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McDonnell C, Elbaaly H, O'Reilly R, Courtney M, Byrne AT. Pulmonary disease in paediatric patients with trisomy 21: a review of imaging findings. Clin Radiol 2025; 84:106857. [PMID: 40073547 DOI: 10.1016/j.crad.2025.106857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 12/23/2024] [Accepted: 02/11/2025] [Indexed: 03/14/2025]
Abstract
AIM Trisomy 21, also known as Down syndrome, is the most common chromosomal abnormality seen in live births and is associated with congenital abnormalities involving multiple organ systems. While the congenital cardiac and gastrointestinal associations of trisomy 21 are well known, the associated pulmonary radiological findings are less widely described. Our objective is to assess the presence, categories, and prevalence of pulmonary radiological findings in patients with trisomy 21, and to describe and provide reference images of these findings. MATERIALS AND METHODS A database of patients with a confirmed diagnosis of trisomy 21 was provided by the congenital cardiac disease clinic. One hundred thirty-four patients who had undergone computed tomography (CT) imaging of the chest were then identified from this database, all of whom had a diagnosis of congenital cardiac disease. A retrospective review of imaging findings of these 134 patients was then conducted by two specialist consultant paediatric radiologists and a paediatric radiology fellow. RESULTS The CTs of 62 patients demonstrated no abnormality. The CTs of the remaining 72 patients were abnormal. Air trapping (present in 35% of patients), subpleural cysts (17%), bronchiectasis (4%), findings suggestive of bronchopulmonary dysplasia (3%), and abnormalities of the tracheobronchial tree (4%) were among the abnormalities demonstrated. CONCLUSION This retrospective review describes the spectrum of thoracic radiological findings seen in patients with trisomy 21. This is of increasing value to practicing radiologists due to the rising life expectancy in this population.
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Affiliation(s)
- C McDonnell
- Department of Radiology, Children's Health Ireland, Dublin, Ireland.
| | - H Elbaaly
- Department of Radiology, Children's Health Ireland, Dublin, Ireland
| | - R O'Reilly
- Department of Respiratory Medicine, Children's Health Ireland, Dublin, Ireland
| | - M Courtney
- Department of Diagnostic Imaging, St James's Hospital, Dublin, Ireland
| | - A T Byrne
- Department of Radiology, Children's Health Ireland, Dublin, Ireland
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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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Tsoi SM, Steurer M, Nawaytou H, Cheung S, Keller RL, Fineman JR. Defining the Typical Course of Persistent Pulmonary Hypertension of the Newborn: When to Think Beyond Reversible Causes. J Pediatr 2024; 273:114131. [PMID: 38823627 DOI: 10.1016/j.jpeds.2024.114131] [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: 03/07/2024] [Revised: 04/17/2024] [Accepted: 05/27/2024] [Indexed: 06/03/2024]
Abstract
OBJECTIVES To describe the typical clinical course of reversible persistent pulmonary hypertension of the newborn (PPHN) from perinatal etiologies and compare that with the clinical course of PPHN due to underlying fetal developmental etiologies. STUDY DESIGN This was a single-center, retrospective cohort study of liveborn newborns either born or transferred to our facility for higher level of care between 2015 and 2020 with gestational age ≥35 weeks and a clinical diagnosis of PPHN in the electronic health record. Newborns with complex congenital heart disease and congenital diaphragmatic hernia were excluded. Using all data available at time of collection, newborns were stratified into 2 groups by PPHN etiology - perinatal and fetal developmental causes. Primary outcomes were age at initiation, discontinuation, and total duration of extracorporeal life support, mechanical ventilation, supplemental oxygen, inhaled nitric oxide, inotropic support, and prostaglandin E1. Our secondary outcome was age at echocardiographic resolution of pulmonary hypertension. Groups were compared by t-test. Time-to-event Kaplan Meier curves described and compared (log-rank test) discontinuation of each therapy. RESULTS Sixty-four (72%) newborns had perinatal etiologies whereas 24 (28%) had fetal developmental etiologies. The resolution of perinatal PPHN was more rapid compared with fetal developmental PPHN. By 10 days of age, more neonates were off inotropes (98% vs 29%, P < .01), decannulated from extracorporeal life support (100% vs 0%, P < .01), extubated (75% vs 37%, P < .01), and had echocardiographic resolution of PH (35% vs 7%, P = .02). CONCLUSIONS An atypical PPHN course, characterized by persistent targeted therapies in the second week of life, warrants further work-up for fetal developmental causes.
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Affiliation(s)
- Stephanie M Tsoi
- Division of Critical Care Medicine, Department of Pediatrics, University of California San Francisco, San Francisco, CA.
| | - Martina Steurer
- Division of Critical Care Medicine, Department of Pediatrics, University of California San Francisco, San Francisco, CA; Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA
| | - Hythem Nawaytou
- Division of Cardiology, Department of Pediatrics, University of California San Francisco, San Francisco, CA
| | - Shannon Cheung
- Division of Critical Care Medicine, Department of Pediatrics, University of California San Francisco, San Francisco, CA
| | - Roberta L Keller
- Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA
| | - Jeffrey R Fineman
- Division of Critical Care Medicine, Department of Pediatrics, University of California San Francisco, San Francisco, CA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA
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Bloom JL, Furniss A, Suresh K, Fuhlbrigge RC, Lamb MM, Rosenberg S, Edwards A, O’Leary ST. The Impact of Altitude at Birth on Perinatal Respiratory Support for Neonates with Trisomy 21. Am J Perinatol 2023; 40:1515-1520. [PMID: 34674211 PMCID: PMC10766162 DOI: 10.1055/s-0041-1736594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Both high altitude and trisomy 21 (T21) status can negatively impact respiratory outcomes. The objective of this study was to examine the association between altitude and perinatal respiratory support in neonates with T21 compared with those without T21. STUDY DESIGN This retrospective cohort study used the United States all-county natality files that included live, singleton, in-hospital births from 2015 to 2019. Descriptive statistics for neonates with and without the primary outcome of sustained assisted ventilation (>6 hours) were compared using t-tests and Chi-squared analyses. Multivariable logistic regression was used to determine the association between respiratory support and the presence of T21, and included an interaction term to determine whether the association between respiratory support and the presence of T21 was modified by elevation at delivery. RESULTS A total of 17,939,006 neonates, 4,059 (0.02%) with T21 and 17,934,947 (99.98%) without, were included in the study. The odds of requiring sustained respiratory support following delivery were 5.95 (95% confidence interval [CI]: 5.31, 6.66), 4.06 (95% CI: 2.39, 6.89), 2.36 (95% CI: 1.64, 3.40), and 5.04 (95% CI: 1.54, 16.54) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevations, respectively. The odds of requiring immediate ventilation support following delivery were 5.01 (95% CI: 4.59, 5.46), 5.90 (95% CI: 4.16, 8.36), 2.86 (95% CI: 2.15, 3.80), and 12.08 (95% CI: 6.78, 21.51) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevation, respectively. CONCLUSION Neonates with T21 have increased odds of requiring respiratory support following delivery when compared with neonates without T21 at all categories of altitude. However, the odds ratios did not increase monotonically with altitude which indicates additional research is critical in understanding the effects of altitude on neonates with T21. KEY POINTS · Neonates with T21 have an increased need for perinatal respiratory support at all altitudes.. · The odds of needing perinatal respiratory support did not increase monotonically with elevation.. · Additional research is critical to understanding the effects of altitude on neonates with T21..
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Affiliation(s)
- Jessica L. Bloom
- Department of Pediatrics, Section of Pediatric Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Anna Furniss
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Krithika Suresh
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado
| | - Robert C. Fuhlbrigge
- Department of Pediatrics, Section of Pediatric Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Molly M. Lamb
- Department of Epidemiology and Center for Global Health, Colorado School of Public Health, Aurora, Colorado
| | - Sophie Rosenberg
- Department of Community and Behavioral Health, Colorado School of Public Health, Aurora, Colorado
| | - Anastasia Edwards
- Colorado Department of Public Health and Environment, Denver, Colorado
| | - Sean T. O’Leary
- Department of Pediatrics, Section of Infectious Disease, Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Taylor K, Lovelace C, Richards B, Tseng S, Ogunleye O, Cua CL. Utility of Screening Fetal Echocardiograms at a Single Institution Following Normal Obstetric Ultrasound in Fetuses with Down Syndrome. Pediatr Cardiol 2023; 44:1514-1519. [PMID: 37351603 DOI: 10.1007/s00246-023-03183-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/12/2023] [Indexed: 06/24/2023]
Abstract
Fetal echocardiograms (F-echo) are recommended in all pregnancies when the fetus has Down syndrome (DS) even if there was a prior obstetric scan (OB-scan) that was normal. The utility of a screening F-echo in this high-risk population when an OB-scan is normal is unknown. Goal of this study was to evaluate if any diagnosis of a critical congenital heart disease (CHD) was missed in a fetus with DS who had a normal OB-scan. Secondary goal was to determine if any CHD was missed postnatally when an OB-scan was read as normal. Retrospective chart review of all fetuses that had a F-echo whose indication was DS between 1/1/2010 to 6/30/2022 was performed. Fetuses were included if they had an OB-scan that was read as normal and had a F-echo. Postnatal transthoracic echocardiogram (pTTE) was reviewed when available. Critical CHD was defined as CHD requiring catheterization or surgical intervention < 1 month of age. One hundred twenty-two F-echo on fetuses with DS were evaluated, of which 48 met inclusion criteria. OB-scan was performed at 20.4 ± 4.5 weeks gestational age and F-echo was performed at 24.0 ± 4.6 weeks gestational age. No patient with a normal OB-scan had a diagnosis of a critical CHD by F-echo (n = 48, negative predictive value = 100%). Evaluating those patients that had an OB-scan and a pTTE (n = 38), 14 patients were diagnosed with CHD (muscular ventricular septal defect (VSD) n = 5, perimembraneous VSD n = 3, secundum atrial septal defect (ASD) n = 2, primum ASD n = 1, transitional atrioventricular septal defect (AVSD) n = 2, and aortic valve abnormality n = 1; negative predictive value = 63.2%). F-echo correctly diagnosed 4 of the 14 missed OB-scan CHD (perimembraneous VSD n = 2, muscular VSD n = 1, and transitional AVSD n = 1). Critical CHD was not missed with a normal OB-scan in this high-risk population. F-echo also missed the majority of CHD when an OB-scan was read as normal. The cost/benefit of screening F-echo in fetuses with DS should be evaluated if a normal OB-scan has been performed, considering all these patients would have a pTTE performed per guidelines.
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Affiliation(s)
- Kacy Taylor
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Casey Lovelace
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | | | - Stephanie Tseng
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Oluseyi Ogunleye
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Clifford L Cua
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
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6
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Ishida S, Nakanishi H, Kosaka Y, Yamaguchi A, Ooka M. Evaluation of newborns with Down syndrome with weight less than 1500 g in the neonatal intensive care unit: A Japanese multicentre study. J Paediatr Child Health 2023; 59:912-918. [PMID: 37114469 DOI: 10.1111/jpc.16418] [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: 05/01/2022] [Revised: 02/05/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023]
Abstract
AIM This study aimed to clarify the characteristics and their mortality-related factors in very low birthweight infants with Down syndrome (DS) in Japan. METHODS This retrospective case-control study enrolled newborns with DS weighing <1500 g admitted to neonatal intensive care unit (NICU) of the perinatal centre registered with the Neonatal Research Network of Japan (NRNJ) database from 2008 to 2019. The clinical characteristics and their mortality-related factors were compared among the Dead group (newborns with DS who died in the NICU), the Survival group (newborns with DS who were alive from the NICU) and the Control group (newborns without congenital or chromosomal condition). RESULTS A total of 53 656 newborns weighing <1500 g were registered in the NRNJ database for 12 years. Of these, 310 (0.6%) were diagnosed with DS: 62 newborns in the Dead group, 248 in the Survival group and 49 786 in the Control group without chromosomal condition. Logistic analysis revealed that there was a significant difference in the mortality-related factors in congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn; the adjusted odds ratios were 8.6, 121 and 9.5, respectively. Newborns with DS weighing <1000 g showed the earliest death in the NICU on the Kaplan-Meier survival curve (P < 0.01). CONCLUSION The mortality rate for newborns with DS weighing <1500 g was 20% (5% in the Control group). The mortality-related factors were complications of congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn.
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Affiliation(s)
- Shuji Ishida
- Department of Pediatrics of Kitasato University Hospital, Sagamihara-shi, Kanagawa, Japan
| | - Hidehiko Nakanishi
- Division of Neonatal Intensive Care Medicine, Research and Development Center for New Medical Frontiers of Kitasato University Hospital, Sagamihara-shi, Kanagawa, Japan
| | - Yukako Kosaka
- Department of Pediatrics of Kitasato University Hospital, Sagamihara-shi, Kanagawa, Japan
| | - Ayano Yamaguchi
- Department of Pediatrics of Kitasato University Hospital, Sagamihara-shi, Kanagawa, Japan
| | - Mari Ooka
- Department of Pediatrics of Kitasato University Hospital, Sagamihara-shi, Kanagawa, Japan
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7
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Abdelrahman EG, Kamal NM, Alharthi S, Albalawi M, Assar E. Down syndrome patients with normal hearts: are they really normal? Medicine (Baltimore) 2023; 102:e32886. [PMID: 36820596 PMCID: PMC9907910 DOI: 10.1097/md.0000000000032886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/13/2023] [Accepted: 01/18/2023] [Indexed: 02/12/2023] Open
Abstract
Even though congenital heart disease is a common finding in down syndrome (DS) patients, some of them have anatomically normal hearts. However, the term "normal" might not be suitable, as these patients usually suffer from functional cardiac dysfunction. Several research highlighted that despite the absence of anatomical heart defects, subtle cardiac function derangements are present in DS patients. We aim to assess cardiac functions by Two-dimensional echocardiography and tissue Doppler imaging (TDI) in pediatric DS patients who have anatomically normal hearts. One hundred seventy-two patients with karyotyping confirmed DS with anatomically normal hearts and 165 healthy normal control children were enrolled in the current study. Their cardiac functions were assessed using both 2-dimensional echocardiography and TDI. Both patients and controls had structurally and anatomically normal hearts. In DS patients, the right side of the heart showed a significant reduction in both systolic and diastolic functions. Systolic dysfunction was evident by significantly decreased levels of Tricuspid annular plane systolic excursion and systolic wave by TDI. Diastolic dysfunction of the right ventricle was evident by prolonged deceleration time by conventional echocardiography and a significant decrease in annular tissue doppler velocity during early diastole/late diastole ratio by TDI. The E/De ratio was significantly increased. Even with anatomically normal hearts, DS patients should undergo cardiac function assessment by echocardiography & TDI. TDI is superior to conventional echocardiography in detecting subtle cardiac dysfunction especially left ventricular diastolic dysfunction in DS patients. TDI showed a significant decrease in the early/atrial ratio of mitral valve annulus and prolongation of left ventricle isometric relaxation time in DS children. Also, the left ventricle E/De ratio was prolonged denoting elevated filling pressures and diastolic dysfunction. This indicates that the TDI has higher sensitivity to detect diastolic dysfunction than conventional Echocardiography. Biventricular TDI-derived myocardial performance index was found to be significantly increased in DS children.
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Affiliation(s)
- Eman G Abdelrahman
- Pediatric department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Naglaa M Kamal
- Pediatric department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sultan Alharthi
- Pediatric department, Alhada Armed Forces Hospital, Taif, KSA
| | - Muflih Albalawi
- Cardiology service department, King Salman Armed Forces Hospital, Tabuk, KSA
| | - Effat Assar
- Pediatric department, Faculty of Medicine, Benha University, Benha, Egypt
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Dimopoulos K, Constantine A, Clift P, Condliffe R, Moledina S, Jansen K, Inuzuka R, Veldtman GR, Cua CL, Tay ELW, Opotowsky AR, Giannakoulas G, Alonso-Gonzalez R, Cordina R, Capone G, Namuyonga J, Scott CH, D’Alto M, Gamero FJ, Chicoine B, Gu H, Limsuwan A, Majekodunmi T, Budts W, Coghlan G, Broberg CS. Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus. Circulation 2023; 147:425-441. [PMID: 36716257 PMCID: PMC9977420 DOI: 10.1161/circulationaha.122.059706] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 10/31/2022] [Indexed: 02/01/2023]
Abstract
Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.
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Affiliation(s)
- Konstantinos Dimopoulos
- Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom (K.D., A.C.)
- National Heart and Lung Institute, Imperial College London, United Kingdom (K.D., A.C.)
| | - Andrew Constantine
- Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom (K.D., A.C.)
- National Heart and Lung Institute, Imperial College London, United Kingdom (K.D., A.C.)
| | - Paul Clift
- Department of Cardiology, Queen Elizabeth Hospital Birmingham, United Kingdom (P.C.)
| | - Robin Condliffe
- Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C.)
| | - Shahin Moledina
- National Paediatric Pulmonary Hypertension Service UK, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom (S.M.)
- Institute of Cardiovascular Science, University College London, United Kingdom (S.M.)
| | - Katrijn Jansen
- Adult Congenital and Paediatric Heart Unit, Freeman Hospital Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (K.J.)
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom (K.J.)
| | - Ryo Inuzuka
- Department of Pediatrics, The University of Tokyo Hospital, Japan (R.I.)
| | - Gruschen R. Veldtman
- Scottish Adult Congenital Cardiac Service, Golden Jubilee Hospital, Glasgow, Scotland, United Kingdom (G.R.V.)
| | - Clifford L. Cua
- The Heart Center, Nationwide Children’s Hospital, Columbus, OH (C.L.C.)
| | - Edgar Lik Wui Tay
- Department of Cardiology, National University Hospital Singapore (E.T.L.W.)
| | - Alexander R. Opotowsky
- The Heart Institute, Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine, OH (A.R.O.)
| | - George Giannakoulas
- Department of Cardiology, AHEPA University Hospital School of Medicine, Aristotle University of Thessaloniki, Greece (G.G.)
| | - Rafael Alonso-Gonzalez
- Division of Cardiology, Toronto General Hospital, University Health Network, Peter Munk Cardiovascular Center, University of Toronto, Canada (R.A.-G.)
- Toronto Adult Congenital Heart Disease Program, Canada (R.A.-G.)
| | - Rachael Cordina
- Department of Cardiology, Royal Prince Alfred Hospital and Sydney Medical School, University of Sydney, New South Wales, Australia (R.C.)
| | - George Capone
- Down Syndrome Clinical and Research Center, Kennedy Krieger Institute, Baltimore, MD (G. Capone)
- Johns Hopkins School of Medicine, Baltimore, MD (G. Capone)
| | - Judith Namuyonga
- Department of Paediatric Cardiology, Uganda Heart Institute, Kampala (J.N.)
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda (J.N.)
| | | | - Michele D’Alto
- Department of Cardiology, University “L. Vanvitelli”–Monaldi Hospital, Naples, Italy (M.D.)
| | - Francisco J. Gamero
- Department of Cardiovascular Surgery, Benjamin Bloom Children’s Hospital, El Salvador (F.J.G.)
| | - Brian Chicoine
- Advocate Medical Group Adult Down Syndrome Center, Park Ridge, IL (B.C.)
| | - Hong Gu
- Department of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical University, China (H.G.)
| | - Alisa Limsuwan
- Division of Pediatric Cardiology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (A.L.)
| | - Tosin Majekodunmi
- Department of Cardiology, Euracare Multi-specialist Hospital, Nigeria (T.M.)
| | - Werner Budts
- Division of Congenital and Structural Cardiology, University Hospitals Leuven, and Department of Cardiovascular Science, Catholic University Leuven, Belgium (W.B.)
| | - Gerry Coghlan
- Department of Cardiology, Royal Free Hospital, London, United Kingdom (G. Coghlan)
| | - Craig S. Broberg
- Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.S.B.)
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9
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Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry. J Pediatr 2023; 252:131-140.e3. [PMID: 36027975 DOI: 10.1016/j.jpeds.2022.08.027] [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: 12/03/2021] [Revised: 08/11/2022] [Accepted: 08/18/2022] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. STUDY DESIGN We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. RESULTS Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension. CONCLUSIONS Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.
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Cardiovascular complications of sleep disordered breathing in the population with Down syndrome. PROGRESS IN PEDIATRIC CARDIOLOGY 2022. [DOI: 10.1016/j.ppedcard.2022.101580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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11
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Morbidity and mortality in neonates with Down Syndrome based on gestational age. J Perinatol 2022; 43:445-451. [PMID: 36131096 DOI: 10.1038/s41372-022-01514-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/23/2022] [Accepted: 09/07/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Greater than 50% of neonates with Down Syndrome (DS) have perinatal complications that require admission to the neonatal intensive care unit (NICU) at birth. Previous studies have shown increased morbidity and mortality rates in neonates without DS delivered prior to 39 weeks of completed gestation. OBJECTIVE To determine if an association exists between gestational age at delivery and adverse outcomes in neonates with DS. STUDY DESIGN Neonates with DS admitted to a large, tertiary care center NICU from 2010 to 2020 were evaluated. Gestational age (GA) was stratified into 4 groups: <34 (preterm), 34-36 (late-preterm), 37-38 (early-term) and ≥39 (term + post-term) completed weeks. Fisher's exact tests were used to evaluate morbidity and mortality rates between groups. RESULT Of the 314 neonates with DS, 10% (N = 31) were <34 weeks, 22% (N = 68) 34-36 weeks, 40% (N = 127) 37-38 weeks, and 28% (N = 88) ≥39 completed weeks at birth. Baseline characteristics were similar between groups. GA at birth <34 weeks was associated with a higher in-hospital mortality rate when compared to those born 37-38 (19% vs. 0%, P < 0.001) and ≥39 (19% vs. 3%, P = 0.01). Neonates with DS born <34 weeks had a higher likelihood of oxygen requirement at time of discharge compared to 34-36, 37-38, and ≥39 groups (P = 0.01; P < 0.001; P < 0.001 respectively). Neonates with DS < 34 weeks were more likely to develop necrotizing enterocolitis (P = 0.02) and require nitric oxide (P = 0.014) compared to neonates with DS ≥ 39. We observed no differences in the need for surgical interventions between groups aside from the rate of gastrostomy/jejunostomy tube placement between 34-36 weeks and 37-38 weeks GA. CONCLUSION Neonates with DS born preterm (<34 weeks) represent a highly vulnerable subgroup. Multidisciplinary strategies are needed to address their higher rates of morbidity and mortality.
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Mahmood B. Persistent pulmonary hypertension of newborn. Semin Pediatr Surg 2022; 31:151202. [PMID: 36038220 DOI: 10.1016/j.sempedsurg.2022.151202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Burhan Mahmood
- Division of Newborn Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pennsylvania, USA.
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Mortality and morbidity of infants with trisomy 21, weighing 1500 grams or less, in Japan. J Hum Genet 2022; 67:623-628. [PMID: 35787654 DOI: 10.1038/s10038-022-01061-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/26/2022] [Accepted: 06/22/2022] [Indexed: 11/09/2022]
Abstract
Although very low birth weight (VLBW) is well studied in neonatology and the perinatal prognosis of VLBW infants has improved over time, little is known about the prognosis of VLBW infants with trisomy 21 (T21). We aimed to investigate the mortality and morbidity of VLBW infants with T21 during NICU admission in Japan, in comparison to those of infants without birth defects (BD-). Maternal and neonatal data of infants weighing 1500 grams or less admitted to the centers of the Neonatal Research Network of Japan from 2003 to 2016 were collected prospectively. Of 60,136 infants, 328 (0.55%) had T21. Although maternal age in the case of T21 infants was higher, maternal complications tended to be less frequent than in those with BD-. Multivariable analysis revealed that morbidities were higher in infants with T21 than in those with BD- but respiratory distress syndrome and retinopathy of prematurity were less frequent in those with T21 (p < 0.001, and p = 0.014, respectively), and no significant difference was observed between the two groups in the proportion of late-onset circulatory collapse of prematurity as well as cystic periventricular leukomalacia (p = 0.739 and p = 0.733, respectively). The survival rate at discharge from the NICU was 77% and 94% for T21 and BD-, respectively. This was the first nationwide survey of VLBW infants with T21 in Japan. Although there were no data regarding the timing of diagnosis, these data will aid prenatal genetic counseling and perinatal management of T21 infants.
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Abstract
Persons with Down syndrome (DS) have an increased reported incidence of pulmonary hypertension (PH). A majority of those with PH have associations with congenital heart disease (CHD) or persistent pulmonary hypertension of the newborn (PPHN); however, there are likely multifactorial contributions that include respiratory comorbidities. PH appears to be most commonly identified early in life, although respiratory challenges may contribute to a later diagnosis or even a recurrence of previously resolved PH in this population. Currently there are few large-scale, prospective, lifetime cohort studies detailing the impact PH has on the population with DS. This review will attempt to summarize the epidemiology and characteristics of PH in this population. This article will additionally review current known and probable risk factors for developing PH, review pathophysiologic mechanisms of disease in the population with DS, and evaluate current screening and management recommendations while suggesting areas for additional or ongoing clinical, translational, and basic science research.
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Affiliation(s)
- Douglas S Bush
- Department of Pediatrics, Division of Pulmonology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1202B, New York, NY, 10029, USA.
| | - D Dunbar Ivy
- Department of Pediatrics, Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA
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Taksande A, Pujari D, Jameel PZ, Taksande B, Meshram R. Prevalence of pulmonary hypertension among children with Down syndrome: A systematic review and meta-analysis. World J Clin Pediatr 2021; 10:177-191. [PMID: 34868894 PMCID: PMC8603643 DOI: 10.5409/wjcp.v10.i6.177] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 05/13/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pulmonary hypertension (PH) has serious short- and long-term consequences. PH is gaining increasing importance in high risk groups such as Down syndrome (DS) as it influences their overall survival and prognosis. Hence, there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management. AIM To determine the prevalence of PH in children with DS. METHODS The authors individually conducted a search of electronic databases manually (Cochrane library, PubMed, EMBASE, Scopus, Web of Science). Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion. The words used in the literature search were "pulmonary hypertension" and "pulmonary arterial hypertension"; "Down syndrome" and "trisomy 21" and "prevalence". The data were analyzed by Comprehensive Meta-Analysis Software Version 2. Risk of bias assessment and STROBE checklist were used for quality assessment. RESULTS Of 1578 articles identified, 17 were selected for final analysis. The pooled prevalence of PH in these studies was 25.5%. Subgroup analysis was carried out for age, gender, region, year of publication, risk of bias and etiology of PH. CONCLUSION This review highlights the increasing prevalence of PH in children with DS. It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management. Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.
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Affiliation(s)
- Amar Taksande
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
| | - Divya Pujari
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
| | - Patel Zeeshan Jameel
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
| | - Bharati Taksande
- Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Wardha 442102, Maharashtra, India
| | - Revat Meshram
- Department of Pediatrics, Jawaharlal Nehru Medical College, Wardha 442004, Maharashtra, India
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Abstract
Neonatal lung biopsy guides important medical decisions when the diagnosis is not clear from prior clinical assessment, imaging, or genetic testing. Common scenarios that lead to biopsy include severe acute respiratory distress in a term neonate, pulmonary hypertension disproportionate to that expected for gestational age or known cardiac anomalies, and assessment of suspected genetic disorder based on clinical features or genetic variant of unknown significance. The differential diagnosis includes genetic developmental disorders, genetic surfactant disorders, vascular disorders, acquired infection, and meconium aspiration. This article describes pathologic patterns in the neonatal lung and correlation with molecular abnormalities, where appropriate.
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Voges I, Nyktari E. Late presentation of shunt lesions in Down syndrome patients: the importance of multidisciplinary assessment and lifelong follow-up. Eur Heart J Case Rep 2021; 5:ytab238. [PMID: 34377920 PMCID: PMC8340798 DOI: 10.1093/ehjcr/ytab238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/25/2021] [Accepted: 05/27/2021] [Indexed: 11/14/2022]
Affiliation(s)
- Inga Voges
- Department of Congenital Heart Disease and Paediatric Cardiology, University Hospital Schleswig-Holstein, Arnold-Heller-Str. 3, 24105 Kiel, Germany
| | - Evangelia Nyktari
- Cardiovascular MRI Unit, BIOATRIKI SA (Biomedicine Group of Companies), Athens, Greece
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Hypoxemia in infants with trisomy 21 in the neonatal intensive care unit. J Perinatol 2021; 41:1448-1453. [PMID: 34035452 PMCID: PMC8576738 DOI: 10.1038/s41372-021-01105-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/26/2021] [Accepted: 05/10/2021] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Newborns with trisomy 21 (T21) often require NICU hospitalization. Oxygen desaturations are frequently observed in these infants, even in the absence of congenital heart defects (CHD). We hypothesized that NICU patients with T21 have more hypoxemia than those without T21. DESIGN All infants with T21 without significant CHD discharged home from the NICU between 2009 and 2018 were included (n = 23). Controls were matched 20:1 for gestational age and length of stay. We compared daily severe hypoxemia events (SpO2 < 80% for ≥10 s) for the whole NICU stay and the pre-discharge week. RESULTS Infants with T21 showed significantly more daily hypoxemia events during their entire NICU stay (median 10 versus 7, p = 0.0064), and more so in their final week (13 versus 7, p = 0.0008). CONCLUSION NICU patients with T21 without CHD experience more severe hypoxemia events than controls, particularly in the week before discharge. Whether this hypoxemia predicts or contributes to adverse outcomes is unknown.
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Abstract
PURPOSE OF REVIEW Pulmonary arterial hypertension (PAH) causes high morbidity and mortality in children. In this review, we discuss advances in diagnosis and treatment of this disorder. RECENT FINDINGS Proceedings published from the 2018 World Symposium updated the definition of pulmonary hypertension to include all adults and children with mean pulmonary artery pressure more than 20 mmHg. Targeted PAH therapy is increasingly used off-label, but in 2017, bosentan became the first Food and Drug Administration-targeted PAH therapy approved for use in children. SUMMARY In recent years, advanced imaging and clinical monitoring have allowed improved risk stratification of pulmonary hypertension patients. New therapies, approved in adults and used off-label in pediatric patients, have led to improved outcomes for affected children.
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Bush D, Galambos C, Dunbar Ivy D. Pulmonary hypertension in children with Down syndrome. Pediatr Pulmonol 2021; 56:621-629. [PMID: 32049444 DOI: 10.1002/ppul.24687] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 01/23/2020] [Indexed: 12/26/2022]
Abstract
Individuals with Down syndrome (DS) have an increased risk of developing pulmonary hypertension (PH). In this review, we explore the epidemiology and clinical characteristics of PH in the population with DS and examine genetic, molecular and clinical contributions to the condition. The presence of an additional copy of chromosome 21 (trisomy 21) increases the risk of developing PH in children with DS through many mechanisms, including increased hemodynamic stress in those with congenital heart disease, hypoxemia through impaired ventilation to perfusion matching secondary to developmental lung abnormalities, pulmonary hypoplasia from pulmonary vascular endothelial dysfunction, and an increase in pulmonary vascular resistance often related to pulmonary comorbidities. We review recent studies looking at novel biomarkers that may help diagnose, predict or monitor PH in the population with DS and examine current cardiopulmonary guidelines for monitoring children with DS. Finally, we review therapeutic interventions specific to PH in individuals with DS. Contemporary work has identified exciting mechanistic pathways including the upregulation of antiangiogenic factors and interferon activity, which may lead to additional biomarkers or therapeutic opportunities. Throughout the manuscript, we identify gaps in our knowledge of the condition as it relates to the population with DS and offer suggestions for future clinical, translational, and basic science research.
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Affiliation(s)
- Douglas Bush
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Csaba Galambos
- Department of Pathology and Laboratory Medicine, University of Colorado School of Medicine, Aurora, Colorado
| | - David Dunbar Ivy
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado
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21
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Shelton AR, Malow B. Neurodevelopmental Disorders Commonly Presenting with Sleep Disturbances. Neurotherapeutics 2021; 18:156-169. [PMID: 33403472 PMCID: PMC8116361 DOI: 10.1007/s13311-020-00982-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2020] [Indexed: 02/04/2023] Open
Abstract
There are multiple disorders of neurodevelopment that present with co-occurring sleep disturbances. Many of these neurodevelopmental disorders (NDD) include sleep disturbances in their diagnostic criteria. Neurobiological, genetic, and environmental factors overlap to cause different sleep disorders in individuals with NDD. Caregivers often present reporting either insomnia or hypersomnia, and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. It is crucial that clinicians understand the different presentations of sleep disturbances in individuals with NDD.
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Affiliation(s)
- Althea Robinson Shelton
- Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave South, Medical Center North A-0118, Nashville, TN, 37232, USA.
| | - Beth Malow
- Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave South, Medical Center North A-0118, Nashville, TN, 37232, USA
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22
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Smith A, Molloy E, Miletin J, Curley A, Balfe J, Franklin O, El-Khuffash A. Longitudinal assessment of cardiac function in infants with Down's syndrome using novel echocardiography techniques - project protocol. HRB Open Res 2020; 3:77. [PMID: 34095748 PMCID: PMC8145226 DOI: 10.12688/hrbopenres.13168.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2020] [Indexed: 11/21/2022] Open
Abstract
Background: Down’s syndrome (DS) is the most common chromosomal abnormality globally. Ireland has one of the highest rates of DS in the western world with an incidence of 1:444 live births. Congenital heart disease (CHD) and pulmonary hypertension (PH) are the commonest morbidities affecting the cardiovascular system in DS. PH is associated with significant morbidity and an increase risk of mortality. The impact of the diagnosis of DS, the presence of CHD and the associated PH on myocardial function during transition and over the first 2 years of age in this population is not well defined and warrants further study. In particular, serial measurements of pulmonary pressures in this population over the first week of age are lacking. This study aims to characterise myocardial function and pulmonary haemodynamics in infants with Down syndrome during the transitional period (over the first week of age) and throughout the first two years of age. Methods: A prospective, observational study utilising novel echocardiography techniques to assess myocardial function and pulmonary haemodynamics over the first two years of age in infants with Down Syndrome. A population of healthy infants without CHD or a diagnosis of DS will be recruited as controls. This study will be conducted across the three Dublin maternity units. Discussion: In total, 70 babies with DS have been enrolled into this study with 292 echocardiograms performed to date. Further evaluation of cardiac performance in DS infants with and without CHD may yield more insight into the pathophysiology of cardiac dysfunction and pulmonary hypertension that are recognised features in these patients. This could aid in our ability to monitor and treat patients, as well as improve our ability to predict outcomes.
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Affiliation(s)
- Aisling Smith
- Department of Neonatology, The Rotunda Hospital, Dublin, Dublin, D01P5W9, Ireland
| | - Eleanor Molloy
- Department of Paediatrics and Child Health, Trinity College Dublin, Dublin, Dublin, D02PN40, Ireland.,Department of Neonatology, Coombe Women and Infants University Hospital, Dublin, Dublin, D08XW7X, Ireland
| | - Jan Miletin
- Department of Neonatology, Coombe Women and Infants University Hospital, Dublin, Dublin, D08XW7X, Ireland
| | - Anna Curley
- Department of Neonatology, The National Maternity Hospital, Dublin, Dublin, D02YH21, Ireland
| | - Joanne Balfe
- Department of Paediatrics, Tallaght University Hospital, Dublin, Dublin, D24NR0A, Ireland
| | - Orla Franklin
- Department of Paediatric Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin, Dublin, D12N512, Ireland
| | - Afif El-Khuffash
- Department of Neonatology, The Rotunda Hospital, Dublin, Dublin, D01P5W9, Ireland.,School of Medicine, Royal College of Surgeons in Ireland, Dublin, Dublin, D02P796, Ireland
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Albinni S, Marx M, Lang IM. Focused Update on Pulmonary Hypertension in Children-Selected Topics of Interest for the Adult Cardiologist. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E420. [PMID: 32825190 PMCID: PMC7559541 DOI: 10.3390/medicina56090420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/13/2020] [Accepted: 08/16/2020] [Indexed: 11/16/2022]
Abstract
Pulmonary hypertensive vascular disease (PHVD), and pulmonary hypertension (PH), which is a broader term, are severe conditions associated with high morbidity and mortality at all ages. Treatment guidelines in childhood are widely adopted from adult data and experience, though big differences may exist regarding aetiology, concomitant conditions and presentation. Over the past few years, paediatric aspects have been incorporated into the common guidelines, which currently address both children and adults with pulmonary hypertension (PH). There are multiple facets of PH in the context of cardiac conditions in childhood. Apart from Eisenmenger syndrome (ES), the broad spectrum of congenital heart disease (CHD) comprises PH in failing Fontan physiology, as well as segmental PH. In this review we provide current data and novel aspects on the pathophysiological background and individual management concepts of these conditions. Moreover, we focus on paediatric left heart failure with PH and its challenging issues, including end stage treatment options, such as mechanical support and paediatric transplantation. PH in the context of rare congenital disorders, such as Scimitar Syndrome and sickle cell disease is discussed. Based on current data, we provide an overview on multiple underlying mechanisms of PH involved in these conditions, and different management strategies in children and adulthood. In addition, we summarize the paediatric aspects and the pros and cons of the recently updated definitions of PH. This review provides deeper insights into some challenging conditions of paediatric PH in order to improve current knowledge and care for children and young adults.
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Affiliation(s)
- Sulaima Albinni
- Paediatric Heart Centre Vienna, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Wien, Austria;
| | - Manfred Marx
- Paediatric Heart Centre Vienna, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Wien, Austria;
| | - Irene M. Lang
- AKH-Vienna, Department of Cardiology, Medical University of Vienna, 1090 Wien, Austria;
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Cooper A, Sisco K, Backes CH, Dutro M, Seabrook R, Santoro SL, Cua CL. Usefulness of Postnatal Echocardiography in Patients with Down Syndrome with Normal Fetal Echocardiograms. Pediatr Cardiol 2019; 40:1716-1721. [PMID: 31541264 DOI: 10.1007/s00246-019-02209-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 08/16/2019] [Indexed: 11/26/2022]
Abstract
The objective of this study is to evaluate if the diagnosis of a complex congenital heart disease (CHD) was missed in a patient with Down syndrome (DS) who had a fetal echocardiogram that was read as normal. Secondary goal of this study was to determine if any CHD was missed postnatally when a fetal echocardiogram was read as normal. A retrospective chart review of children with DS at Nationwide Children's Hospital whose birthdates were between 1/1/2010 and 12/31/2017 was performed. Patients were included if they had a fetal echocardiogram that was read as normal and also had a postnatal echocardiogram performed. One hundred twenty fetal echocardiograms on patients with DS were performed, of which 45 patients met the inclusion criteria. No patient was diagnosed with a complex CHD postnatally, with a negative predictive value = 100%. Thirteen patients were diagnosed with CHD postnatally, with a negative predictive value of 71.1%. All 13 patients had either a murmur (11) or an abnormal EKG (9). One patient died at 8 days of life due to pulmonary hypertension complications. Five patients had resolution of their CHD, 2 patients have near resolution, 2 patients are being followed for their atrial septal defects and 3 underwent intervention (septum primum surgical repair = 1, PDA catheter occlusion = 2). Complex CHD was not missed on any fetal echocardiograms performed on patients with DS. All the other patients who had CHD diagnosed postnatally had an abnormal finding on evaluation. Further studies evaluating echocardiographic imaging recommendations are needed to maximize care in this patient population.
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Affiliation(s)
- Amy Cooper
- Heart Center, Nationwide Children's Hospital, Columbus, OH, USA
| | - Kacy Sisco
- Heart Center, Nationwide Children's Hospital, Columbus, OH, USA
| | - Carl H Backes
- Heart Center, Nationwide Children's Hospital, Columbus, OH, USA
- Section of Perinatology, Nationwide Children's Hospital, Columbus, OH, USA
| | - Marc Dutro
- Heart Center, Nationwide Children's Hospital, Columbus, OH, USA
| | - Ruth Seabrook
- Section of Perinatology, Nationwide Children's Hospital, Columbus, OH, USA
| | - Stephanie L Santoro
- Division of Medical Genetics, Massachusetts General Hospital, Boston, MA, USA
| | - Clifford L Cua
- Heart Center, Nationwide Children's Hospital, Columbus, OH, USA.
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Schultz A, Olorundami OA, Teng RJ, Jarzembowski J, Shi ZZ, Kumar SN, Pritchard K, Konduri GG, Afolayan AJ. Decreased OLA1 (Obg-Like ATPase-1) Expression Drives Ubiquitin-Proteasome Pathways to Downregulate Mitochondrial SOD2 (Superoxide Dismutase) in Persistent Pulmonary Hypertension of the Newborn. Hypertension 2019; 74:957-966. [PMID: 31476900 PMCID: PMC6739165 DOI: 10.1161/hypertensionaha.119.13430] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 08/07/2019] [Indexed: 11/16/2022]
Abstract
Persistent pulmonary hypertension of the newborn (PPHN) is a failure of pulmonary vascular resistance to decline at birth rapidly. One principal mechanism implicated in PPHN development is mitochondrial oxidative stress. Expression and activity of mitochondrial SOD2 (superoxide dismutase) are decreased in PPHN; however, the mechanism remains unknown. Recently, OLA1 (Obg-like ATPase-1) was shown to act as a critical regulator of proteins controlling cell response to stress including Hsp70, an obligate chaperone for SOD2. Here, we investigated whether OLA1 is causally linked to PPHN. Compared with controls, SOD2 expression is reduced in distal-pulmonary arteries (PAs) from patients with PPHN and fetal-lamb models. Disruptions of the SOD2 gene reproduced PPHN phenotypes, manifested by elevated right ventricular systolic pressure, PA-endothelial cells apoptosis, and PA-smooth muscle cells proliferation. Analyses of SOD2 protein dynamics revealed higher ubiquitinated-SOD2 protein levels in PPHN-lambs, suggesting dysregulated protein ubiquitination. OLA1 controls multiple proteostatic mechanisms and is overexpressed in response to stress. We demonstrated that OLA1 acts as a molecular chaperone, and its activity is induced by stress. Strikingly, OLA1 expression is decreased in distal-PAs from PPHN-patients and fetal-lambs. OLA1 deficiency enhanced CHIP affinity for Hsp70-SOD2 complexes, facilitating SOD2 degradation. Consequently, mitochondrial H2O2 formation is impaired, leading to XIAP (X-linked inhibitor of apoptosis) overexpression that suppresses caspase activity in PA-smooth muscle cells, allowing them to survive and proliferate, contributing to PA remodeling. In-vivo, ola1-/- downregulated SOD2 expression, induced distal-PA remodeling, and right ventricular hypertrophy. We conclude that decreased OLA1 expression accounts for SOD2 downregulation and, therefore, a therapeutic target in PPHN treatments.
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Affiliation(s)
- Adam Schultz
- Department of Pediatrics, Division of Neonatology, Cardiovascular Research Center, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226
- Department of Pediatrics, Children Hospital of Wisconsin, Milwaukee, WI, 53226
| | | | - Ru-Jeng Teng
- Department of Pediatrics, Division of Neonatology, Cardiovascular Research Center, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226
- Department of Pediatrics, Children Hospital of Wisconsin, Milwaukee, WI, 53226
| | - Jason Jarzembowski
- Department of Pathology, Children Hospital of Wisconsin, Milwaukee. WI. 53226
| | | | - Suresh N Kumar
- Department of Pediatrics, Children Hospital of Wisconsin, Milwaukee, WI, 53226
- Department of Pathology, Children Hospital of Wisconsin, Milwaukee. WI. 53226
| | - Kirkwood Pritchard
- Department of Surgery, Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee. WI. 53226
| | - Girija G. Konduri
- Department of Pediatrics, Division of Neonatology, Cardiovascular Research Center, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226
- Department of Pediatrics, Children Hospital of Wisconsin, Milwaukee, WI, 53226
| | - Adeleye J. Afolayan
- Department of Pediatrics, Division of Neonatology, Cardiovascular Research Center, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226
- Department of Pediatrics, Children Hospital of Wisconsin, Milwaukee, WI, 53226
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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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Lee JS, Cha SG, Kim GB, Lee SY, Song MK, Kwon HW, Bae EJ, Kwak JG, Kim WH, Lee JR. Reversibility of Pulmonary Hypertension Following Surgical Atrial Septal Defect Closure in Children with Down Syndrome. J Cardiovasc Imaging 2019; 27:247-253. [PMID: 31614394 PMCID: PMC6795567 DOI: 10.4250/jcvi.2019.27.e33] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 05/08/2019] [Accepted: 05/08/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Many Down syndrome (DS) patients have an atrial septal defect (ASD) and associated pulmonary hypertension (PH) from early childhood. ASD closure in DS patients with PH is often controversial due to concerns regarding exacerbation of PH. The aim of this study was to investigate the clinical outcome following surgical ASD closure in children with DS. METHODS We retrospectively reviewed the medical records of DS patients who underwent surgical ASD patch closure from January 2000 to December 2016. RESULTS A total of 15 patients underwent surgery for ASD. Prior to ASD patch closure, nine patients were diagnosed with PH, three of whom took medications for PH. The mean age of patients at ASD patch closure was 17.3 months, and the mean diameter of the ASD was 10.2 mm. Three patients who took medications for severe PH underwent ASD patch closure at ages 7, 12, and 25 months. Two patients continued medication for an additional 13 and 21 months, and one patient remained on medication 52 months after ASD closure. PH did not recur following discontinuation of selective pulmonary vasodilators in two patients. Although a moderate degree of PH remained in one patient due to a chronic lung problem, it was improved compared to before ASD closure. No PH was observed in the remaining 12 patients following ASD closure. CONCLUSIONS A large ASD can be closed even in DS patients with severe PH during early childhood with the support of multiple selective pulmonary vasodilators.
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Affiliation(s)
- Jue Seong Lee
- Department of Pediatrics, Korea University College of Medicine and Korea University Medical Center, Seoul, Korea
| | - Seul Gi Cha
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Gi Beom Kim
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
| | - Sang Yun Lee
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Mi Kyoung Song
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Hye Won Kwon
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Eun Jung Bae
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Jae Gun Kwak
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital, Seoul, Korea
| | - Woong Han Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital, Seoul, Korea
| | - Jeong Ryul Lee
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital, Seoul, Korea
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Bush D, Galambos C, Ivy DD, Abman SH, Wolter-Warmerdam K, Hickey F. Clinical Characteristics and Risk Factors for Developing Pulmonary Hypertension in Children with Down Syndrome. J Pediatr 2018; 202:212-219.e2. [PMID: 30025669 DOI: 10.1016/j.jpeds.2018.06.031] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 04/24/2018] [Accepted: 06/12/2018] [Indexed: 01/02/2023]
Abstract
OBJECTIVES To determine the incidence, characteristics of, and risk factors contributing to the development of pulmonary hypertension in children with Down syndrome. STUDY DESIGN This retrospective, review of a large cohort (n = 1242) of children with Down syndrome receiving care at a specialized referral center evaluated clinical data and serial echocardiograms from a clinic database and electronic medical records. Pulmonary hypertension characteristics and comorbidities were reviewed. Pulmonary hypertension was considered transient if echocardiographic evidence of pulmonary hypertension resolved without recurrence, persistent if no resolution, and recurrent if evidence of pulmonary hypertension returned after a period of resolution. RESULTS The incidence of pulmonary hypertension in children with Down syndrome was 28% (n = 346). Median age at initial diagnosis was 5 days (range: 0-7067 days). Pulmonary hypertension was differentiated into transient (70%), persistent (15%), and recurrent (15%) disease. Median duration of transient pulmonary hypertension was 8 months (range: 0.1-130.2 months). Median age at recurrence was 2.5 years (range 0.2-11.5 years). Initial pulmonary hypertension diagnosis was classified as World Health Organization group I disease in 82%, with 45% associated with congenital heart disease (CHD), and 38% persistent pulmonary hypertension of the newborn (PPHN). The pulmonary hypertension recurrence rate was significant and similar for both those with initial PPHN (12%) and non-PPHN (16%). A majority (87%) of patients with recurrent pulmonary hypertension were classified as World Health Organization group III. Frequently identified comorbid conditions included CHD, obstructive sleep apnea, intermittent hypoxia, and recurrent pneumonia. CONCLUSIONS Pulmonary hypertension is common in children with Down syndrome, is typically transient, and related to CHD or PPHN but can recur in the setting of respiratory disease such as obstructive sleep apnea, intermittent hypoxia, and recurrent pneumonia.
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Affiliation(s)
- Douglas Bush
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
| | - Csaba Galambos
- Department of Pathology, University of Colorado School of Medicine, Aurora, CO; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - D Dunbar Ivy
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Steven H Abman
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | | | - Francis Hickey
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
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Trucco F, Chatwin M, Semple T, Rosenthal M, Bush A, Tan HL. Sleep disordered breathing and ventilatory support in children with Down syndrome. Pediatr Pulmonol 2018; 53:1414-1421. [PMID: 29992744 DOI: 10.1002/ppul.24122] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 06/11/2018] [Indexed: 01/09/2023]
Abstract
STUDY OBJECTIVES Obstructive sleep apnoea (OSAS) in children with Down syndrome (DS) is now well recognized, but other forms of sleep disordered breathing (SDB) in this population are less well described. Anecdotally, respiratory support for SDB treatment in this population is not easily tolerated. We aimed to characterize the types of SDB in children with DS referred to a tertiary respiratory center and to assess the effectiveness and adherence to respiratory support. METHODS Retrospective study of DS patients <18 years old under follow-up at a tertiary respiratory center. Anthropometrics, comorbidities, sleep study results, and details of respiratory support were collected. Satisfactory adherence to oxygen (O2 ), Continuous Positive Airway Pressure (CPAP), or bilevel noninvasive ventilation (NIV) was defined as use >4 h/night for >50% nights. RESULTS Sixty patients were included, median age 1.5 (0.7-5.3) years; 49 (82%) had congenital heart disease, 16 (27%) pulmonary hypertension, 28 (47%) gastroesophageal reflux, 38 (63%) swallowing impairment; 16/17 who underwent CT scanning had evidence of aspiration. Forty-two had SDB: 27 (61%) OSAS (10 mild, 5 moderate, 12 severe), 11 (25%) central apnoeas, 19 (32%) nocturnal hypoventilation. Twenty-six had baseline saturations <95%. Lower SpO2 correlated with pulmonary hypertension (r2 = 0.1, P = 0.04). Thirty-nine (65%) patients started respiratory support (14 O2 , 18 CPAP, 7 NIV) and 22 (56%) have regularly used it. After a 1.9 years follow up 11/24 had satisfactory adherence to CPAP/NIV (average use 8 h/night). CONCLUSIONS Our results confirm the high prevalence of OSAS in children with DS. A significant number also have low baseline saturations, central apnoeas, and nocturnal hypoventilation. Contrary to popular belief, more than half of children with DS had satisfactory adherence to respiratory support.
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Affiliation(s)
- Federica Trucco
- Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom.,Pediatric Neurology and Muscle Disease Unit, Istituto Giannina Gaslini, Genova, Italy
| | - Michelle Chatwin
- Academic and Clinical Department of Sleep and Breathing and NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom
| | - Thomas Semple
- Department of Radiology, Royal Brompton Hospital, London, United Kingdom
| | - Mark Rosenthal
- Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom
| | - Andrew Bush
- Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom.,National Heart and Lung Institute, Imperial College, London, United Kingdom
| | - Hui-Leng Tan
- Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom
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NICU management and outcomes of infants with trisomy 21 without major anomalies. J Perinatol 2018; 38:1068-1073. [PMID: 29795453 PMCID: PMC6335104 DOI: 10.1038/s41372-018-0136-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 04/20/2018] [Accepted: 04/24/2018] [Indexed: 11/08/2022]
Abstract
OBJECTIVE To describe how trisomy 21 affects neonatal intensive care management and outcomes of full-term infants without congenital anomalies. STUDY DESIGN Retrospective cohort of full-term infants without anomalies with and without trisomy 21 admitted to Pediatrix NICUs from 2005 to 2012. We compared diagnoses, management, length of stay, and discharge outcomes. RESULTS In all, 4623 infants with trisomy 21 and 606 770 infants without trisomy 21 were identified. One-third of infants in the NICU with and without trisomy 21 were full term without major anomalies. Trisomy 21 infants had more respiratory distress, thrombocytopenia, feeding problems, and pulmonary hypertension. They received respiratory support for a longer period of time and had a longer length of stay. CONCLUSION One-third of infants with trisomy 21 admitted to the NICU are full term without major anomalies. Common diagnoses and greater respiratory needs place infants with trisomy 21 at risk for longer length of stay.
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Duffy V, Gomez D, Rycus P, Rivera B, Santoro SL, Backes CH, Cua CL. Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Adult Patients With Down Syndrome. Artif Organs 2018; 42:921-925. [PMID: 29774549 DOI: 10.1111/aor.13160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 02/20/2018] [Accepted: 03/19/2018] [Indexed: 12/16/2022]
Abstract
Patients with Down syndrome (DS) may have multiple medical issues that place them at risk for requiring extracorporeal membrane oxygenation. Use of extracorporeal membrane oxygenation in pediatric patients with Down syndrome has been described, but minimal data exist for extracorporeal membrane oxygenation use in adults with Down syndrome. The goal of this study was to describe the clinical characteristics and to determine if there were differences between adult extracorporeal membrane oxygenation patients with Down syndrome that were alive (aDS) versus those that died (dDS) prior to hospital discharge. Patients with Down syndrome that were 18 years and older registered in the Extracorporeal Life Support Organization registry from 1983 to 2016 were analyzed. Demographics and extracorporeal membrane oxygenation characteristics were recorded. A total of 21 adults with Down syndrome were identified. Incidence of extracorporeal membrane oxygenation in adults with Down syndrome was 0.88 per 1000 extracorporeal membrane oxygenation procedures. Hospital mortality was 57.1% (12/21). There were no significant differences between aDS versus dDS for age (24.9 ± 4.8 vs. 28.1 ± 10.2 years), weight (90.7 ± 13.0 vs. 79.1 ± 27.0 kg), gender (4 males vs. 8 males), initial pH (7.18 ± 0.19 vs. 7.27 ± 0.16), or initial pO2 (51.7 ± 13.9 vs. 45.4 ± 19.9), respectively. There were no significant differences between aDS versus dDS in duration of extracorporeal membrane oxygenation run (239 ± 159 h vs. 455 ± 570 h, respectively), ventilator or extracorporeal membrane oxygenation mode, and nitric oxide use. aDS had fewer incidences of mechanical and neurologic complications (41.7% vs. 0.0%, P < 0.05) versus dDS. There were no other significant differences in complication rates between the two groups. Use of extracorporeal membrane oxygenation in the adult population with Down syndrome is significantly less compared to the pediatric population with Down syndrome. Baseline characteristics are not predictive of overall survival. There were minimal differences noted between aDS versus dDS during their extracorporeal membrane oxygenation course. Mortality rates are similar to non-Down syndrome patients placed on extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation may be a reasonable option for adult patients with Down syndrome requiring intensive care.
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Affiliation(s)
- Vicky Duffy
- Heart Center, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
| | - Daniel Gomez
- Heart Center, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
| | - Peter Rycus
- Extracorporeal Life Support Organization, Ann Arbor, MI, USA
| | - Brian Rivera
- Heart Center, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
| | - Stephanie L Santoro
- Heart Center, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
| | - Carl H Backes
- Heart Center, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
| | - Clifford L Cua
- Heart Center, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA
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Martin T, Smith A, Breatnach CR, Kent E, Shanahan I, Boyle M, Levy PT, Franklin O, El-Khuffash A. Infants Born with Down Syndrome: Burden of Disease in the Early Neonatal Period. J Pediatr 2018; 193:21-26. [PMID: 29174996 DOI: 10.1016/j.jpeds.2017.09.046] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 07/28/2017] [Accepted: 09/19/2017] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To evaluate the incidence of direct admission of infants with Down syndrome to the postnatal ward (well newborn nursery) vs the neonatal intensive care unit (NICU), and to describe the incidence of congenital heart disease (CHD) and pulmonary hypertension (PH). STUDY DESIGN This retrospective cohort study of Down syndrome used the maternal/infant database (2011-2016) at the Rotunda Hospital in Dublin, Ireland. Admission location, early neonatal morbidities, outcomes, and duration of stay were evaluated and regression analyses were conducted to identify risk factors associated with morbidity and mortality. RESULTS Of the 121 infants with Down syndrome, 54 (45%) were initially admitted to the postnatal ward, but 38 (70%) were later admitted to the NICU. Low oxygen saturation profile was the most common cause for the initial and subsequent admission to the NICU. Sixty-six percent of the infants (80/121) had CHD, 34% (41/121) had PH, and 6% died. Risk factors independently associated with primary NICU admission included antenatal diagnosis of Down syndrome, presence of CHD, PH, and the need for ventilation. CONCLUSIONS Infants with Down syndrome initially admitted to the postnatal ward have a high likelihood of requiring NICU admission. Overall, high rates of neonatal morbidity were noted, including rates of PH that were higher than previously reported. Proper screening of all infants with Down syndrome for CHD and PH is recommended to facilitate timely diagnoses and potentially shorten the duration of the hospital stay.
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Affiliation(s)
- Therese Martin
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Aisling Smith
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Colm R Breatnach
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Etaoin Kent
- Department of Obstetrics and Gynecology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ita Shanahan
- Department of Obstetrics and Gynecology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Michael Boyle
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland
| | - Phillip T Levy
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO; Goryeb Children's Hospital, Atlantic Health System, Morristown, NJ
| | - Orla Franklin
- Department of Pediatric Cardiology, Our Lady's Children's Hospital, Dublin, Ireland
| | - Afif El-Khuffash
- Department of Neonatology, The Rotunda Hospital, Dublin, Ireland; School of Medicine (Department of Pediatrics), Royal College of Surgeons in Ireland, Dublin, Ireland.
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Mann JP, Statnikov E, Modi N, Johnson N, Springett A, Morris JK. Management and outcomes of neonates with down syndrome admitted to neonatal units. ACTA ACUST UNITED AC 2017; 106:468-74. [PMID: 27301559 DOI: 10.1002/bdra.23513] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 03/22/2016] [Indexed: 11/09/2022]
Abstract
BACKGROUND Neonates with Down syndrome have an increased risk of being admitted to a neonatal unit compared with unaffected neonates. We aimed to estimate the proportion of neonates with Down syndrome admitted to a neonatal unit and compare their management and outcomes with other neonatal admissions. METHODS Case-control study of neonates born from 2009 to 2011 admitted to 122 NHS Neonatal Units in England using data from the National Down Syndrome Cytogenetic Register and the National Neonatal Research Database. For each neonate with Down syndrome, three neonates admitted to the same unit in the same month and born at the same gestation were identified. RESULTS Forty-six percent of neonates with Down syndrome were admitted to a neonatal unit. Boys were more likely to be admitted than girls (odds ratio = 1.7; 95% confidence interval, 1.4-2.0). Neonates with Down syndrome required more intensive or high dependency care compared with unaffected neonates (37% vs. 27%. p < 0.01) and stayed in neonatal units for longer (11 days vs. 5 days, p < 0.01). A total of 31% of neonates with Down syndrome required respiratory support compared with 22% (p < 0.001) of unaffected neonates, and 11% were discharged requiring oxygen supplementation compared with 3% (p < 0.001) of unaffected neonates. A total of 3% of neonates with Down syndrome died in a neonatal unit compared with 1% (p = 0.01) of unaffected neonates. CONCLUSION Neonates with Down syndrome are more likely than unaffected neonates to be admitted to a neonatal unit, have a prolonged stay, and be discharged home on supplemental oxygen. Birth Defects Research (Part A) 106:468-474, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Jake P Mann
- Department of paediatrics, University of Cambridge, Cambridge, United Kingdom
| | - Eugene Statnikov
- Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Hospital campus, London, United Kingdom
| | - Neena Modi
- Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Hospital campus, London, United Kingdom
| | - Nik Johnson
- Children's unit, Hinchingbrooke Hospital, Huntingdon, United Kingdom
| | - Anna Springett
- Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Joan K Morris
- Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
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Alnemri AM. Black lung persistent pulmonary hypertension of the newborn. Saudi experience with sildenafil and nitric oxide. Saudi Med J 2017; 38:97-100. [PMID: 28042638 PMCID: PMC5278074 DOI: 10.15537/smj.2017.1.16223] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Objectives: To determine the clinical presentation, risk factors, diagnosis, and treatment outcome of Saudi infants with black lung persistent pulmonary hypertension of the newborn (PPHN). Methods: This is a retrospective review of all neonates with PPHN presented to the Armed Force Hospital Southern Region, Kingdom of Saudi Arabia from January 2012 to December 2014. Results: Ten term and near term infants presented with PPHN were included. Maternal diabetes and Down syndrome were the most common identified risk factors for PPHN in the study group. Nine infants were treated with oral sildenafil and did not require mechanical ventilation. Only one infant required mechanical ventilation and inhaled nitric oxide in addition to oral sildenafil. Conclusion: Most of the patients in this cohort with PPHN had risk factors, they did not require mechanical ventilation and responded well to oral sildenafil.
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Affiliation(s)
- AbdulRahman M Alnemri
- Neonatal Intensive Care Unit, and Coeliac Disease Research Chair, Department of Pediatrics, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.
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Abstract
Failure of the normal circulatory adaptation to extrauterine life results in persistent pulmonary hypertension of the newborn (PPHN). Although this condition is most often secondary to parenchymal lung disease or lung hypoplasia, it may also be idiopathic. PPHN is characterized by elevated pulmonary vascular resistance with resultant right-to-left shunting of blood and hypoxemia. Although the preliminary diagnosis of PPHN is often based on differential cyanosis and labile hypoxemia, the diagnosis is confirmed by echocardiography. Management strategies include optimal lung recruitment and use of surfactant in patients with parenchymal lung disease, maintaining optimal oxygenation and stable blood pressures, avoidance of respiratory and metabolic acidosis and alkalosis, and pulmonary vasodilator therapy. Extracorporeal membrane oxygenation is considered when medical management fails. Although mortality associated with PPHN has decreased significantly with improvements in medical care, there remains the potential risk for neurodevelopmental disability which warrants close follow-up of affected infants after discharge.
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Affiliation(s)
- Mamta Fuloria
- Department of Pediatrics, Albert Einstein College of Medicine and the Children's Hospital at Montefiore, Bronx, NY, USA
| | - Judy L Aschner
- Departments of Pediatrics and Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine and the Children's Hospital at Montefiore, Bronx, NY, USA.
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Cua CL, Haque U, Santoro S, Nicholson L, Backes CH. Differences in mortality characteristics in neonates with Down's syndrome. J Perinatol 2017; 37:427-431. [PMID: 28079865 DOI: 10.1038/jp.2016.246] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 10/19/2016] [Accepted: 12/01/2016] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Neonates with Down's syndrome (nDS) may have multiple medical issues that place them at increased risk for mortality during the newborn period. Goal of this study was to determine if there are differences in baseline characteristics, medical complications or procedures performed during hospitalization between nDS who survived versus those who died during initial hospitalization. STUDY DESIGN Data from 2000 to 2014 were reviewed using the Pediatric Health Information Systems (PHIS) database on all DS patients admitted to the hospital <30 days postnatal life. Baseline demographics, medical complications, procedures performed and mortality were recorded. Patients were divided into nDS patients who were discharged alive (nDS-a) versus nDS patients who died (nDS-d). Multivariate logistic analysis with odds ratios was performed to determine significant predictors of death. A P<0.05 was considered significant. RESULTS A total of 5737 nDS were evaluated. Overall mortality was 7.5% (431/5737). nDS-d were more likely than nDS-a to have a lower birth weight (1.0 (0.9 to 1.0)), presence of a diaphragmatic hernia (6.9 (1.9 to 25.1), or a cardiac diagnosis of a pulmonary venous abnormality (6.8 (1.9 to 24.4)), Ebstein's anomaly (3.2 (1.2 to 8.5)) or left-sided obstructive lesion (2.0 (1.3 to 3.0). nDS-d were more likely to develop hydrops (5.7 (3.5 to 9.5)) and necrotizing enterocolitis (1.7 (1.2 to 2.6)). In addition, nDS-d had significantly higher odds of requiring mechanical ventilation (20.7 (9.9 to 43.1)) or extracorporeal membrane oxygenation (8.7 (4.7 to 16.1)). CONCLUSIONS A number of characteristics, specifically certain cardiac diagnosis, place nDS at increased risk for mortality. Furthermore, development of specific medical complications or need for particular procedures increases the odds for mortality in nDS. Caregivers should be cognizant that they are taking care of a high-risk population nDS with an increased risk for mortality if these variables are present.
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Affiliation(s)
- C L Cua
- Department of Pediatrics, Heart Center, Nationwide Children's Hospital, Columbus Children's Hospital, Columbus, OH, USA
| | - U Haque
- Department of Pediatrics, Heart Center, Nationwide Children's Hospital, Columbus Children's Hospital, Columbus, OH, USA
| | - S Santoro
- Department of Pediatrics, Heart Center, Nationwide Children's Hospital, Columbus Children's Hospital, Columbus, OH, USA
| | - L Nicholson
- Department of Pediatrics, Heart Center, Nationwide Children's Hospital, Columbus Children's Hospital, Columbus, OH, USA
| | - C H Backes
- Department of Pediatrics, Heart Center, Nationwide Children's Hospital, Columbus Children's Hospital, Columbus, OH, USA
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Colvin KL, Yeager ME. What people with Down Syndrome can teach us about cardiopulmonary disease. Eur Respir Rev 2017; 26:26/143/160098. [DOI: 10.1183/16000617.0098-2016] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 11/13/2016] [Indexed: 12/19/2022] Open
Abstract
Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations (particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.
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Balli S, Yucel IK, Kibar AE, Ece I, Dalkiran ES, Candan S. Assessment of cardiac function in absence of congenital and acquired heart disease in patients with Down syndrome. World J Pediatr 2016; 12:463-469. [PMID: 27059745 DOI: 10.1007/s12519-016-0012-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 01/12/2015] [Indexed: 01/11/2023]
Abstract
BACKGROUND Extra genetic material in patients with Down syndrome (DS) may affect the function of any organ system. We evaluated cardiac functions using conventional tissue Doppler and two-dimensional speckle tracking echocardiography in patients with DS in the absence of congenital and acquired heart disease in patients. METHODS A total of 115 patients with DS between 6 and 13 years of age with clinically and anatomically normal heart and 55 healthy children were included in this cross-sectional study. DS was diagnosed by a karyotype test. Patients with mosaic type were not included in this study. Systolic and diastolic functions were evaluated by echocardiography. RESULTS Pulsed waved Doppler transmitral early/late inflow velocity (E/A), tissue Doppler mitral annular early/late diastolic peak velocity (Ea/Aa), transtricuspid E/A and tricuspid valve annulus Ea/Aa, pulmonary venous Doppler systolic/diastolic (S/D) wave ratio were lower in patients with Down syndrome than in the control group (P=0.04, P=0.001, P<0.05, P<0.001, P<0.001, respectively). Mitral and tricuspid annular Ea were lower in patients with DS (P<0.001). The right and left ventricular myocardial performance indexes were higher in patients with DS than in the controls (P<0.01). They had significantly higher left ventricular mass, ejection fraction, the mitral annular plane systolic excursion values. However, the Down syndrome group compared with the controls had a lower strain values examined by two-dimensional longitudinal speckle-tracking strain echocardiography. CONCLUSION These findings suggest conventional tissue Doppler and two-dimensional longitudinal speckletracking strain echocardiography were useful methods of investigating ventricular function and identifying a higher incidence of biventricular dysfunction in patients with Down syndrome compared with the healthy controls.
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Affiliation(s)
- Sevket Balli
- Department of Pediatric Cardiology, Balikesir Ataturk Hospital, Balikesir, Turkey.
| | - Ilker Kemal Yucel
- Department of Pediatric Cardilogy, Siyami Ersek Education and Research Hospital, Istanbul, Turkey
| | - Ayse Esin Kibar
- Department of Pediatric Cardiology, Children's Hospital, Mersin, Turkey
| | - Ibrahim Ece
- Department of Pediatric Cardiology, Yuzuncu Yil University of Medicine, Van, Turkey
| | | | - Sukru Candan
- Department of Medical Genetics, Balikesir Ataturk Hospital, Balikesir, Turkey
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Galambos C, Minic AD, Bush D, Nguyen D, Dodson B, Seedorf G, Abman SH. Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension. PLoS One 2016; 11:e0159005. [PMID: 27487163 PMCID: PMC4972384 DOI: 10.1371/journal.pone.0159005] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 06/24/2016] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND AND AIMS Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero. METHODS Human fetal lung tissue from DS and non-DS subjects were obtained from a biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and wall thickness were determined by morphometric analysis. RESULTS The angiogenesis array identified up-regulation of three anti-angiogenic genes: COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase 3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002; respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects. CONCLUSIONS We conclude that lung anti-angiogenic factors, including COL18A1 (ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is decreased in subjects with DS. We speculate that increased fetal lung anti-angiogenic factor expression due to trisomy 21 impairs lung vascular growth and signaling, which impairs alveolarization and contributes to high risk for PAH during infancy.
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Affiliation(s)
- Csaba Galambos
- Departments of Pathology and Laboratory Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
- The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
- * E-mail:
| | - Angela D. Minic
- Departments of Pathology and Laboratory Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
- The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
| | - Douglas Bush
- Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
- The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
| | - Dominique Nguyen
- University of Notre Dame, South Bend, Indiana, United States of America
| | - Blair Dodson
- Pediatric Surgery, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
- The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
| | - Gregory Seedorf
- The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
| | - Steven H. Abman
- Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
- The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, United States of America
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Extracorporeal Membrane Oxygenation Incidence, Characteristics, and Outcomes in Neonatal Down Syndrome Patients. ASAIO J 2016; 62:477-81. [DOI: 10.1097/mat.0000000000000359] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Lewanda AF, Matisoff A, Revenis M, Harahsheh A, Futterman C, Nino G, Greenberg J, Myseros JS, Rosenbaum KN, Summar M. Preoperative evaluation and comprehensive risk assessment for children with Down syndrome. Paediatr Anaesth 2016; 26:356-62. [PMID: 26749540 DOI: 10.1111/pan.12841] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/01/2015] [Indexed: 01/24/2023]
Abstract
Down syndrome is a common chromosome disorder affecting all body systems. This creates unique physiologic concerns that can affect safety during anesthesia and surgery. Little consensus exists, however, on the best way to evaluate children with Down syndrome in preparation for surgery. We review a number of salient topics affecting these children in the perioperative period, including cervical spine instability, cardiovascular abnormalities, pulmonary hypertension, upper airway obstruction, hematologic disturbances, prematurity, low birth weight, and the use of supplements and alternative therapies. Recommendations include obtaining a complete blood count to detect an increased risk for bleeding or stroke, and cardiology evaluation to identify patients with pulmonary hypertension, as well as undiagnosed or residual heart disease. Pediatric cardiac anesthesiologists and intensivists should be involved as needed. The potential for cervical spine instability should be considered, and the anesthesiologist may wish to have several options available both for the medications and equipment used. The child's family should always be asked if he or she is on any nutritional supplements, as some products marketed to families may have secondary effects such as inhibition of platelet function. Using this evaluation in presurgical planning will allow physicians to better consider the individual circumstances for their patients with Down syndrome. Our goal was to optimize patient safety by choosing the most appropriate setting and perioperative personnel, and to mitigate those risk factors amenable to intervention.
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Affiliation(s)
- Amy Feldman Lewanda
- Division of Genetics & Metabolism, Children's National Health System, Washington, DC, USA
| | - Andrew Matisoff
- Divisions of Anesthesiology, Sedation, and Perioperative Medicine, Children's National Health System, Washington, DC, USA
| | - Mary Revenis
- Division of Neonatology, Children's National Health System, Washington, DC, USA
| | - Ashraf Harahsheh
- Division of Cardiology, Children's National Health System, Washington, DC, USA
| | - Craig Futterman
- Division of Critical Care Medicine, Children's National Health System, Washington, DC, USA
| | - Gustavo Nino
- Divisions of Pulmonary Medicine and Sleep Medicine, Children's National Health System, Washington, DC, USA
| | - Jay Greenberg
- Divisions of Hematology and Oncology, Children's National Health System, Washington, DC, USA
| | - John S Myseros
- Division of Neurosurgery, Children's National Health System, Washington, DC, USA
| | - Kenneth N Rosenbaum
- Division of Genetics & Metabolism, Children's National Health System, Washington, DC, USA
| | - Marshall Summar
- Division of Genetics & Metabolism, Children's National Health System, Washington, DC, USA
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Abstract
KEY POINTS Respiratory distress is a common presenting feature among newborn infants.Prompt investigation to ascertain the underlying diagnosis and appropriate subsequent management is important to improve outcomes.Many of the underlying causes of respiratory distress in a newborn are unique to this age group.A chest radiograph is crucial to assist in diagnosis of an underlying cause. EDUCATIONAL AIMS To inform readers of the common respiratory problems encountered in neonatology and the evidence-based management of these conditions.To enable readers to develop a framework for diagnosis of an infant with respiratory distress. The first hours and days of life are of crucial importance for the newborn infant as the infant adapts to the extra-uterine environment. The newborn infant is vulnerable to a range of respiratory diseases, many unique to this period of early life as the developing fluid-filled fetal lungs adapt to the extrauterine environment. The clinical signs of respiratory distress are important to recognise and further investigate, to identify the underlying cause. The epidemiology, diagnostic features and management of common neonatal respiratory conditions are covered in this review article aimed at all healthcare professionals who come into contact with newborn infants.
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Affiliation(s)
| | | | - Sailesh Kotecha
- Department of Child Health, School of Medicine, Cardiff University, Cardiff, UK
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Abstract
Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia.
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Extracorporeal Membrane Oxygenation in Pediatric Trisomy 21: 30 Years of Experience from the Extracorporeal Life Support Organization Registry. J Pediatr 2015; 167:403-8. [PMID: 25982140 DOI: 10.1016/j.jpeds.2015.04.048] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 03/12/2015] [Accepted: 04/15/2015] [Indexed: 11/23/2022]
Abstract
OBJECTIVES To describe the use of extracorporeal membrane oxygenation (ECMO) in patients with trisomy 21 (T21), to identify risk factors for hospital mortality, and to compare outcomes with those of patients without T21. STUDY DESIGN Children under age 18 years registered in the Extracorporeal Life Support Organization Registry were included. Comparisons between patients with T21 and patients without T21 were performed using the χ(2) or Wilcoxon rank-sum test and multivariable logistic regression. RESULTS The study cohort included 623 patients with T21 and 46 239 patients without T21. The prevalence of T21 was 13.5/1000 patients receiving ECMO. ECMO utilization in patients with T21 increased over time, with 60% of cases occurring in the last decade. There was no significant difference in survival between patients without T21 and those with T21 (63% vs 57%; P = .23). In patients with T21, independent risk factors for mortality before cannulation were a cardiac indication for ECMO support and milrinone use (P ≤ .001 for both). Multivariable risk factors for mortality on ECMO included hemorrhagic, neurologic, renal, and pulmonary complications (P < .04 for all). CONCLUSION The use of ECMO in patients with T21 has increased over time. Patients with a cardiac indication for ECMO have higher mortality compared with those supported for respiratory indications. Despite differences in indications for ECMO, patients with T21 have similar hospital survival as those without T21; thus, by itself, a diagnosis of T21 should not be considered a risk factor for in-hospital mortality when contemplating ECMO cannulation.
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Espinola-Zavaleta N, Soto ME, Romero-Gonzalez A, Gómez-Puente LDC, Muñoz-Castellanos L, Gopal AS, Keirns C, Lupi-Herrera E. Prevalence of Congenital Heart Disease and Pulmonary Hypertension in Down's Syndrome: An Echocardiographic Study. J Cardiovasc Ultrasound 2015; 23:72-7. [PMID: 26140148 PMCID: PMC4486181 DOI: 10.4250/jcu.2015.23.2.72] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/25/2015] [Accepted: 05/19/2015] [Indexed: 01/29/2023] Open
Abstract
Background Down's syndrome (DS) is a genetic anomaly, which undergoes increased morbidity and mortality when associated with congenital heart disease (CHD). The aims of the study were to determine the prevalence of CHD and pulmonary hypertension (PH) in DS. Methods One hundred twenty-seven patients with DS living in Mexico City were evaluated by physical exam, electrocardiogram and echocardiogram. Results CHD was found in 40%. In 80% (n = 102) PH was present [systolic pulmonary artery pressure (SPAP) of 47 ± 19 mm Hg and mean pulmonary artery pressure (MPAP) of 32 ± 11 mm Hg]. Patients with CHD and PH were classified as having 1) no shunt (n = 18) with SPAP of 37 ± 9 mm Hg and MPAP of 25 ± 6 mm Hg and 2) with shunt (n = 26) with PASP of 57 ± 29 mm Hg and MPAP of 38 ± 19 mm Hg (p ≤ 0.001). In those without CHD or with CHD without shunt (n = 76), SPAP was 37 ± 19 mm Hg and the MPAP 25 ± 6 mm Hg. The prevalence of PH in DS was 5.9% at one year and 15% at 10 years. The odds ratio of PH in DS with CHD was 7.3 vs. 3 without CHD. Conclusion DS has a high prevalence of CHD and PH. PH prevalence increases when it is associated with CHD. The pathophysiology of PH in DS without CHD should be studied in the near future. Echocardiography is an indispensible tool for evaluation of DS.
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Affiliation(s)
- Nilda Espinola-Zavaleta
- ABC Medical Center I.A.P, Cardiovascular Division, Mexico City, Mexico. ; National Institute of Cardiology "Ignacio Chavez", Echocardiography in Out-Patient Clinic, Immunology Department, Embryology Department, Mexico City, Mexico
| | - María Elena Soto
- ABC Medical Center I.A.P, Cardiovascular Division, Mexico City, Mexico. ; National Institute of Cardiology "Ignacio Chavez", Echocardiography in Out-Patient Clinic, Immunology Department, Embryology Department, Mexico City, Mexico
| | - Angel Romero-Gonzalez
- National Institute of Cardiology "Ignacio Chavez", Echocardiography in Out-Patient Clinic, Immunology Department, Embryology Department, Mexico City, Mexico
| | | | - Luis Muñoz-Castellanos
- National Institute of Cardiology "Ignacio Chavez", Echocardiography in Out-Patient Clinic, Immunology Department, Embryology Department, Mexico City, Mexico
| | - Aasha S Gopal
- St. Francis Hospital, Cardiac Imaging, New York, USA
| | - Candace Keirns
- Massachusetts General Hospital, Interpreters Service, Boston, USA
| | - Eulo Lupi-Herrera
- ABC Medical Center I.A.P, Cardiovascular Division, Mexico City, Mexico
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Damico R, Kolb TM, Valera L, Wang L, Housten T, Tedford RJ, Kass DA, Rafaels N, Gao L, Barnes KC, Benza RL, Rand JL, Hamid R, Loyd JE, Robbins IM, Hemnes AR, Chung WK, Austin ED, Drummond MB, Mathai SC, Hassoun PM. Serum endostatin is a genetically determined predictor of survival in pulmonary arterial hypertension. Am J Respir Crit Care Med 2015; 191:208-18. [PMID: 25489667 DOI: 10.1164/rccm.201409-1742oc] [Citation(s) in RCA: 92] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
RATIONALE Pulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH. OBJECTIVES We sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH. METHODS We measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minute-walk distance, invasive hemodynamics, and laboratory chemistries. MEASUREMENTS AND MAIN RESULTS Serum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality. CONCLUSIONS Our data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.
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Lal C, White DR, Joseph JE, van Bakergem K, LaRosa A. Sleep-Disordered Breathing in Down Syndrome. Chest 2015; 147:570-579. [PMID: 25644910 DOI: 10.1378/chest.14-0266] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Affiliation(s)
- Chitra Lal
- Department of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, Charleston, SC.
| | - David R White
- Department of Pediatric Otolaryngology, Medical University of South Carolina, Charleston, SC
| | - Jane E Joseph
- Department of Neurosciences, Medical University of South Carolina, Charleston, SC
| | - Karen van Bakergem
- Department of Pediatrics, Division of Developmental-Behavioral Pediatrics, Medical University of South Carolina, Charleston, SC
| | - Angela LaRosa
- Department of Pediatrics, Division of Developmental-Behavioral Pediatrics, Medical University of South Carolina, Charleston, SC
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Aguilar Cordero MJ, Mur Villar N, García García I. Evaluation of pain in healthy newborns and in newborns with developmental problems (Down syndrome). Pain Manag Nurs 2014; 16:267-72. [PMID: 25439126 DOI: 10.1016/j.pmn.2014.08.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 07/31/2014] [Accepted: 08/04/2014] [Indexed: 11/20/2022]
Abstract
Newborns are often subjected to invasive and painful medical procedures. This happens even more frequently when they require hospitalization. The aim of this paper was to evaluate pain in healthy newborns and in newborns with Down syndrome (DS). We performed a prospective cohort study in the neonatal service of the San Cecilio University Hospital in Granada (Spain) from January 2008 to September 2013. The universe of our study comprised a study group of 20 newborns with DS and a control group of 20 newborns without DS. All of the infants were hospitalized, and thus had to undergo painful medical procedures. The variables studied were basal recovery time (as reflected in crying and the normalization of biological constants), number of punctures, oxygen saturation, heartbeat, blood pressure, response to skin-to-skin contact, and gestational age. The evaluation was performed during blood extraction, vein canalization, and heel puncture. The significant differences in the basal recovery time between the two groups of newborns indicated that those with DS were slower to express pain, and when they did, their response was not as clearly defined as that of babies without DS. The oxygen saturation in babies with DS after the puncture was found to be significantly lower than that of the control group (p < .001). The results of this study revealed that babies with DS were not as quick to perceive pain after a puncture. However, when pain was finally perceived, it persisted for a longer time. This situation should be taken into account in the design of pharmacologic and nonpharmacologic therapies.
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Affiliation(s)
- Maria José Aguilar Cordero
- Department of Nursing, Faculty of Healthcare Science, University of Granada, Granada, Spain, Nurse at the San Cecilio University Hospital of Granada, Spain.
| | - Norma Mur Villar
- University Medical of Cienfuegos, Cuba, Research Assistant at Research Group CTS 367, Andalusian Research Plan, Andalusian Regional Government, Spain
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Bester K. The syndromic child and anaesthesia. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2014. [DOI: 10.1080/22201181.2014.979633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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