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Despite a growing number of adults with intellectual and developmental disabilities (IDD) and documented risk for adverse outcomes as they age, little is known about the health and healthcare patterns of adults with different IDD throughout adulthood. This study uses Wisconsin Medicaid claims data to characterize health conditions among adults with IDD. Results indicate high prevalence of asthma, diabetes, heart disease, and hypertension. Heart disease rates were particularly high, having been observed among 39% of autistic adults, 64% of autistic adults with intellectual disability (ID), 67% of adults with Down syndrome, and 75% of adults with ID only. Given there are no known biological differences underlying increased morbidities among most people with IDD, developing inclusive prevention measures should be prioritized in future research., (©AAIDD.)

Background: Studies investigating the quality of the diet and dietary intake of children with Down syndrome (DS) are required because the features attributed to the syndrome can affect growth, development and quality of life., Methods: This cross-sectional study was conducted with 77 Brazilian children with DS between 5 and 36 months of age receiving care at the multidisciplinary outpatient clinic of the University Hospital. Participants' sociodemographic, dietary and anthropometric data were collected from the care protocols. Dietary data were collected from 24-h recalls and dietary practices were assessed according to the WHO dietary guidelines. Associations between inadequate feeding practices and demographic variables were assessed using logistic regression models., Results: Fruits, milk or infant formula, vegetables, beans and meat were among the five most consumed foods by the children investigated. Overall, we observed a high number of cases of early weaning (50.6%), low minimum dietary diversity (MDD; 40.3%), inadequate consistency for age (64.9%), early presence of ultra-processed foods (76.6%), sugars and sweets (33.8%) in the diet of the children with DS. In the associations of inadequate feeding practices by age group, low MDD [odds ratio (OR): 18.6; 95% confidence interval (CI): 3.4; 57.1] and inadequate consistency (OR: 6.65; 95% CI: 1.8; 24.7) were more frequent among children aged below 12 months while this relationship was inverse for early introduction of sugar and sweets (OR: 0.04; 95% CI: 0.01; 0.29)., Conclusion: Our findings showed a high number of cases of inadequate dietary practices in children with DS investigated, which could adversely affect the long-term health of this population., (© 2024 John Wiley & Sons and MENCAP.)

Background: Down syndrome (DS) is one of the most common chromosomal abnormalities, and children with DS have increased risks of receiving diagnoses of specific comorbidities., Aims: This study aimed to assess the frequencies and relationships between sleep problems, gastrointestinal (GI) symptoms, comorbid psychopathology, and challenging behavior., Methods and Procedures: The Children's Sleep Habits Questionnaire, Gastrointestinal Symptom Inventory, Autism Spectrum Disorder-Comorbid for Children, and Behavior Problems Inventory-Short Form were completed by 123 parents of children and adolescents with DS., Outcomes and Results: The frequency of GI symptoms was 74.8 %, with high frequencies also found for: sleep problems (100 %), challenging behavior (100 %), and moderate to severe levels of comorbid psychopathology (tantrum=80 %; repetitive behavior=63 %; avoidant behavior=82 %; worry/depressed=61 %; conduct behavior=100 %; over-eating=100 %; under-eating=100 %). A significant moderate correlation was found between total GI symptoms and self-injurious behavior frequency. Children who presented with abdominal pain engaged in self-injurious behavior more frequently than those with no abdominal pain., Conclusions and Implications: Findings indicated a high frequency of sleep problems, comorbid psychopathology, GI symptoms, and challenging behavior and demonstrated a relationship between GI symptoms and self-injurious behavior in children and adolescents with DS. This research illustrated the importance of investigating comorbid conditions in individuals with DS. WHAT THIS PAPER ADDS?: Down Syndrome (DS) is a genetic condition characterized by trisomy 21 and is a leading cause of intellectual disability worldwide. The prevalence of DS is commonly associated with advanced maternal age and is associated with multiple comorbid conditions. The current study aimed to investigate the frequency of and relationship between sleep problems, gastrointestinal symptoms, comorbid psychopathology, and challenging behavior in children and adolescents with DS. High-frequency levels were found for sleep problems (100 %), challenging behavior (100 %), gastrointestinal symptoms (74.8 %), and moderate to severe levels of the different comorbid psychopathologies (tantrum=80 %; repetitive behavior=63 %; avoidant behavior=82 %; worry/depressed=61 %; conduct behavior=100 %; over-eating=100 %; under-eating=100 %). Results indicated a significant difference in self-injurious behavior frequency between individuals who presented with abdominal pain and those who did not. This study is the first to investigate the relationship of multiple comorbid conditions in a sample of children with DS. This paper adds to the literature by demonstrating the frequency of a number of comorbid conditions in children and adolescents with DS. The paper also adds novel findings to the literature by investigating the relationships between comorbid conditions in this population. The findings of this paper highlighted the frequency and comorbidities that exist between gastrointestinal symptoms, sleep problems, comorbid psychopathology, and challenging behavior. Analyses indicated that those who presented with abdominal pain, engaged in self-injurious behavior more frequently. Sleep problems, gastrointestinal symptoms, comorbid psychopathology, and challenging behavior in children and adolescents with Down Syndrome., Competing Interests: Declaration of Competing Interest All the authors of this article declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population., Methods: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy., Results: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1)., Conclusions: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

A 2003 survey revealed the scope of mothers' dissatisfaction with their postnatal support following a diagnosis of Down syndrome (DS). Substantial proportions of mothers reported that providers conveyed diagnoses with pity, emphasized negative aspects of DS, and neglected to provide adequate materials explaining DS. This study follows up on the 2003 survey by assessing whether parents' experiences have improved. Four DS nonprofit organizations, which participated in the original study, distributed a mixed-methods survey to families who have had children with DS between 2003 and 2022. Quantitative analysis assessed correlations among responses and differences between the 2003 and 2022 survey groups. Open-ended responses were qualitatively analyzed. Compared to the 2003 findings, parents' perceptions of their postnatal care have not improved (N = 89). Parents are increasingly likely to report that their providers pitied them, omitted positive aspects of DS, and provided insufficient materials describing DS. Substantial proportions of parents reported fear (77%) and anxiety (79%), only 24% described receiving adequate explanatory materials, and parents were 45% likelier to report that physicians discussed negative aspects of DS than positive aspects. Qualitatively, substantial numbers of parents recounted insensitive conduct by providers. These results suggest that despite interventions, parents' experiences of postnatal diagnoses of DS have not improved over time. Certain provider behaviors-such as describing positive aspects of DS and providing comprehensive explanatory materials-can reduce fear and anxiety, pointing to directions for reform., (© 2024 Wiley Periodicals LLC.)

Aim: This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines., Methods: This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGβ values ≥10 MoM. Complementary exams and outcomes were analyzed., Results: The calculated frequency was 0.05% for hCGβ ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta., Conclusion: This study establishes the frequency of hCG or hCGβ values ≥10 MoM, presents a flow chart that optimizes follow-up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Age and gender specific growth charts for Indian children with Down syndrome (DS) based on longitudinal data have not been published. To establish percentile growth charts for DS children inhabiting northwestern parts of India, body weight and length/height of 1125 (Male: 752, Female: 373) children with DS aged <1 month to 10 years, enrolled from the "Genetics Clinic" were measured at half yearly age intervals in the "Growth Clinic" of the Institute from August 1994 to November 2018. A total of 2089 observations were made on these children using standardized anthropometric techniques and instruments following a prospective mixed-longitudinal growth research design. Using the LMS method, age and sex-specific percentile growth charts (<1 month to 10 years) for weight, and length/ height were generated. Unpaired t-test was used to compare mean growth attainments of study children with those of DS patients representing other population groups as well as their normal Multicentre Growth Reference Study (MGRS and Indian Academy of Pediatrics (IAP) counterparts. The 50th percentile growth curves for both weight and length/height of Indian children with DS demonstrated a regular increase. As compared to their normal MGRS and Indian (IAP) counterparts, the children with DS had lower weight and height attainments. The boys and girls with Down syndrome showed short stature (height < 3rd centile) from the age of 1 year till 10 years and also became underweight beyond 5 years. As compared to their normal counterparts, children with Down syndrome exhibited compromised auxological attainments. The use of growth charts presented herein may be used to compare and monitor growth and nutritional status of Indian children with Down syndrome., (© 2024 Wiley Periodicals LLC.)

Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08-1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13-2.03, p = 0.006)., Conclusions: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality., What Is Known: • Down syndrome individuals often face an increased risk of congenital heart diseases. • Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients., What Is New: • This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. • It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. • Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals., (© 2024. The Author(s).)

Background: Down syndrome (DS) is the most prevalent chromosomal disorder, being the leading cause of intellectual disability. The increased life expectancy of individuals with DS has led to a shift in the incidence of non-communicable chronic diseases, resulting in new concerns, particularly cardiovascular disease (CVD) and Alzheimer's disease. This study aimed to analyse the blood lipid profile of a large DS cohort to establish a baseline for evaluating health risk parameters., Methods: A comprehensive literature search was conducted on PubMed and Virtual Health Library databases to identify original articles published before July 2022. Selected studies were included in the meta-analysis., Results: Fifteen studies reporting serum lipid levels in individuals with DS were incorporated into the analysis. The meta-analysis used the means and standard deviations extracted from the selected studies. The analysis encompassed 671 participants in the DS group and 898 euploid controls. The results indicated significant differences in total cholesterol [C] (mean difference [MD]: -3.34; CI: 95%: -4.94 to -1.73; P < 0.0001), HDL-C (MD: -3.39; CI: 95%: -6.72 to -0.06; P = 0.05) and triglycerides (MD: 21.48; CI: 95%: 9.32 to 33.65; P = 0.0005) levels between individuals with DS and their control counterparts., Conclusions: Individuals with DS have less favourable blood lipid concentrations than their controls, particularly HDL-C, triglycerides, and total-C, even when grouped by age. These findings underscore the importance of closer monitoring of lipid profiles in people with DS and the necessity for specific cut-offs for this population, considering the risk for ischemic heart and Alzheimer's diseases., (© 2024 John Wiley & Sons and MENCAP.)

Purpose: We utilized a population database to address the paucity of data around pregnancy outcomes in women with Down syndrome (DS)., Methods: We conducted a retrospective study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample Database over 11 years, from 2004 to 2014. A delivery cohort was created using ICD-9 codes. ICD-9 code 758.0 was used to extract the cases of maternal DS. Pregnant women with DS (study group) were matched based on age, race, income, and health insurance type to women without DS (control) at a ratio of 1:20., Results: There were a total of 9,096,788 deliveries during the study period. Of those, 184 pregnant women were found to have DS. The matched control group was 3680. After matching, most of the pregnancy and delivery outcomes, such as pregnancy-induced hypertension, gestational diabetes, preterm premature rupture of membrane, chorioamnionitis, cesarean section, operative vaginal delivery, or blood transfusion were similar between participants with and without DS. However, patients with DS were at increased risk of giving birth prematurely (aOR 3.09, 95% CI 2.06-4.62), and having adverse neonatal outcomes such as small for gestational age (aOR 2.70, 95% CI 1.54-4.73), intrauterine fetal demise (aOR 22.45, 95% CI 12.02-41.93), congenital anomalies (aOR 7.92, 95% CI 4.11-15.24), and fetal chromosomal abnormalities., Conclusion: Neonates to mothers with DS are at increased risk of prematurity and other neonatal adverse outcomes. Hence, counseling patients with DS about these risks and increased antenatal surveillance is advised., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 patient control cohort at the Mount Sinai Health System in New York, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, are exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: People with intellectual disabilities may experience frailty earlier than the general population. This scoping review aimed to investigate how frailty is defined, assessed, and managed in adults with an intellectual disability; factors associated with frailty; and the potential impact of COVID-19 on frailty identification and management., Method: Databases were searched from January 2016 to July 2023 for studies that investigated frailty in individuals with intellectual disabilities., Results: Twenty studies met the inclusion criteria. Frailty prevalence varied between 9% and 84%. Greater severity of intellectual disability, presence of Down syndrome, older age, polypharmacy, and group home living were associated with frailty. Multiagency working, trusted relationships and provision of evidence-based information may all be beneficial in frailty management., Conclusion: Frailty is common for people with intellectual disabilities and is best identified with measures specifically designed for this population. Future research should evaluate interventions to manage frailty and improve lives., (© 2024 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Purpose: We previously designed the Down Syndrome Societal Services and Supports Survey (DS-4S) to measure country-specific supports for people with Down syndrome (DS) across multiple life domains (healthcare, education, policy, independence, and community inclusion). We now report and analyze the results., Methods: We partnered with international DS consortia, who distributed the DS-4S to 154 cumulative members representing over 100 countries. Organizations were included if they had a holistic focus on the lives of people with DS and if at least 50% of their members either have DS or are family members of people with DS. Factor analysis was used to analyze the results., Results: We received survey responses from 55 different organizations in 50 countries who met inclusion criteria. Each country had complete data for at least 4 of the 5 domains. The lowest 5 scores were from countries in Africa and Asia; the highest 5 scores were in Europe and North America., Conclusion: The responses to the DS-4S stratified countries within each surveyed domain. The DS-4S can now be used to track countries' progress over time and to determine which countries have best practices that might be replicated. We will publish the results and update them biennially at www.DownSyndromeQualityOfLife.com., Competing Interests: Conflict of Interest Dr de Graaf works for the Dutch Down Syndrome Foundation, a non-profit organization. He had a daughter with Down syndrome, who passed away in 2005 at the age of 15. Dr Santoro receives research funding from the LuMind IDSC Down Syndrome Foundation to conduct clinical trials for people with DS and serves on the Executive Board for the Massachusetts Down Syndrome Congress, the Board of the Down Syndrome Medical Interest Group, and the Executive Board of the American Academy of Pediatrics Council on Genetics. Dr Skladzien worked for Down Syndrome Australia, a non-profit peak organization representing people with Down syndrome and their families in Australia. Dr Skotko serves in a non-paid capacity on the Honorary Board of Directors for the Massachusetts Down Syndrome Congress and the Professional Advisory Committee for the National Center for Prenatal and Postnatal Down Syndrome Resources. Dr Skotko receives compensation for consulting on Down syndrome through Gerson Lehrman Group. Within the past 2 years, Dr Skotko has received annual book royalties from Woodbine House, Inc, and research funding from AC Immune and LuMind Research Down Syndrome Foundation to conduct clinical trials for people with Down syndrome. Dr Skotko is occasionally asked to serve as an expert witness for legal cases where Down syndrome is discussed. He receives speaking stipends with various Down syndrome non-profit organizations. Dr Skotko has a sister with Down syndrome. Mr Buckley works for Down Syndrome Education International, a nonprofit that supports young people with Down syndrome and their families. He had a sister with Down syndrome who passed away in 2020, aged 51. All other authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Introduction: People with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co-occurring conditions among adults with DS from five European countries., Methods: Data from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis., Results: Mean ages of AD diagnosis ranged between 51.4 (SD 7.0) years (United Kingdom) and 55.6 (SD 6.8) years (France). Sleep-related and mental health problems were associated with earlier age of AD diagnosis. The higher number of co-occurring conditions the more likely the person with DS is diagnosed with AD at an earlier age., Discussion: Mean age of AD diagnosis in DS was relatively consistent across countries. However, co-occurring conditions varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS., Highlights: Mean age of AD diagnosis was relatively consistent between countries Sleep problems and mental health problems were associated with earlier age of AD diagnosis APOE ε4 carriers were diagnosed with AD at an earlier age compared to non-carriers Number of co-occurring conditions was associated with earlier age of AD diagnosis No differences between level of intellectual disability and mean age of AD diagnosis., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: The aim of this study was to analyze the outcomes of newborns with Down syndrome admitted to three neonatal intensive care units in the city of Rio de Janeiro, Brazil., Methods: A retrospective cohort study was conducted by analyzing the medical records between 2014 and 2018 of newborns with Down syndrome admitted to three neonatal intensive care units. The following variables were analyzed: maternal and perinatal data, neonatal malformations, neonatal intensive care unit intercurrences, and outcomes., Results: A total of 119 newborns with Down syndrome were recruited, and 112 were selected for analysis. The most common maternal age group was >35 years (72.07%), the most common type of delivery was cesarean section (83.93%), and the majority of cases were male (53.57%). The most common reasons for neonatal intensive care unit hospitalization were congenital heart disease (57.66%) and prematurity (23.21%). The most common form of feeding was a combination of human milk and formula (83.93%). The second most common malformation was duodenal atresia (9.82%). The most common complications during neonatal intensive care unit hospitalization were transient tachypnea of the newborn (63.39%), hypoglycemia (18.75%), pulmonary hypertension (7.14%), and sepsis (7.14%). The mean length of stay in the neonatal intensive care unit was 27 days. The most common outcome was discharge (82.14%). Furthermore, 12.50% of newborns were transferred to an external neonatal intensive care unit, and 6% died., Conclusion: Newborns with Down syndrome are more likely to be admitted to the neonatal intensive care unit, and the length of hospital stay is longer due to complications related to congenital malformations common to this syndrome and prematurity.

Background: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used., Results: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome., Conclusions: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome., (© 2024. The Author(s).)

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Molinari, Fossati, Nicolosi, Di Marco, Faraguna, Limido, Ocello, Pellegrinelli, Lattuada, Gazzarri, Lazzerotti, Sala, Vimercati, Capitoli, Daolio, Biondi, Balduzzi and Cattoni.)

Assess creatinine levels in French children with Down syndrome (DS) on the basis of the relationship between creatinine levels and age. The study included 279 children with DS aged 0 to 10 years who had been regularly monitored between 2004 and 2021 in a single genetics department and who had had at least one creatinine measurement. The creatinine level curves were established by estimating the median and the quantiles of order 2.5 and 97.5% according to age. A Generalized Additive Model for Location, Scale, and Shape was used. The results showed higher creatinine levels in children with DS than in children from the general population.   Conclusion: The present results allow to propose an original chart of creatinine levels according to age in French children with DS, which should help optimize their medical management and improve the early detection of renal diseases. What is Known: • Creatinine is a product of muscle breakdown and depends on muscle mass and children with Down syndrome have muscle and growth characteristics that differ from those of the general paediatric population. • Serum creatinine values in Japanese children with DS are higher than those of children from the general Japanese population. What is New: • Creatinine values in French children with DS are higher than those of children from the general French population. • The proposed original chart for creatinine values according to age, specifically designed for individuals up to 10 years old, should serve for further investigation, prevention, and follow-up of children with DS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality., Patients and Methods: Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables., Results: We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50-59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30-3.77]) or cancer (aOR 2.79 [2.07-3.75]), gross aspiration's admission (aOR 2.59 [2.20-3.04]), immobility (aOR 2.31 [1.46-3-62]), and readmission within 30 days (aOR 2.43 [2.06-2.86]) were identified as predictors of mortality., Conclusions: Adults with DS have a high in-hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia., (© 2023 John Wiley & Sons Ltd.)

Purpose: Children with Down Syndrome (DS) have a high prevalence of obstructive sleep apnea (OSA). We aimed to assess OSA prevalence in a single center cohort of children with DS, identify associated risk factors of obstructive respiratory events, and examine the influence of different sleep stages and body positions on respiratory events distribution., Methods: Single center retrospective study that included children with DS who underwent overnight polysomnogram (PSG). OSA severity was categorized by obstructive apnea-hypopnea index (OAHI) as mild (1.5-4.9 events/h), moderate (5-9.9 events/h), and severe (≥ 10 events/h). A logistic regression analysis was used to examine the association between OSA-related risk factors in normal and abnormal OAHI category and in REM and Non-REM predominant AHI groups., Results: PSG data were available for 192 children with a median age of 5 years (IQR 7). OSA prevalence was 82.3% (27.1% mild, 19.8% moderate, and 35.4% severe). A logistic regression model identified BMI and being an African American as significant predictors for OAHI severity. In children with OSA, the median OAHI was 7.6 and obstructive respiratory events were more common in REM sleep and in the supine position. The median REM OAHI was 20 events/h (IQR: 24.4), whereas the median Non-REM OAHI was 5.2 events/h (IQR: 12.6 p < 0.0001). Similarly, supine OAHI was 11.6 (IQR: 19.3) and off supine OAHI was 6.6 (IQR: 11.6, p = 0.0004). Age was a significant predictor (p = 0.012) for Non-REM predominant OSA which was present in 15.2% of children with OSA., Conclusion: Children with DS have a high prevalence of OSA. Higher BMI and being an African American were significant associated risk factors for higher OAHI. Obstructive respiratory events in children with DS occur predominantly in REM sleep and in the supine position. Non-REM predominant distribution of respiratory events was noted in older children with DS., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile., Methods: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m 2 ), normal (BMI 18.5-24.9 kg/m 2 ), overweight (BMI 25-29.9 kg/m 2 ) and obese (BMI ≥ 30 kg/m 2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin., Results: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001)., Conclusions: The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome., (© 2023 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Aims: Data on halitosis among individuals with Down syndrome (DS) are scarce. The aim was to evaluate factors associated with the occurrence of halitosis reported by parents/caregivers (P/Cs) in individuals with DS., Methods and Results: A cross-sectional study was conducted in non-governmental assistance institutions in the State of Minas Gerais-Brazil. P/Cs have answered an electronic questionnaire with sociodemographic, behavioral and oral health data. Factors associated with halitosis were evaluated by multivariate logistic regression. The sample comprised 227 P/Cs (age 48.8 ± 13.2 years; 82.9% mothers) of individuals with DS (age 20.8 ± 13.5 years). The prevalence of halitosis in the total sample was 34.4% (n = 78) and its occurrence was associated: 1) in individuals with DS ≤18 years old (26.2%; n = 27)-negative perception of oral health (OR = 3.91); 2) in individuals with DS > 18 years (41.1%; n = 51)-gingival bleeding (OR = 4.53), absence of tongue brushing (OR = 4.50), negative perception of oral health (OR = 2.72)., Conclusions: The occurrence of halitosis in individuals with DS reported by P/Cs was relevant and associated with dental factors, having a negative impact on the perception of oral health. Oral hygiene practices, especially tongue brushing, should be reinforced to prevent and control halitosis., (© 2023 Special Care Dentistry Association and Wiley Periodicals LLC.)

Background: Young children with an intellectual disability have a higher risk of developing challenging behaviour (CB). Early identification of risk factors for CB allows for earlier intervention. The aim of the current study was to assess the prevalence and correlates of CB in preschool-aged children with an intellectual disability in Riyadh (Saudi Arabia)., Methods: One hundred twenty parents of preschool-aged (3-6 years old) children who had been diagnosed (DSM-5 criteria) with an intellectual disability completed an online cross-sectional survey that included demographic, CB and child adaptive skills measures. The relationship between CB and 15 potential correlates (e.g. gender and degree of disability) was examined using independent samples t-tests and chi-squared tests., Results: Most preschool-aged (3-6 years old) children with an intellectual disability exhibited CB (78.8%, 95% CI [70.3, 85.8]), with a 63.2% prevalence rate for self-injurious behaviours (95% C [53.8, 72.0]), a 57.6% rate for aggressive destructive behaviours (95% CI [48.2, 66.7]) and a 25% rate for stereotypy (95% CI [17.7, 34.0]). The likelihood of a child engaging in self-injurious and stereotyped behaviours was higher in those with autism and intellectual disability. Children with Down syndrome displayed fewer stereotyped behaviours. Low adaptive skill levels were associated with increased overall CB, self-injurious and stereotyped behaviours., Conclusions: The identified correlates of CB in this population and cultural context align with the international evidence base. Findings have implications for the importance of early systematic screening of CB in preschool-aged children in Saudi Arabia and other similar contexts. Preventative measures are suggested for preschool-aged children with an intellectual disability who are more likely to demonstrate CB, such as those with autism and poor adaptive behaviours., (© 2023 The Authors. Journal of Intellectual Disability Research published by John Wiley & Sons and MENCAP.)

Code status is a label in the medical record indicating a patient's wishes for end-of-life (EOL) care in the event of a cardiopulmonary arrest. People with intellectual disabilities had a higher risk of both diagnosis and mortality from coronavirus infections (COVID-19) than the general population. Clinicians and disability advocates raised concerns that bias, diagnostic overshadowing, and ableism could impact the allocation of code status and treatment options, for patients with intellectual disabilities, including Down syndrome (DS). To study this, retrospective claims data from the Vizient® Clinical Data Base (used with permission of Vizient, all rights reserved.) of inpatient encounters with pneumonia (PNA) and/or COVID-19 at 825 hospitals from January 2019 to June 2022 were included. Claims data was analyzed for risk of mortality and risk of "Do Not Resuscitate" (DNR) status upon admission, considering patient age, admission source, Elixhauser comorbidities (excluding behavioral health), and DS. Logistic regression models with backward selection were created. In total, 1,739,549 inpatient encounters with diagnoses of COVID-19, PNA, or both were included. After controlling for other risk factors, a person with a diagnosis of DS and a diagnosis of COVID-19 PNA had 6.321 odds ratio of having a DNR status ordered at admission to the hospital compared with those with COVID-19 PNA without DS. The diagnosis of DS had the strongest association with DNR status after controlling for other risk factors. Open and honest discussions among healthcare professionals to foster equitable approaches to EOL care and code status are needed., (© 2023 Wiley Periodicals LLC.)

Aim: To compare oral health indicators of children/adolescents with Down syndrome (DS) with a group of children/adolescents without DS., Methods and Results: This cross-sectional study included 144 individuals with DS, ages 4 to 18 years, matched for age and sex with a group of 144 individuals without DS, and their parents/caregivers. Parents/caregivers completed a questionnaire regarding sociodemographic information and habits related to their children's oral health. Clinical examination of the children/adolescents evaluated dental caries experience (DMFT/dmft), bleeding on periodontal probing, presence of visible plaque, clinical consequences of untreated dental caries (PUFA/pufa), and malocclusion (DAI). The chi-square test, linear by linear test, and Mann-Whitney test were used to compare the variables between the groups (p < .05). Children/adolescents without DS brushed their teeth more times per day (p < .001) and had a higher frequency of daily sugar intake (p < .001). The children/adolescents in the DS group had a greater presence of gingival bleeding (p < .001) and had a greater number of cases of "severe malocclusion" and "very severe malocclusion" (p = .001). No difference was found in the prevalence of dental caries between the two groups., Conclusion: The children/adolescents in the DS group had a greater presence of gingival bleeding during the clinical examination and had a greater need for orthodontic treatment., (© 2023 Special Care Dentistry Association and Wiley Periodicals LLC.)

Background: Controversial data exist about the impact of Down syndrome on outcomes after surgical repair of atrioventricular septal defect., Aims: (A) assess trends and outcomes of atrioventricular septal defect with and without Down syndrome and (B) determine risk factors associated with adverse outcomes after atrioventricular septal defect repair., Methods: We queried The National Inpatient Sample using International Classification of Disease codes for patients with atrioventricular septal defect < 1 year of age from 2000 to 2018. Patients' characteristics, co-morbidities, mortality, and healthcare utilisation were evaluated by comparing those with versus without Down syndrome., Results: In total, 2,318,706 patients with CHD were examined; of them, 61,101 (2.6%) had atrioventricular septal defect. The incidence of hospitalisation in infants with atrioventricular septal defect ranged from 4.5 to 7.5% of all infants hospitalised with CHD per year. A total of 33,453 (54.7%) patients were associated with Down syndrome. Double outlet right ventricle, coarctation of the aorta, and tetralogy of Fallot were the most commonly associated with CHD in 6.9, 5.7, and 4.3% of patients, respectively. Overall atrioventricular septal defect mortality was 6.3%. Multivariate analysis revealed that prematurity, low birth weight, pulmonary hypertension, and heart block were associated with mortality. Down syndrome was associated with a higher incidence of pulmonary hypertension (4.3 versus 2.8%, p < 0.001), less arrhythmia (6.6 versus 11.2%, p < 0.001), shorter duration for mechanical ventilation, shorter hospital stay, and less perioperative mortality (2.4 versus 11.1%, p < 0.001)., Conclusion: Trends in atrioventricular septal defect hospitalisation had been stable over time. Perioperative mortality in atrioventricular septal defect was associated with prematurity, low birth weight, pulmonary hypertension, heart block, acute kidney injury, and septicaemia. Down syndrome was present in more than half of atrioventricular septal defect patients and was associated with a higher incidence of pulmonary hypertension but less arrhythmia, lower mortality, shorter hospital stay, and less resource utilisation.

Introduction: Down syndrome (DS) is associated with multiple comorbid conditions and chronic immune dysfunction. Persons with DS who contract COVID-19 are at high risk for complications and have a poor prognosis. We aimed to study the clinical symptoms, laboratory and biochemical profiles, radiologic findings, treatment, and outcomes of patients with DS and COVID-19., Method: We systematically searched PubMed, MEDLINE, Web of Science, Scopus, and the Cochrane Library using the keywords COVID-19 or coronavirus or SARS-CoV-2 and DS or trisomy 21. Seventeen articles were identified: eight case reports and nine case series published from December 2019 through March 2022, with a total of 55 cases., Results: Patients averaged 24.8 years (26 days to 60 years); 29 of the patients were male. The most common symptoms were fever, dyspnea, and cough. Gastrointestinal and upper respiratory tract symptoms were commonly reported for pediatric patients. The most common comorbidities present in patients with DS were obesity (49.0%), hypothyroidism (21.6%) and obstructive sleep apnea (15.6%). The patients were hospitalized for a mean of 14.8 days. When the patients were compared with the general COVID-19 population, the mean number of hospitalized days was higher. Most patients had leukopenia, lymphopenia, and elevated inflammatory markers (d-dimer and C-reactive protein). Bilateral infiltrations and bilateral ground-glass opacifications were frequently seen in chest radiographs and chest computed tomographic imaging. Most of the patients were treated with methylprednisolone, macrolides, and hydroxychloroquine. Of the 55 patients, 22 died. The mean age of the patients who died was 42.8 years. Mortality rate was higher in individuals with DS over 40 years of age., Conclusion: More studies are needed to better understand COVID-19 infections among persons with DS. In addition, the study was limited by a lack of statistical analyses and a specific comparison group., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

The Pediatric Integrated Care Survey (PICS) is validated for use to measure the caregiver reported experience of integration and efficiency of all the aspects of their child. We began using the PICS survey to track changes in the patient experience, including throughout changing models of care during the COVID-19 pandemic. From February 2019 to June 2023, 62 responses from caregivers of individuals seen in the Massachusetts General Hospital Down Syndrome Program completed the PICS. Responses were scored using the standardized PICS user manual, and descriptive statistics were completed. The raw scores and composite monthly scores of the PICs were graphed in statistical process control charts. The average PICS score was 12.0 (range 2-19) out of a maximum score of 19; no shifts or trends were seen. Items with lowest scores indicated greatest opportunities for improvement related to: advice from other care team members, impact of decisions on the whole family, things causing stress or making it hard because of child's health, and offering opportunities to connect with other families. Studying the PICS in a specialty clinic for Down syndrome for the first time has established a baseline for future quality improvement work and interventions to increase care integration., (© 2023 Wiley Periodicals LLC.)

Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into a specialty Down Syndrome Program, with the goals of better understanding the incidence, course, and impact of co-occurring medical, neurodevelopmental, and mental health conditions in DS. We describe the process of developing the database, including a systematic approach to data collection and database infrastructure, and report on feasibility, challenges, and solutions of initial implementation. Between March 2018 and November 2021, data from 842 patients (ages 4.8 months to 26 years) was collected. Challenges included caregiver form completion as well as time and personnel required for successful implementation. With full integration into clinical visit flow, the database proved to be feasible. The database enables identification of patterns of development and health throughout the lifespan and it facilitates future data sharing and collaborative research to advance care., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with Down syndrome (DS) are at risk of multiorgan dysfunction; kidney and urological impairment are common. This is due to a likely increased risk of congenital kidney and urological malformations (odds ratio of 4.5 compared to the general population in one study), more frequent associated comorbidities at risk of kidney dysfunction (such as prematurity in 9-24% of children, intrauterine growth retardation or low birth weight in 20%, and congenital heart disease in 44%), and more frequent lower urinary tract dysfunction (reported in 27-77% of children with DS). If present, malformations and comorbidities at risk of kidney dysfunction warrant regular kidney monitoring in addition to their treatment. Serum creatinine in children with DS has been shown to be higher than in the general population and asymptomatic hyperuricemia is reported in 12-33% of children or young adults with DS. Moreover cryptorchidism and testicular cancer are also more common and should be detected by clinical examination. Thus, persons with DS at risk of presenting kidney and urological impairment should be identified by prenatal ultrasonography, comorbidities at risk of kidney sequelae considered, and during regular medical follow-up, clinically examined and questioned to diagnose testicular anomalies and lower urinary tract dysfunction. This is of importance as such kidney and urological impairments are associated with impaired quality of life and mental health, and risk of kidney failure., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

In Chile, there are no validated instruments for the evaluation of quality of life (QoL) of people with Down syndrome (DS). To analyze construct validity and reliability of the KidsLife-Down scale in Chile to measure QoL in people with DS aged from 4 to 21 years. Families of boys, girls, and young people with DS between 4 and 21 years were invited to participate. The scale was answered by relatives or caregivers. To assess the internal consistency, reliability tests were performed using Cronbach's alpha coefficient. A confirmatory factor analysis was performed. The scale was answered by 531 relatives or caregivers. Cronbach's coefficient was greater than 0.7 in all the items. The confirmatory factor analysis of the scale allowed its validation for clinical use in the Chilean population. "Kids Life Down-Chile" scale has adequate psychometric properties to be used in clinical practice and to help us improve QoL with better support strategies., (© 2023 Wiley Periodicals LLC.)

Sleep problems are common in children and adolescents, particularly those with Neurodevelopmental Disorders. With the changes in daily habits resulting from the COVID-19 pandemic, we have analyzed sleep characteristics, during social isolation, in Brazilian children and adolescents aged between 4 and 12 years with Autism Spectrum Disorder (N = 267), Down Syndrome (N = 74), and typical development (N = 312). The ASD group presented with worse indicators of sleep habits in the Children's Sleep Habits Questionnaire (CSHQ-BR) and fell asleep later during the pandemic. The entire group started fall asleep and waking up later during the pandemic - as well as waking up more often during the night. These results may contribute to parental guidance and sleep habit-related interventions during and after the COVID-19 pandemic., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms., Material and Methods: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register., Results: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies., Conclusion: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: The life expectancy of people with Down syndrome (DS) is limited by Alzheimer's disease (AD)-related deaths, mainly due to respiratory infections. The emergence of the COVID-19 pandemic could have changed known, past trends in mortality in this population. We analysed the differences in causes of mortality between individuals with DS deceased before and after the onset of the pandemic., Method: This is a cross-sectional study of adults with DS recruited at a tertiary, university outpatient clinic in Madrid, Spain. Demographic and clinical data were retrospectively collected from their medical records, including information on their deaths, if any., Results: Five hundred seventy-two adults were included in the study, and 67 (11.7%) died. The main cause of death was respiratory infections, which occurred in 36 participants [9 (45.0%) before, and 27 (58.7%) after the appearance of COVID-19]. No significant differences were found in the determinants of pre-pandemic and post-pandemic death after adjusting for age and AD, except for an association between the use of psychotropic medication and death in the post-pandemic period (odds ratio: 2.24; 95% confidence interval: 1.04-4.82). Vaccination against COVID-19 showed a marked protective effect against mortality (odds ratio: 0.0002; 95% confidence interval: 6.7e10 -6 to 0.004)., Conclusions: The appearance of COVID-19 has not impacted the overall trend of increase in mean age of death of adults with DS in our milieu, probably thanks to the very important protective effect of vaccination, which supports prioritising people with DS in future immunisation campaigns. The association between psychotropic medication use and mortality requires further exploration., (© 2023 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: Increasing survival among patients with congenital heart disease (CHD) has recently been reported. However, the impact of Down syndrome (DS) in patients with CHD is still debated. We aimed to estimate survival in patients with CHD with versus without DS compared with matched controls from the general population without CHD or DS., Methods and Results: We linked data from Swedish health registries to identify patients with CHD born between 1970 and 2017. Data from the Total Population Register were used to match each patient with CHD by sex and birth year with 8 controls without CHD or DS. A Cox proportional regression model was used to estimate mortality risk, and Kaplan-Meier curves were analyzed for the survival analysis. We identified 3285 patients with CHD-DS, 64 529 patients with CHD without DS, and 26 128 matched controls. The mortality risk was 25.1 times higher (95% CI, 21.3-29.5) in patients with CHD-DS versus controls. The mortality rate was 2 times higher (95% CI, 1.94-2.31) for patients with CHD with versus without DS. Lower mortality was found during the second versus first birth periods in patients with CHD-DS compared with controls; hazard ratio: 46.8 (95% CI, 29.5-74.0) and 17.7 (95% CI, 12.8-24.42) in those born between 1970 and 1989 versus 1990 and 2017, respectively., Conclusions: In this retrospective cohort study, the mortality risk among patients with CHD-DS was 25 times higher compared with matched controls and 2 times higher compared with patients with CHD without DS. Survival was higher in patients with CHD-DS born after versus before 1990, coinciding with the modern era of congenital heart care.

Objective: To describe the distribution of expressive language abilities of individuals with Down syndrome (DS) in a clinical sample and characterize demographic, environmental, and medical factors associated with varying expressive language profiles., Methods: Cross-sectional analysis was completed on a sample of 345 individuals with DS between the ages of 4 and 22 years who were enrolled into a longitudinal clinical database between March 2018 and August 2021. Expressive language-related items on a standardized caregiver-reported questionnaire assessing domains of functioning in neurodevelopmental disorders were used to conduct latent variable modeling and determine caregiver-reported expressive language (CREL) classes across the sample. Linear regression was used to explore associations between CREL classes and predictor variables., Results: Latent variable modeling revealed 3 distinct classes of CREL abilities representing higher, middle, and lower CREL. Individuals in the lower CREL class were more likely to be female, to use sign language or visual communication systems, have reduced pronunciation, attend private or residential school, and to be in a substantially separate classroom. Membership was not predicted by complex medical histories or co-occurring neurodevelopmental diagnoses., Conclusion: Caregiver-reported expressive language abilities in a cohort of individuals with DS were variable, with most of the individuals belonging to higher or middle CREL classes, relative to one another. Additional studies are indicated to understand factors that predict higher expressive language ability and explore how to direct services to individuals who are at risk of more profound language delays., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS., Objective: To characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis., Methods: Multimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2 ± 6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants., Results: A sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status., Conclusions: Insomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.

Few studies have reported the survival outcomes of myeloid leukemia associated with Down syndrome (DS) in resource-limited countries. This study aimed to compare characteristics and survival outcomes of children with acute myeloid leukemia (AML) between those with and without DS in Thailand. The medical records of AML patients aged 0-15 years treated in a major tertiary center in Southern Thailand between October 1978 and December 2019 were reviewed retrospectively. The overall (OS) and event-free survivals (EFS) rates were calculated using the Kaplan-Meier method. A total of 362 AML patients were included, of which 41 (11.3%) had DS. The mean age at diagnosis of the DS patients was 2.5 ± 1.9 years and most of them (90.2%) were under the age of five. The DS patients had lower initial white blood cell counts and peripheral blasts compared to the non-DS patients. The AML-M7 subtype was more common in the DS than in the non-DS patients (80.5% vs. 9.1%, p  < 0.01, respectively). The 5-year OS and EFS rates of the DS patients were lower compared to the non-DS patients (12.9% vs. 20.5%, p  = 0.05 and 13.7% vs. 18.4%, p  = 0.03, respectively). DS patients had a significantly higher rate of early and treatment-related deaths compared to non-DS patients (30.3% vs. 13.5%, p  < 0.01 and 39.4% vs. 19.5%, p  = 0.02, respectively). Over the study period, there were a decrease in early death rate and an increase in survival rates of DS patients, which suggests that chemotherapy regimens and supportive care have improved over time.

Background and Aim: Chromosomal analysis is a laboratory technique used to examine the chromosomes of an individual, offering insights into chromosome numbers, structures, and arrangements to diagnose and comprehend genetic diseases. This retrospective study provides a comprehensive understanding of the distribution by indications in a large cohort of 14,242 patients and the frequency of chromosomal abnormalities in different clinical populations., Method: The study examined various indications for karyotype evaluation, with recurrent pregnancy loss being the most common indication, followed by intellectual disability, dysmorphic features, congenital anomalies, and developmental delay., Results: The overall chromosomal abnormality rate was found to be 5.4%, with numerical abnormalities accounting for the majority of cases (61.7%). Trisomies, particularly trisomy 21, were the most frequent numerical abnormalities. In terms of structural abnormalities, inversions and translocations were the most commonly identified. The rates of chromosomal anomalies varied in specific indications such as amenorrhea, disorders of sex development, and Turner syndrome. The study also highlighted significant differences between males and females in the presence of chromosomal abnormalities across certain indications. Males exhibited a higher incidence of chromosomal abnormalities in cases of Down syndrome and infertility, whereas females showed higher abnormalities in terms of recurrent pregnancy loss., Conclusion: While this study provides valuable insights into the frequency and distribution of chromosomal abnormalities, it has limitations, including its retrospective design and reliance on data from a single medical genetics department. Nevertheless, the findings emphasize the importance of karyotype analysis in diagnosing chromosomal disorders and providing appropriate management, while also pointing to potential gender-related variations in chromosomal abnormalities that warrant further investigation., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Children with Down syndrome (DS) frequently have concomitant clinical problems. There are no studies in the literature evaluating gross motor development and handgrip strength in the presence of congenital heart disease (CHD), which is one of the most common comorbidities in population with DS. The aim of this study was to compare cardiopulmonary parameters, gross motor development and handgrip strength in children with DS with and without CHD., Methods: A total of 28 children with DS (14 with CHD and 14 without CHD) were evaluated. Demographic data and cardiopulmonary parameters were recorded. Gross motor development and handgrip strength were assessed., Results: Children with DS and CHD had lower GMFM-88 scores and right handgrip strength and higher Wang respiratory score than children with DS and no CHD (P < 0.05). GMFM-88 scores were moderately correlated with resting oxygen saturation (r = 0.46, P = 0.01) and right handgrip strength (r = 0.67, P < 0.001)., Conclusions: Peripheral muscle strength and oxygen saturation may be factors affecting gross motor development in children with DS. From this point of view, evaluating cardiopulmonary parameters, motor development and handgrip strength in children with DS and CHD is important to identify risks, provide early intervention and support development., (© 2023 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Introduction: This cross-sectional study aimed to (1) compare family management between families of children with autism spectrum disorder (ASD) or Down syndrome and (2) evaluate the contribution of the child (ASD behaviors, feeding difficulties, sleep disturbances), caregiver (mental health) and family (social support) factors to the caregiver's perceived condition management ability and effort., Method: Eighty-five caregivers (56 ASD, 29 Down syndrome) completed quantitative instruments online. Data analysis included independent samples t-tests and multiple linear regression., Results: There were no significant differences in the dimensions of family management between groups. More ASD behaviors were associated with lower condition management ability and higher condition management effort. Lower perceived social support and higher caregiver age were associated with lower condition management ability., Discussion: Integrating care into family life may be more challenging when the child has more social differences and behavioral rigidity. Nursing care should include an assessment of family social support., Competing Interests: CONFLICTS OF INTEREST None to report., (Copyright © 2023 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background: This study investigated the prevalence, risk factors and severity of corneal tomographic features of keratoconus in Down syndrome (DS). Additionally, previous studies indicate anomalous corneal features in DS, without keratoconus, this study characterised corneal features in DS without keratoconus., Methods: This prospective observational study included participants with DS ≥10 years old. Keratoconus diagnosis, risk factors and corneal tomographic characteristics were recorded. Participants underwent slit-lamp biomicroscopy, Scheimpflug corneal tomography, corneal topography and autorefraction. A diagnosis of keratoconus (DS-KC), suspect keratoconus (DS-SK) and non-keratoconus (DS-NK) was made based on expert review of scans by three fellowship trained anterior segment ophthalmologists. Corneal tomography parameters from one eye of each participant were analysed., Results: Keratoconus affected 50 (26.3%) of 190 participants, diagnosed by corneal tomography, topography or slit-lamp signs. Corneal hydrops affected 14.0% of DS-KC participants. Eye rubbing was a significant risk factor for keratoconus (p = 0.036). 175 (92%) participants could undertake corneal tomography of which tomography assessment alone identified 47 (26.9%) DS-KC participants, 64 (36.6%) DS-SK participants and 64 (36.6%) DS-NK participants. Significant differences (p < 0.001) were identified when the DS-KC, DS-SK and DS-NK groups were compared in maximum keratometry and posterior elevation at the thinnest point respectively: median (interquartile range) 50.20 (10.30D), 47.60 (1.95D), 46.50 (2.40D); 24.0 (38.00 μm), 10.00 (13.75 μm), 8.00 (6.00 μm). The DS-SK and DS-NK cohorts had similar minimum pachymetry, however, had several significantly different parameters among which included greater maximum keratometry, posterior elevation at the thinnest point in the DS-SK group., Conclusions: Keratoconus is common in DS. Keratoconus screening with corneal tomography is recommended for early detection., (© 2023 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Few regular national clinical data are available for individuals with Down's syndrome (IDS) bearing in mind that they are subject to countries variations in medical termination of pregnancy and screening. Individuals < 65 in 2019 were selected in view of the low number of older IDS. Thus, 98% of 52.4 million people with correct data were included from the national health data system. IDS (35,342) were identified on the basis of the International Classification of Diseases 10th revision code (Q90). Risk ratios (RR) were calculated to compare the frequencies in 2019 between IDS and individual without Down's syndrome (IWDS) of use of health care. The prevalence of IDS was 0.07% (48% women), comorbidities were more frequent, especially in younger patients (24% < 1 year had another comorbidity, RR = 20), as was the percentage of deaths (4.6%, RR = 10). Overall, tumours were less frequent in IDS compared with IWDS (1.2%, RR = 0.7) except for certain leukaemias and testicular tumours (0.3%, RR = 4). Cardiac malformations (5.2%, RR = 52), dementia (1.2%, RR = 29), mental retardation (5%, RR = 21) and epilepsy (4%, RR = 9) were also more frequent in IDS. The most frequent hospital diagnoses for IDS were: aspiration pneumonia (0.7%, RR = 89), respiratory failure (0.4%, RR = 17), sleep apnoea (1.1%, RR = 8), cryptorchidism (0.3%, RR = 5.9), protein-energy malnutrition (0.1%, RR = 7), type 1 diabetes (0.2%, RR = 2.8) and hypothyroidism (0.1%, RR = 72). IDS were more likely to use emergency services (9%, RR = 2.4), short hospital stay (24%, RR = 1.6) or hospitalisation at home (0.6%, RR = 6). They consulted certain specialists two to three times more frequently than IWDS, for example cardiologists (17%, RR = 2.6). This study is the first detailed national study comparing IDS and non-IDS by age group. These results could help to optimize prenatal healthcare, medical and social support., (© 2023. The Author(s).)

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment., (© 2023 Wiley Periodicals LLC.)

Background: Bruxism is a parafunctional activity characterised by grinding or clenching of teeth and is a common oral health concern in individuals with down syndrome (DS). Understanding the prevalence of bruxism in this population is crucial for developing effective management strategies. This systematic review and meta-analysis is aimed to investigate the prevalence of bruxism among individuals with DS and explore its association with other oral health issues., Methods: A comprehensive search was conducted across multiple electronic databases to identify relevant studies. Cross-sectional and observational studies were included. Data on bruxism prevalence and associated factors were extracted, and a meta-analysis was performed using both fixed-effects (FE) and random-effects (RE) models of MedCalc software. Heterogeneity among studies was assessed using I 2 statistics. New Castle-Ottawa Scale was used to evaluate methodological quality of the included studies., Results: Eight studies met the pre-defined inclusion criteria and were included in the analysis. Seven studies used a questionnaire to assess bruxism. The pooled proportion estimate for occurrence of DS across the included studies was found to be 0.33 (95% CI: 0.22-0.45) as per the RE model and 0.35 (95% CI: 0.31-0.450) as per FE model in the quantitative analysis. All studies exhibited good methodological quality., Conclusion: This systematic review and meta-analysis provide evidence of a significant prevalence of bruxism among individuals with DS. The findings highlight the association of bruxism with other oral health issues and specific chromosomal abnormalities. Comprehensive oral health assessments, including diagnostic procedures like Polysomnography, are essential for addressing the unique oral health needs of individuals with DS. Further studies are recommended with a valid tool for the diagnosis. Early interventions and management strategies need to be tailored to this population, considering the multifaceted nature of oral health concerns in individuals with DS., (© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

Background: Screening for trisomy 21 provides pregnant women with accurate risk information. Different algorithms are used to screen for trisomy 21 in South Africa (SA). The Fetal Medicine Foundation (FMF) provides software to screen for trisomy 21 in the first trimester by ultrasound or a combination of ultrasound and biochemistry (combined screening), and requires regular and stringent quality control. With αlpha software, first trimester combined screening and screening with biochemistry alone in the first or second trimester are possible. The αlpha screening requires quality control of biochemical tests, but not of ultrasound measurements. Ideally, a screening test should have a high detection and a low screen positive rate. Despite the availability of these screening programmes, only a minority of infants with trisomy 21 are detected prenatally, raising questions about the effectiveness of screening., Objectives: To determine the screen positive and detection rates of prenatal screening for trisomy 21 in the SA private healthcare system., Methods: Data from the three largest laboratories collected between 2010 and 2015 were linked with genetic tests to assess screen positive and detection rates. Biochemical screening alone with αlpha software (first or second trimester) and combined screening using either FMF or αlpha software were compared., Results: One-third of an estimated 675 000 pregnancies in private practice in the 6-year study period underwent screening. There were 687 cases of trisomy 21 in 225 021 pregnancies, with only 239 (35%) diagnosed prenatally. The screen positive rates were 11.8% for first trimester biochemistry, 7.6% for second trimester biochemistry, 7.3% for first trimester FMF software ultrasound alone, 3.7% for combined first trimester screening with FMF software, and 3.5% for combined first trimester screening with αlpha software. The detection rates for a 5% false positive rate were 63% for first trimester biochemistry, 69% for second trimester biochemistry, 95% for combined first trimester screening with FMF software and 80% for combined first trimester screening with αlpha software. Detection and confirmation rates were highest with FMF software., Conclusion: Screening with FMF software has a similar screen positive rate and better detection rate than screening with αlpha software. The low prenatal detection rate of trisomy 21 is mainly due to a low prevalence of screening. More research is needed in the SA setting to explore why screening and confirmatory testing after high-risk results are not performed in many pregnancies.

Purpose: Patients with Down Syndrome (DS) showed multiple comorbidities, including thyroid disorders, obesity, and metabolic derangement. Different thyroid hormone (THs) patterns and sensitivity to thyroid hormone indices (STHI) seem to be associated with metabolic disorders. The study's aim was to evaluate the prevalence of metabolic syndrome (MS) in pediatric patients affected by DS, taking into consideration the relationship between the metabolic parameters, THs and STHI., Methods: We enlisted 50 euthyroid patients with DS (9.03 ± 4.46). Clinical parameters, TSH, FT3, FT4 and the presence of MS were recorded. Indexes of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were also detected. Thirty healthy subjects were included as a control group., Results: MS was detected in 12% of the subjects with DS. FT3, FT4, and TSH levels were higher in DS than in the control group (p < 0.01); higher levels of FT3/FT4 ratio, TSHI and TT3RI and lower TT4RI values (p < 0.01) were also detected. A significant correlation was detected between FT3 and fasting blood glucose (FBG) (R = 0.46), triglyceride (TG) (r = 0.37), total (r = 0.55) and high density lipoprotein-cholesterol (HDL-C) (r = - 0.38), diastolic blood pressure (DBP) (r = - 0.4); FT3/FT4 ratio and waist circumference (WC) (r = 0.36); TSHI and total (r = 0.30) and HDL cholesterol (r = - 0.31); TT4RI and HDL cholesterol (r = - 0.31); TT3RI and total (r = 0.39) and HDL cholesterol (r = - 032)., Conclusion: We confirmed a higher MS prevalence in children with DS compared to the control group. A significant association between THs, STHI, and the glucose and lipid metabolism parameters was detected supporting their role in metabolic alterations related to the DS., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)