Healthcare experiences of patients with Down syndrome who are Black, African American, of African descent, or of mixed race.

Scant research has explored the healthcare experiences of people with Down syndrome (DS) in the United States who are Black, African American, of African descent, or of mixed race. The purpose of this study was to identify and describe the barriers and facilitators that such patients and their caregivers face when accessing healthcare. We gathered data in three ways: focus groups with caregivers, a national survey completed by caregivers, and in-depth interviews with primary care providers. Many caregivers and primary care physicians felt that patients with DS who are Black, African American, of African descent, or of mixed race receive a lower quality of medical care than their white counterparts with DS. Caregivers mentioned feeling tired of being reminded by the medical community about their race and wanting acknowledgment that raising a child with DS can be hard at times. Many felt that the medical community's conscious and unconscious racial biases do negatively impact the care of their loved ones with DS. Caregivers desired more race concordant medical providers or, when not possible, medical providers who are willing to learn more about DS and build trusted, longitudinal relationships. Primary care providers discussed the need for funded resources and support services to effectively care for their patients with DS.

Kinship, Connective Care, and Disability in Jordan.

Temporalities of care shape the lives of families raising children with Down syndrome in Jordan. As they age, parents grapple with the future's uncertainties and often circle back to questions of marriage. Marriage is a key symbol of adulthood, shaping futures and actualities of care by distributing gendered and generational labor among kin. Over time, children with Down syndrome depart from the normative trajectories embedded in these kinship- and marriage-based systems of care, leaving them stuck. While parents worry about care futures, they and their grown children contend with constricting opportunities in the present.

Trends and predictions for survival and mortality in individuals with Down syndrome in Brazil: A 21-year analysis.

BACKGROUND: Regional heterogeneities and sociodemographic characteristics affect mortality and population survival in Brazil. However, for individuals with Down syndrome (DS) this information remains unknown. In this study, we analysed survival and mortality rates among DS individuals in the five Brazilian geographic regions. In addition, we investigated whether there is an association between mortality and sociodemographic factors across administrative regions. METHODS: Data between 1996 and 2016, comprising 10 028 records of deaths of individuals with DS, were collected from database records of the Department of Informatics of the Unified Health System. Data on race/ethnicity, sex, age and years of schooling were defined for the association analyses. Survival data were analysed according to the Kaplan-Meier method and Cox regression model. RESULTS: The number of deaths among people with DS has increased in recent years. Children are more susceptible to death, especially in the first years of life. Individuals living in the northern region, Indigenous women and people with no years of schooling have higher mortality. In the Southeast and South region, for White and Yellow, survival is related to a higher level of education. Ethnic factors and years of schooling influence risk for mortality across the administrative regions. CONCLUSIONS: These findings show that sociodemographic characteristics affect survival and are associated with the risk of mortality for people with DS. In addition, this suggests that differences in access to health services among Brazilian regions, especially in the first years of life, may affect the survival of individuals with DS.

A 5-Year Retrospective Review of the Health Supervision Received by Children with Down Syndrome at a South African Regional Hospital.

INTRODUCTION: In 2011, the American Academy of Paediatrics (AAP) published revised health supervision guidelines for children with Down syndrome (DS). In the absence of South African guidelines, we described the health supervision received by children with DS at a rural regional hospital in the Western Cape, South Africa compared with the AAP guidelines. METHODS: This was a 5-year retrospective description of the implementation of the 2011 AAP guidelines at the DS clinic at Worcester Provincial Hospital (WPH), specifically related to screening for and management of cardiac, thyroid, hearing and haematological disorders. RESULTS: Sixty-two children received care at WPH DS clinic during the study period. Thirty-six (58%) children lived in Worcester while 26 (42%) children were referred from peripheral hospitals. The median age at first clinic visit was 0.5 years [inter-quartile range (IQR) 0.2-1.2], a total of 177 person-years of follow-up with a median duration of 1.8 years (IQR 0.3-4.8). Two deaths occurred during the study period. Forty-nine (79%) children had a screening echocardiogram performed, the median age at first echocardiogram was 0.8 years (IQR 0.2-1.4). Five (14%) children from WPH compared with no children from the peripheral hospitals received the echocardiogram within the first month of life in keeping with AAP guidance (p = 0.06). Those requiring cardiac surgery were operated on at a median age of 2 years (IQR 0.9-2.3). Compared with the AAP guidelines, within the first month of life 17 (27%) children had a thyroid screen, 20 (32%) children had a full blood count and 7 (11%) children had a hearing assessment. CONCLUSION: AAP guidelines for health supervision in DS are challenging to achieve within our local health system. The development and advocacy for a South African DS health supervision guideline that can be applied not only in specialist clinics might improve the care of children with DS.

A candidate gene analysis and GWAS for genes associated with maternal nondisjunction of chromosome 21.

Human nondisjunction errors in oocytes are the leading cause of pregnancy loss, and for pregnancies that continue to term, the leading cause of intellectual disabilities and birth defects. For the first time, we have conducted a candidate gene and genome-wide association study to identify genes associated with maternal nondisjunction of chromosome 21 as a first step to understand predisposing factors. A total of 2,186 study participants were genotyped on the HumanOmniExpressExome-8v1-2 array. These participants included 749 live birth offspring with standard trisomy 21 and 1,437 parents. Genotypes from the parents and child were then used to identify mothers with nondisjunction errors derived in the oocyte and to establish the type of error (meiosis I or meiosis II). We performed a unique set of subgroup comparisons designed to leverage our previous work suggesting that the etiologies of meiosis I and meiosis II nondisjunction differ for trisomy 21. For the candidate gene analysis, we selected genes associated with chromosome dynamics early in meiosis and genes associated with human global recombination counts. Several candidate genes showed strong associations with maternal nondisjunction of chromosome 21, demonstrating that genetic variants associated with normal variation in meiotic processes can be risk factors for nondisjunction. The genome-wide analysis also suggested several new potentially associated loci, although follow-up studies using independent samples are required.

Spectral Domain Optical Coherence Tomography in Detecting Sub-Clinical Retinal Findings in Asian Indian Children with Down Syndrome.

Purpose: Trisomy 21, also known as Down syndrome (DS), is the most common trisomy worldwide. Although ocular associations have been reported, retinal anatomy and pathology remain uninvestigated. We evaluate the role of spectral domain optical coherence tomography (SD-OCT) in analyzing foveal morphology of children with DS. Methods: Nineteen consecutive DS children and eight controls were enrolled under a cross-sectional study in an institutional practice. All subjects underwent SD-OCT imaging on a hand-held device. The morphology and thickness of central fovea, inner retinal layers, outer retina, and photoreceptor layers were measured and compared with age-group sub-analysis. Results: Mean age of the cases was 24 months (3-78 months). All cases and controls had a normal fundus on ophthalmoscopy and foveal thickness was comparable (p = 0.718). Inner retinal fusion was complete in the foveal center in only three eyes (15.8%) of cases compared to all eyes (100%) of controls (p < 0.001). The outer plexiform layer was normal in 10 eyes of cases (52.6%) compared to all eyes (100%) of the controls. Only 10 eyes of DS (52.6%) had a normal external limiting membrane, compared to all eyes of controls (100%, p = 0.01). The interdigitation zone (outer segment) was normal in one (5.3%) case compared to eight (67%) controls (p = 0.001). On subgroup analysis, in older cohorts, cases had a greater proportion of abnormal layers compared to controls. Visual acuity was found to be lower in cases when compared to controls, although not significant (p = 0.19). Conclusion: DS babies have abnormal foveal morphology and persistence of inner retinal layers. This may assist our understanding of their visual development.

How to correct the impact of ethnicity on effectiveness of the second trimester maternal serum screen of fetal Down syndrome?

Objectives: To compare the performance of second trimester maternal serum screen (MSS) for fetal Down syndrome in Thai population between the conventional method using Caucasian reference ranges with ethnic factor correction (CRR-EC) and the method using specific Thai reference ranges (TRRs). Methods: A prospective database of the MSS project was accessed. The concentrations of alpha fetoprotein (AFP), beta-hCG, and uE3 were converted to their multiple of medians (MoMs) by two methods; CRR-EC for Asian women and TRR. The detection rate and false positive rate derived from the two methods were compared. Results: Of 20,229 cases, 35 women had fetal Down syndrome. The detection rates of both methods were comparable, whereas the false-positive rate of TRR was significantly lower (8.8 versus 11.7%; p < .001). The improvement was mainly caused by more accuracy of the MoMs of beta-hCG, not AFP/uE3, based on TRR. Conclusions: The effectiveness of MSS could be improved by using our own reference ranges instead of using ethnic factor correction. With TRR, the false-positive rate or the number of invasive diagnoses could be significantly decreased without compromise of the detection rate. To improve MSS performance, each population should use its own reference ranges.

Comparing Maternal Serum Screening Markers Among IVF and Spontaneous Conceptions in Ontario Through Registry Data.

OBJECTIVE: The objectives of this study were as follows: (1) to investigate the accuracy of IVF identification on the prenatal screening record from prenatal screening laboratories; (2) to compare the screening markers in IVF and non-IVF pregnancies in the population of Ontario; and (3) to propose more appropriate IVF adjustment factors for the Ontario population. METHODS: Two years of IVF treatment, data from all fertility clinics in Ontario were merged with the corresponding prenatal screening data from all five prenatal screening labs. New adjustment factors for IVF were developed for each maternal serum screening marker and nuchal translucency measurement. Means and SDs and linear regression models were reported for all prenatal screening records, as well as for records that had IVF identified through the prenatal screening requisition and records that were identified through the Canadian Assisted Reproductive Technologies Register (CARTR) Plus database. RESULTS: Significant differences between IVF and non-IVF groups on the basis of the prenatal screening requisition information and CARTR Plus information were found among the ethnicity-adjusted mean multiple of the medians for alpha fetoprotein, first trimester pregnancy-associated plasma protein A, second trimester unconjugated estradiol, first trimester human chorionic gonadotropin, total human chorionic gonadotropin, and dimeric inhibin A. CONCLUSION: This study proposed alternate IVF adjustment factors that will produce more accurate screening results within the population of Ontario.

Strong impact of ethnicity on effectiveness of the first trimester maternal serum screen of fetal Down syndrome.

OBJECTIVES: The objective of this study is to compare the effectiveness of first-trimester maternal serum screening (MSS) for fetal Down syndrome among Thai women between the method using Caucasian reference ranges with racial factor correction (CRR-RC) and that using Thai reference ranges (TRR). METHODS: A prospective database of MSS was accessed. The levels of PAPP-A and beta-hCG were calculated to determine their MoMs (multiple of medians) by two methods: (1) CRR-RC for Asian women and (2) TRR. The MoMs from both methods were used to determine the fetal risk. RESULTS: Of 24,885 women including 36 fetuses with Down syndrome, the detection rates were significantly higher with TRR when compared with CRR-RC, 77.8 and 63.9%, respectively, p < .001. Additionally, the false-positive rates were significantly lower with TRR when compared to CRR-RC (7.5 versus 12.5%, respectively, p < .001) Conclusions: The effectiveness of MSS was much better by using our own reference ranges rather than the method of racial factor correction. The important insight is that ethnicity strongly impacts on the effectiveness that cannot be completely corrected by ethnic factor. MSS derived by the CRR-RC in other regions should be interpreted with high precaution, especially where the biophysical characteristics of the women are much different from Caucasian population.

Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects.

One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.

Ethnicity and Language Proficiency Differences in the Provision of and Intention to Use Prenatal Screening for Down's Syndrome and Congenital Anomalies. A Prospective, Non-selected, Register-Based Study in the Netherlands.

Objective We aimed to conduct an analysis of the associations between the information provision procedure of prenatal screening for Down's syndrome and congenital anomalies and the intention to participate in prenatal screening (PS) of ethnicity groups and Dutch language proficiency groups. Design Using a prospective web-based registration form, we asked counselors (midwives, general practitioners, nurses and gynecologists) to report whether and how they offered information about PS to pregnant women. Duration The study was conducted from 2008 to 2010. Participants We collected data on the characteristics of the women who received an information offer about PS from counselors. Measurements Measures included socio-demographic and language proficiency level (LPL) characteristics, key elements of the provision procedure of PS, and intentional participation in PS. Findings The dataset represents 37% of the total population in the study area. Women with a non-native Dutch background and/or insufficient Dutch LPL received fewer information offers about PS, faced a reduced chance of receiving counseling, and showed lower intentional participation rates for PS. Key Conclusions Women with a non-native Dutch background and/or with an insufficient LPL are underserved in the Dutch PS program. These findings present evidence indicating that the fundamental principle of the Dutch Population Screening Act, namely, equal access to PS for all pregnant women, is not being realized. Implications for Practice Therefore, the study findings are important for national and international healthcare, policy makers and governmental professionals to allow ethnic and LPL-related differences in the provision and intentional uptake of PS.

Normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in a specific ethnicity.

OBJECTIVE: To establish normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in southern Thai women, and to compare these reference levels with Caucasian-specific and northern Thai models. METHODS: A cross-sectional study was conducted in 1,150 normal singleton pregnancy women to determine serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG) concentrations in women from southern Thailand. The predicted median values were compared with published equations for Caucasians and northern Thai women. RESULTS: The best-fitting regression equations for the expected median serum levels of PAPP-A (mIU/L) and free ß- hCG (ng/mL) according to maternal weight (Wt in kg) and gestational age (GA in days) were: [Formula: see text] and [Formula: see text] Both equations were selected with a statistically significant contribution (p< 0.05). Compared with the Caucasian model, the median values of PAPP-A were higher and the median values of free ß-hCG were lower in the southern Thai women. And compared with the northern Thai models, the median values of both biomarkers were lower in southern Thai women. CONCLUSION: The study has successfully developed maternal-weight- and gestational-age-adjusted median normative models to convert the PAPP-A and free ß-hCG levels into their Multiple of Median equivalents in southern Thai women. These models confirmed ethnic differences.

Estimation of the number of people with Down syndrome in the United States.

PURPOSE: An accurate accounting of persons with Down syndrome (DS) has remained elusive because no population-based registries exist in the United States. The purpose of this study was to estimate this population size by age, race, and ethnicity. METHODS: We predicted the number of people with DS in different age groups for different calendar years using estimations of the number of live births of children with DS from 1900 onward and constructing DS-specific mortality rates from previous studies. RESULTS: We estimate that the number of people with DS living in the United States has grown from 49,923 in 1950 to 206,366 in 2010, which includes 138,019 non-Hispanic whites, 27,141 non-Hispanic blacks, 32,933 Hispanics, 6,747 Asians/Pacific Islanders, and 1,527 American Indians/American Natives. Population prevalence of DS in the United States, as of 2010, was estimated at 6.7 per 10,000 inhabitants (or 1 in 1,499). CONCLUSION: Until 2008, DS was a rare disease. In more recent decades, the population growth of people with DS has leveled off for non-Hispanic whites as a consequence of elective terminations. Changes in childhood survival have impacted the age distribution of people with DS, with more people in their fourth, fifth, and sixth decades of life.Genet Med 19 4, 439-447.

Adaptation in families of children with Down syndrome in East Asian countries: an integrative review.

AIM: The purpose of this integrative literature review was to understand the experiences of East Asian families of children with Down syndrome and identify factors affecting their adaptation in the Resiliency Model of Family Stress, Adjustment and Adaptation. BACKGROUND: Socio-cultural factors influence how well families adapt following the birth of a child with Down syndrome. Existing literature in this area has focused primarily on families from Western cultures. This is problematic because nurses care for families from all over the world. Therefore, the focus of this review is on families of children with Down syndrome living in East Asia, where Confucianism is dominant. DESIGN: Integrative literature review. DATA SOURCES: Online databases (i.e. PubMed, CINAHL and PsycINFO) and a public search engine (i.e. Google Scholar) were used along with manual searches of reference lists and major journals. Studies were limited to original publications written in English and published between 1990-2014. REVIEW METHODS: Two authors independently performed integrative review processes proposed by Whittemore and Knafl and a quality assessment using the Mixed Methods Appraisal Tool. RESULTS: Like families in Western cultures, some East Asian families of children with Down syndrome adapted well and even thrived while others struggled. Various socio-cultural factors, including some associated with Confucianism, played a role in how individuals, dyads and families adapted. CONCLUSION: An understanding of socio-cultural influences can help nurses implement culturally sensitive family-centred interventions with families of children with Down syndrome. It may also facilitate policy changes concerning resources for these families.

Prenatal screening, diagnosis, and termination of pregnancy in First Nations and rural women.

OBJECTIVES: The objectives of the study were to assess differences in utilization of maternal serum screening (MSS) and prenatal diagnostic testing between population subgroups and to determine the impact on chromosomal anomaly birth rates. METHODS: This population-based cohort study included all female residents from Saskatchewan, Canada, who delivered a baby, experienced a fetal loss, or had a pregnancy termination between 2000 and 2005. In total, 93 171 women were included in the study dataset, with a subset (n = 35 527) evaluated to identify predictors of screening and diagnostic testing. Incidence and live birth prevalence of Down syndrome were compared across populations. RESULTS: MSS uptake was lower in First Nations (FN) women (9.6% vs 28.4%), and living in a rural health region moderated the difference (p < 0.001). Consequently, fewer chromosomal anomalies were prenatally diagnosed in FN women than in the rest of the population (8.3% vs 27%). Terminations of pregnancy for fetal anomaly occurred at a lower frequency amongst FN women (0.64 vs 1.34, per 1000 pregnancies), resulting in a smaller effect on Down syndrome birth rates. CONCLUSION: Utilization of MSS and diagnostic testing was lower in FN and rural populations. Further research will be necessary to understand the relevance of value preferences and access barriers. © 2016 John Wiley & Sons, Ltd.

Contributions to Racial Disparity in Mortality among Children with Down Syndrome.

OBJECTIVE: To evaluate whether racial differences across a variety of medical factors collected in a longitudinal clinical database at a specialty clinical for children with Down syndrome provide insight into contributors to racial disparity in mortality. STUDY DESIGN: Comprehensive medical histories of 763 children receiving medical care at a Down syndrome specialty clinic were retrospectively reviewed regarding prenatal, postnatal, and medical issues, as well as subspecialty referrals. Frequency calculations and logistic regression were performed. The National Death Index was used to query death record databases to correlate medical histories with mortality data. RESULTS: Prenatal drug use and intubation were significantly more frequent, but hyperbilirubinemia was significantly less frequent, in black children compared with white children with Down syndrome. Among children with Down syndrome aged <5 years, significant increases in referral to cardiology were seen for black children compared with white children. Trends were seen in an increased incidence of congenital heart disease for black children. Correlations with death records did not demonstrate differences in rates of cardiac-related deaths. Minimal racial disparity was seen for all other measures investigated. CONCLUSION: Racial disparity in mortality exists, but the underlying cause remains unidentified despite use of a comprehensive, longitudinal database of individuals with Down syndrome and review of death records. Referrals to cardiology might be a clue to the underlying cause, perhaps as an indicator of access to care, but cardiac disease does not account for the disparity in mortality.

Decision-making for non-invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy.

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self-determination, independence, and self-sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non-invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi-structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision-making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision-making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision-making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches.