Clinical Value of Serum miR-124 and miR-200C Combined with Ultrasound NT in Screening Down Syndrome in Elderly Puerperae in the Second Trimester.

Objective: To evaluate the clinical value of serum miR-124 and miR-200C combined with ultrasound NT in screening Down syndrome (DS) in elderly puerperae during the second trimester. Methods: 84 elderly pregnant women at high risk of DS were included (DS group: 58, non-DS group: 26). Serum markers (uE3, ß-hCG, AFP, miR-124, and miR-200C) were measured. Differences in markers between groups were analyzed, and a prediction model was used for DS evaluation. Results: The DS group showed higher smoking, drinking, and radiation exposure rates (P < .05). MOM values of ß-hCG and AFP were higher, while MOM value of uE3 was lower in the DS group (P < .05). MiR-124 and miR-200C were up-regulated in the DS group (P < .05). The prediction model and ROC curve analysis indicated the diagnostic value of the markers for DS (AUC = 0.779, 0.817, 0.780, 0.884, 0.887, P < .05). MiR-124 had the highest diagnostic specificity. Conclusion: MiR-124 and miR-200C can serve as auxiliary serum markers for early screening of DS in elderly puerperae during the second trimester.

Evaluation of dental anxiety in children with Down's syndrome using dog-assisted therapy: A pilot study.

BACKGROUND: Dental anxiety and fear are the major treatment challenges faced by pediatric dentists. Oral hygiene in children with Down's syndrome is highly compromised in comparison to their healthy counterparts. Animal-assisted therapy, through dogs, has been beneficial in alleviating dental fear and anxiety in healthy pediatric population. AIM: The aim of the study was to assess the impact of dog-assisted therapy (DAT) on children with Down's syndrome undergoing dental examination and fluoride varnish application in dental operatory. MATERIALS AND METHODS: Twenty children with Down's syndrome between 5 and 12 years of age were selected. Group A (intervention group): DAT was carried out in the dental operatory. Group B (control group): Dental treatment was performed in the absence of a therapy dog in the dental operatory. Anxiety levels were evaluated by recording the pulse rate and revised modified faces version of the Modified Child Dental Anxiety Scale (MCDAS[f]). STATISTICAL ANALYSIS: The intergroup comparison of pulse rate was done using an unpaired t-test, whereas the variation in intragroup pulse rate was analyzed using the Analysis of Variance test. The anxiety scores were subjected to a paired t-test for intragroup comparison with P < 0.05 considered to be statistically significant. RESULTS: Reduction in dental anxiety was observed in the intervention group (P < 0.001). CONCLUSION: DAT can be used as an effective behavior management technique for children with Down's syndrome undergoing dental examination and simple dental procedures in the dental operatory.

Brain activity and upper limb movement analysis in children with Down syndrome undergoing transcranial direct current stimulation combined with virtual reality training: study protocol for a randomized controlled trial.

BACKGROUND: Children with Down syndrome have poorer functional and sensory skills compared to children with typical development. Virtual reality (VR) training could help improve these skills. Moreover, transcranial direct current stimulation (tDCS) has achieved promising results in terms of enhancing the effects of physical and sensory therapy by modulating cortical excitability. METHODS/DESIGN: Two investigations are proposed: (1) an observational study with a convenience sample consisting of children with Down syndrome (group 1-cognitive age of 6 to 12 years according to the Wechsler Abbreviated Scale of Intelligence) and children with typical development 6 to 12 years of age (group 2). Both groups will undergo evaluations on a single day involving a three-dimensional analysis of upper limb movements, an analysis of muscle activity of the biceps and brachial triceps muscles and an analysis of visuospatial and cognitive-motor variables. (2) Analysis of clinical intervention: a pilot study and clinical trial will be conducted involving individuals with Down syndrome (cognitive age of 6 to 12 years according to the Wechsler Abbreviated Scale of Intelligence). The sample will be defined after conducting a pilot study with the same methodology as that to be used in the main study. The participants will be randomly allocated to two groups: An experimental group submitted to anodal tDCS combined with a VR game and a manual motor task and a control group submitted to sham tDCS combined with a VR game and a manual motor task. The training protocol will involve 10 sessions of active or sham tDCS during memory and motor task games. Three 20-min sessions will be held per week for a total of 10 sessions. Evaluations will be performed on three different occasions: pre-intervention, post-intervention (after 10 sessions) and follow-up (1 month after the intervention). Evaluations will consist of analyses of electroencephalographic signals, electromyographic signals of the biceps and triceps brachii, and the three-dimensional reconstruction of the reaching movement. The results will be analyzed statistically with the significance level set at 5% (p ≤ 0.05). DISCUSSION: The optimization of the results obtained with virtual reality training is believed to be related to the interactive experience with a wide range of activities and scenarios involving multiple sensory channels and the creation of exercises, the intensity of which can be adjusted to the needs of children. Therefore, the proposed study aims to complement the literature with further information on tDCS and VR training considering different variables to provide the scientific community with clinical data on this combination of interventions. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC) protocol number RBR-43pk59 registered on 2019 March 27 https://ensaiosclinicos.gov.br/rg/RBR-43pk59 and Human Research Ethics Committee number 3.608.521 approved on 2019 September 30. Protocol version 2021 October 20. Any changes to the protocol will be reported to the committees and approved. Informed consent will be obtained from all participants by the clinical research coordinator and principal investigator.

Differential auditory brain response abnormalities in two intellectual disability conditions: SYNGAP1 mutations and Down syndrome.

OBJECTIVE: Altered sensory processing is common in intellectual disability (ID). Here, we study electroencephalographic responses to auditory stimulation in human subjects presenting a rare condition (mutations in SYNGAP1) which causes ID, epilepsy and autism. METHODS: Auditory evoked potentials, time-frequency and inter-trial coherence analyses were used to compare subjects with SYNGAP1 mutations with Down syndrome (DS) and neurotypical (NT) participants (N = 61 ranging from three to 19 years of age). RESULTS: Altered synchronization in the brain responses to sound were found in both ID groups. The SYNGAP1 mutations group showed less phase-locking in early time windows and lower frequency bands compared to NT, and in later time windows compared to NT and DS. Time-frequency analysis showed more power in beta-gamma in the SYNGAP1 group compared to NT participants. CONCLUSIONS: This study indicated reduced synchronization as well as more high frequencies power in SYNGAP1 mutations, while maintained synchronization was found in the DS group. These results might reflect dysfunctional sensory information processing caused by excitation/inhibition imbalance, or an imperfect compensatory mechanism in SYNGAP1 mutations individuals. SIGNIFICANCE: Our study is the first to reveal brain response abnormalities in auditory sensory processing in SYNGAP1 mutations individuals, that are distinct from DS, another ID condition.

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome.

Clinical observations and preclinical studies both suggest that Down syndrome (DS) may be associated with significant metabolic and bioenergetic alterations. However, the relevant scientific literature has not yet been systematically reviewed. The aim of the current study was to conduct a meta-analysis of metabolites involved in bioenergetics pathways in DS to conclusively determine the difference between DS and control subjects. We discuss these findings and their potential relevance in the context of pathogenesis and experimental therapy of DS. Articles published before July 1, 2020, were identified by using the search terms "Down syndrome" and "metabolite name" or "trisomy 21" and "metabolite name". Moreover, DS-related metabolomics studies and bioenergetics literature were also reviewed. 41 published reports and associated databases were identified, from which the descriptive information and the relevant metabolomic parameters were extracted and analyzed. Mixed effect model revealed the following changes in DS: significantly decreased ATP, CoQ10, homocysteine, serine, arginine and tyrosine; slightly decreased ADP; significantly increased uric acid, succinate, lactate and cysteine; slightly increased phosphate, pyruvate and citrate. However, the concentrations of AMP, 2,3-diphosphoglycerate, glucose, and glutamine were comparable in the DS vs. control populations. We conclude that cells of subjects with DS are in a pseudo-hypoxic state: the cellular metabolic and bio-energetic mechanisms exhibit pathophysiological alterations that resemble the cellular responses associated with hypoxia, even though the supply of the cells with oxygen is not disrupted. This fundamental alteration may be, at least in part, responsible for a variety of functional deficits associated with DS, including reduced exercise difference, impaired neurocognitive status and neurodegeneration.

Obstetric professionals' perceptions of non-invasive prenatal testing for Down syndrome: clinical usefulness compared with existing tests and ethical implications.

BACKGROUND: While non-invasive prenatal testing (NIPT) for fetal aneuploidy is commercially available in many countries, little is known about how obstetric professionals in non-Western populations perceive the clinical usefulness of NIPT in comparison with existing first-trimester combined screening (FTS) for Down syndrome (DS) or invasive prenatal diagnosis (IPD), or perceptions of their ethical concerns arising from the use of NIPT. METHODS: A cross-sectional survey among 327 obstetric professionals (237 midwives, 90 obstetricians) in Hong Kong. RESULTS: Compared to FTS, NIPT was believed to: provide more psychological benefits and enable earlier consideration of termination of pregnancy. Compared to IPD, NIPT was believed to: provide less psychological stress for high-risk women and more psychological assurance for low-risk women, and offer an advantage to detect chromosomal abnormalities earlier. Significant differences in perceived clinical usefulness were found by profession and healthcare sector: (1) obstetricians reported more certain views towards the usefulness of NIPT than midwives and (2) professionals in the public sector perceived less usefulness of NIPT than the private sector. Beliefs about earlier detection of DS using NIPT were associated with ethical concerns about increasing abortion. Participants believing that NIPT provided psychological assurance among low-risk women were less likely to be concerned about ethical issues relating to informed decision-making and pre-test consultation for NIPT. CONCLUSIONS: Our findings suggest the need for political debate initially on how to ensure pregnant women accessing public services are informed about commercially available more advanced technology, but also on the potential implementation of NIPT within public services to improve access and equity to DS screening services.

The effectiveness of the computerized visual perceptual training program on individuals with Down syndrome: An fMRI study.

This study investigated the effectiveness of the Computerized Visual Perception Training (CVPT) program on individuals with Down syndrome (DS, mean age=13.17±4.35years, age range: 6.54-20.75 years). All participants have mild intellectual disability classified by the standard IQ measures (mean=61.2, ranges from 55 to 68). Both the Test of Visual Perceptual Skill- Third Edition (TVPS-3) and functional magnetic resonance imaging (fMRI) were used to evaluate the training outcomes. Results of TVPS-3 and fMRI showed that DS group had visual perceptual deficits and abnormal neural networks related to visual organization. The results showed that DS intervention group had significant improvements on TVPS-3 after intervention. The fMRI results indicated more activation in superior and inferior parietal lobes (spatial manipulation), as well as precentral gyrus and dorsal premotor cortex (motor imagery) in DS intervention group. The CVPT program was effective in improving visual perceptual functions and enhancing associated cortical activations in DS.

A Framework for Describing the Influence of Service Organisation and Delivery on Participation in Fetal Anomaly Screening in England.

Objective. The aim of this research was to explore the influence of service organisation and delivery on providers and users' interactions and decision-making in the context of Down's syndrome screening. Methods. A qualitative descriptive study involving online interviews conducted with a purposive sample of 34 community midwives, 35 pregnant women, and 15 partners from two maternity services in different health districts in England. Data were analysed using a combination of grounded theory principles and content analysis and a framework was developed. Results. The main emerging concepts were organisational constraints, power, routinisation, and tensions. Providers were concerned about being time-limited that encouraged routine, minimal information-giving and lacked skills to check users' understanding. Users reported their participation was influenced by providers' attitudes, the ambience of the environment, asymmetric power relations, and the offer and perception of screening as a routine test. Discordance between the national programme's policy of nondirective informed choice and providers' actions of recommending and arranging screening appointments was unexpected. Additionally, providers and users differing perceptions of emotional effects of information, beliefs, and expectations created tensions within them, between them, and in the antenatal environment. Conclusions. A move towards a social model of care may be beneficial to empower service users and create less tension for providers and users.

Resolution of liver disease in transient abnormal myelopoiesis with fish oil emulsion.

Neonates with Down syndrome are at risk of developing transient abnormal myelopoiesis (TAM), which is characterized by transient clonal myeloproliferation of the blast cells. TAM can resolve spontaneously, but some patients die at an early age due to organ failure. Liver fibrosis in TAM is a life-threatening condition, but treatment options have not yet been established. Here, we report on the case of an infant with TAM complicated by liver disease, whose hyperbilirubinemia was successfully ameliorated with omega-3 fatty acid (ω3FA) lipid emulsion. Timely ω3FA lipid emulsion may be a feasible treatment for liver disease in TAM before serious liver damage develops.

Detecting celiac disease in patients with Down syndrome.

The main purposes of this undertaking were to determine how often patients with Down syndrome (DS) are screened for celiac disease (CD) across five DS specialty clinics, which symptoms of CD are most often reported to DS specialty providers at these clinics, and, how many individuals were diagnosed with CD by these clinics. This was accomplished by following 663 individuals with DS for 1 year, across five clinics in different states specializing in the comprehensive care of people with DS. Of the 663 participants, 114 individuals were screened for CD at their visit to a DS specialty clinic. Protracted constipation (43.2%) and refractory behavioral problems (23.7%) were symptoms most often reported to DS specialty providers. During the 1 year study period, 13 patients screened positive for CD by serology. Of those, eight underwent duodenal biopsy, and three were diagnosed with CD. We conclude that CD is an important consideration in the comprehensive care of individuals with DS. However, while symptoms are common, diagnoses are infrequent in DS specialty clinics. © 2016 Wiley Periodicals, Inc.

Integrated care for Down syndrome.

Down syndrome (DS), caused by an extra copy of chromosome 21 (trisomy 21), is the most intensively studied human aneuploidy condition. It is the leading cause of intellectual disability and birth defects. Although most prenatally diagnosed DS fetuses are aborted in Taiwan, there are still some infants with DS who are diagnosed after birth. In addition to intellectual disability, people with DS face systemic problems that include short stature, dysmorphism, congenital heart disease, congenital anomalies of gastrointestinal and genitourinary tracts, abnormal endocrine function, leukemia and leukemoid reactions. To provide better care for people with DS in Taiwan, we began the DS multi-disciplinary clinic that has opened once per month since November 2013. The multi-disciplinary clinic consists of several subspecialists who provide care for DS people. To date, approximately 200 patients have used the clinic. The average number of patients who use the clinic per month is 27±6 with a mean patient age of 16±12 years old (range 0.3-53 years). The average number of patients per specialist on each clinic day is 5.2±4.9 (range 0.5-20.9 patients). We focus on early detection and prevention of medical and developmental issues associated with DS. This coordinated approach allows DS patients and family to have more comprehensive care.

First trimester screening cut-offs for noninvasive prenatal testing as a contingent screen: Balancing detection and screen-positive rates for trisomy 21.

OBJECTIVE: To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing. MATERIALS AND METHODS: First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed. RESULTS: The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women >35 years as screen positive would increase the screen-positive rate and detection rates to 30.2% and 97.2%. CONCLUSION: Variation in screening risk cut-off and the use of maternal age to assess eligibility for noninvasive testing could significantly impact the demand for, and cost of, the test. A contingent first trimester screening approach for risk assessment is superior to the use of a combination of screening and maternal age alone. These data will inform decisions regarding the criteria used to determine eligibility for publicly funded noninvasive prenatal testing.

Down syndrome screening information in midwifery practices in the Netherlands: Strategies to integrate biomedical information.

The aim of this qualitative study was to analyse counselling with regard to prenatal screening in midwifery consultations in the Netherlands where a national prenatal screening programme has only existed since 2007, after years of social and political debates. The methodology is based on in situ observations of 25 counselling consultations in four midwifery practices in two main cities in the Netherlands. The results of this study show that, since midwives are obliged to offer information on Down syndrome screening to all pregnant women (2007), they have to deal with the communication of medical screening information using biostatistical concepts to explain risks, calculations, probabilities and chromosomal anomalies. In order to avoid the risk of medicalization of their consultation, midwives develop strategies that allow them to integrate this new biomedical discourse while maintaining their low medicalized approach of midwife-led care. One of their main strategies is to switch from 'alarming' biomedical messages to 'reassuring words' in order to manage the anxiety induced by the information and to keep the control over their low medicalized consultation. They also tend to distance themselves from the obligation to talk about screening. The way midwives handle these counselling consultations allows them to respect their obligation to propose information, and to remain faithful to their struggle to protect the natural process of pregnancy as well as their professional autonomy.

Midwives and information on prenatal testing with focus on Down syndrome.

OBJECTIVE: To investigate midwives' knowledge of prenatal diagnosis especially Down syndrome, information given by midwives to parents, expectant parents' requests for information and how midwives perceive their own competence to give information. METHOD: A cross-sectional, prospective study with a questionnaire was completed by 64 out of 70 midwives working in the outpatient antenatal care in Uppsala County, Sweden. RESULTS: The midwives had varying and in some areas low levels of knowledge about Down syndrome. Information about Down syndrome was most often given only when asked for or when there was an increased probability of a Down syndrome pregnancy. The most common questions from expectant parents concerned test methods and risk assessments while questions regarding symptoms of Down syndrome and consequences of having a child with Down syndrome were uncommon. The majority (83-89%) had insufficient or no education regarding different prenatal tests. Only two midwives (3%) had received education about Down syndrome, and 9% felt they had sufficient knowledge to inform about the syndrome. More education about prenatal tests and Down syndrome was desired by 94%. CONCLUSION: It is important to ensure that midwives in antenatal care have sufficient knowledge to inform expectant parents about the conditions screened for. © 2015 John Wiley & Sons, Ltd.

Prenatal screening, reproductive choice, and public health.

One widely held view of prenatal screening (PNS) is that its foremost aim is, or should be, to enable reproductive choice; this is the Pure Choice view. The article critiques this position by comparing it with an alternative: Public Health Pluralism. It is argued that there are good reasons to prefer the latter, including the following. (1) Public Health Pluralism does not, as is often supposed, render PNS more vulnerable to eugenics-objections. (2) The Pure Choice view, if followed through to its logical conclusions, may have unpalatable implications, such as extending choice well beyond health screening. (3) Any sensible version of Public Health Pluralism will be capable of taking on board the moral seriousness of abortion and will advocate, where practicable, alternative means of reducing the prevalence of disease and disability. (4) Public Health Pluralism is at least as well-equipped as the Pure Choice model to deal with autonomy and consent issues.

Explaining variation in Down's syndrome screening uptake: comparing the Netherlands with England and Denmark using documentary analysis and expert stakeholder interviews.

BACKGROUND: The offer of prenatal Down's syndrome screening is part of routine antenatal care in most of Europe; however screening uptake varies significantly across countries. Although a decision to accept or reject screening is a personal choice, it is unlikely that the widely differing uptake rates across countries can be explained by variation in individual values alone.The aim of this study was to compare Down's syndrome screening policies and programmes in the Netherlands, where uptake is relatively low (<30%) with England and Denmark where uptake is higher (74 and > 90% respectively), in an attempt to explain the observed variation in national uptake rates. METHODS: We used a mixed methods approach with an embedded design: a) documentary analysis and b) expert stakeholder analysis. National central statistical offices and legal documents were studied first to gain insight in demographic characteristics, cultural background, organization and structure of healthcare followed by documentary analysis of primary and secondary sources on relevant documents on DSS policies and programme. To enhance interpretation of these findings we performed in-depth interviews with relevant expert stakeholders. RESULTS: There were many similarities in the demographics, healthcare systems, government abortion legislation and Down's syndrome screening policy across the studied countries. However, the additional cost for Down's syndrome screening over and above standard antenatal care in the Netherlands and an emphasis on the 'right not to know' about screening in this country were identified as potential explanations for the 'low' uptake rates of Down's syndrome screening in the Netherlands. The social context and positive framing of the offer at the service delivery level may play a role in the relatively high uptake rates in Denmark. CONCLUSIONS: This paper makes an important contribution to understanding how macro-level demographic, social and healthcare delivery factors may have an impact on national uptake rates for Down's syndrome screening. It has suggested a number of policy level and system characteristics that may go some way to explaining the relatively low uptake rates of Down's syndrome screening in the Netherlands when compared to England and Denmark.