Sustainability of personal social networks of people with Down syndrome.

Research continues to demonstrate that the characteristics of one's social network could have an impact on the development of Alzheimer's disease. Given the predisposition of people with Down syndrome to develop Alzheimer's disease, analysis of their social networks has become an emerging focus. Previous pilot research demonstrated that the personal networks of people with DS could be quantitatively analyzed, with no difference between self-report and parent-proxy report. This manuscript focuses on a 12-month follow-up period with the same original participants (24 adults with Down syndrome). Their social networks demonstrated sustainability, but not improvement, as reported by people with DS (mean network size: 8.88; mean density: 0.73; mean constraint: 0.44; mean effective size: 3.58; mean max degree: 6.04; mean degree: 4.78) and their proxies (mean network size: 7.90; mean density: 0.82; mean constraint: 53.13; mean effective size: 2.87; mean max degree: 5.19; mean degree: 4.30). Intentional and continued efforts are likely needed in order to improve the social network measures of people with Down syndrome.

Impact of a prenatal screening program on the Down syndrome phenotype: An interrupted time series analysis.

INTRODUCTION: We hypothesized that children with Down syndrome who were born after the implementation of first-trimester combined screening for trisomy 13, 18, and 21 and a second-trimester ultrasound scan in Denmark would show a milder syndrome phenotype. We investigated the birth biometry, prevalence of congenital malformations, and early childhood morbidity of children with Down syndrome before and after implementation of this screening program. MATERIAL AND METHODS: A nationwide register-based study of all live born singletons with Down syndrome in Denmark from 1995 to 2018. In interrupted time series analyses, we studied the temporal developments in birth biometry, prevalence of congenital malformations, and early childhood morbidity related to the implementation of a national prenatal screening program. RESULTS: We included 602 singletons with Down syndrome born before and 308 after implementation of the screening program. Z-scores of birthweight and head circumference increased over time before screening, but this temporal development changed after implementation by -0.05 (95% confidence interval [CI]: -0.11 to 0.01) and -0.05 (95% CI -0.12 to 0.02), respectively. Just after implementation, the prevalence of non-severe congenital heart disease decreased (relative change in odds 0.48 [95% CI: 0.24-0.94]). For severe congenital heart disease, atrioventricular septal defect, and non-heart malformations, this change was 1.16 (95% CI: 0.56-2.41), 0.95 (95% CI: 0.43-2.03), and 0.98 (95% CI: 0.33-2.76), respectively. For all malformations, pre-existing temporal developments did not change following implementation of screening. The implementation was associated with higher odds of admission to a neonatal intensive care unit (relative change 1.98 [95% CI: 0.76-5.26]) and an increased risk of hearing impairment (risk difference 3.4% [95% CI: -0.4% to 7.1%]). In contrast, the implementation was not associated with the incidence of hospital admissions by 2 years of age or with the probability of a thyroid disorder. CONCLUSIONS: After implementation of a national prenatal screening program, we did not observe a milder Down syndrome phenotype apart from an apparent reduction in the proportion of children with non-severe congenital heart disease; this result is, however, limited by small numbers.

Inclusion of sex chromosomes in noninvasive prenatal testing in Asia, Australia, Europe and the USA: A survey study.

OBJECTIVE: To examine the extent to which sex chromosomes are included in current noninvasive prenatal testing (NIPT) and the reporting practices with respect to fetal chromosomal sex and sex chromosome aberrations (SCAs), in addition to an update on the general implementation of NIPT. METHOD: A questionnaire addressing the research objectives was distributed by email to fetal medicine and clinical genetics experts in Asia, Australia, Europe and the USA. RESULTS: Guidelines on NIPT are available in the majority of the included countries. Not all existing guidelines address reporting of fetal chromosomal sex and SCAs. In most settings, NIPT frequently includes sex chromosomes (five Australian states, China, Hong Kong, Israel, Singapore, Thailand, USA and 23 of 31 European countries). This occurs most often by default or when parents wish to know fetal sex. In most settings, a potential SCA is reported by stating the risk hereof as "low" or "high" and/or by naming the SCA. Less than 50% of all pregnant women receive NIPT according to respondents from three Australian states, China, Israel, Singapore, Thailand and 24 of 31 European countries. However, this percentage, the genomic coverage of NIPT and its application as primary or secondary screening vary by setting. CONCLUSION: In most of the studied countries/states, NIPT commonly includes sex chromosomes. The reporting practices concerning fetal chromosomal sex and SCAs are diverse and most commonly not addressed by guidelines. In general, NIPT is variably implemented across countries/states.

Is the first-trimester combined screening result associated with the phenotype of Down syndrome? A population-based cohort study.

OBJECTIVE: To investigate if the Down syndrome phenotype differs according to the result of first-trimester combined screening (FTS). METHOD: We included all Down syndrome cases diagnosed by karyotype in pregnancy or after birth in Denmark during 2005-2018. We compared screen positive (odds ≥1:300) and screen negative (odds <1:300) cases as well as screen result subgroups with respect to anthropometrics, congenital malformations, childhood diseases, and hospitalization. RESULTS: Absolute measures of fetal and birth anthropometrics were comparable between groups. A prenatal malformation diagnosis was more prevalent among screen positive than screen negative cases. Analyses suggested that this could reflect a detection bias. Cases with a screen result of 1:2-1:10 had a higher probability of being diagnosed with a malformation prenatally and with severe congenital heart disease (CHD) postnatally compared with a result of 1:11-1:300. Screen positive cases more often had non-severe CHD but less often a non-heart malformation compared with screen negative cases, while proportions of severe CHD were similar in these groups. Data on hospitalizations showed inconsistent results. CONCLUSION: The 1:300 screening threshold had limited or no value in predicting Down syndrome phenotype severity. In contrast, cases with a screen result between 1:2 and 1:10 may represent a more severe phenotype.

Parenting a child with Down syndrome: A qualitative study of everyday practices in Danish families.

Genetic counseling about Down syndrome is suggested to include information on a future family life. However, there is an insufficient knowledge on the potential impact of parenting a child with Down syndrome on parents' everyday practices. We aimed to address this gap by exploring the experienced everyday practices of parents in families where a child has Down syndrome. Taking a qualitative approach, we conducted semi-structured interviews with 25 parents of children with Down syndrome aged 4-12 years. Using reflexive thematic analysis, we identified two themes concerned with the parents' practice. The first, 'Supporting our child', describes how the parents perceived their child as a valuable human being and how this perception founded parents' support of the child's development and social interactions. The second, 'Managing our family life', demonstrates how the parents acted to manage a family life that had become the 'new normal' including being alert toward the child, shaping the practical and logistical framework of daily life, and balancing between being at home and away from home. Overall, the analysis presents an everyday practice aimed at a desirable future for the child with Down syndrome and at a management of everyday life on the family's own terms. In conclusion, this study provides specific knowledge on parents' everyday practice, which may inform genetic counseling about Down syndrome and be of value to service providers.

Increased prenatal detection of 22q11.2 deletion and 22q11.2 duplication after introduction of nationwide prenatal screening for trisomy 21, trisomy 13, and trisomy 18.

OBJECTIVE: To evaluate time of diagnosis of 22q11.2 deletion and 22q11.2 duplication as well as trisomies 21, 13, and 18 before and after introduction of a prenatal screening program including combined first-trimester screening (cFTS) for the trisomies in Denmark in 2004. METHOD: Cross-sectional, population-based register study employing The Danish Cytogenetic Central Register. Proportions of cases diagnosed 1998-2004 and 2005-2017 were compared before 14+0 and 22+0 weeks and birth (prenatal cases) or up to 1 or 10 years of age (postnatal cases). RESULTS: In total, 4562 cases were included. From 1998-2004 to 2005-2017, the proportion of 22q11.2 deletion cases identified prenatally increased from 4.3% (95% CI: 0.9-12.0%) to 27.3% (21.2-34.0%), while for 22q11.2 duplication an increase from 0/6 to 26/87 (prenatal cases/all cases) was observed. Similarly, proportions of trisomies 21, 13, and 18 detected before birth increased. A greater proportion of the studied conditions was identified earlier in pregnancy, but not generally earlier in the postnatal course. CONCLUSION: Proportions of 22q11.2 deletion and 22q11.2 duplication identified prenatally increased after introduction of a prenatal screening program not aimed specifically to identify these conditions,. A greater proportion of all cases were detected earlier in pregnancy, but not earlier postnatally, following introduction of screening.

Preadmission antidepressant use and bladder cancer: a population-based cohort study of stage at diagnosis, time to surgery, and surgical outcomes.

BACKGROUND: Among cancer patients, prior antidepressant use has been associated with impaired survival. This could be due to differences in stage at diagnosis, in receipt of treatment, or in treatment complications. The purpose of this study was, therefore, to examine if preadmission antidepressant use in patients with bladder cancer is associated with tumor stage at diagnosis, rate of cystectomy, and surgical outcomes, including survival. METHODS: We performed a registry-based cohort study including all patients with incident invasive bladder cancer in Denmark 2005-2015. Exposure was defined as redemption of two or more antidepressant prescriptions one year before cancer diagnosis. We compared tumor stage using logistic regression, postsurgical inpatient length of stay using linear regression, and other outcomes using Cox regression. All results were adjusted for age, sex, comorbidity, and marital status. RESULTS: Among 10,427 bladder cancer patients, 10% were antidepressant users. At diagnosis, 51% of users and 52% of non-users had muscle-invasive disease. However, upon adjustment for age, sex, comorbidity, and marital status, users had lower odds of muscle-invasive disease (adjusted odds ratio 0.86 (95% confidence interval (CI) 0.74-0.99)). Among patients with muscle-invasive disease, fewer users than non-users had surgery within three months (15% vs. 24%, adjusted hazard ratio (aHR) 0.75 (95% CI 0.59-0.95)). Of 2532 patients undergoing surgery, 6% were antidepressant users. Postsurgical inpatient length of stay did not differ between users and non-users. The 30-day cumulative incidence of readmission was higher for users (41% vs. 33%, aHR 1.33 (95% CI 1.05-1.67)), while the 90-day incidence of postoperative procedures was 44% for users and 38% for non-users (aHR 1.18 (95% CI 0.93-1.51)). One-year mortality was comparable in users (15%) and non-users (14%). CONCLUSIONS: Antidepressant use in bladder cancer patients was associated with less advanced stage at diagnosis and lower rate of cystectomy. After cystectomy, users had higher rate of readmission and postoperative procedures than non-users, but we found no difference in length of stay or one-year mortality. The results point to the importance of differentiated clinical care according to individual patient characteristics.