kochilas
- Division of Cardiology, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
- Department of Pediatrics, Emory University, Atlanta, Georgia, USA
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Rocha LO, Miyague NI, Solarewicz LA, Fernandes-Silva MM. Impact of Age and of the Patent Ductus Arteriosus on Pulmonary Hemodynamics in Children with Complete Atrioventricular Septal Defect. Pediatr Cardiol 2024:10.1007/s00246-024-03636-0. [PMID: 39223337 DOI: 10.1007/s00246-024-03636-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Abstract
Complete atrioventricular septal defect (CAVSD) can lead to the development of pulmonary obstructive vascular disease due to high pulmonary blood flow and pressures. This study aimed to evaluate the changes in pulmonary hemodynamics with aging and with patent ductus arteriosus (PDA) in children with CAVSD. We retrospectively evaluated 137 children (94% with trisomy 21, median age of 195 (25-2963) days, 58.4% female) with CASVD referred to cardiac catheterization from January 2000 to December 2020. Those with associated congenital heart disease, except PDA, had been excluded. They were divided into three age terciles (T1, T2, and T3). Aging was directly associated with higher mean (T1: 34.2 ± 9.1; T2: 37.1 ± 5.8; T3: 42 ± 10.6 mmHg, p < 0.001) and diastolic (T1: 19.4 ± 5.3; T2 21.6 ± 5.0; T3: 26.0 ± 9.5 mmHg, P < 0.001) pulmonary arterial pressures, and with higher pulmonary vascular resistance (T1: 3.24 ± 1.69, T2: 3.47 ± 1.19; T3: 4.49 ± 3.91 Wu.m2, p = 0.023). This resulted in a loss of eligibility for anatomical correction, which became evident only after 300 days of age. PDA was associated with a higher mean (37.2 [35.9; 38.5] vs. 41.3 [37.5; 45.0] mmHg, p = 0.049) and diastolic (21.7 [20.7; 22.6] vs. 26.4 [24.1; 29.0] mmHg, p = 0.001) pulmonary pressure, and resistor-compliance time (0.28 [0.26; 0.29] vs. 0.36 [0.31; 0.40], p = 0.001) after adjusting for age and sex. In children with CAVSD, aging was associated with worsening of pulmonary vascular hemodynamics, particularly when PDA was associated, resulting in loss of eligibility for anatomical correction after 10 months of age as the first surgical option.
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Drakopoulou M, Vlachakis PK, Tsioufis C, Tousoulis D. Congenital heart "Challenges" in Down syndrome. World J Cardiol 2024; 16:217-220. [PMID: 38817649 PMCID: PMC11135325 DOI: 10.4330/wjc.v16.i5.217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 04/18/2024] [Accepted: 05/13/2024] [Indexed: 05/23/2024] Open
Abstract
In this editorial, we comment on the article by Kong et al published in the recent issue of the World Journal of Cardiology. In this interesting case, the authors present the challenges faced in managing a 13-year-old patient with Down syndrome (DS) and congenital heart disease (CHD) associated with pulmonary arterial hypertension. In this distinct population, the Authors underscore the need for early diagnosis and management as well as the need of a multidisciplinary approach for decision making. It seems that the occurrence of CHD in patients with DS adds layers of complexity to their clinical management. This editorial aims to provide a comprehensive overview of the intricate interplay between DS and congenital heart disorders, offering insights into the nuanced diagnostic and therapeutic considerations for physicians.
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Affiliation(s)
- Maria Drakopoulou
- Department of First Cardiology, Hippokration General Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece.
| | - Panayotis K Vlachakis
- Department of First Cardiology, Hippokration General Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Costas Tsioufis
- Department of First Cardiology, Hippokration General Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Dimitris Tousoulis
- Department of First Cardiology, Hippokration General Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
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Bhende VV, Tandon R, Krishnakumar M, Patel RM, Sharma AS. Successful Cardiac Surgical Management in a Trisomy 21 Child After Long-Term Hospitalization Associated With Bronchopneumonia and Hepatitis C Virus Seropositivity: A Case Report. Cureus 2024; 16:e61309. [PMID: 38813073 PMCID: PMC11135605 DOI: 10.7759/cureus.61309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/29/2024] [Indexed: 05/31/2024] Open
Abstract
A 31-month-old girl with trisomy 21 (Down syndrome) was seen in the emergency department of pediatrics because of oxygen desaturation associated with features of lower respiratory tract infections. She was born at full term and diagnosed with congenital heart disease (CHD) having ventricular septal defect (VSD), and patent ductus arteriosus (PDA); consequently, she underwent corrective surgery after adequate optimization of treatment. Incidentally, she was detected to have the presence of anti-hepatitis C virus (HCV) antibodies. In this case report, we mainly focus on the multi-modal approach to medical and surgical management.
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Affiliation(s)
- Vishal V Bhende
- Pediatric Cardiac Surgery, Bhanubhai and Madhuben Patel Cardiac Centre, Shree Krishna Hospital, Bhaikaka University, Karamsad, IND
| | - Rahul Tandon
- Pediatrics, Pramukhswami Medical College, Shree Krishna Hospital, Bhaikaka University, Karamsad, IND
| | | | - Rupal M Patel
- Microbiology, Pramukhswami Medical College, Shree Krishna Hospital, Bhaikaka University, Karamsad, IND
| | - Ashwin S Sharma
- Internal Medicine, Gujarat Cancer Society Medical College, Hospital and Research Centre, Ahmedabad, IND
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Narayan P, Richter F, Morton S. Genetics and etiology of congenital heart disease. Curr Top Dev Biol 2024; 156:297-331. [PMID: 38556426 DOI: 10.1016/bs.ctdb.2024.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
Congenital heart disease (CHD) is the most common severe birth anomaly, affecting almost 1% of infants. Most CHD is genetic, but only 40% of patients have an identifiable genetic risk factor for CHD. Chromosomal variation contributes significantly to CHD but is not readily amenable to biological follow-up due to the number of affected genes and lack of evolutionary synteny. The first CHD genes were implicated in extended families with syndromic CHD based on the segregation of risk alleles in affected family members. These have been complemented by more CHD gene discoveries in large-scale cohort studies. However, fewer than half of the 440 estimated human CHD risk genes have been identified, and the molecular mechanisms underlying CHD genetics remains incompletely understood. Therefore, model organisms and cell-based models are essential tools for improving our understanding of cardiac development and CHD genetic risk. Recent advances in genome editing, cell-specific genetic manipulation of model organisms, and differentiation of human induced pluripotent stem cells have recently enabled the characterization of developmental stages. In this chapter, we will summarize the latest studies in CHD genetics and the strengths of various study methodologies. We identify opportunities for future work that will continue to further CHD knowledge and ultimately enable better diagnosis, prognosis, treatment, and prevention of CHD.
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Affiliation(s)
| | - Felix Richter
- Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Sarah Morton
- Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
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Batta A, Hatwal J. Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome. World J Cardiol 2024; 16:1-4. [PMID: 38313390 PMCID: PMC10835471 DOI: 10.4330/wjc.v16.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/03/2023] [Accepted: 12/18/2023] [Indexed: 01/19/2024] Open
Abstract
Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50% of them having associated congenital heart disease (CHD). Shunt lesions account for around 75% of all CHDs in Down syndrome. Down syndrome patients, especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension (PH) compared with shunt lesions in general population. This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality. However, despite clear recommendations, there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible. Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt. It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heart-lung transplant. However, despite the guidelines laid by authorities, the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them. The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.
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Affiliation(s)
- Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India.
| | - Juniali Hatwal
- Department of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
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Engsner S, Giang KW, Dellborg M, Fedchenko M, Eriksson P, Mandalenakis Z. Impact of Down Syndrome on Survival Among Patients With Congenital Heart Disease. J Am Heart Assoc 2024; 13:e031392. [PMID: 38214262 PMCID: PMC10926807 DOI: 10.1161/jaha.123.031392] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 10/17/2023] [Indexed: 01/13/2024]
Abstract
BACKGROUND Increasing survival among patients with congenital heart disease (CHD) has recently been reported. However, the impact of Down syndrome (DS) in patients with CHD is still debated. We aimed to estimate survival in patients with CHD with versus without DS compared with matched controls from the general population without CHD or DS. METHODS AND RESULTS We linked data from Swedish health registries to identify patients with CHD born between 1970 and 2017. Data from the Total Population Register were used to match each patient with CHD by sex and birth year with 8 controls without CHD or DS. A Cox proportional regression model was used to estimate mortality risk, and Kaplan-Meier curves were analyzed for the survival analysis. We identified 3285 patients with CHD-DS, 64 529 patients with CHD without DS, and 26 128 matched controls. The mortality risk was 25.1 times higher (95% CI, 21.3-29.5) in patients with CHD-DS versus controls. The mortality rate was 2 times higher (95% CI, 1.94-2.31) for patients with CHD with versus without DS. Lower mortality was found during the second versus first birth periods in patients with CHD-DS compared with controls; hazard ratio: 46.8 (95% CI, 29.5-74.0) and 17.7 (95% CI, 12.8-24.42) in those born between 1970 and 1989 versus 1990 and 2017, respectively. CONCLUSIONS In this retrospective cohort study, the mortality risk among patients with CHD-DS was 25 times higher compared with matched controls and 2 times higher compared with patients with CHD without DS. Survival was higher in patients with CHD-DS born after versus before 1990, coinciding with the modern era of congenital heart care.
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Affiliation(s)
- Stella Engsner
- Department of Molecular and Clinical MedicineInstitute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburgSweden
| | - Kok Wai Giang
- Department of Molecular and Clinical MedicineInstitute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburgSweden
- Department of Medicine, Geriatrics and Emergency Medicine, Region Västra GötalandSahlgrenska University Hospital/ÖstraGothenburgSweden
| | - Mikael Dellborg
- Department of Molecular and Clinical MedicineInstitute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburgSweden
- Department of Medicine, Geriatrics and Emergency Medicine, Region Västra GötalandSahlgrenska University Hospital/ÖstraGothenburgSweden
| | - Maria Fedchenko
- Department of Molecular and Clinical MedicineInstitute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburgSweden
- Department of Medicine, Geriatrics and Emergency Medicine, Region Västra GötalandSahlgrenska University Hospital/ÖstraGothenburgSweden
| | - Peter Eriksson
- Department of Molecular and Clinical MedicineInstitute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburgSweden
- Department of Medicine, Geriatrics and Emergency Medicine, Region Västra GötalandSahlgrenska University Hospital/ÖstraGothenburgSweden
- Adult Congenital Heart Unit, Department of MedicineSahlgrenska University Hospital/ÖstraGothenburgSweden
| | - Zacharias Mandalenakis
- Department of Molecular and Clinical MedicineInstitute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburgSweden
- Department of Medicine, Geriatrics and Emergency Medicine, Region Västra GötalandSahlgrenska University Hospital/ÖstraGothenburgSweden
- Adult Congenital Heart Unit, Department of MedicineSahlgrenska University Hospital/ÖstraGothenburgSweden
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Baumer NT, Hojlo MA, Pawlowski KG, Milliken AL, Lombardo AM, Sargado S, Soccorso C, Davidson EJ, Barbaresi WJ. Co-occurring conditions in Down syndrome: Findings from a clinical database. AMERICAN JOURNAL OF MEDICAL GENETICS. PART C, SEMINARS IN MEDICAL GENETICS 2023; 193:e32072. [PMID: 37873945 DOI: 10.1002/ajmg.c.32072] [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: 08/01/2023] [Revised: 10/03/2023] [Accepted: 10/06/2023] [Indexed: 10/25/2023]
Abstract
Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.
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Affiliation(s)
- Nicole T Baumer
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
- Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Margaret A Hojlo
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Katherine G Pawlowski
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Anna L Milliken
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Angela M Lombardo
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Sabrina Sargado
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Cara Soccorso
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Emily J Davidson
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
- Division of General Pediatrics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - William J Barbaresi
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Salvi PS, Cowles RA. The Burden of Congenital Heart Disease and Urogenital Lesions in a National Cohort of Hirschsprung Patients. J Pediatr Surg 2023; 58:2165-2170. [PMID: 37481371 DOI: 10.1016/j.jpedsurg.2023.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 06/10/2023] [Accepted: 06/22/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND Hirschsprung's disease (HSCR) is often associated with other congenital and chromosomal defects. This study aimed to describe the prevalence of congenital heart disease (CHD) and congenital urogenital lesions in children with HSCR, with and without Trisomy 21 and other associated anomalies, to guide appropriate screening. METHODS The Pediatric Health Information System was queried for patients with HSCR who underwent surgical treatment between 2016 and 2021. The prevalence of CHD, congenital urogenital lesions, Trisomy 21 and other congenital syndromes were calculated. Multivariable regression modeling was used to identify predictors of postoperative intensive care unit (ICU) admission and postoperative length of stay (LOS). RESULTS Of 2021 HSCR patients at 47 children's hospitals, 264 (13.1%) had CHD, 244 (12.1%) had Trisomy 21, and 103 (5.1%) had a congenital urogenital lesion. The prevalence of CHD (49.6 vs. 8.1%, P < 0.001) and of undergoing a cardiac intervention with associated CHD (40.5 vs. 23.1%, P = 0.002) were higher in patients with Trisomy 21 compared to those without. CHD was associated with an increased likelihood of postoperative ICU admission (OR: 1.6, 95% CI: 1.1, 2.2) and greater postoperative LOS (IRR: 2.6, 95% CI: 2.6, 2.7), irrespective of Trisomy 21 diagnosis. CONCLUSIONS The prevalence of CHD among HSCR patients (13.1%) was higher than previously reported, and CHD patients required more resource-intensive care after pull-through. While Trisomy 21 was associated with higher rates of CHD and cardiac intervention, 8.1% of HSCR patients without Trisomy 21 had CHD. Screening echocardiogram should be considered in all children diagnosed with HSCR, as CHD may influence perioperative risk stratification. However, screening renal ultrasound may have limited utility given the low prevalence of urogenital lesions in this population. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Pooja S Salvi
- Weill Cornell Medical College, Department of Surgery, New York, NY, USA
| | - Robert A Cowles
- Yale School of Medicine, Department of Surgery, Division of Pediatric Surgery, New Haven, CT, USA.
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Mouat JS, Li S, Myint SS, Laufer BI, Lupo PJ, Schraw JM, Woodhouse JP, de Smith AJ, LaSalle JM. Epigenomic signature of major congenital heart defects in newborns with Down syndrome. Hum Genomics 2023; 17:92. [PMID: 37803336 PMCID: PMC10559462 DOI: 10.1186/s40246-023-00540-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 10/02/2023] [Indexed: 10/08/2023] Open
Abstract
BACKGROUND Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs. METHODS We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: (1) 45 DS-CHD (27 female, 18 male) and (2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD versus DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell-type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS versus typical development (TD) WGBS NDBS samples. RESULTS We found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percentage of CHD-associated DMRs than background regions were differentially methylated in DS versus TD samples. CONCLUSIONS A sex-specific signature of DNA methylation was detected in NDBS of DS-CHD compared to DS non-CHD individuals. This supports the hypothesis that epigenetics can reflect the variability of phenotypes in DS, particularly CHDs.
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Affiliation(s)
- Julia S Mouat
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, USA
- Perinatal Origins of Disparities Center, University of California, Davis, CA, USA
- Genome Center, University of California, Davis, CA, USA
- MIND Institute, University of California, Davis, CA, USA
| | - Shaobo Li
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Swe Swe Myint
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Benjamin I Laufer
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, USA
- Perinatal Origins of Disparities Center, University of California, Davis, CA, USA
- Genome Center, University of California, Davis, CA, USA
- MIND Institute, University of California, Davis, CA, USA
| | - Philip J Lupo
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Jeremy M Schraw
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - John P Woodhouse
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Adam J de Smith
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Janine M LaSalle
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, USA.
- Perinatal Origins of Disparities Center, University of California, Davis, CA, USA.
- Genome Center, University of California, Davis, CA, USA.
- MIND Institute, University of California, Davis, CA, USA.
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Zugayar D, Berkovits R, Tenenbaum A, Erez E, Arbell D, Koplewitz BZ. Post-operative anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. Eur J Pediatr 2023; 182:4529-4535. [PMID: 37507598 DOI: 10.1007/s00431-023-05127-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 07/13/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023]
Abstract
Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in 100 children without Trisomy 21 who underwent cardiac surgery. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the control group (P = 0.0094). CONCLUSIONS A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center. WHAT IS KNOWN • Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated. WHAT IS NEW • There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed.
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Affiliation(s)
- Diaa Zugayar
- Departments of Pediatric Surgery, Hadassah Medical Center, Jerusalem, Israel
| | - Reuven Berkovits
- Departments of Pediatrics, Hadassah Medical Center, Jerusalem, Israel
| | - Ariel Tenenbaum
- Departments of Pediatrics, Hadassah Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
| | - Eldad Erez
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
- Departments of Cardiac and Chest Surgery, Hadassah Medical Center, Jerusalem, Israel
| | - Dan Arbell
- Departments of Pediatric Surgery, Hadassah Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
| | - Benjamin Z Koplewitz
- Faculty of Medicine, Hebrew University, Jerusalem, Israel.
- Departments of Diagnostic Imaging, Hadassah Medical Center, Hebrew University, POB 12000, 91000, Jerusalem, Israel.
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Huang YN, Huang JY, Wang CH, Su PH. Long-Term Non-Congenital Cardiac and Renal Complications in Down Syndrome: A Study of 32,936 Patients. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1351. [PMID: 37628350 PMCID: PMC10453106 DOI: 10.3390/children10081351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 07/27/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10-year incidence of cardiac, renal, and urinary tract complications in Down syndrome versus matched controls. METHODS This retrospective cohort study utilized a large collaborative database. We identified 32,444 patients with Down syndrome and matched controls, excluding those with pre-follow-up target events. Covariates included demographics, lifestyle factors, and comorbidities. Outcomes were ischemic heart disease, hypertension, hypothyroidism, epilepsy, urinary tract infections and chronic kidney disease. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression and plotted Kaplan-Meier survival curves. FINDINGS Over 10 years, Down syndrome patients showed a 3.7-fold higher ischemic heart disease risk (95% CI: 3.0-4.6) and a 1.6-fold higher hypertension risk (95% CI: 1.4-1.8) versus controls. Hypothyroidism (HR = 2.0; 95% CI: 1.7-2.4), epilepsy (HR = 4.5; 95% CI: 3.5-5.8), and urinary tract infection (HR = 3.9; 95% CI: 3.4-4.6) risks were also higher. Chronic kidney disease risk was 2.7-fold greater (95% CI: 2.1-3.5). Survival analysis confirmed a significantly higher incidence of all outcomes in Down syndrome (p < 0.0001). INTERPRETATION This large study found major health challenges in Down syndrome, with risks 3- to 5-fold higher for chronic conditions versus matched controls over 10 years. Though survival remains high with proper care, focusing resources on the prevention and management of complications in this high-risk group can optimize well-being across the lifespan. Future research accounting for limitations here would provide definitive estimates of disease risk in Down syndrome to guide targeted health strategies.
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Affiliation(s)
- Yu-Nan Huang
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402306, Taiwan (C.-H.W.)
- School of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan
| | - Jing-Yang Huang
- Center for Health Data Science, Chung Shan Medical University Hospital, Taichung 402306, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan
| | - Chung-Hsing Wang
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402306, Taiwan (C.-H.W.)
- School of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan
- Division of Genetics and Metabolism, Children’s Hospital of China Medical University, Taichung 404327, Taiwan
- School of Medicine, China Medical University, Taichung 404327, Taiwan
| | - Pen-Hua Su
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402306, Taiwan (C.-H.W.)
- School of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan
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15
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Briggs P, Barsoum M, Soffe K. Challenges faced by women with learning disabilities, when they reach the menopause transition. Post Reprod Health 2023; 29:113-118. [PMID: 37322002 DOI: 10.1177/20533691231179797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
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16
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Mouat JS, Li S, Myint SS, Laufer BI, Lupo PJ, Schraw JM, Woodhouse JP, de Smith AJ, LaSalle JM. Epigenomic signature of major congenital heart defects in newborns with Down syndrome. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.05.02.23289417. [PMID: 37205408 PMCID: PMC10187438 DOI: 10.1101/2023.05.02.23289417] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Background Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS) but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs. Methods We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: 1) 45 DS-CHD (27 female, 18 male) and 2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD vs DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS vs typical development (TD) WGBS NDBS samples. Results We found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3,938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percentage of CHD-associated DMRs than background regions were differentially methylated in DS vs TD samples. Conclusions A sex-specific signature of DNA methylation was detected in NDBS of DS-CHD compared to DS non-CHD individuals. This supports the hypothesis that epigenetics can reflect the variability of phenotypes in DS, particularly CHDs.
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Affiliation(s)
- Julia S Mouat
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA USA
- Perinatal Origins of Disparities Center, University of California, Davis, CA USA
- Genome Center, University of California, Davis, CA USA
- MIND Institute, University of California, Davis, CA USA
| | - Shaobo Li
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA USA
| | - Swe Swe Myint
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA USA
| | - Benjamin I Laufer
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA USA
- Perinatal Origins of Disparities Center, University of California, Davis, CA USA
- Genome Center, University of California, Davis, CA USA
- MIND Institute, University of California, Davis, CA USA
| | - Philip J Lupo
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
| | - Jeremy M Schraw
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
| | - John P Woodhouse
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
| | - Adam J de Smith
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA USA
| | - Janine M LaSalle
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA USA
- Perinatal Origins of Disparities Center, University of California, Davis, CA USA
- Genome Center, University of California, Davis, CA USA
- MIND Institute, University of California, Davis, CA USA
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17
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Arnold SH, Figueroa AA, Wiegmann AL, Lee J, Padala S, Hamati F, Hansdorfer MA, Tragos C. Long-Term Outcomes After External Maxillary Distraction Surgery in Patients With Down Syndrome. J Craniofac Surg 2023; 34:1045-1053. [PMID: 36882912 DOI: 10.1097/scs.0000000000009203] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 10/23/2022] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND Patients with Down syndrome have severe facial deformities that can precipitate functional consequences and social stigmatization. Craniofacial surgical intervention can play a role in improving these symptoms and patient quality of life. The objective of this study was to investigate the long-term outcomes of distraction osteogenesis and orthognathic surgical intervention in patients with Down syndrome. MATERIALS AND METHODS Charts of 3 patients with Down syndrome who were treated with external maxillary distraction osteogenesis were retrospectively reviewed. The patients' caregivers were prospectively interviewed between 10 and 15 years after surgery to determine surgical stability, long-term function, and quality of life status. RESULTS All patients and their caregivers reported excellent results with improvements in function and quality of life. Facial skeletal changes have been stable over time. The cephalometric analysis demonstrated significant maxillary advancement in all 3 patients and mandibular changes to correct mandibular prognathism and asymmetry in the patient who underwent finishing orthognathic surgery. CONCLUSIONS External maxillary distraction osteogenesis and orthognathic surgery may be considered in select patients with Down syndrome as part of their multidisciplinary health care. These interventions can result in long-term improvements in patient function and quality of life.
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Affiliation(s)
- Sydney H Arnold
- Department of Surgery, Division of Plastic and Reconstructive Surgery, Rush Craniofacial Center, Rush University Medical Center, Chicago, IL
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18
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King TC, Karan A, Edwards L, Jacob R. Screening Echocardiography in Adults with Down Syndrome. South Med J 2023; 116:440-442. [PMID: 37137482 DOI: 10.14423/smj.0000000000001548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Down syndrome is the most common chromosomal disorder in the United States, occurring in about 14.14/10,000 births. It is associated with multiple medical anomalies, including cardiac, gastrointestinal, musculoskeletal, and genitourinary abnormalities, which increases the burden of morbidity for this patient population. Management is typically directed toward optimizing health and function throughout childhood and into adulthood; however, consensus regarding their management in adulthood is controversial. The burden of congenital cardiac diseases in children with trisomy 21 is well established, seen in more than 40% of cases. Although screening echocardiography is performed routinely within 1 month of birth, current consensus advocates for diagnostic echocardiography only in symptomatic adults with Down syndrome. Here, we advocate that screening echocardiography should be performed routinely in this patient population at all ages, particularly in late adolescence and early adulthood, because of a high percentage of residual cardiac defects and an increased risk of developing valvular and structural cardiac disease.
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Affiliation(s)
- Thomas C King
- From the Division of General Internal Medicine, University of Florida College of Medicine, Jacksonville
| | - Abhinav Karan
- From the Division of General Internal Medicine, University of Florida College of Medicine, Jacksonville
| | - Linda Edwards
- From the Division of General Internal Medicine, University of Florida College of Medicine, Jacksonville
| | - Rafik Jacob
- From the Division of General Internal Medicine, University of Florida College of Medicine, Jacksonville
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19
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Hu H, Geng Z, Zhang S, Xu Y, Wang Q, Chen S, Zhang B, Sun K, Lu Y. Rare copy number variation analysis identifies disease-related variants in atrioventricular septal defect patients. Front Genet 2023; 14:1075349. [PMID: 36816019 PMCID: PMC9936062 DOI: 10.3389/fgene.2023.1075349] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 01/25/2023] [Indexed: 02/05/2023] Open
Abstract
Atrioventricular septal defect (AVSD) is a deleterious subtype of congenital heart diseases (CHD) characterized by atrioventricular canal defect. The pathogenic genetic changes of AVSD remain elusive, particularly for copy number variation (CNV), a large segment variation of the genome, which is one of the major forms of genetic variants resulting in congenital heart diseases. In the present study, we recruited 150 AVSD cases and 100 healthy subjects as controls for whole exome sequencing (WES). We identified total 4255 rare CNVs using exon Hidden Markov model (XHMM) and screened rare CNVs by eliminating common CNVs based on controls and Database of Genomic Variants (DGV). Each patient contained at least 9 CNVs, and the CNV burden was prominently presented in chromosomes 19,22,21&16. Small CNVs (<500 kb) were frequently observed. By leveraging gene-based burden test, we further identified 20 candidate AVSD-risk genes. Among them, DYRK1A, OBSCN and TTN were presented in the core disease network of CHD and highly and dynamically expressed in the heart during the development, which indicated they possessed the high potency to be AVSD-susceptible genes. These findings not only provided a roadmap for finally unveiling the genetic cause of AVSD, but also provided more resources and proofs for clinical genetics.
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Affiliation(s)
- Huan Hu
- Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zilong Geng
- Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shasha Zhang
- Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuejuan Xu
- Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qingjie Wang
- Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Sun Chen
- Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Bing Zhang
- Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China,*Correspondence: Bing Zhang, ; Kun Sun, ; Yanan Lu,
| | - Kun Sun
- Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,*Correspondence: Bing Zhang, ; Kun Sun, ; Yanan Lu,
| | - Yanan Lu
- Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,*Correspondence: Bing Zhang, ; Kun Sun, ; Yanan Lu,
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20
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Muacevic A, Adler JR, Alharbi AM, Al Talib SA, Sultan SM, Bahawi YO. Quality of Life Among Down Syndrome Patients With and Without Congenital Heart Disease at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Cureus 2023; 15:e33553. [PMID: 36779158 PMCID: PMC9908089 DOI: 10.7759/cureus.33553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2023] [Indexed: 01/10/2023] Open
Abstract
Background Congenital heart diseases (CHD) are common in Down syndrome patients who will often have additional anomalies, in which the presence of them and their management are expected to impact their quality of life (QoL). There are limited studies trying to evaluate the impact of CHD on the QoL in children with Down syndrome. Methods The present study comprised 97 Down syndrome children. The children's parents responded to phone interviews filling out TNO-AZL (Netherlands Organisation for Applied Scientific Research Academic Medical Centre) Preschool Quality of Life (TAPQOL) and TNO-AZL Child Quality of Life Parent Form (TACQOL-PF) questionnaires. Children were divided into two groups according to their age: group A (one to five years) and group B (six to 15 years). The results were analyzed using Statistical Package for Social Sciences (SPSS) software, version 21 (IBM Corp., Armonk, NY). Results CHD negatively affected motor skills in younger but not older children. All other QoL-related parameters were unaffected by CHD. Conclusion Down syndrome children with CHD demonstrated similar QoL to Down syndrome children without CHD, with the exception of having a lower motor outcome as infants/toddlers. This difference improved with time and did not exist in older children.
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21
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Steffensen EH, Pedersen LH, Lou S, Vogel I. Is the first-trimester combined screening result associated with the phenotype of Down syndrome? A population-based cohort study. Prenat Diagn 2023; 43:51-61. [PMID: 36471906 PMCID: PMC10108102 DOI: 10.1002/pd.6284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/19/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To investigate if the Down syndrome phenotype differs according to the result of first-trimester combined screening (FTS). METHOD We included all Down syndrome cases diagnosed by karyotype in pregnancy or after birth in Denmark during 2005-2018. We compared screen positive (odds ≥1:300) and screen negative (odds <1:300) cases as well as screen result subgroups with respect to anthropometrics, congenital malformations, childhood diseases, and hospitalization. RESULTS Absolute measures of fetal and birth anthropometrics were comparable between groups. A prenatal malformation diagnosis was more prevalent among screen positive than screen negative cases. Analyses suggested that this could reflect a detection bias. Cases with a screen result of 1:2-1:10 had a higher probability of being diagnosed with a malformation prenatally and with severe congenital heart disease (CHD) postnatally compared with a result of 1:11-1:300. Screen positive cases more often had non-severe CHD but less often a non-heart malformation compared with screen negative cases, while proportions of severe CHD were similar in these groups. Data on hospitalizations showed inconsistent results. CONCLUSION The 1:300 screening threshold had limited or no value in predicting Down syndrome phenotype severity. In contrast, cases with a screen result between 1:2 and 1:10 may represent a more severe phenotype.
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Affiliation(s)
- Ellen Hollands Steffensen
- Center for Fetal Diagnostics, Aarhus University, Aarhus, Denmark.,Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Lars Henning Pedersen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.,Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Stina Lou
- Center for Fetal Diagnostics, Aarhus University, Aarhus, Denmark.,DEFACTUM - Public Health & Health Services Research, Aarhus, Denmark
| | - Ida Vogel
- Center for Fetal Diagnostics, Aarhus University, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
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22
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Fraser HG, Krakow A, Lin A, Harris H, Andras LA, Skaggs DL, Flynn JM, Fletcher ND. Outcomes of Posterior Spinal Fusion in Pediatric Patients with Down Syndrome. J Bone Joint Surg Am 2022; 104:2068-2073. [PMID: 36166508 DOI: 10.2106/jbjs.22.00588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Trisomy 21 or Down syndrome is associated with multiple orthopaedic manifestations. Although cervical instability is the most common spinal condition associated with Down syndrome, the prevalence of scoliosis has been estimated at 4.8% to 8.7%. Very few prior studies have documented the role of spinal fusion in this population, and all have included ≤10 patients. METHODS An institutional review board-approved multicenter retrospective analysis of patients with Down syndrome treated with spinal fusion between January 2009 and December 2019 was performed by cross-referencing Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10) codes. Patients were followed for ≥2 years, with a mean follow-up of 3.77 years. Clinical and radiographic outcomes were collected, and complications were documented using the Clavien-Dindo-Sink (CDS) classification. RESULTS A total of 23 patients were included: 96% had ≥1 medical comorbidities, including 16 (70%) with congenital heart disease, of whom 88% had previous cardiac surgery, and 10 (44%) with thyroid disorders. All 23 patients underwent posterior spinal fusion. The mean estimated blood loss was 617 ± 459 mL, the mean length of the surgical procedure was 290 ± 92.7 minutes, and the mean length of hospital stay was 6.03 ± 2.91 days. The major Cobb angle measured 61.7° ± 17.6°, which corrected to 19.4° ± 14.8° (68.6% correction; p < 0.001), with well-maintained correction at 2 years of 22.0° ± 10.3° (64.3% correction; p = 0.158). Thirteen (57%) of 23 patients had a change in curve of >5°. There were no intraoperative complications; however, 12 patients (52%) sustained postoperative complications (e.g., need for reoperation, implant failure, and pulmonary complications), including 6 patients with CDS type 3 or 4 (e.g., wound dehiscence, late superficial abscess, pleural effusion, pseudarthrosis, and readmission for hypoxia). Four patients (17%) required a revision surgical procedure. One patient (4%) required an unplanned intensive care unit admission. CONCLUSIONS Although instrumented spinal fusion can effectively correct spinal deformity in these patients, complications are more frequent than in children with adolescent idiopathic scoliosis, with over half of patients sustaining a complication. LEVEL OF EVIDENCE Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Helyn G Fraser
- Department of Orthopaedic Surgery, Emory University, Atlanta, Georgia
| | - Arielle Krakow
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Adrian Lin
- Children's Hospital of Los Angeles, Los Angeles, California
| | - Hilary Harris
- Department of Orthopaedics, Children's Healthcare of Atlanta, Atlanta, Georgia
| | | | - David L Skaggs
- Children's Hospital of Los Angeles, Los Angeles, California
| | - John M Flynn
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Nicholas D Fletcher
- Department of Orthopaedics, Children's Healthcare of Atlanta, Atlanta, Georgia
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A Randomised Crossover Trial of Behaviour Guidance Techniques on Children with Special Health Care Needs during Dental Treatment: The Physiological Variations. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9101526. [PMID: 36291461 PMCID: PMC9600869 DOI: 10.3390/children9101526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 09/14/2022] [Accepted: 09/14/2022] [Indexed: 11/07/2022]
Abstract
Passive immobilisation is regarded as able to potentially cause physical distress and intense anxiety manifestations. The study aims to investigate the physiological variations of children with special health care needs while using a Papoose board and a combination of basic behaviour guidance during dental treatment. This is a randomised crossover trial involving 90 children with special health care needs receiving standard dental care with two methods of behaviour guidance sequentially. Exposure A is a combination of tell-show-do, distraction, and positive reinforcement, while exposure B is passive immobilisation with a Papoose board. The subject child’s blood pressure, heart rate, and oxygen saturation level were measured at four different times during dental treatment. In total, 74 children’s physiological data were successfully collected with a mean age of 9.85 years (SD = 2.71). Further, 64.9% of the children were diagnosed with autism spectrum disorder, 12.2% with attention deficit hyperactivity disorder, 9.5% with intellectual disability, 8.1% with Down syndrome, 2.2% with global developmental delay, and 1.1% with dyslexia and cerebral palsy, respectively. The measurement of children’s blood pressure, heart rate, and oxygen saturation level with the application of a Papoose board or a combination of the basic behaviour guidance revealed no significant changes (p > 0.05). The use of a Papoose board is safe and has no discernible influence on the child’s physiological responses.
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24
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Rehman Y, Wazir HD, Akbar A, Khan AM, Hussain I, Afridi A, Gul H, Sadia H. Congenital Heart Disease and Its Association in Children With Down Syndrome. Cureus 2022; 14:e29176. [PMID: 36258963 PMCID: PMC9568679 DOI: 10.7759/cureus.29176] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 12/02/2022] Open
Abstract
Objective The objective is to determine the frequency of different congenital heart diseases and their association in children with Down syndrome (DS). Methodology This cross-sectional observational study was conducted in the pediatric department of Peshawar Institute of Cardiology, Peshawar, Pakistan from August 2021 to July 2022. A total of 123 children with DS and congenital heart disease (CHD) were included in this cross-sectional study. Detailed history and examination were performed, and findings were documented on performed pro forma. Diagnosis of CHD was confirmed through two-dimensional (2D) and Doppler echocardiography performed by a pediatric cardiologist. Patients were managed according to standard protocols and guidelines. The data including age, gender, mother's age at the time of birth, type of CHD and growth failure were documented and analyzed. Percentages were used to express frequencies. Results The mean age was 2.2 years ± 3.4 years (interquartile range (IQR): 10 days to 14 years). There were 65 (52.8%) male and 58 (47.1%) female patients. Out of 123 patients, 101 (82.1%) had acyanotic CHD and 22 (17.8%) had cyanotic CHD. Among acyanotic CHD, isolated ventricular septal defect (VSD) was the most common observation in 23 (22.3%) and among cyanotic CHD, tetralogy of Fallot (TOF) in seven (31.8%) patients. The most common associations of CHD were VSD+ patent ductus arteriosus (PDA) in 11 (9%) patients and atrial septal defect (ASD)+PDA in nine (7.3%) patients. The median age of the mother at delivery was 31 years (interquartile range (IQR): 20 years to 45 years). Growth failure was seen in 70 (56.9%) patients. Conclusion Based on our data, VSD is the most common CHD followed by a complete atrio-VSD (CAVSD) in children with DS. The most common association of CHD in DS is VSD with PDA. Growth failure is seen in most of the patients with DS having a CHD.
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25
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Oviedo GR, Carbó-Carreté M, Guerra-Balic M, Tamulevicius N, Esquius L, Guàrdia-Olmos J, Javierre C. Hemodynamic and cardiorespiratory responses to submaximal and maximal exercise in adults with Down syndrome. Front Physiol 2022; 13:905795. [PMID: 36060693 PMCID: PMC9437284 DOI: 10.3389/fphys.2022.905795] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 06/29/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction: The genetic disorder causing Down syndrome (DS) affects the cardiorespiratory and hemodynamic parameters. When exercising, sufficient blood flow is necessary for active muscles. Cardiac output (Q) must be proportional to the peripheral requirements. In case the stroke volume (SV) is lower, the heart rate (HR) will increase further in order to maintain an adequate blood flow in the active territories (HR compensatory response). People with DS have a lower HR response to maximal exercise. Nevertheless, the response of the hemodynamic and cardiorespiratory parameters during the submaximal phases of maximal exercise was not well studied.Objective: to evaluate cardiorespiratory and hemodynamic parameters 1) during submaximal and 2) maximal metabolic treadmill test in individuals with and without DS.Methods: fifteen adults with DS (age = 27.33 ± 4.98 years old; n = 12 males/3 females) and 15 adults without disabilities, matched by age and sex, participated in this cross-sectional study. Peak and submaximal cardiorespiratory and hemodynamic parameters were measured during a treadmill test. Linear mixed-effects models were used to analyse interactions between the variables. Post-hoc analyses were employed to assess within and between-group differences.Results: The DS group showed lower peak values for ventilation (VE), respiratory exchange ratio (RER), tidal volume (VT), ventilatory equivalent for O2 (VEqO2), end-tidal partial pressure for O2 (PETO2), O2 uptake (VO2) and CO2 production (all p < 0 .050), Q, SV, systolic and diastolic blood pressure (SBP, DBP), and HR (all p < 0 .050). There were group-by-time interactions (all p < 0 .050) for all ventilatory submaximal values. Significant group and time differences were observed for VE; RER; respiratory rate (RR); VEqO2; PETO2; VO2, and VT (all p < 0 .050). There were also group-by-time interactions (all p < 0 .050) and group and time differences for SBP, mean arterial blood pressure (MAP) and HR (all p < 0.010).Conclusion: During submaximal exercise, we verified a compensatory response of HR, and greater VE and VO2 in the individuals with DS. In addition, we were able to observe that the DS group had a reduced SBP and MAP response to submaximal exercise. On the other hand, we found that adults with DS have lower peak hemodynamic and cardiorespiratory values, and a lower cardiac reserve. Further research is warranted to investigate the effects of these results on the general health of adults with DS and the impact of long-term exercise programs on these parameters.
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Affiliation(s)
- Guillermo R. Oviedo
- Faculty of Psychology, Education and Sport Science Blanquerna, University Ramon Llull, Barcelona, Spain
- School of Health Science Blanquerna, University Ramon Llull, Barcelona, Spain
- *Correspondence: Guillermo R. Oviedo,
| | - María Carbó-Carreté
- Serra Hunter Fellow, Department of Cognition, Development and Educational Psychology, Faculty of Psychology, University of Barcelona, Barcelona, Spain
- Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - Myriam Guerra-Balic
- Faculty of Psychology, Education and Sport Science Blanquerna, University Ramon Llull, Barcelona, Spain
| | - Nauris Tamulevicius
- Department of Health Sciences and Human Performance, College of Natural and Health Sciences, The University of Tampa, Tampa, FL, United States
| | - Laura Esquius
- Foodlab Research Group, Faculty of Health Sciences, Universitat Oberta de Catalunya, Barcelona, Spain
| | - Joan Guàrdia-Olmos
- Institute of Neuroscience, University of Barcelona, Barcelona, Spain
- Department of Social Psychology and Quantitative Psychology, Faculty of Psychology, University of Barcelona, Barcelona, Spain
- Universitat de Barcelona Institute of Complex Systems, Barcelona, Spain
| | - Casimiro Javierre
- Department of Physiological Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
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26
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Hines CB, Simmons SA. Down Syndrome: A Review of Key Perioperative Implications. AORN J 2022; 116:4-20. [PMID: 35758744 DOI: 10.1002/aorn.13712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/22/2021] [Accepted: 12/12/2021] [Indexed: 11/11/2022]
Abstract
Down syndrome (DS) is the most common chromosomal abnormality in humans that is compatible with life. This syndrome occurs when there is an extra copy of the 21st chromosome. Down syndrome is associated with numerous comorbidities that can pose challenges for the perioperative nurse caring for a patient with DS undergoing surgery. These challenges can affect the patient assessment, communication with the patient, and patient safety (eg, preventing complications). As the life expectancy of people with DS has increased, so too have the chances that perioperative nurses will care for a patient with this disorder. This article reviews the pathophysiology of DS, discusses common comorbidities that may directly affect perioperative care, and reviews an exemplar case study that demonstrates how personnel with knowledge of DS can positively influence surgical team decision making for these patients in the perioperative setting.
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27
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Godown J, Fountain D, Bansal N, Ameduri R, Anderson S, Beasley G, Burstein D, Knecht K, Molina K, Pye S, Richmond M, Spinner JA, Watanabe K, West S, Reinhardt Z, Scheel J, Urschel S, Villa C, Hollander SA. Heart Transplantation in Children With Down Syndrome. J Am Heart Assoc 2022; 11:e024883. [PMID: 35574952 PMCID: PMC9238550 DOI: 10.1161/jaha.121.024883] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Children with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post– HTx outcomes in children with DS. Methods and Results This is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High‐risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow‐up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS (P=non‐significant for all). Conclusions Waitlist and post‐HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.
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Affiliation(s)
- Justin Godown
- Division of Pediatric Cardiology Monroe Carell Jr. Children’s Hospital at VanderbiltNashville TN
| | - Darlene Fountain
- Division of Pediatric Cardiology Monroe Carell Jr. Children’s Hospital at VanderbiltNashville TN
| | - Neha Bansal
- Division of Pediatric Cardiology Children’s Hospital at MontefioreBronx NY
| | - Rebecca Ameduri
- Division of Pediatric Cardiology University of Minnesota Minneapolis MN
| | - Susan Anderson
- Division of Pediatric Cardiology University of Minnesota Minneapolis MN
| | - Gary Beasley
- Division of Pediatric Cardiology LeBonheur Children's HospitalMemphis TN
| | - Danielle Burstein
- Division of Pediatric Cardiology Children's Hospital of PhiladelphiaPhiladelphia PA
| | - Kenneth Knecht
- Division of Pediatric Cardiology Arkansas Children's HospitalLittle Rock AR
| | - Kimberly Molina
- Division of Pediatric Cardiology Primary Children's HospitalSalt Lake City UT
| | - Sherry Pye
- Division of Pediatric Cardiology Arkansas Children's HospitalLittle Rock AR
| | - Marc Richmond
- Division of Pediatric Cardiology Columbia University Medical Center New York NY
| | - Joseph A. Spinner
- Division of Pediatric Cardiology Texas Children's HospitalHouston TX
| | - Kae Watanabe
- Division of Pediatric Cardiology Lurie Children's HospitalChicago IL
| | - Shawn West
- Division of Pediatric Cardiology Children's Hospital of PittsburghPittsburgh PA
| | - Zdenka Reinhardt
- Division of Pediatric Cardiology Freeman Hospital The Newcastle upon TyneUnited Kingdom
| | - Janet Scheel
- Division of Pediatric Cardiology Washington University St. Louis MO
| | - Simon Urschel
- Division of Pediatric Cardiology University of Alberta Edmonton AB Canada
| | - Chet Villa
- Division of Pediatric Cardiology Cincinnati Children's Hospital Medical Center Cincinnati OH
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Esperanza RA, Evans A, Tucker D, Paranjothy S, Hurt L. Hospital admissions in infants with Down syndrome: a record-linked population-based cohort study in Wales. JOURNAL OF INTELLECTUAL DISABILITY RESEARCH : JIDR 2022; 66:225-239. [PMID: 34859911 PMCID: PMC9376940 DOI: 10.1111/jir.12903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 10/26/2021] [Accepted: 10/29/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Despite recent advances, mortality in children with Down syndrome remains five times higher than in the general population. This study aims to describe the burden, patterns and causes of hospital admissions in infants with Down syndrome, and compare this with infants without Down syndrome in a population-based cohort. METHODS This study used data from the Wales Electronic Cohort for Children, a cohort of all children born in Wales between 1990 and 2012. The cohort was generated from routine administrative data, linked to create an anonymised data set within the Secure Anonymised Information Linkage databank. This analysis is based on all infants born between January 2003 and January 2012 who were followed to their first birthday, a move out of Wales, death, or until 31 October 2012 (end of follow-up). Infants with Down syndrome were identified using the Congenital Anomaly Register and Information Service in Wales. Multivariable Cox regression was used to compare the time to first hospital admission. Admission codes were used to identify the commonest indications for hospitalisation and to determine the presence of other congenital anomalies. RESULTS We included 324 060 children, 356 of whom had Down syndrome. Of infants with Down syndrome, 80.3% had at least one hospital inpatient admission during the first year of life, compared with 32.9% of infants without Down syndrome. These first admissions were earlier [median of 6 days interquartile range (IQR) (3, 72) compared with 45 days [IQR 6, 166)] and longer [median of 4 days (IQR 1, 15) compared with 1 day (IQR 0, 3)] than in infants without Down syndrome. The most common causes of admissions were congenital abnormalities, respiratory diseases, conditions originating in the perinatal period and infectious diseases. The presence of other congenital abnormalities increased hospitalisations in all infants, but more so in infants with Down syndrome who spent a median of 21 days in hospital (IQR 11, 47) during their first year of life. CONCLUSION Infants with Down syndrome are at high risk for early, more frequent and longer hospital admissions. Congenital heart disease and respiratory infections remain a major burden in this population. More research is needed to understand how to better manage these conditions particularly in the first month of life when most admissions occur.
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Affiliation(s)
- R. A. Esperanza
- School of MedicineCardiff UniversityCardiffUK
- Cwm Taf Morgannwg University Health BoardMerthyr TydfilUK
| | - A. Evans
- Division of Population Medicine, School of MedicineCardiff UniversityCardiffUK
| | - D. Tucker
- Congenital Anomaly Register and Information ServicePublic Health WalesSwanseaUK
| | - S. Paranjothy
- Division of Population Medicine, School of MedicineCardiff UniversityCardiffUK
- Centre for Health Data ScienceUniversity of AberdeenAberdeenUK
| | - L. Hurt
- Division of Population Medicine, School of MedicineCardiff UniversityCardiffUK
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29
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Motegi N, Yamaoka Y, Moriichi A, Morisaki N. Causes of death in patients with Down syndrome in 2014-2016: A population study in Japan. Am J Med Genet A 2021; 188:224-236. [PMID: 34622557 PMCID: PMC9292866 DOI: 10.1002/ajmg.a.62526] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 07/28/2021] [Accepted: 09/18/2021] [Indexed: 11/06/2022]
Abstract
Despite the higher mortality rates in patients with Down syndrome compared with the general Japanese population, the life span has dramatically increased in Japan and other countries. We aimed to clarify recent causes of death in patients with Down syndrome in Japan. We calculated proportionate mortality and standardized mortality odds ratios (SMORs) among all deaths registered with Down syndrome as the cause of death (ICD‐10 code, Q90) in the Japanese National Death Registry Database in 2014–2016. In the study period, 762 in patients with Down syndrome died. The main causes of death were pneumonia/respiratory infections (20.5%), congenital malformations of the circulatory system (11.2%), other diseases of the circulatory system (9.2%), and aspiration pneumonia (8.4%). The SMORs (95% confidence intervals) were higher for natural death, defined as death of an elderly person with no other cause of death to be mentioned (55.73 [36.92–84.12]), early‐onset Alzheimer's disease, defined as Alzheimer's disease with onset <65 years of age (29.36 [16.44–52.44]), aspiration pneumonia (18.33 [14.03–23.96]), pneumonia/respiratory infections (8.11 [6.76–9.73]), congenital malformations of the circulatory system (8.07 [5.98–10.88]), and leukemia/lymphoma (2.16 [1.55–2.99]) but lower for malignant solid tumors (0.04 [0.02–0.06]) in patients with Down syndrome. Patients with Down syndrome had the greatest relative risk of dying from natural death, early‐onset Alzheimer's disease, and respiratory illnesses, highlighting the need for appropriate medical, health, and welfare services.
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Affiliation(s)
- Narumi Motegi
- Department of Specific Pediatric Chronic Disease Information, National Center for Child Health and Development, Tokyo, Japan.,Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University, Kyoto, Japan
| | - Yui Yamaoka
- Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
| | - Akinori Moriichi
- Department of Specific Pediatric Chronic Disease Information, National Center for Child Health and Development, Tokyo, Japan
| | - Naho Morisaki
- Department of Social Medicine, National Center for Child Health and Development, Tokyo, Japan
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30
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Liao P, Vajdic C, Trollor J, Reppermund S. Prevalence and incidence of physical health conditions in people with intellectual disability - a systematic review. PLoS One 2021; 16:e0256294. [PMID: 34428249 PMCID: PMC8384165 DOI: 10.1371/journal.pone.0256294] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 08/03/2021] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVE To synthesize evidence on the prevalence and incidence of physical health conditions in people with intellectual disability (ID). METHODS We searched Medline, PsycInfo, and Embase for eligible studies and extracted the prevalence, incidence, and risk of physical health conditions in people with ID. RESULTS Of 131 eligible studies, we synthesized results from 77 moderate- to high-quality studies, which was mainly limited to high-income countries. The highest prevalence estimates were observed for epilepsy, ear and eye disorders, cerebral palsy, obesity, osteoporosis, congenital heart defects, and thyroid disorders. Some conditions were more common in people with a genetic syndrome. Compared with the general population, many health conditions occur more frequently among people with ID, including asthma and diabetes, while some conditions such as non-congenital circulatory diseases and solid cancers occur at the same or lower rate. The latter associations may reflect under-detection. CONCLUSIONS People with ID have a health profile more complex than previously known. There is a pressing need for targeted, evidence-informed population health initiatives including preventative programs for this population.
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Affiliation(s)
- Peiwen Liao
- Department of Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia
| | - Claire Vajdic
- Centre for Big Data Research in Health, University of New South Wales, Sydney, Australia
| | - Julian Trollor
- Department of Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia
| | - Simone Reppermund
- Department of Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia
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31
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Naumova OY, Lipschutz R, Rychkov SY, Zhukova OV, Grigorenko EL. DNA Methylation Alterations in Blood Cells of Toddlers with Down Syndrome. Genes (Basel) 2021; 12:genes12081115. [PMID: 34440289 PMCID: PMC8391316 DOI: 10.3390/genes12081115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/15/2021] [Accepted: 07/20/2021] [Indexed: 11/16/2022] Open
Abstract
Recent research has provided evidence on genome-wide alterations in DNA methylation patterns due to trisomy 21, which have been detected in various tissues of individuals with Down syndrome (DS) across different developmental stages. Here, we report new data on the systematic genome-wide DNA methylation perturbations in blood cells of individuals with DS from a previously understudied age group—young children. We show that the study findings are highly consistent with those from the prior literature. In addition, utilizing relevant published data from two other developmental stages, neonatal and adult, we track a quasi-longitudinal trend in the DS-associated DNA methylation patterns as a systematic epigenomic destabilization with age.
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Affiliation(s)
- Oxana Yu. Naumova
- Vavilov Institute of General Genetics RAS, 119991 Moscow, Russia; (S.Y.R.); (O.V.Z.)
- Department of Psychology, University of Houston, Houston, TX 77204, USA;
- Correspondence: or (O.Y.N.); (E.L.G.)
| | - Rebecca Lipschutz
- Department of Psychology, University of Houston, Houston, TX 77204, USA;
| | - Sergey Yu. Rychkov
- Vavilov Institute of General Genetics RAS, 119991 Moscow, Russia; (S.Y.R.); (O.V.Z.)
| | - Olga V. Zhukova
- Vavilov Institute of General Genetics RAS, 119991 Moscow, Russia; (S.Y.R.); (O.V.Z.)
| | - Elena L. Grigorenko
- Department of Psychology, University of Houston, Houston, TX 77204, USA;
- Department of Psychology, Saint-Petersburg State University, 199034 Saint Petersburg, Russia
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Correspondence: or (O.Y.N.); (E.L.G.)
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32
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Castillo Lam JE, Elías Adauto OE, Huamán Benancio GP. [Congenital heart disease associated with the most prevalent chromosomal syndromes: a literature review]. ARCHIVOS PERUANOS DE CARDIOLOGIA Y CIRUGIA CARDIOVASCULAR 2021; 2:187-195. [PMID: 37727523 PMCID: PMC10506540 DOI: 10.47487/apcyccv.v2i3.155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 09/25/2021] [Indexed: 09/21/2023]
Abstract
Most frequent chromosomal syndromes like Down, Patau, Edwards, Turner, and Williams affect the pediatric population in various ways, and congenital heart disease explains the altered quality of life they suffer. There is a lack of studies reviewing the cardiac anomalies in these syndromes, and the ones that exist are publications from past decades. We reviewed databases such as MEDLINE, LILACS, SCIELO, and Google Scholar, selecting the best possible evidence, and each chromosomal syndrome was investigated in relation to congenital heart disease, constituting five search groups. The article shows the characteristics of each heart disease described in the studies reviewed, the author, date of publication, country, and population studied, as well as a brief description of the frequency of the disease and its mortality. The results described in this review were contrasted with previous existing literature to verify if there was correspondence between the reported frequencies. The most frequent congenital heart diseases were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), atrial septal defect (ASD), and persistent ductus arteriosus (PDA) in Down syndrome patients, PDA, ASD, and VSD in Patau syndrome patients, AVSD, PDA and valvular defects in Edwards syndrome, bicuspid aortic valve, aortic coarctation and aortic stenosis in Turner syndrome, and supravalvular aortic stenosis and pulmonary stenosis in Williams syndrome.
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Affiliation(s)
- José Eduardo Castillo Lam
- Universidad Peruana Cayetano Heredia. Lima, PerúUniversidad Peruana Cayetano HerediaUniversidad Peruana Cayetano HerediaLimaPeru
| | - Oscar Eduardo Elías Adauto
- Universidad Peruana Cayetano Heredia. Lima, PerúUniversidad Peruana Cayetano HerediaUniversidad Peruana Cayetano HerediaLimaPeru
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33
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Malinzak EB. Perioperative care of adults with Down syndrome: a narrative review. Can J Anaesth 2021; 68:1549-1561. [PMID: 34165727 DOI: 10.1007/s12630-021-02052-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/12/2021] [Accepted: 05/12/2021] [Indexed: 10/21/2022] Open
Abstract
Because of enhanced life expectancy due to medical and surgical therapeutic advances, it is estimated that there are more adults than children living with Down syndrome (DS), or trisomy 21, in the United States. Therefore, DS can no longer be considered a syndrome limited to the pediatric population. These patients are presenting for surgery and anesthesia in adult care settings, where anesthesiologists will encounter these patients more frequently. As these patients age, their commonly associated co-morbidities not only progress, but they also develop other cardiac, respiratory, gastrointestinal, and neurologic conditions. The manifestations and consequences of chronic disease can present new challenges for the anesthesiologist and require expertise and judgement to minimize patient risk. The purpose of this narrative review is to describe the common pediatric co-morbidities associated with DS and discuss the age-acquired manifestations. Additionally, considerations for anesthetic care of the adult with DS will be presented, including the preoperative assessment, intraoperative management, and postoperative care.
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Affiliation(s)
- Elizabeth B Malinzak
- Department of Anesthesiology, Duke University School of Medicine, DUMC 3094, Durham, NC, 27710, USA.
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34
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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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Delany DR, Gaydos SS, Romeo DA, Henderson HT, Fogg KL, McKeta AS, Kavarana MN, Costello JM. Down syndrome and congenital heart disease: perioperative planning and management. JOURNAL OF CONGENITAL CARDIOLOGY 2021. [PMCID: PMC8056195 DOI: 10.1186/s40949-021-00061-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Approximately 50% of newborns with Down syndrome have congenital heart disease. Non-cardiac comorbidities may also be present. Many of the principles and strategies of perioperative evaluation and management for patients with congenital heart disease apply to those with Down syndrome. Nevertheless, careful planning for cardiac surgery is required, evaluating for both cardiac and noncardiac disease, with careful consideration of the risk for pulmonary hypertension. In this manuscript, for children with Down syndrome and hemodynamically significant congenital heart disease, we will summarize the epidemiology of heart defects that warrant intervention. We will review perioperative planning for this unique population, including anesthetic considerations, common postoperative issues, nutritional strategies, and discharge planning. Special considerations for single ventricle palliation and heart transplantation evaluation will also be discussed. Overall, the risk of mortality with cardiac surgery in pediatric patients with Down syndrome is no more than the general population, except for those with functional single ventricle heart defects. Underlying comorbidities may contribute to postoperative complications and increased length of stay. A strong understanding of cardiac and non-cardiac considerations in children with Down syndrome will help clinicians optimize perioperative care and long-term outcomes.
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Peterson JK, Kochilas LK, Knight J, McCracken C, Thomas AS, Moller JH, Setty SP. Long-Term Survival and Causes of Death in Children with Trisomy 21 After Congenital Heart Surgery. J Pediatr 2021; 231:246-253.e3. [PMID: 33359302 PMCID: PMC8005470 DOI: 10.1016/j.jpeds.2020.12.058] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 12/12/2020] [Accepted: 12/17/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To evaluate long-term transplant-free survival and causes of death in the trisomy 21 (T21) population after surgery for congenital heart disease (CHD) in comparison with patients who are euploidic. STUDY DESIGN This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, enriched with prospectively collected data from the National Death Index and the Organ Procurement and Transplantation Network for patients with sufficient direct identifiers. Kaplan-Meier survival plots were generated and multivariable Cox proportional hazards models were used to examine risk factors for mortality between patients with T21 and 1:1 matched patients with comparable CHD who are euploidic. RESULTS A long-term survival analysis was completed for 3376 patients with T21 (75 155 person-years) who met inclusion criteria. The 30-year survival rate for patients with T21 ranged from 92.1% for ventricular septal defect to 65.3% for complex common atrioventricular canal. Of these, 2185 patients with T21 were successfully matched with a patient who was euploidic. After a median follow-up of 22.86 years (IQR, 19.45-27.14 years), 213 deaths occurred in the T21 group (9.7%) compared with 123 (5.6%) in the euploidic comparators. After adjustment for age, sex, era, CHD complexity, and initial palliation, the hazard ratio of CHD-related mortality was 1.34 times higher in patients with T21 (95% CI, 0.92-1.97; P = .127). CONCLUSIONS CHD-related mortality for patients with T21 after cardiac surgical intervention is comparable with euploidic comparators. Children with T21 require lifelong surveillance for co-occurring conditions associated with their chromosomal abnormality.
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Affiliation(s)
- Jennifer K. Peterson
- Johns Hopkins University School of Nursing, 525 North Wolfe Street, Baltimore, MD 21205
| | - Lazaros K. Kochilas
- Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322,Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322
| | - Jessica Knight
- Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, 101 Buck Road, Athens, GA 30602
| | - Courtney McCracken
- Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322
| | - Amanda S. Thomas
- Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322
| | - James H. Moller
- Departments of Pediatrics and Medicine, University of Minnesota, 420 Delaware St SE, MMC 508, Minneapolis, MN 55455
| | - Shaun P. Setty
- Long Beach Memorial Heart and Vascular Institute, 2801 Atlantic Avenue, Long Beach, CA 90806,Children’s Heart Institute, MemorialCare Miller Children’s and Women’s Hospital, 2801 Atlantic Avenue, Long Beach, CA 90806
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Alhuzaimi AN, Alotaibi NM, Alsuhaibani GI, Alanazi RK, Temsah MH. Congenital Heart Defect and Pulmonary Hypertension in Children With Down Syndrome: Clinical Profile Over Two Decades. Cureus 2021; 13:e13212. [PMID: 33585145 PMCID: PMC7872499 DOI: 10.7759/cureus.13212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Objectives: To describe the frequency and spectrum of congenital heart defects (CHD) and pulmonary hypertension among pediatric patients with Down syndrome (DS) in Saudi Arabia. Methods: A cross-sectional, retrospective study of the cardiac anomalies among pediatric patients (0-18 years) with DS had been seen and evaluated in one center from August 2001 to October 2020. The demographic data, the reason for referral, echocardiography data including presence and type of CHD, systolic function, atrioventricular regurgitation, and pulmonary hypertension (PHTN) were analyzed. Results: Among the 468 pediatric patients with DS, 275 (58.8%) had one or more congenital heart defects (CHD). The most common types of CHD among DS pediatric patients were ventricular septal defect (29.45%), atrial septal defect (ASD) secundum (26.9%) and atrioventricular septal defect (AVSD) (22.9%), and moderate to large patent ductus arteriosus (PDA) (9.1%). Pulmonary hypertension analyzed in children older than two months of age and was present in 21.5% of patients with CHD and 2.2% of patients with no CHD. Multivariate logistic regression showed the presence of AVSD, large PDA, and ASD secundum which all independent predictors of pulmonary hypertension. Conclusion: Almost 60% of DS patients have CHD with pulmonary hypertension which affect almost one-fifth of patients with CHD. AVSD, hemodynamically significant PDA, and ASD secundum were the most common lesions associated with pulmonary hypertension.
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Affiliation(s)
- Abdullah N Alhuzaimi
- Pediatric Cardiology, Department of Cardiac Science, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Najoud M Alotaibi
- Pediatric Cardiology, Department of Cardiac Science, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Ghadah I Alsuhaibani
- Pediatric Cardiology, Department of Cardiac Science, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Reem K Alanazi
- Pediatric Cardiology, Department of Cardiac Science, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Mohamad-Hani Temsah
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, SAU
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Valentini D, Di Camillo C, Mirante N, Vallogini G, Olivini N, Baban A, Buzzonetti L, Galeotti A, Raponi M, Villani A. Medical conditions of children and young people with Down syndrome. JOURNAL OF INTELLECTUAL DISABILITY RESEARCH : JIDR 2021; 65:199-209. [PMID: 33426738 DOI: 10.1111/jir.12804] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 09/29/2020] [Accepted: 11/21/2020] [Indexed: 06/12/2023]
Abstract
BACKGROUND The life expectancy of people with Down syndrome (DS) has significantly increased in the last decades. We describe the congenital malformations and main comorbidities of a cohort of children and young people with DS and analyse their differences according to age and gender groups. METHODS This retrospective cross-sectional study was conducted at DS centre of Bambino Gesù Children's Hospital in Rome (Italy). The period for reviewing all electronic health records ran from July 2016 to September 2017. We collected data on clinical conditions and compared them with the general paediatric population. Moreover, we compared the main comorbidities, dental diseases and body mass index data between age groups. RESULTS Seven hundred sixty-three children and young people with DS included in this study were aged 7.45 ± 5.49 years. Gender distribution included 58.19% male patients. The majority of our population (71.04%) came from central regions of Italy. Respiratory diseases (19%), congenital heart defects (72.23%), malocclusions (58.62%), astigmatism (20.31%), farsightedness (16.51%), near-sightedness (12.19%) and autoimmune hypothyroidism (3.28%) were more frequent in our population compared with the typical paediatric population. Upper respiratory tract infections and underweight were significantly more frequent in the youngest children, whereas dental diseases, refractive errors, obesity and autoimmune hypothyroidism increased over age. CONCLUSIONS Children and young people with DS present a high prevalence of potentially treatable medical conditions making multidisciplinary teams a mandatory need for this population.
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Affiliation(s)
- D Valentini
- Pediatric Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - C Di Camillo
- Pediatric Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - N Mirante
- Pediatric Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - G Vallogini
- Unit of Dentistry, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - N Olivini
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart - ERN GUARD-Heart HCP, Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children Hospital-IRCCS, Rome, Italy
| | - A Baban
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart - ERN GUARD-Heart HCP, Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children Hospital-IRCCS, Rome, Italy
| | - L Buzzonetti
- Department of Ophthalmology, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - A Galeotti
- Unit of Dentistry, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - M Raponi
- Medical Directorate, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - A Villani
- Pediatric Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
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39
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Santoro SL, Steffensen EH. Congenital heart disease in Down syndrome – A review of temporal changes. JOURNAL OF CONGENITAL CARDIOLOGY 2021. [DOI: 10.1186/s40949-020-00055-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Abstract
Background
Congenital heart disease (CHD) is a well-known co-occurring condition in Down syndrome (DS). We aimed to review the literature to evaluate the current evidence to address key questions.
Methods
A series of key questions were formulated a priori to inform the search strategy and review process. These addressed the topics of prevalence, type of CHD, severity, and screening. Using the National Library of Medicine database, PubMed, detailed literature searches were performed. The quality of available evidence was then evaluated, the existing literature was summarized, and knowledge gaps were identified.
Results
Fifty-six relevant original articles were identified which addressed at least one key question. Study details, including: research design, internal validity, external validity, and relevant results are presented. The total prevalence of CHD reported in DS ranged from 20 to 57.9%. In later decades, the prevalence remained constant at 40—55%. The types and classification of CHD varied considerably between studies. Some studies indicate a trend towards a milder phenotype, but this was not consistent. Over time, some studies observed an improved prognosis for CHD in DS. Studies investigating screening for CHD by physical examination, chest X-ray, and electrocardiogram report sensitivities of 71–95%.
Conclusion
To further improve knowledge on CHD in DS, we suggest that future studies cover a wide range of nations and regions, with a longitudinal design, and account for potential confounding factors.
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40
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Motegi N, Morisaki N, Suto M, Tamai H, Mori R, Nakayama T. Secular trends in longevity among people with Down syndrome in Japan, 1995-2016. Pediatr Int 2021; 63:94-101. [PMID: 32567109 DOI: 10.1111/ped.14354] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 05/21/2020] [Accepted: 06/11/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Life expectancy in Japan has increased dramatically and is one of the longest in the world. However, the changes in lifespan in Japanese individuals with congenital diseases remain unknown. We investigated secular changes in the lifespan of people with Down syndrome over the last 20 years. METHODS We observed secular trends in the number of stillbirths, deaths and the mortality rates at ages 20, 40, and 60 among all deaths registered with Down syndrome as the cause of death (ICD10 code: Q90) in the Japan national death registry database between 1995 and 2016. Changes in the median age at death between 1995-2005 and 2006-2016 were investigated based on sex and history of surgery. RESULTS We identified 240 stillbirths and 1,099 deaths in this period. The annual number of stillbirths and deaths above the age of 1 year increased, whereas the number of deaths below 1 year did not change. The proportional mortality indicator at ages 20, 40, and 60 increased from 21.7%, 11.7%, and 1.7% in 1995 to 69.9%, 66.7%, and 36.6% in 2016, respectively. The median age at death was higher in females, individuals without a surgical history, and deaths occurring in 2006-2016. The median age at death increased over the period in those without a surgical history. CONCLUSIONS The age at death among people with Down syndrome has increased over the last 20 years, with currently 1 in 3 persons living over 60 years, necessitating adequate social welfare services in this aging population.
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Affiliation(s)
- Narumi Motegi
- Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University, Kyoto, Japan
- Department of Social Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
| | - Naho Morisaki
- Department of Social Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
| | - Maiko Suto
- Department of Health Policy, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
| | - Hiroshi Tamai
- Department of Pediatrics, Osaka Medical College, Kyoto, Japan
| | - Rintaro Mori
- Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takeo Nakayama
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
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Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes. Genes (Basel) 2020; 11:genes11121428. [PMID: 33260695 PMCID: PMC7761327 DOI: 10.3390/genes11121428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/26/2020] [Accepted: 11/26/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Congenital heart defects (CHDs) are present in about 40-60% of newborns with Down syndrome (DS). Patients with DS can also develop acquired cardiac disorders. Mouse models suggest that a critical 3.7 Mb region located on human chromosome 21 (HSA21) could explain the association with CHDs. This region includes a cluster of genes (IFNAR1, IFNAR2, IFNGR2, IL10RB) encoding for interferon receptors (IFN-Rs). Other genes located on different chromosomes, such as the vascular endothelial growth factor A (VEGFA), have been shown to be involved in cardiac defects. So, we investigated the association between single nucleotide polymorphisms (SNPs) in IFNAR2, IFNGR2, IL10RB and VEGFA genes, and the presence of CHDs or acquired cardiac defects in patients with DS. METHODS Individuals (n = 102) with DS, and age- and gender-matched controls (n = 96), were genotyped for four SNPs (rs2229207, rs2834213, rs2834167 and rs3025039) using KASPar assays. RESULTS We found that the IFNGR2 rs2834213 G homozygous genotype and IL10RB rs2834167G-positive genotypes were more common in patients with DSand significantly associated with heart disorders, while VEGFA rs3025039T-positive genotypes (T/*) were less prevalent in patients with CHDs. CONCLUSIONS We identified some candidate risk SNPs for CHDs and acquired heart defects in DS. Our data suggest that a complex architecture of risk alleles with interplay effects may contribute to the high variability of DS phenotypes.
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Chen A, Ahmad M, Flescher A, Freeman WL, Little S, Martins PN, Veatch RM, Wightman A, Ladin K. Access to transplantation for persons with intellectual disability: Strategies for nondiscrimination. Am J Transplant 2020; 20:2009-2016. [PMID: 31873978 DOI: 10.1111/ajt.15755] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 11/21/2019] [Accepted: 12/14/2019] [Indexed: 01/25/2023]
Abstract
Disqualifying patients with intellectual disabilities (ID) from transplantation has received growing attention from the media, state legislatures, the Office of Civil Rights, and recently the National Council on Disability, as well as internationally. Compared with evidence-based criteria used to determine transplant eligibility, the ID criterion remains controversial because of its potential to be discriminatory, subjective, and because its relationship to outcomes is uncertain. Use of ID in determining transplant candidacy may stem partly from perceived worse adherence and outcomes for patients with ID, fear of penalties to transplant centers for poor outcomes, and stigma surrounding the quality of life for people with ID. However, using ID as a contraindication to solid organ transplantation is not evidence-based and reduces equitable access to transplantation, disadvantaging an already vulnerable population. Variability and lack of transparency in referral and evaluation allows for gatekeeping, threatens patient autonomy, limits access to lifesaving treatment, and may be seen as unfair. We examine the benefits and harms of using ID as a transplant eligibility criterion, review current clinical evidence and ethical considerations, and make recommendations for transplant teams and regulatory agencies to ensure fair access to transplant for individuals with ID.
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Affiliation(s)
- Ashton Chen
- Department of Pediatrics, Wake Forest University Medical School, Winston-Salem, North Carolina, USA
| | - Mahwish Ahmad
- Center for Bioethics, Cleveland Clinic, Cleveland, Ohio, USA.,Department of Bioethics, Case Western Reserve School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Andrew Flescher
- Program in Public Health, Department of Family, Population, and Preventive Medicine, Stony Brook University, Stony Brook, New York, USA
| | | | | | - Paulo N Martins
- Department of Surgery, Division of Transplantation, University of Massachusetts, Worcester, Massachusetts, USA
| | - Robert M Veatch
- Kennedy Institute of Ethics, Georgetown University, District of Columbia, Washington, USA
| | - Aaron Wightman
- Divisions of Nephrology and Bioethics and Palliative Care, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, Washington, USA
| | - Keren Ladin
- Departments of Occupational Therapy and Community Health, Tufts University, Medford, Massachusetts, USA
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Finnerty DT, Griffin M. Recent Developments in Cardiology Procedures for Adult Congenital Heart Disease: The Anesthesiologist's Perspective. J Cardiothorac Vasc Anesth 2020; 35:741-751. [PMID: 32762881 DOI: 10.1053/j.jvca.2020.07.037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/27/2020] [Accepted: 07/09/2020] [Indexed: 12/17/2022]
Abstract
Many children born today with congenital heart disease can expect to live long into adulthood. Improvements in surgical technique and anesthetic and perioperative care have significantly increased the number of survivors. Unfortunately, as these patients progress through life they frequently require further interventions. Although surgical intervention may be required frequently, these patients can be managed in the cardiac catheterization or electrophysiology laboratory. Surgical correction of tetralogy of Fallot can leave patients with pulmonary valve dysfunction later in life. A percutaneous approach is now available for these patients, which can obviate the need for resternotomy. During deployment of the valve, anesthesiologists should be aware that compression of coronary arteries can occur. Adult congenital heart disease (ACHD) patients often require pacemaker/implantable cardioverter- defibrillator (ICD) insertion or ablation therapy. These patients may have altered cardiac anatomy, which can make endovascular procedures extremely challenging. Recent developments have made these procedures safer and more efficient. A number of congenital cardiac conditions can also be associated with orofacial abnormalities. ACHD patients, as a result, can present with challenging airways. The catheterization laboratory may not be the optimum environment for the anesthesiologist to manage a difficult airway. The requirement of transesophageal echocardiography for some cath eterization procedures needs to be considered when deciding on an airway management plan. Knowledge of the underlying cardiac anatomy and the planned procedure is advised when providing anesthesia for this complex patient group outside the theater setting.
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Affiliation(s)
- Dylan T Finnerty
- Division of Anesthesiology, Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine, University College Dublin, Dublin, Ireland.
| | - Michael Griffin
- Division of Anesthesiology, Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine, University College Dublin, Dublin, Ireland
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Dhillon GS, Ghanayem NS, Broda CR, Lalani SR, Mery CM, Shekerdemian LS, Staffa SJ, Morris SA. An Analysis of Hospital Mortality After Cardiac Operations in Children With Down Syndrome. Semin Thorac Cardiovasc Surg 2020; 32:947-957. [PMID: 32621963 DOI: 10.1053/j.semtcvs.2020.06.037] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 06/27/2020] [Indexed: 11/11/2022]
Abstract
Children with Down syndrome (DS) have lower mortality compared to nonsyndromic (NS) children after atrioventricular septal defect (AVSD) repair. Limited data exist regarding hospital mortality and utilization after other congenital heart disease (CHD) operations in DS. We compared hospital mortality and utilization after CHD operations in both populations and hypothesized that the survival benefit in children with DS is not consistent across CHD lesions. The Texas Inpatient Public Use Datafile was queried for all patients <18 years old undergoing operations for CHD between 1999 and 2016. Hospital mortality, length-of-stay and charges were compared between DS and NS groups, stratified by CHD operation using mixed-effects multivariable analyses and propensity score matching analyses adjusting for prematurity, low birth weight, age, and sex. Over the 18-year period, 2841 cases with DS underwent CHD operations compared to 25,063 NS cases. The most common types of interventions performed in DS were AVSD repair, isolated ventricular septal defect (VSD) repair and tetralogy of Fallot (TOF) repair. By multivariable analyses, DS was associated with lower mortality after isolated AVSD repair (RR 0.40 [IQR 0.20-0.79]), and higher hospital mortality after bidirectional Glenn anastomosis (BDG) (RR 5.17 [IQR 2.10-12.77]) and TOF/pulmonary atresia repair (RR 9.71 [IQR 2.16-43.68]) compared to NS children. Similar results were noted using propensity score matching. Children with DS had lower mortality after AVSD repair than NS children, but higher mortality after operations for BDG and TOF/pulmonary atresia. Further study is needed to determine if the presence of pulmonary hypertension in DS modifies the association between DS and mortality depending on cardiac lesion.
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Affiliation(s)
- Gurpreet S Dhillon
- Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts.
| | - Nancy S Ghanayem
- Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
| | - Christopher R Broda
- Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
| | - Seema R Lalani
- Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
| | - Carlos M Mery
- Texas Center for Pediatric and Congenital Heart Disease, University of Texas Dell Medical School and Dell Children's Medical Center, Austin, Texas
| | - Lara S Shekerdemian
- Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
| | - Steven J Staffa
- Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts
| | - Shaine A Morris
- Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas
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45
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Baban A, Olivini N, Cantarutti N, Calì F, Vitello C, Valentini D, Adorisio R, Calcagni G, Alesi V, Di Mambro C, Villani A, Dallapiccola B, Digilio MC, Marino B, Carotti A, Drago F. Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect. Am J Med Genet A 2020; 182:1342-1350. [PMID: 32319738 DOI: 10.1002/ajmg.a.61586] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 02/24/2020] [Accepted: 03/16/2020] [Indexed: 12/19/2022]
Abstract
Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single-center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all-cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan-Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients.
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Affiliation(s)
- Anwar Baban
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Nicole Olivini
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Nicoletta Cantarutti
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Federica Calì
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Carmen Vitello
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Diletta Valentini
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Rachele Adorisio
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Giulio Calcagni
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Viola Alesi
- Medical Genetics Unit, Medical Genetics Laboratory, Pediatric Cardiology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Corrado Di Mambro
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Alberto Villani
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Bruno Dallapiccola
- Scientific Directorate, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Maria Cristina Digilio
- Medical Genetics Unit, Medical Genetics Laboratory, Pediatric Cardiology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Bruno Marino
- Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Adriano Carotti
- Pediatric Cardiac Surgery Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Fabrizio Drago
- Pediatric Cardiology and Cardiac Arrhythmias Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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46
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LaCombe JM, Roper RJ. Skeletal dynamics of Down syndrome: A developing perspective. Bone 2020; 133:115215. [PMID: 31887437 PMCID: PMC7044033 DOI: 10.1016/j.bone.2019.115215] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 12/05/2019] [Accepted: 12/24/2019] [Indexed: 01/14/2023]
Abstract
Individuals with Down syndrome (DS) display distinctive skeletal morphology compared to the general population, but disparate descriptions, methodologies, analyses, and populations sampled have led to diverging conclusions about this unique skeletal phenotype. As individuals with DS are living longer, they may be at a higher risk of aging disorders such as osteoporosis and increased fracture risk. Sexual dimorphism has been suggested between males and females with DS in which males, not females, experience an earlier decline in bone mineral density (BMD). Unfortunately, studies focusing on skeletal health related to Trisomy 21 (Ts21) are few in number and often too underpowered to answer questions about skeletal development, resultant osteoporosis, and sexual dimorphism, especially in stages of bone accrual. Further confounding the field are the varied methods of bone imaging, analysis, and data interpretation. This review takes a critical look at the current knowledge of DS skeletal phenotypes, both from human and mouse studies, and presents knowledge gaps that need to be addressed, differences in research methodologies and analyses that affect the interpretation of results, and proposes guidelines for overcoming obstacles to understand skeletal traits associated with DS. By examining our current knowledge of bone in individuals with Ts21, a trajectory for future studies may be established to provide meaningful solutions for understanding the development of and improving skeletal structures in individuals with and without DS.
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Affiliation(s)
- Jonathan M LaCombe
- Department of Biology, Indiana University-Purdue University Indianapolis, United States of America
| | - Randall J Roper
- Department of Biology, Indiana University-Purdue University Indianapolis, United States of America.
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Zahari N, Mat Bah MN, A Razak H, Thong MK. Ten-year trend in prevalence and outcome of Down syndrome with congenital heart disease in a middle-income country. Eur J Pediatr 2019; 178:1267-1274. [PMID: 31222391 DOI: 10.1007/s00431-019-03403-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 05/17/2019] [Accepted: 05/29/2019] [Indexed: 01/02/2023]
Abstract
Limited data are available on the survival of patients with Down syndrome and congenital heart disease (CHD) from middle-income countries. This retrospective cohort study was performed to determine the trends in the prevalence and survival of such patients born from January 2006 to December 2015 in Malaysia. Among 754 patients with Down syndrome, 414 (55%) had CHD, and no significant trend was observed during the 10 years. Of these 414 patients, 30% had lesions that closed spontaneously, 35% underwent surgery/intervention, 9% died before surgery/intervention, and 10% were treated with comfort care. The overall mortality rate was 23%, the median age at death was 7.6 months, and no significant changes occurred over time. The early and late post-surgery/intervention mortality rates were 0.7% and 9.0%, respectively. Most deaths were of non-cardiac causes. The overall 1-, 5-, and 10-year survival rates were 85.5%, 74.6%, and 72.9%, respectively. Patients with severe lesions, persistent pulmonary hypertension of the newborn, atrioventricular septal defect, and pulmonary hypertension had low survival at 1 year of age.Conclusion: The prevalence of CHD in patients with Down syndrome is similar between Malaysia and high-income countries. The lower survival rate is attributed to limited expertise and resources which limit timely surgery. What is Known: • The survival of patients with Down syndrome with congenital heart disease (CHD) has improved in high-income countries. However, little is known about the survival of patients with Down syndrome with CHD from middle-income countries. • In the Caucasian population, atrioventricular septal defect is the most common type of CHD associated with Down syndrome. What is New: • In middle-income countries, the prevalence of CHD is the same as in high-income countries, but with a lower survival rate. • In the Asian population, ventricular septal defect is the most common type of CHD in patients with Down syndrome.
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Affiliation(s)
- Norazah Zahari
- Department of Pediatrics, Faculty of Medicine, University of Malaya, Jalan Universiti, 50603, Kuala Lumpur, Malaysia.
| | - Mohd Nizam Mat Bah
- Department of Pediatrics, Hospital Sultanah Aminah Johor Bahru, Ministry of Health Malaysia, Johor Bahru, Johor, Malaysia
| | - Hasliza A Razak
- Department of Pediatrics, Hospital Sultanah Aminah Johor Bahru, Ministry of Health Malaysia, Johor Bahru, Johor, Malaysia
| | - Meow-Keong Thong
- Department of Pediatrics, Faculty of Medicine, University of Malaya, Jalan Universiti, 50603, Kuala Lumpur, Malaysia
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48
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Grabeklis AR, Skalny AV, Skalnaya AA, Zhegalova IV, Notova SV, Mazaletskaya AL, Skalnaya MG, Tinkov AA. Hair Mineral and Trace Element Content in Children with Down's Syndrome. Biol Trace Elem Res 2019; 188:230-238. [PMID: 30209729 DOI: 10.1007/s12011-018-1506-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 09/02/2018] [Indexed: 10/28/2022]
Abstract
The objective of the present study was to assess the level of minerals and trace elements in 40 children with Down's syndrome and 40 controls aged 1-2 years old. Hair mineral and trace element analysis was performed using inductively coupled plasma mass spectrometry. The obtained data demonstrate that hair levels of Mg, P, I, Cr, Si, Zn, and Pb in Down's syndrome patients exceeded the respective control values by 36, 36, 93, 57, 45, 28, and 54%, whereas hair mercury was more than twofold lower in children with Down's syndrome. The observed difference in the levels of trace elements was age-dependent. In particular, in 1-year-olds, major differences were observed for essential elements (Cr, Si, Zn), whereas in 2-year-olds-for toxic elements (Hg, Pb). At the same time, hair P levels in Down's syndrome patients were 14 and 35% higher at the age of 1 and 2 years in comparison to the respective controls. Multiple regression analysis demonstrated that a model incorporating all elements, being characterized by a significant group difference, accounted for 42.5% of status variability. At the same time, only hair phosphorus was significantly interrelated with Down's syndrome status (β = 0.478; p < 0.001). Principal component analysis (PCA) used As, Ca, Cr, Fe, Hg, I, Mg, P, Pb, Se, Si, Sn, and Zn as predictors, with the resulting R2 = 0.559. The OPLS-DA models also separated between Down's and health control groups. Therefore, 1-2-year-old patients with Down's syndrome are characterized by significant alterations of mineral and trace element status.
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Affiliation(s)
- Andrey R Grabeklis
- Yaroslavl State University, Yaroslavl, Russia
- Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
| | - Anatoly V Skalny
- Yaroslavl State University, Yaroslavl, Russia.
- Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation.
- All-Russian Research Institute of Medicinal and Aromatic Plants (VILAR), Moscow, Russia.
| | | | - Irina V Zhegalova
- Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
| | - Svetlana V Notova
- Orenburg State University, Orenburg, Russia
- Federal Research Centre of Biological Systems and Agro-technologies of the Russian Academy of Sciences, Orenburg, Russia
| | | | - Margarita G Skalnaya
- Yaroslavl State University, Yaroslavl, Russia
- Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
| | - Alexey A Tinkov
- Yaroslavl State University, Yaroslavl, Russia
- Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
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49
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Underlying factors of recurrent infections in patients with down syndrome. North Clin Istanb 2018; 5:163-168. [PMID: 30374487 PMCID: PMC6191560 DOI: 10.14744/nci.2017.69379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 07/30/2017] [Indexed: 11/20/2022] Open
Abstract
Down syndrome is the most common chromosomal aberration. Patientswith Down syndrome suffer more infections than those without the disease. Underlying immunological disorders are consideredto be the reason for the increasing frequency of infections in patients with Down syndrome. In addition, some anatomical abnormalities in the respiratory tractaccompanying Down syndrome can disturb the innate immunity and contribute to the increase in infection rate. Respiratory tract infections are one of the most common causes of mortality in patients with Down syndrome. Awareness of the underlying reason for frequent respiratory tract infections should result in a decrease in mortality among these patients and contribute to an improvementin their quality of life.
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50
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Johannes J, Greutmann M, Tobler D, Bouchardy J, Stambach D, Wustmann K, Schwitz F, Schwerzmann M. The impact of trisomy 21 on treatment modalities and outcome in adults with congenital heart disease in Switzerland. Pulm Circ 2018; 9:2045894018811147. [PMID: 30338722 PMCID: PMC6287318 DOI: 10.1177/2045894018811147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Trisomy 21 (T21) is associated in 40-45% of cases with heart defects, most commonly shunt lesions. These defects, if not repaired, can lead to irreversible shunt-induced pulmonary hypertension (i.e. Eisenmenger syndrome [ES]). In ES patients, intracardiac repair is no longer possible, but selective pulmonary vasodilators may increase exercise capacity and improve prognosis. This study aimed to estimate the prevalence of cardiac defects and ES in adult T21 patients and to assess the impact of T21 on treatment modalities and outcome in ES patients. A questionnaire was sent to 6906 Swiss physicians inviting them to indicate the number of adults with T21 under their care (survey report). We also analyzed all adults with ES (with and without T21) included in the Swiss Adult Congenital HEart disease Registry (SACHER) and studied the impact of T21 on the use of selective pulmonary vasodilators and survival. In the survey, 348 physicians cared for 695 adult T21 patients. Overall, 24% of T21 survey patients were known to have a cardiac defect, one in four with a defect had developed ES and 13% of those with ES were on specific pulmonary vasodilators. In SACHER, ES was present in 2% of adults with congenital heart disease and selective pulmonary vasodilators were used in 68% of ES patients with T21. In SACHER, survival during follow-up was worse with higher nt-proBNP levels (hazard ratio [HR] = 1.15 per 1000 units, 95% confidence interval [CI] = 1.02-1.29) and lower left ventricular ejection fraction (HR = 1.07 per percent decrease, 95% CI = 1.01-1.13). Age at inclusion and T21 did not affect survival. The prevalence of cardiac defects in adults with T21 in Switzerland is half the prevalence in children. T21 is over-represented among adults with ES. Raised awareness of the therapeutic options for T21 patients with ES is warranted.
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Affiliation(s)
- Judith Johannes
- 1 Center for Congenital Heart Disease, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Matthias Greutmann
- 2 University Heart Center, Department of Cardiology, University of Zurich, Zurich, Switzerland
| | - Daniel Tobler
- 3 Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Judith Bouchardy
- 4 Department of Cardiology and Cardiac Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.,5 Division of Cardiology, Hôpitaux Universitaires de Genève (HUG), Genève, Switzerland
| | | | - Kerstin Wustmann
- 1 Center for Congenital Heart Disease, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Fabienne Schwitz
- 1 Center for Congenital Heart Disease, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Markus Schwerzmann
- 1 Center for Congenital Heart Disease, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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