BACKGROUND: Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is \'double-positive\'-a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes.
METHODS: We conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes.
RESULTS: From 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4-15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9-3.7), aRD 10.0% (95%CI 4.8-15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4-94.8), aRD 34.0% (95%CI 29.2-38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth.
CONCLUSIONS: Although rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities.

UNASSIGNED: Down syndrome (DS) negatively impacts the well-being of affected individuals. This study aimed to summarise the evidence on quality of life (QOL) of children and young adults with DS using quantitative measures from caregivers\' perspective and identify factors that affected their QOL.
UNASSIGNED: Database search was conducted on PubMed, Embase, Web of Science and CINAHL on 24 April 2024. Meta-analysis using random effects model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532).
UNASSIGNED: Seventeen studies involving 3038 children with DS using various QOL measures were included: Pediatric Quality of Life Inventory (PedsQL) (8 studies), KIDSCREEN (4 studies), KidsLife (2 studies), The Netherlands Organization for Applied Scientific Research Academic Medical Center Children\'s QOL (2 studies) and Personal Outcome Scale (1 study). Meta-analysis on PedsQL studies compared scores between children with DS and typically developing (TD) children. Total scale score was lower in children with DS (mean 70.28, 95% confidence interval [CI] 64.31-76.24) compared to TD children (mean 88.17, 95% CI 80.50-95.83). All subdomains of PedsQL were also lower in children with DS. Within the domain of psychosocial health, children with DS had statistically significant lower social functioning (standardised mean difference -1.40, 95% CI -2.27 to -0.53) and school functioning (standardised mean difference -1.09, 95% CI -1.55 to -0.62) scores, but similar emotional functioning scores. Qualitative synthesis revealed poorer subdomain QOL compared to TD children, especially in social functioning and cognitive functioning. QOL worsened during adolescent years. Family variables (parental education and occupation) did not affect parental perception of children\'s QOL. Children with DS who had higher intelligent quotient had better QOL.
UNASSIGNED: Children with DS have lower caregiver-reported QOL than TD children, especially in social functioning and school functioning subdomains.

UNASSIGNED: The aims of this systematic review and meta-analysis are to synthesise quality of life (QOL) of family caregivers of children and young adults with Down syndrome (DS) and determine factors affecting their QOL.
UNASSIGNED: This review was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Key search terms were \"quality of life\", \"down syndrome\" and \"trisomy 21\". Meta-analysis using random effect model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532).
UNASSIGNED: Eighteen studies with 1956 caregivers were included. Of the 10 studies utilising the World Health Organization Quality of Life Instrument-Brief Version, 5 were included in the meta-analysis. Psychosocial domain had the highest score with mean (95% confidence interval [CI]) of 63.18 (39.10-87.25). Scores were poorer in physical, environmental and social domains: 59.36 (28.24-90.48), 59.82 (19.57-100.07) and 59.83 (44.24-75.41), respectively. Studies were heterogenous with I2 values ranging from 99-100% (P<0.01). The remaining 8 studies used 6 other instruments. Qualitative synthesis revealed that caregivers\' QOL was adversely affected by child-related factors, such as level of functional independence, developmental delay, presence of multiple comorbidities, impaired activities of daily living and poor sleep quality. Environmental factors that adversely affected caregivers\' QOL included number of children, housing and support from the family. Personal factors that affected caregivers\' QOL included age, being a single mother, low education and low income.
UNASSIGNED: QOL of caregivers of children with DS was lower than population reference data. Understand-ing the factors that influence family caregivers\' QOL is an essential step towards improving the QOL of caregivers and their children with DS.

BACKGROUND: Previous studies have demonstrated worse outcomes for Hirschsprung\'s disease (HD) procedures in Trisomy 21 (T21) patients. Using a large national database, we sought to investigate surgical outcomes in HD patients with T21 compared to non-T21 patients.
METHODS: We utilized the deidentified National Surgical Quality Improvement Program Pediatric database from 2012 to 2021. Using International Classification of Diseases, Ninth Revision codes, children <18 y old with HD were included and stratified by T21 diagnosis. Demographics, Current Procedural Terminology codes, case characteristics, length of hospital stay, and postoperative complications were analyzed.
RESULTS: Of 3456 HD patients, 12.0% (n = 413) patients had a concurrent diagnosis of T21. Pull-through (PT) procedures accounted for 54.9% of surgeries (n = 1896), of which 10.0% (n = 189) had T21. T21 patients who underwent PT had a younger gestational age (P < 0.0001), cardiac risk factors (P < 0.0001), hematologic disorders (P < 0.0001), higher American Society of Anesthesiologists class (P < 0.0001), and were older at their index operation (P = 0.03). Though operative times were similar, T21 patients had a longer total length of stay (P = 0.0263), postoperative length of stay (P = 0.0033), and more unplanned reoperations (P = 0.0094). Though only significant in unadjusted analyses, T21 patients had more postoperative complications after PT (P = 0.0034), specifically deep surgical site infections (P = 0.009), organ/space surgical site infections (P = 0.004), wound disruption (P < 0.001), and sepsis (P = 0.025).
CONCLUSIONS: We confirm significant differences exist between T21 and non-T21 patients undergoing HD procedures, particularly increased total length of stay, postoperative length of stay, and unplanned reoperations. Understanding these differences will lead to more optimal treatment plans for this unique patient population.

Adults with Down syndrome (DS) have unique health care needs with evidence-based care guidelines to address these. Yet, the 2020 adult guidelines were unstudied; we aimed to assess adherence to these guidelines. We reviewed clinical and demographic data from medical charts of 327 adults with DS who were seen in the MGH DSP. We calculated adherence to care guidelines and analyzed correlations between both demographic traits and clinical results. Mean adherence rate to each of the nine adult guidelines was 67.3%. Adherence rates that were below our mean adherence rate included colonoscopy (42.9%), iron (41.9%), audiology specialist (35.8%), and audiogram (35.2%). We found four significant correlations: assigned females at birth had a significantly higher body mass index (BMI) than assigned males at birth (p < 0.001), Hispanic patients had a significantly higher BMI than other patients (p = 0.015), Hispanic patients had a significantly higher rate of diabetes than other patients (p = 0.036), and Black patients had a significantly lower rate of hypothyroidism than other patients (p = 0.004). We assessed the adherence rates to adult DS guidelines and highlighted disparities in healthcare for patients with DS to inform clinicians on how to improve care for patients with DS.

Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18-25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits and Dyrk1a was trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21.

UNASSIGNED: Ventricular echogenic foci are small structures within the hearts of some fetuses. These small areas result from increased echogenicity in the ventricles of fetuses located near the papillary muscles. An association between these foci and chromosomal abnormalities in fetuses has been reported. Considering that chromosomal abnormalities are a major cause of prenatal death, this study aimed to determine the value of fetal echogenic foci as markers for chromosomal abnormalities.
UNASSIGNED: Fetal echocardiography was performed by an experienced cardiologist on 149 pregnant women in the second trimester. Of these, 75 were reported to have positive echogenic foci, and 74 were reported to have no echogenic foci. Subsequently, the three chromosomal anomalies including trisomies 21, 18, and 13 were examined. The information of the individuals, including gestational age and echogenic foci, was recorded.
UNASSIGNED: Based on the findings of the present study, seven infants (4.7%) had trisomy 21, four infants (2.7%) had trisomy 13, and six infants (4.1%) had trisomy 18. The mean gestational age of pregnant women with positive and negative echogenic foci was 21.07±3.23 and 21.03±3.09, respectively. No significant relationship was found between ventricular echogenic foci and trisomy 21, 18, or 13.
UNASSIGNED: The present study suggests no significant relation between the presence of echogenic foci and chromosomal trisomies. This finding indicates that additional tests are required to confirm chromosomal abnormalities when echogenic intracardiac foci are present, especially in high-risk fetuses. Moreover, the absence of echogenic focus does not rule out chromosomal disorders.

BACKGROUND: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS.
METHODS: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available.
RESULTS: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73).
CONCLUSIONS: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation.

UNASSIGNED: Potential clinical interventions to mitigate or eliminate symptoms of Down syndrome (DS) continue to be an active area of pre-clinical and clinical research. However, views of members of the DS community have yet to be fully explored.
UNASSIGNED: We conducted a survey with parents/caregivers of people with DS (n = 532) to explore interest in potential therapeutic approaches during fetal development or childhood that may improve neurocognition and modulate the DS phenotype. We qualitatively analyzed open-ended responses.
UNASSIGNED: Some respondents rejected the development of therapies for DS categorically as being fundamentally ableist and promoting the erasure of diverse individuals. Many reflected tensions between the desire to improve quality of life and an aversion to erasure of a child\'s personality.
UNASSIGNED: Findings suggest that views on identity, personality, and disability may influence the acceptance of new interventions, especially if they are thought to mitigate positive attributes of the phenotype or negatively influence social acceptance of people with DS.
Prenatal and pediatric approaches to reduce the signs of Down syndrome are being investigated.Parents of children with Down syndrome expressed conflicted feelings about the idea of removing signs of Down syndrome from their child.Many parents expressed that Down syndrome was a valued part of their child and should not be taken away.Findings suggest that greater communication between the Down syndrome community and the research community is necessary to ensure that research aligns with their values and priorities of the patient community.