Cell-free DNA for Down syndrome screening in obese women: Is it a cost-effective strategy?

OBJECTIVE: Determine cost differences between cell-free DNA (cfDNA) and serum integrated screening (INT) in obese women given the limitations of aneuploidy screening in this population. METHODS: Using a decision-analytic model, we estimated the cost-effectiveness of trisomy 21 screening in class III obese women using cfDNA compared with INT. Primary outcomes of the model were cost, number of unnecessary invasive tests, procedure-related fetal losses, and missed cases of trisomy 21. RESULTS: In base case, the mean cost of cfDNA was $498 greater than INT ($1399 vs $901). cfDNA resulted in lower probabilities of unnecessary invasive testing (2.9% vs 3.5%), procedure-related loss (0.015% vs 0.019%), and missed cases of T21 (0.00013% vs 0.02%). cfDNA cost $87 485 per unnecessary invasive test avoided, $11 million per procedure-related fetal loss avoided, and $2.2 million per missed case of T21 avoided. In sensitivity analysis, when the probability of insufficient fetal fraction is assumed to be >25%, cfDNA is both costlier than INT and results in more unnecessary invasive testing (a dominated strategy). CONCLUSION: When the probability of insufficient fetal fraction more than 25% (a maternal weight of ≥300 lbs), cfDNA is costlier and results in more unnecessary invasive testing than INT.

Estimating Nationwide Prevalence of Live Births with Down Syndrome and Their Medical Expenditures in Korea.

BACKGROUND: This study aimed to estimate the nationwide prevalence of live births with Down syndrome (DS) and its trends and compare the observed and model-based predicted prevalence rates. Further, we compared the direct medical expenditures among DS and non-DS patients. METHODS: Using the health administrative data of Health Insurance Review and Assessment in Korea, we selected 2,301 children with DS who were born between 2007 and 2016 to estimate the prevalence of live births with DS, and 12,265 non-DS children who were born between 2010 and 2014 to compare the direct medical expenditures among patients. RESULTS: The prevalence of live births with DS was 5.03 per 10,000 births in 9 years, and 13% of children with DS were medical aid recipients during the study period. The medical expenditure of children with DS was about 10-fold higher than that of non-DS children and their out-of-pocket expenditure was about twice as high. CONCLUSION: The prevalence of live birth with DS is high in the low socioeconomic group and the healthcare costs for the children with DS are significantly higher than those for non-DS children. Therefore, health authorities should help mothers at lower socioeconomic levels to receive adequate antenatal care and consider the cost of medical care for children with DS.

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.

A cost-effectiveness analysis of cell free DNA as a replacement for serum screening for Down syndrome.

OBJECTIVE: The aim of this article is to determine the cost effectiveness of cell free DNA (cfDNA) as a replacement for integrated screening using a societal cost perspective. METHOD: This study used Monte-Carlo simulation with one-way and probabilistic sensitivity analysis. RESULTS: Cell free DNA is more effective and less costly than integrated screening. The incremental cost-effectiveness ratio for cfDNA relative to the integrated test was -$277 955 per case detected (95th percent confidence interval -$881 882 to $532 785). CONCLUSION: Cell free DNA screening is a cost-effective replacement for maternal serum screening when the lifetime costs of Down syndrome live births are considered. The adoption of cfDNA screening would save approximately $277 955 for each additional case detected over integrated screening.

Hospitalizations and associated costs in a population-based study of children with Down syndrome born in Florida.

BACKGROUND: Our objective was to examine differences in hospital resource usage for children with Down syndrome by age and the presence of other birth defects, particularly severe and nonsevere congenital heart defects (CHDs). METHODS: This was a retrospective, population-based, statewide study of children with Down syndrome born 1998 to 2007, identified by the Florida Birth Defects Registry (FBDR) and linked to hospital discharge records for 1 to 10 years after birth. To evaluate hospital resource usage, descriptive statistics on number of hospitalized days and hospital costs were calculated. Results were stratified by isolated Down syndrome (no other coded major birth defect); presence of severe and nonsevere CHDs; and presence of major FBDR-eligible birth defects without CHDs. RESULTS: For 2552 children with Down syndrome, there were 6856 inpatient admissions, of which 68.9% occurred during the first year of life (infancy). Of the 2552 children, 31.7% (n = 808) had isolated Down syndrome, 24.0% (n = 612) had severe CHDs, 36.3% (n = 927) had nonsevere CHDs, and 8.0% (n = 205) had a major FBDR-eligible birth defect in the absence of CHD. Infants in all three nonisolated DS groups had significantly higher hospital costs compared with those with isolated Down syndrome. From infancy through age 4, children with severe CHDs had the highest inpatient costs compared with children in the other sub-groups. CONCLUSION: Results support findings that for children with Down syndrome the presence of other anomalies influences hospital use and costs, and children with severe CHDs have greater hospital resource usage than children with other CHDs or major birth defects without CHDs.

Health care in adults with Down syndrome: a longitudinal cohort study.

BACKGROUND: Individuals with Down syndrome increasingly survive into adulthood, yet little is known about their healthcare patterns as adults. Our study sought to characterise patterns of health care among adults with Down syndrome based on whether they had fully transitioned to adult-oriented providers by their inception in this cohort. METHODS: In this retrospective observational cohort study, healthcare utilisation and annualised patient charges were evaluated in patients with Down syndrome aged 18-45 years who received care in a single academic health centre from 2000 to 2008. Comparisons were made based on patients' provider mix (only adult-focused or 'mixed' child- and adult-focused providers). RESULTS: The cohort included 205 patients with median index age = 28 years; 52% of these adult patients had incompletely transitioned to adult providers and received components of their care from child-focused providers. A higher proportion of these 'mixed' patients were seen exclusively by subspecialty providers (mixed = 81%, adult = 46%, P < 0.001), suggesting a need for higher intensity specialised services. Patients in the mixed provider group incurred higher annualised charges in analyses adjusted for age, mortality, total annualised encounters, and number of subspecialty disciplines accessed. These differences were most pronounced when stratified by whether patients were hospitalised during the study period (e.g., difference in adjusted means between mixed versus adult provider groups: $571 without hospitalisation, $19,061 with hospitalisation). CONCLUSIONS: In this unique longitudinal cohort of over 200 adults aged 18-45 years with Down syndrome, over half demonstrated incomplete transition to adult care. Persistent use of child-focused care, often with a subspecialty emphasis, has implications for healthcare charges. Future studies must identify reasons for distinct care patterns, examine their relationship with clinical outcomes, and evaluate which provider types deliver the highest quality care for adults with Down syndrome and a wide variety of comorbidities.

A comparison study of depression and quality of life in Turkish mothers of children with Down syndrome, cerebral palsy, and autism spectrum disorder.

This study aimed to compare the quality of life and depression levels in Turkish mothers of children with Down syndrome, cerebral palsy, and Autism Spectrum Disorder (ASD). An additional purpose is to identify whether the depression and quality of life levels of the mothers differ significantly based on demographic variables. Two hundred fifty-two mothers participated in the study. The World Health Organization's Quality of Life-BREF (WHOQOL-BREF-TR) assessment instrument was used to determine the mothers' quality of life and the Beck Depression Inventory (BDI) to characterize their depression. Mothers of children with cerebral palsy had significantly lower quality of life scores on the environment and national environment domains of the WHOQOL-BREF-TR than those of children with Down syndrome. No significant difference was observed in the depression of mothers. With increasing education and income, quality of life of the mothers increased whereas depression decreased. Moreover, depression increased and quality of life decreased in older mothers. Furthermore, the findings indicated significant negative correlations between mothers' depression and quality of life scores on all domains of the WHOQOL-BREF-TR.

Down syndrome-associated periodontitis: a critical review of the literature.

Down syndrome, or trisomy 21 (T21), was first described by John Langdon Down in 1866. Down identified the phenotypic expression of patients with circulation and coordination problems as having Down syndrome. More than a century later, Jerome Lejeune hypothesized that nondysjunction during meiosis could lead to trisomy of the 21st chromosome. The incidence of T21 is one in 800 to 1,000 live births in the United States. Generally, these patients now live to age 50 and some to age 60. As life expectancy increases, medical and social costs garner greater attention. Also, societal changes have allowed for better quality of life. Dental practitioners are challenged by the high incidence of early onset aggressive periodontal disease in T21; these patients have higher levels of periodontal pathogens and periodontitis-associated interproximal bone loss. The complex anatomy, physiology, immunology, and microbiology underscore the need for further investigation in specific areas related to dental treatment of these patients. This article is a critical review of the periodontal research concerning T21. Creating awareness enables dental professionals who have the power and knowledge to appropriately address the needs of those affected by T21.

National profile of children with Down syndrome: disease burden, access to care, and family impact.

OBJECTIVE: To measure the co-morbidities associated with Down syndrome compared with those in other children with special health care needs (CSHCN). Additionally, to examine reported access to care, family impact, and unmet needs for children with Down syndrome compared with other CSHCN. STUDY DESIGN: An analysis was conducted on the nationally representative 2005 to 2006 National Survey of Children with Special Health Care Needs. Bivariate analyses compared children with Down syndrome with all other CSHCN. Multivariate analyses examined the role of demographic, socioeconomic, and medical factors on measures of care receipt and family impact. RESULTS: An estimated 98,000 CSHCN have Down syndrome nationally. Compared with other CSHCN, children with Down syndrome had a greater number of co-morbid conditions, were more likely to have unmet needs, faced greater family impacts, and were less likely to have access to a medical home. These differences become more pronounced for children without insurance and from low socioeconomic status families. CONCLUSIONS: Children with Down syndrome disproportionately face greater disease burden, more negatively pronounced family impacts, and greater unmet needs than other CSHCN. Promoting medical homes at the practice level and use of those services by children with Down syndrome and other CSHCN may help mitigate these family impacts.

Direct health care costs of children and adolescents with Down syndrome.

OBJECTIVE: To assess the direct annual health care costs for children and adolescents with Down syndrome in Western Australia and to explore the variation in health care use including respite, according to age and disease profile. STUDY DESIGN: Population-based data were derived from a cross-sectional questionnaire that was distributed to all families who had a child with Down syndrome as old as 25 years of age in Western Australia. RESULTS: Seventy-three percent of families (363/500) responded to the survey. Mean annual cost was $4209 Australian dollars ($4287 US dollars) for direct health care including hospital, medical, pharmaceutical, respite and therapy, with a median cost of $1701. Overall, costs decreased with age. The decline in costs was a result of decreasing use of hospital, medical, and therapy costs with age. Conversely, respite increased with age and also with dependency. Health care costs were greater in all age groups with increasing dependency and for an earlier or current diagnosis of congenital heart disease. Annual health care costs did not vary with parental income, including cost of respite. CONCLUSIONS: Direct health care costs for children with Down syndrome decrease with age to approximate population costs, although costs of respite show an increasing trend.

Cost-effectiveness and accuracy of prenatal Down syndrome screening strategies: should the combined test continue to be widely used?

OBJECTIVE: We analyzed the cost-effectiveness (CE) and performances of commonly used prenatal Down syndrome (DS) screening strategies. STUDY DESIGN: We performed computer simulations to compare 8 screening options by applying empirical data from Serum, Urine, and Ultrasound Screening Study trials on the population of 110,948 pregnancies. Screening strategies outcomes, CE ratios, and incremental CE ratios were measured. RESULTS: The most CE DS screening strategy was the contingent screening method (CE ratio of Can$26,833 per DS case). Its incremental CE ratio compared to the second-most CE strategy (serum integrated screening) was Can$3815 per DS birth detected. Among the procedures respecting guidelines, our results identified the combined test as the screening strategy with the highest CE ratio (Can$47,358) and the highest number of procedure-related euploid miscarriages (n = 71). CONCLUSION: In regard to CE, contingent screening is the best choice. The combined test, which is the most popular screening strategy, shows many limitations.

The choice of detecting Down syndrome: does money matter?

The prenatal diagnosis of Down syndrome (amniocentesis) presents parents with a complex dilemma which requires comparing the risk of giving birth to an affected child and the risk of losing an unaffected child through amniocentesis-related miscarriage. Building on the specific features of the French Health insurance system, this paper shows that variation in the monetary costs of the diagnosis procedure may have a very significant impact on how parents solve this ethical dilemma. The French institutions make it possible to compare otherwise similar women facing very different reimbursement schemes and we find that eligibility to full reimbursement has a largely positive effect on the probability of taking an amniocentesis test. By contrast, the sole fact of being labelled 'high-risk' by the Health system seems to have, as such, only a modest effect on subsequent choices. Finally, building on available information on post-amniocentesis outcomes, we report new evidence suggesting that amniocentesis increases the risk of premature birth and low weight at birth.

The direct health care cost to Medicare of Down syndrome dementia as compared with Alzheimer's disease among 2015 Californian beneficiaries.

BACKGROUND: Aging individuals with Down syndrome (DS) are at increased risk of dementia due to trisomy of chromosome 21 on which the amyloid precursor protein gene is located and with increased life expectancy. Yet, little is known about the costs associated with DS dementia and how this compares to Alzheimer's disease (AD). OBJECTIVE: To better understand direct healthcare costs and care consumption in DS dementia, we compared the total cost of care to US Medicare and the drivers of these medical expenditures in individuals with DS with and without dementia, and in those with AD without DS. METHODS: The effect of dementia in DS on costs and care utilization was estimated with 2015 California Medicare fee-for-service data (parts A and B). Among 3,001,977 Californian Medicare beneficiaries, 353 individuals had DS with dementia (age 45-89 years). We compared their number of chronic comorbidity conditions among 27 and their care and Medicare costs to those of age- and sex-matched individuals with DS without dementia and those with AD without DS. RESULTS: Medicare annual cost per beneficiary was a mean of 43.5% and 82.2% higher with DS dementia (mean $35,011) than DS without dementia (mean $24,401) and AD without dementia (mean $19,212), related to greater utilization of inpatient services. DS dementia was associated with increased level of multimorbidity (mean of 3.4 conditions in addition to dementia vs. 2.7 and 2.2 conditions for DS without dementia and AD, respectively), with more emergency room visits (88% vs. 76.5% and 54.4%) and with more primary care physician visits (91.2% vs. 87.3% and 81.3%). CONCLUSION: DS adults with dementia have higher health care costs than DS adults without dementia and adults with AD. Understanding costs and complex health care needs in DS dementia could facilitate management of adult and geriatric care resources for these high-need high-cost individuals.

Optimizing Fetal Aneuploidy Screening in an Austere Military Clinical Environment: A Prenatal Cost Comparison.

INTRODUCTION: Austere clinical settings, including remote military installations, face unique challenges in screening pregnant women for aneuploidy. The objective of this study was to compare the direct and indirect prenatal costs of traditional 2-part serum-based screening to cell-free DNA (cfDNA) for detection of trisomies 18 and 21 for a military treatment facility with limited in-house perinatal resources. MATERIALS AND METHODS: We identified Naval Hospital Guantanamo Bay as a surrogate for an austere clinical environment. A prenatal cost of care analysis incorporating direct and indirect expenses was performed to compare the 2 aneuploidy screening strategies for a theoretical cohort of 100 patients for detection of trisomies 18 and 21. The baseline aneuploidy uptake rate was determined using a historical cohort. Test performance characteristics were obtained from the contracting laboratory. Aneuploidy rates and costs were calculated using previously published data. RESULTS: Assuming a baseline screen uptake rate of 87%, initial screening using the traditional approach would directly cost $8,285.01 versus $44,140.32 with cfDNA. Considering indirect costs such as travel, consultative services, evaluation and follow-up testing of an abnormal screen result, and lost productivity, the cost difference narrows to $14,458.25 over a 5- to 6-year period. Cost equivalence is achieved when cfDNA is priced at $341.17 per test. CONCLUSION: Cell-free DNA as an initial screening strategy offers enhanced detection rates for trisomies 18 and 21 but remains more costly than traditional screening when incorporating direct and indirect expenses. In a low volume setting with limited resources, the added cost may be justified given the implications of unrecognized aneuploidy.

Cost-effectiveness of prenatal screening and diagnostic strategies for Down syndrome: A microsimulation modeling analysis.

OBJECTIVES: Down syndrome (DS) is the most frequently occurring fetal chromosomal abnormality and different prenatal screening strategies are used for determining risk of DS worldwide. New non-invasive prenatal testing (NIPT), which uses cell-free fetal DNA in maternal blood can provide benefits due to its higher sensitivity and specificity in comparison to conventional screening tests. This study aimed to assess the cost-effectiveness of using population-level NIPT in fetal aneuploidy screening for DS. METHODS: We developed a microsimulation decision-analytic model to perform a probabilistic cost-effectiveness analysis (CEA) of prenatal screening and diagnostic strategies for DS. The model followed individual simulated pregnant women through the pregnancy pathway. The comparators were serum-only screening, contingent NIPT (i.e., NIPT as a second-tier screening test) and universal NIPT (i.e., NIPT as a first-tier screening test). To address uncertainty around the model parameters, the expected values of costs and quality-adjusted life-years (QALYs) in the base case and all scenario analyses were obtained through probabilistic analysis from a Monte Carlo simulation. RESULTS: Base case and scenario analyses were conducted by repeating the micro-simulation 1,000 times for a sample of 45,605 pregnant women per the population of British Columbia, Canada (N = 4.8 million). Preliminary results of the sequential CEAs showed that contingent NIPT was a dominant strategy compared to serum-only screening. Compared with contingent NIPT, universal NIPT at the current test price was not cost-effective with an incremental cost-effectiveness ratio over $100,000/QALY. Contingent NIPT also had the lowest cost per DS case detected among these three strategies. CONCLUSION: Including NIPT in existing prenatal screening for DS is shown to be beneficial over conventional testing. However, at current prices, implementation of NIPT as a second-tier screening test is more cost-effective than deploying it as a universal test.

Out-of-pocket expenditures and care time for children with Down Syndrome: A single-hospital study in Mexico City.

AIM: To examine the burden of out-of-pocket household expenditures and time spent on care by families responsible for children with Down Syndrome (DS). METHODS: A cross-sectional analysis was performed after surveying families of children with DS. The children all received medical care at the Hospital Infantil de México Federico Gomez (HIMFG), a National Institute of Health. Data were collected on out-of-pocket household expenditures for the medical care of these children. The percentage of such expenditure was calculated in relation to available household expenditure (after subtracting the cost of food/housing), and the percentage of households with catastrophic expenditure. Finally, the time spent on the care of the child was assessed. RESULTS: The socioeconomic analysis showed that 67% of the households with children with DS who received medical care in the HIMFG were within the lower four deciles (I-IV) of expenses, indicating a limited ability to pay for medical services. Yearly out-of-pocket expenditures for a child with DS represented 27% of the available household expenditure, which is equivalent to $464 for the United States dollars (USD). On average, 33% of families with DS children had catastrophic expenses, and 46% of the families had to borrow money to pay for medical expenses. The percentage of catastrophic expenditure was greater for a household with children aged five or older compared with households with younger children. The regression analysis revealed that the age of the child is the most significant factor determining the time spent on care. CONCLUSIONS: Some Mexican families of children with DS incur substantial out-of-pocket expenditures, which constitute an economic burden for families of children who received medical care at the HIMFG.

The contingent use of cell-free fetal DNA for prenatal screening of trisomies 21, 18, 13 in pregnant women within a national health service: A budget impact analysis.

OBJECTIVE: Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) is highly accurate in the detection of common fetal autosomal trisomies. Aim of this project was to investigate short-term costs and clinical outcomes of the contingent use of cffDNA for prenatal screening of trisomies 21, 18, 13 within a national health service (NHS). METHODS: An economic analysis was developed from the perspective of the Italian NHS to compare two possible scenarios for managing pregnant women: women managed according to the Standard of Care screening (SoC) vs a cffDNA scenario, where Harmony Prenatal Test was introduced as a second line screening choice for women with an "at risk" result from SoC screening. RESULTS: The introduction of cffDNA as a second line screening test, conditional to a risk ≥ 1:1,000 from SoC screening, showed a 3% increase in the detection of trisomies, with a 71% decrease in the number of invasive tests performed. Total short-term costs (pregnancy management until childbirth) decreased by € 19 million (from € 84.5 to 65.5 million). CONCLUSION: The adoption of the Harmony Prenatal Test in women resulting at risk from SoC screening, implied a greater number of trisomies detection, together with a reduction of the healthcare costs.

Cost and efficacy comparison of prenatal recall and reflex DNA screening for trisomy 21, 18 and 13.

OBJECTIVE: To compare costs and efficacy of reflex and recall prenatal DNA screening for trisomy 21, 18 and 13 (affected pregnancies). In both methods women have Combined test markers measured. With recall screening, women with a high Combined test risk are recalled for counselling and offered a DNA blood test or invasive diagnostic testing. With reflex screening, a DNA analysis is automatically performed on plasma collected when blood was collected for measurement of the Combined test markers. METHODS: Published data were used to estimate, for each method, using various unit costs and risk cut-offs, the cost per woman screened, cost per affected pregnancy diagnosed, and for a given number of women screened, numbers of affected pregnancies diagnosed, unaffected pregnancies with positive results, and women with unaffected pregnancies having invasive diagnostic testing. RESULTS: Cost per woman screened is lower with reflex v recall screening: £37 v £38, and £11,043 v £11,178 per affected pregnancy diagnosed (DNA £250, Combined test markers risk cut-off 1 in 150). Reflex screening results in similar numbers of affected pregnancies diagnosed, with 100-fold fewer false-positives and 20-fold fewer women with unaffected pregnancies having invasive diagnostic testing. CONCLUSIONS: Reflex DNA screening is less expensive, more cost-effective, and safer than recall screening.

Pediatric acquired subglottic stenosis: Associated costs and comorbidities of 7,981 hospitalizations.

OBJECTIVES: Numerous risk factors have been characterized for acquired subglottic stenosis (ASGS) in the pediatric population. This analysis explores the comorbidities of hospitalized ASGS patients in the United States and associated costs and length of stay (LOS). METHODS: A retrospective analysis of the Kids' Inpatient Database (KID) from 2009 to 2012 for inpatients ≤ 20 years of age who were diagnosed with ASGS. International Classification of Diseases, Clinical Modification, Version 9 diagnosis codes were used to extract diagnoses of interest from 14, 045, 425 weighted discharges across 4179 hospitals in the United States. An algorithm was created to identify the most common co-diagnoses and subsequently evaluated for total charges and LOS. RESULTS: ASGS was found in 7981 (0.06%) of total discharges. The mean LOS in discharges with ASGS is 13.11 days while the mean total charge in discharges with ASGS is $114,625; these values are significantly greater in discharges with ASGS than discharges without ASGS. Patients with ASGS have greater odds of being co-diagnosed with gastroesophageal reflux, Trisomy 21, other upper airway anomalies and asthma, while they have lower odds of being diagnosed with prematurity and dehydration. Aside from Trisomy 21 and asthma, hospitalizations of ASGS patients with the aforementioned comorbidities incurred a greater LOS and mean total charge. CONCLUSION: Our analysis identifies numerous comorbidities in children with ASGS that are associated with increased resource utilization amongst US hospitalizations. The practicing otolaryngologist should continue to advocate interdisciplinary care and be aware of the need for future controlled studies that investigate the management of such comorbidities.