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.

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.

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.

UNASSIGNED: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results.
UNASSIGNED: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses.
UNASSIGNED: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased.
UNASSIGNED: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

BACKGROUND: Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10-year incidence of cardiac, renal, and urinary tract complications in Down syndrome versus matched controls.
METHODS: This retrospective cohort study utilized a large collaborative database. We identified 32,444 patients with Down syndrome and matched controls, excluding those with pre-follow-up target events. Covariates included demographics, lifestyle factors, and comorbidities. Outcomes were ischemic heart disease, hypertension, hypothyroidism, epilepsy, urinary tract infections and chronic kidney disease. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression and plotted Kaplan-Meier survival curves.
RESULTS: Over 10 years, Down syndrome patients showed a 3.7-fold higher ischemic heart disease risk (95% CI: 3.0-4.6) and a 1.6-fold higher hypertension risk (95% CI: 1.4-1.8) versus controls. Hypothyroidism (HR = 2.0; 95% CI: 1.7-2.4), epilepsy (HR = 4.5; 95% CI: 3.5-5.8), and urinary tract infection (HR = 3.9; 95% CI: 3.4-4.6) risks were also higher. Chronic kidney disease risk was 2.7-fold greater (95% CI: 2.1-3.5). Survival analysis confirmed a significantly higher incidence of all outcomes in Down syndrome (p < 0.0001).
CONCLUSIONS: This large study found major health challenges in Down syndrome, with risks 3- to 5-fold higher for chronic conditions versus matched controls over 10 years. Though survival remains high with proper care, focusing resources on the prevention and management of complications in this high-risk group can optimize well-being across the lifespan. Future research accounting for limitations here would provide definitive estimates of disease risk in Down syndrome to guide targeted health strategies.

Introduction Periodontal diseases, caused by gram-negative bacteria, often begin as gingivitis and can progress to periodontitis, characterized by inflammation extending to the periodontal ligament and alveolar bone. Individuals with Down syndrome (DS) commonly exhibit poorer oral hygiene and a higher prevalence of severe chronic periodontitis. This study aimed to identify unregulated risk factors in DS that contribute to increased periodontal breakdown. Materials and methods We conducted a study with 60 age-matched patients, including 20 DS patients from Balavihar Special School and 40 systemically healthy patients with and without periodontitis from Thai Moogambigai Dental College and Hospital. We collected patients\' complete case histories and blood samples for evaluating matrix metalloproteinase 8 (MMP8) and matrix metalloproteinase 9 (MMP9) levels. All patients underwent nonsurgical periodontal therapy, and the samples were processed at the Central Research Laboratory at Meenakshi Ammal Dental College and Hospital. We calculated each group\'s mean and standard deviation and compared them using one-way analysis of variance and Kruskal-Wallis tests, followed by post hoc (Tukey honestly significant difference) multiple group comparisons. Statistical analysis was performed using Statistical Product and Service Solutions (SPSS) Statistics for Windows, Version 17.0. (Chicago: SPSS Inc.). Results The mean value of MMP8 in the DS group with chronic periodontitis was -18.1895, which was statistically significant (P<.001) compared to the mean value of -20.3720 in systemically healthy subjects with chronic periodontitis and -21.7120 in systemically healthy controls. Similarly, the mean value of MMP9 in the DS group with chronic periodontitis was 18.6455, which was statistically significant (P<.001) compared to the mean values of 19.8540 in systemically healthy subjects with chronic periodontitis and 25.2505 in systemically healthy controls. These findings indicate that DS subjects exhibit increased levels of pro-inflammatory cytokines MMP8 and MMP9, serving as markers for identifying periodontal disease. The mean differences in MMP8 and MMP9 in the DS group with chronic periodontitis showed highly statistically significant levels compared to both systemically healthy groups. Conclusion This study aimed to identify unregulated risk factors in DS that contribute to increased periodontal breakdown. Our findings revealed elevated MMP8 and MMP9 in DS patients with periodontitis, indicating an increased risk for early development of destructive forms of periodontal disease in this population. Extensive gingival tissue inflammation, bleeding on probing, increasing probing depths, loss of periodontal attachment, and alveolar bone loss are all common symptoms.

Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity.
This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13.
This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome.
A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %.
Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

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Children with Down syndrome (DS) often undergo flexible bronchoscopies (FB) due to common respiratory symptoms.
To examine the indications, findings, and complications of FB in pediatric DS patients.
A retrospective case-control study on FB performed in DS pediatric patients between 2004 and 2021 in a tertiary center. DS patients were matched to controls (1:3) based on age, gender, and ethnicity. Data collected included demographics, comorbidities, indications, findings, and complications.
Fifty DS patients (median age 1.36 years, 56% males) and 150 controls (median age 1.27 years, 56% males), were included. Evaluation for obstructive sleep apnea and oxygen dependence were more common indications among DS (38% vs. 8%, 22% vs. 4%, p < 0.01, respectively). Normal bronchoscopy was less frequent in DS compared with controls (8% vs. 28%, p = 0.01). Soft palate incompetence and tracheal bronchus were more frequent in DS (12% vs. 3.3%, p = 0.024, 8% vs. 0.7%, p = 0.02, respectively). Complications were more frequent in DS (22% vs. 9.3%, incidence rate ratio [IRR] 2.36, p = 0.028). In DS, cardiac anomalies (IRR 3.96, p < 0.01), pulmonary hypertension (IRR 3.76, p = 0.006), and pediatric intensive care unit (PICU) hospitalization before the procedure (IRR 4.2, p < 0.001) were associated with higher complication rates. In a multivariate regression model, history of cardiac disease and PICU hospitalization before the procedure, but not DS, were independent risk factors for complications with an IRR of 4 and 3.1, respectively (p = 0.006, p = 0.05).
DS pediatric patients undergoing FB are a unique population with specific indications and findings. DS pediatric patients with cardiac anomalies and pulmonary hypertension are at the highest risk for complications.

Background: West syndrome (WS) is a frequent epileptic encephalopathy associated with Down syndrome (DS). This study evaluated an outpatient protocol for WS in patients with DS who received vigabatrin (VGB) or VGB plus adrenocorticotrophic hormone. Methods: We analyzed infants treated in two neuropediatric centers from 2001-2021. We reviewed perinatal and familial history of epilepsy, spasm onset, treatment lag, electroencephalogram, neuroimaging, progression to epilepsy, and other neurological conditions. The outcomes were electroclinical resolution (ECR), relapses, and epilepsy progression. Results: Nineteen infants were included; 57.8% were male. The average spasm onset, follow-up, and treatment lag were 6.4 months, 8.15 years, and 2.33 months, respectively. Almost 74% had ECR after protocol intervention and minor epilepsy progression. Relapses occurred during combined therapy. Conclusions: The treatment protocol, especially combined therapy, was effective for WS in DS, impacting epilepsy progression and indicating the effectiveness of combined therapy to treat WS in patients with trisomy 21.