Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus.

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.

The Pediatric Integrated Care Survey (PICS) in a multidisciplinary clinic for Down syndrome.

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.

Retrospective review of the code status of individuals with Down syndrome during the COVID-19 era.

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.

Dysregulation of the Immune System in a Natural History Study of 1299 Individuals with Down Syndrome.

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.

Results of inaugural international Down Syndrome Societal Services and Supports survey.

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.

Adapting a quality of life scale for children and young people with Down syndrome in Chile.

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.

Growth charts for weight and height of Indian children with Down syndrome.

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.

COVID-19 infection in children, adolescents, and young adults with Down syndrome and hematologic malignancies.

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.

Kidney and urological involvement in Down syndrome: frequent, underestimated, but associated with impaired quality of life and risk of kidney failure.

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.

Creatinine levels in French children with Down syndrome up to ten years old.

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.

Nationwide hospitalizations of patients with down syndrome and congenital heart disease over a 15-year period.

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.

Maternal age and the risk of fetal aneuploidy: A nationwide cohort study of more than 500 000 singleton pregnancies in Denmark from 2008 to 2017.

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.

Prevalence, associated risk factors, and respiratory event distribution of obstructive sleep apnea in children with Down syndrome.

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.

Evaluation of chromosomal abnormalities in the postnatal cohort: A single-center study on 14,242 patients.

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.

The etiology of Down syndrome: Maternal MCM9 polymorphisms increase risk of reduced recombination and nondisjunction of chromosome 21 during meiosis I within oocyte.

Altered patterns of recombination on 21q have long been associated with the nondisjunction chromosome 21 within oocytes and the increased risk of having a child with Down syndrome. Unfortunately the genetic etiology of these altered patterns of recombination have yet to be elucidated. We for the first time genotyped the gene MCM9, a candidate gene for recombination regulation and DNA repair in mothers with or without children with Down syndrome. In our approach, we identified the location of recombination on the maternal chromosome 21 using short tandem repeat markers, then stratified our population by the origin of meiotic error and age at conception. We observed that twenty-five out of forty-one single nucleotide polymorphic sites within MCM9 exhibited an association with meiosis I error (N = 700), but not with meiosis II error (N = 125). This association was maternal age-independent. Several variants exhibited aprotective association with MI error, some were neutral. Maternal age stratified characterization of cases revealed that MCM9 risk variants were associated with an increased chance of reduced recombination on 21q within oocytes. The spatial distribution of single observed recombination events revealed no significant change in the location of recombination among women harbouring MCM9 risk, protective, or neutral variant. Additionally, we identified a total of six novel polymorphic variants and two novel alleles that were either risk imparting or protective against meiosis I nondisjunction. In silico analyses using five different programs suggest the risk variants either cause a change in protein function or may alter the splicing pattern of transcripts and disrupt the proportion of different isoforms of MCM9 products within oocytes. These observations bring us a significant step closer to understanding the molecular basis of recombination errors in chromosome 21 nondisjunction within oocytes that leads to birth of child with Down syndrome.

Keratoconus in Down syndrome: Prevalence, risk factors, severity and corneal tomographic characteristics.

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.

A systematic review and meta-analysis of serum lipid concentrations in people with Down syndrome.

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.

Investigation of cardiopulmonary parameters, motor development and muscle strength in children with Down syndrome with and without congenital heart disease.

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.

Challenging behaviour and its correlates in preschool-aged children with an intellectual disability in Saudi Arabia.

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.

Causes of mortality among adults with Down syndrome before and after the COVID-19 pandemic in Spain.

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.