Clinical practice: The care of children with Down syndrome

Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available

Decreased antibody response after severe acute respiratory syndrome coronavirus 2 vaccination in patients with Down syndrom

The risk of a severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those >40 years of age. After primary SARS-CoV-2 vaccination, the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1-specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, messenger RNA [mRNA]-1273, or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after 2 mRNA vaccinations or after 2 ChAdOx1 vaccinations. After 2 mRNA vaccinations, lower antibody concentrations were seen with increasing age. In this prospective cohort study that included 222 adults with Down syndrome, a significantly lower antibody response was found after SARS-CoV-2 mRNA or vector vaccination compared to healthy controls. After mRNA vaccination, lower antibodies were found with increasing age

Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome

UNLABELLED: The risk of a severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those >40 years of age. After primary SARS-CoV-2 vaccination, the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1-specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, messenger RNA [mRNA]-1273, or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after 2 mRNA vaccinations or after 2 ChAdOx1 vaccinations. After 2 mRNA vaccinations, lower antibody concentrations were seen with increasing age. CLINICAL TRIALS REGISTRATION: NCT05145348

Confounding of the association between radiation exposure from CT scans and risk of leukemia and brain tumors by cancer susceptibility syndromes

Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of pediatric CT scans. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk. Since empirical evidence is lacking in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome and other CSS. Moreover, tuberous sclerosis complex, von Hippel-Lindau disease, neurofibromatosis type 1 and other CSS do not meaningfully confound RRs for brain tumors. Empirical data on the use of CT scans among CSS patients is urgently needed. Our assessment indicates that associations with radiation exposure from pediatric CT scans and leukemia or brain tumors reported in previous studies are unlikely to be substantially confounded by unmeasured CS

Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability

Various genes may influence intestinal barrier function, including MAGI2, MY09B, and PARD3, which are associated with celiac disease. Because direct measurement of intestinal permeability is difficult, antibodies against gliadin (AGA) and Baker's yeast (anti-Saccharomyces cerevisiae antibodies [ASCA]) can be used as an indirect test. The objective of this study was to investigate whether intestinal permeability, represented by AGA, was correlated with MAGI2, MY09B, and PARD3. Analyses were performed in patients with Down syndrome, a population with suspected increased intestinal permeability. Correlations between AGA and ASCA were investigated. Patients with Down syndrome (n = 126) were genotyped for six single-nucleotide polymorphisms in MAGI2 (rs1496770, rs6962966, rs9640699), MY09B (rs1457092, rs2305764), and PARD3 (rs10763976). An allele dosage association of these risk genes and AGA levels was performed. The correlation between AGA and ASCA was studied. A strong correlation was found between AGA and ASCA (p <0.01). The patient group with one or more risk genotypes had lower mean AGA levels (trend test p = 0.007) and consisted of a larger number of patients with normal AGA levels (p = 9.3 x 10(-5)). Celiac-associated risk genotypes are associated with lower AGA values instead of elevated ones. Thus, other immunologic phenomena play a role in the increased prevalence of elevated AGA in patients with Down syndrome, possibly involving altered induction and/or maintenance of tolerance. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved

Incidence and risk factors of post-operative arrhythmias and sudden cardiac death after atrioventricular septal defect (AVSD) correction: Up to 47 years of follow-up

Background: Atrioventricular septal defect (AVSD) has an incidence of 4-5.3 per 10.000 live births and is associated with Down syndrome (DS). Data on arrhythmias and sudden cardiac death (SCD) after AVSD correction is scarce.& para;& para;Aim: To analyse the incidence of post-operative arrhythmias and SCD after AVSD correction and explore risk factors.& para;& para;Methods: This is a retrospective multicenter study including patients after biventricular AVSD correction. Univariate and multivariate analyses were performed to explore risk factors.& para;& para;Results: A total of 415 patients were included with a mean follow-up duration of 9 years (range; <30 days-47 years). Early post-operative SVTs were documented in 33 patients (8%) and late post-operative SVTs in 15 patients (3.6%). Non-syndromic AVSD (p = 0.022, HR = 2.64; 95% CI = 1.15-6.04) and cAVSD (p = 0.005, HR = 3.7; 95% CI = 1.39-7.51) were independent risk factors for early post-operative SVTs and significant more late post-operative SVTs occurred in non-syndromic patients (p = 0.016, HR = 6.38; 95% CI = 1.42-28.71) and in pAVSD (p = 0.045, HR = 3.703; 95% CI = 1.03-13.32). Fifteen patients (3.6%) received a pacemaker. Non-syndromic AVSD (p = 0.008. HR = 15.82; 95% CI = 2.04-122.47), pAVSD (p = 0.017, HR = 6.26; 95% CI = 1.39-28.28) and re-operation (p = 0.007, HR = 4.911; 95% CI = 1.54-15.64) were independent risk factors for postoperative pacemaker implantation. Late life-threatening ventricular arrhythmias and SCD occurred in 0.5% and 1.7% respectively.& para;& para;Conclusion: There is good long-term survival after AVSD correction and incidence of SCD is low. Non-syndromic AVSD and cAVSD are independent risk factors for early post-operative SVTs. Non-syndromic AVSD patients have significant more early 3rd degree AVB and late post-operative SVTs. Non-syndromic patients with partial AVSD who have undergone reoperation have a significant higher risk of pacemaker implantation. (C) 2017 Elsevier B.V. All rights reserve

Down syndrome: A novel risk factor for respiratory syncytial virus bronchiolitis - A prospective birth-cohort study

OBJECTIVES. Respiratory syncytial virus is the single-most important cause of lower respiratory tract infections in children. Preterm birth and congenital heart disease are known risk factors for severe respiratory syncytial virus infections. Although Down syndrome is associated with a high risk of respiratory tract infections, little is known about the incidence of respiratory syncytial virus infections in this group. The aim of our study was to determine the incidence of respiratory syncytial virus lower respiratory tract infection-associated hospitalization among children with Down syndrome. PATIENTS AND METHODS. We performed a retrospective observational study and a prospective nationwide birth-cohort study of children with Down syndrome. The retrospective cohort comprised 176 children with Down syndrome. A birth cohort of 219 children with Down syndrome was prospectively followed until 2 years of age. All 276 siblings of the birth cohort were used as controls. RESULTS. Of the 395 patients with Down syndrome, 180 (45.6%) had a known risk factor for severe respiratory syncytial virus infections; 39 (9.9%) of these were hospitalized for respiratory syncytial virus lower respiratory tract infections. Two control children (0.7%) versus 9 term children with Down syndrome without congenital heart disease (7.6%) were hospitalized for respiratory syncytial virus lower respiratory tract infections. The median duration of hospitalization was 10 days; mechanical ventilation was required for 5 children (12.8%). CONCLUSIONS. This is the first study, to our knowledge, to demonstrate that Down syndrome is a novel independent risk factor for severe respiratory syncytial virus lower respiratory tract infections. These findings should prompt studies to investigate possible mechanisms that underlie severe respiratory syncytial virus lower respiratory tract infections in children with Down syndrome. The effect of respiratory syncytial virus prophylaxis in this specific population needs to be established

Increased Pro-inflammatory Cytokine Production in Down syndrome Children Upon Stimulation with Live Influenza A Virus

Purpose Children with down syndrome (DS) have an increased susceptibility to infections, due to altered humoral and/or cellular immunity. The aim of this study was to determine the cytokine production in whole blood of children with DS upon stimulation with live influenza A virus. Methods Whole blood of 61 children with DS and 57 of their healthy siblings was stimulated with 2.5x10(4) TCID50/ml influenza A virus during 6, 24, and 48 h. TNF-alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12p70, IFN-alpha, IFN-gamma concentrations, and viral load were measured at all time points. Results At most of the time points, TNF-alpha, IL-1 beta, IL-6, and IL-8 concentrations were significantly higher in children with DS following stimulation with live influenza A virus. IFN-alpha and IFN-gamma levels were also significantly higher in the DS group. Viral clearance, however, was equal in both groups. Conclusions Children with DS have an altered immune response to influenza A virus. The production of higher levels of pro-inflammatory cytokines may be responsible for a more severe clinical course of viral disease in these childre