Prenatal diagnosis of BACs-on-Beads assay in 1520 cases from Fujian Province, China.

BACKGROUND: The aim of this study was to evaluate the application of BACs-on-Beads (BoBs™) assay for rapid detection of chromosomal abnormalities for prenatal diagnosis (PND). METHODS: A total of 1520 samples, including seven chorionic villi biopsy samples, 1328 amniotic fluid samples, and 185 umbilical cord samples from pregnant women were collected to detect the chromosomal abnormalities using BoBs™ assay and karyotyping. Furthermore, abnormal specimens were verified by chromosome microarray analysis (CMA) and fluorescence in situ hybridization (FISH). RESULTS: The results demonstrated that the success rate of karyotyping and BoBs™ assay in PND was 98.09% and 100%, respectively. BoBs™ assay was concordant with karyotyping for Trisomy 21, Trisomy 18, and Trisomy 13, sex chromosomal aneuploidy, Wolf-Hirschhorn syndrome, and mosaicism. BoBs™ assay also detected Smith-Magenis syndrome, Williams-Beuren syndrome, DiGeorge syndrome, Miller-Dieker syndrome, Prader-Willi syndrome, Xp22.31 microdeletions, 22q11.2, and 17p11.2 microduplications. However, karyotyping failed to show these chromosomal abnormalities. A case of 8q21.2q23.3 duplication which was found by karyotyping was not detected by BoBs™ assay. Furthermore, all these chromosomal abnormalities were consistent with CMA and FISH verifications. According to the reports, we estimated that the detection rates of karyotyping, BoBs™, and CMA in the present study were 4.28%, 4.93%, and 5%, respectively, which is consistent with the results of a previous study. The respective costs for the three methods were about $135-145, $270-290, and $540-580. CONCLUSION: BoBs™ assay is considered a reliable, rapid test for use in PND. A variety of comprehensive technological applications can complement each other in PND, in order to maximize the diagnosis rate and reduce the occurrence of birth defects.

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.

An economic analysis of chromosome testing in couples with children who have structural chromosome abnormalities.

BACKGROUND: Structural chromosome abnormalities can cause significant negative reproductive outcomes as they typically result in morbidity and mortality of newborns. The prevalence of structural chromosomal abnormalities in live births is at least 0.05%, of which many of them have parental origins. It is uncommon to predict structural chromosome abnormalities at birth in the first child but it is possible to prevent repeated abnormalities through screening and diagnostic programmes. This study will provide an economic analysis of the prenatal detection of these abnormalities. METHODS: A cost-benefit analysis using a decision analytic model was employed to compare the status quo (doing nothing) with two interventional strategies. The first strategy (Strategy I) is preconceptional screening plus amniocentesis, and the second strategy (Strategy II) is amniocentesis alone. The monetary values in Thai baht (THB) were adjusted to international dollars (I$) using purchasing power parity (PPP) (I$1 = THB 17.60 for the year 2013). The robustness of the results was tested by applying a probabilistic sensitivity analysis. RESULTS: Both diagnostic strategies can reduce approximately 10.7-11.1 births with abnormal chromosomes per 1,000 diagnosed couples. The benefit cost ratios were 1.62 for Strategy I and 1.24 for Strategy II. Net present values per 1,000 diagnoses in couples were I$464,000 for Strategy I and I$267,000 for Strategy II. The probabilistic sensitivity analysis suggested that the cost-benefit analysis was sufficiently robust, confirming that both strategies provided higher benefits than costs. CONCLUSIONS: Since the benefits of both diagnostic strategies exceeded their costs, both strategies are economical-with Strategy I being more economically attractive. Strategy I is superior to Strategy II because it decreases the risk of normal children potentially dying from the amniocentesis process.

The impact of financing of screening tests on utilization and outcomes: The case of amniocentesis.

We use a 1993 policy change in Israel's public healthcare system that lowered the eligibility age for amniocentesis to 35 to study the effects of financing of screening tests. Financing is found to have increased amniocentesis testing by about 35%. At ages above the eligibility threshold, utilization rates rose to roughly 33%, reflection nearly full takeup among prospective users of amniocentesis. Additionally, whereas below the age-35 threshold amniocentesis utilization rates increase with maternal age, this relation is muted above this age. Finally, no evidence is found that financing affects outcomes such as pregnancy terminations and births of children with Down syndrome. These results support the view that women above the eligibility threshold tend to refrain from acquiring inexpensive information about their degree of risk that absent the financing they would acquire, and instead, undergo the accurate and costly test regardless of additional information that noninvasive screening would provide.

Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways.

OBJECTIVE: Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice. METHOD: Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders. RESULTS: For autosomal dominant conditions, where NIPD molecular techniques are straightforward, NIPD cost £314 less than invasive testing. NIPD for autosomal recessive and X-linked conditions requires more complicated technical approaches and total costs were more than invasive testing, e.g. NIPD for spinal muscular atrophy was £1090 more than invasive testing. Impact of test uptake on costs was assessed using sickle cell disorder as an example. Anticipated high uptake of NIPD resulted in an incremental cost of NIPD over invasive testing of £48 635 per 100 pregnancies at risk of sickle cell disorder. CONCLUSION: Total costs of NIPD are dependent upon the complexity of the testing technique required. Anticipated increased demand for testing may have economic implications for prenatal diagnostic services. Ethical issues requiring further consideration are highlighted including directing resources to NIPD when used for information only and restricting access to safe tests if it is not cost-effective to develop NIPD for rare conditions. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Uptake of non-invasive prenatal testing in Chinese women: money matters.

OBJECTIVE: To determine the influence of free invasive prenatal testing on the uptake of non-invasive prenatal testing (NIPT). STUDY DESIGN: Over a 2-year period at a Chinese tertiary prenatal diagnostic unit, women at risk of fetal trisomy were given the option of NIPT or invasive prenatal testing. Invasive prenatal testing was offered free of charge to women with a local Hukou (household registration); however, women without a local Hukou were charged for invasive prenatal testing. Both women with and without a local Hukou were charged for NIPT. RESULTS: During the first year, 2647 women with a positive trisomy 21 screening test were referred (474 women with a local Hukou and 2173 women without a local Hukou). Only 1.6% of the women with a local Hukou underwent NIPT, while this proportion was 20.6% in the women without a local Hukou. During the second year, the price of NIPT was reduced. The total number of women referred was 3047 (502 women with a local Hukou and 2545 women without a local Hukou). The uptake of NIPT in women without a local Hukou doubled, but the uptake of NIPT remained stable in women with a local Hukou. CONCLUSION: The financial impact on the uptake of NIPT should not be underestimated.

The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis.

OBJECTIVE: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy. Clinical trials have shown high sensitivity and specificity for trisomy 21 (T21) in both high-risk and average-risk populations. Although its great potential for prenatal medicine is evident, more information regarding the consequences of implementing NIPT in a national programme for prenatal screening is required. STUDY DESIGN: A decision-analytic model was developed to compare costs and outcomes of current clinical practice in The Netherlands using conventional screening only, with two alternatives: implementing NIPT as an optional secondary screening test for those pregnancies complicated by a high risk for T21, and implementing NIPT as primary screening test, replacing conventional screening. Probability estimates were derived from a systematic review of international literature. Costs were determined from a health-care perspective. Data were analysed to obtain outcomes, total costs, relative costs and incremental cost-effectiveness ratios (ICERs) for the different strategies. Sensitivity analysis was used to assess the impact of assumptions on model results. RESULTS: Implementing NIPT as an optional secondary, or as primary screening test will increase T21 detection rate by 36% (from 46.8% to 63.5%) and 54% (from 46.8% to 72.0%), simultaneously decreasing the average risk of procedure-related miscarriage by 44% (from 0.0168% to 0.0094% per pregnant woman) and 62% (from 0.0168% to 0.0064% per pregnant woman), respectively. None of the strategies clearly dominated: current clinical practice is the least costly, whereas implementing NIPT will cause total costs of the programme to increase by 21% (from €257.09 to €311.74 per pregnant woman), leading to an ICER of k€94 per detected case of T21, when utilised as an optional secondary screening test and by 157% (from €257.09 to €660.94 per pregnant woman), leading to an ICER of k€460 per detected case of T21, when utilised as primary screening test. However, implementing NIPT as triage test did result in the lowest expected relative costs per case of T21 diagnosed (k€141). CONCLUSION: NIPT should be implemented in national health care as an optional secondary screening test for those pregnancies complicated by a high risk for T21.

Routine measurement of amniotic fluid alpha-fetoprotein and acetylcholinesterase: the need for a reevaluation.

OBJECTIVE: The objective of the study was to evaluate whether the current screening regimen of measuring amniotic fluid alpha-fetoprotein (AF-AFP) at the time of amniocentesis and reflex acetylcholinesterase testing vs ultrasound alone to detect neural tube and ventral wall defects offers improved diagnostic accuracy and cost benefit. STUDY DESIGN: A retrospective chart review on all patients who had amniocentesis performed at 1 center over the past 11 years was performed. Those with an elevated AF-AFP were compared with those whose AF-AFP was within normal limits. Ultrasound findings and outcomes were reviewed in all cases to assess whether neural tube defects (NTDs) or ventral wall defects (VWDs) were missed by AF-AFP or ultrasound screening. A cost-benefit analysis was then performed. RESULTS: Of 6232 women who underwent amniocentesis between January 2002 and December 2012, 81 had an elevated AF-AFP with or without a positive acetylcholinesterase (AChE). Of these 81 women, 13 had NTDs and 5 had VWDs. The sensitivity of the detailed ultrasound was 100% in detecting NTDs and VWDs, whereas that of the AF-AFP ranged from 22% to 77%, with the inclusion of AChE. The total expenditure for AF-AFP in our sample set (n = 6232 amniocentesis at $76.00 per AF-AFP) was $473,632, and all NTDs and VWDs were detected by ultrasound. Translated to a national laboratory (>42,447 samples/year), the cost savings in 2011 alone would be $3,225,972. CONCLUSION: Given the accuracy of high-resolution ultrasound in the detection of both NTDs and VWDs, measuring AF-AFP and AChE as a reflex-screening test is not a cost-effective approach.

The price of performance: a cost and performance analysis of the implementation of cell-free fetal DNA testing for Down syndrome in Ontario, Canada.

OBJECTIVE: To examine the cost and performance implications of introducing cell-free fetal DNA (cffDNA) testing within modeled scenarios in a publicly funded Canadian provincial Down syndrome (DS) prenatal screening program. METHOD: Two clinical algorithms were created: the first to represent the current screening program and the second to represent one that incorporates cffDNA testing. From these algorithms, eight distinct scenarios were modeled to examine: (1) the current program (no cffDNA), (2) the current program with first trimester screening (FTS) as the nuchal translucency-based primary screen (no cffDNA), (3) a program substituting current screening with primary cffDNA, (4) contingent cffDNA with current FTS performance, (5) contingent cffDNA at a fixed price to result in overall cost neutrality,(6) contingent cffDNA with an improved detection rate (DR) of FTS, (7) contingent cffDNA with higher uptake of FTS, and (8) contingent cffDNA with optimized FTS (higher uptake and improved DR). RESULTS: This modeling study demonstrates that introducing contingent cffDNA testing improves performance by increasing the number of cases of DS detected prenatally, and reducing the number of amniocenteses performed and concomitant iatrogenic pregnancy loss of pregnancies not affected by DS. Costs are modestly increased, although the cost per case of DS detected is decreased with contingent cffDNA testing. CONCLUSION: Contingent models of cffDNA testing can improve overall screening performance while maintaining the provision of an 11- to 13-week scan. Costs are modestly increased, but cost per prenatally detected case of DS is decreased.

Maternal cfDNA screening for Down syndrome--a cost sensitivity analysis.

OBJECTIVE: This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening. METHODS: A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta-analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection. RESULTS: The main factor was the unit cost of cfDNA testing. For example, replacing a combined test costing $150 with 3% false-positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when replacing a quadruple test and higher for a 5% false-positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10% to 20% women were selected for cfDNA testing by conventional screening was considerably more cost-efficient. Costs were sensitive to cfDNA uptake. CONCLUSION: Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs fall substantially. Until this happens, the contingent use of cfDNA is recommended.

Economic analysis of chromosome testing in couples with recurrent miscarriage to prevent handicapped offspring.

STUDY QUESTION: Which strategy is least expensive to prevent the birth of a handicapped child in couples with recurrent miscarriage (RM); parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents, or amniocentesis in all ongoing pregnancies without the knowledge of parental carrier status? SUMMARY ANSWER: For virtually all couples with RM amniocentesis in all ongoing pregnancies without the knowledge of parental carrier status is less expensive in preventing the birth of a handicapped child than parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents. WHAT IS KNOWN ALREADY: One of the causes of RM is a balanced chromosome abnormality in one of the partners. If one of the partners is carrier of a balanced structural chromosomal abnormality, the risk of offspring with an unbalanced structural chromosome abnormality is increased. Like all couples, couples with RM also have an age-dependent risk for fetal aneuploidy, of which trisomy 21 is most common. STUDY DESIGN, SIZE, DURATION: Model-based economic analysis to compare costs and effects of two strategies in couples with RM to prevent the birth of a handicapped child in case of ongoing pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Comparison of two strategies in women with RM: strategy (I) parental chromosome analysis followed by amniocentesis in pregnancy in case of carrier status of one of the parents and strategy (II) amniocentesis in all ongoing pregnancies without the knowledge of carrier status. No testing was the reference strategy. Data on probabilities and costs were derived from the literature. Incremental costs and effects were calculated [incremental cost-effectiveness ratio (ICER)]. Effectiveness was expressed as the number of prevented births of handicapped child equivalents compared with no testing. In these calculations, the birth of a handicapped child was valued 10 times worse than the loss of a viable pregnancy due to amniocentesis. MAIN RESULTS AND THE ROLE OF CHANCE: Depending on the risk for carrier status, the ICER for Strategy I (parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents) varied between € 226,000 and € 6,556,000 per prevented handicapped child equivalent. For Strategy II (amniocentesis in all ongoing pregnancies without the knowledge of carrier status), the ICER varied between € 2000 and € 233 000 per prevented handicapped child equivalent. Strategy I was less expensive than Strategy II only for a small subgroup of couples with maternal age <23 years, three or more previous miscarriages and a family history of RM. LIMITATIONS, REASONS FOR CAUTION: Our analysis is not a plea for amniocentesis in all women with RM. Individual risk assessment with serum markers and nuchal translucency is probably more effective at lower cost. WIDER IMPLICATIONS OF THE FINDINGS: This analysis can be used by clinicians to explain the chances of adverse pregnancy outcome in couples with RM, as well as by policy makers in health-care economics. Future guidelines on RM might be more restrictive from the perspective of the limited health-care resources that we have available.

Same-day prenatal diagnosis of common chromosomal aneuploidies using microfluidics-fluorescence in situ hybridization.

Rapid molecular prenatal diagnostic methods, such as fluorescence in situ hybridization (FISH), quantitative fluorescence-PCR, and multiplex ligation-dependent probe amplification, can detect common fetal aneuploidies within 24 to 48 h. However, specific diagnosis or aneuploidy exclusion should be ideally available within the same day as fetal sampling to alleviate parental anxiety. Microfluidic technologies integrate different steps into a microchip, saving time and costs. We have developed a cost-effective, same-day prenatal diagnostic FISH assay using microfluidics. Amniotic fluids (1-4 mL from 40 pregnant women at 15-22 weeks of gestation) were fixed with Carnoy's before loading into the microchannels of a microfluidic FISH-integrated nanostructured device. The glass slides were coated with nanostructured titanium dioxide to facilitate cell adhesion. Pretreatment and hybridization were performed within the microchannels. Fifty nuclei were counted by two independent analysts, and all results were validated with their respective karyotypes. Of the 40 samples, we found three cases of fetal aneuploidies (trisomies 13, 18, and 21), whereas the remaining 37 cases were normal. Results were concordant with their karyotypes and ready to be released within 3 h of sample receipt. Microfluidic FISH, using 20-fold less than the recommended amount of probe, is a cost-effective method to diagnose common fetal aneuploidies within the same day of fetal sampling.

Economic evaluation of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis: a cost-minimization analysis.

PURPOSE: To assess the cost-effectiveness of Multiplex Ligation-dependent Probe Amplification (MLPA, P095 kit) compared to karyotyping. METHODS: A cost-minimization analysis alongside a nationwide prospective clinical study of 4,585 women undergoing amniocentesis on behalf of their age (≥36 years), an increased risk following first trimester prenatal screening or parental anxiety. RESULTS: Diagnostic accuracy of MLPA (P095 kit) was comparable to karyotyping (1.0 95% CI 0.999-1.0). Health-related quality of life did not differ between the strategies (summary physical health: mean difference 0.31, p = 0.82; summary mental health: mean difference 1.91, p = 0.22). Short-term costs were lower for MLPA: mean difference 315.68 (bootstrap 95% CI 315.63-315.74; -44.4%). The long-term costs were slightly higher for MLPA: mean difference 76.42 (bootstrap 95% CI 71.32-81.52; +8.6%). Total costs were on average 240.13 (bootstrap 95% CI 235.02-245.23; -14.9%) lower in favor of MLPA. Cost differences were sensitive to proportion of terminated pregnancies, sample throughput, individual choice and performance of tests in one laboratory, but not to failure rate or the exclusion of polluted samples. CONCLUSION: From an economic perspective, MLPA is the preferred prenatal diagnostic strategy in women who undergo amniocentesis on behalf of their age, following prenatal screening or parental anxiety.

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.

Selective laser photocoagulation versus serial amniodrainage for the treatment of twin-twin transfusion syndrome: a cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of selective laser photocoagulation (SLP) with serial amniodrainage (AD) in the treatment of twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: Using decision-analysis modeling, we compared the cost-effectiveness of using laser photocoagulation with AD for the treatment of TTTS. The analysis was carried out from a societal perspective using a theoretical cohort of 1000 women with TTTS. Costs included the costs of procedures, perinatal complications from TTTS and of resources used for raising a child with cerebral palsy (CP) following TTTS. One-way, multiway and probabilistic (Monte Carlo) sensitivity analyses were carried out for all model variables. The main outcome measures were: cost per quality-adjusted life years (QALYs) gained from treating TTTS. RESULT: On the basis of the available data, the decision model favors SLP as the most cost-effective treatment option compared with AD. Using the theoretical cohort, laser photocoagulation will result in an overall perinatal survival of 59.3% compared with 51.5% for AD. The frequency of children with CP after laser would be 8.5% compared with 15.4% after AD. Sensitivity analyses showed the model to be robust over a wide range of values for the variables, except when the overall survival associated with AD is >62%. Above that survival rate, AD was the more cost-effective therapy. CONCLUSION: Under a wide range of circumstances, the most cost-effective therapy for TTTS is SLP.

A cost-effectiveness analysis of prenatal screening strategies for Down syndrome.

OBJECTIVE: To evaluate which Down syndrome screening strategy is the most cost-effective. METHODS: Using decision-analysis modeling, we compared the cost-effectiveness of 9 screening strategies for Down syndrome: 1) no screening, 2) first-trimester nuchal translucency (NT) only, 3) first-trimester combined NT and serum screen, 4) first-trimester serum only, 5) quadruple screen, 6) integrated screening, 7) sequential screening, 8) integrated serum only, or 9) maternal age. Costs included cost of tests and resources used for raising a child with Down syndrome. One-way and multiway sensitivity analyses were performed for all model variables. The main outcome measures were cost per Down syndrome case detected, rate of delivering a liveborn neonate with Down syndrome, and rate of diagnostic procedure-related pregnancy loss for each strategy. RESULTS: Sequential screening detected more Down syndrome cases compared with the other strategies, but it had a higher procedure-related loss rate. Integrated serum screening was the most cost-effective strategy. Sensitivity analyses revealed the model to be robust over a wide range of values for the variables. The addition of the cost of genetic sonogram to the second-trimester strategies resulted in first-trimester combined screening becoming the most cost-effective strategy. CONCLUSION: Within our baseline assumptions, integrated serum screening was the most cost-effective screening strategy for Down syndrome. If the cost of nuchal translucency is less than dollars 57 or when genetic sonogram is included in the second-trimester strategies, first-trimester combined screening became the most cost-effective strategy. LEVEL OF EVIDENCE: III.

Assessment of demand for prenatal diagnostic testing using willingness to pay.

OBJECTIVE: To investigate the demand for invasive prenatal diagnostic testing (amniocentesis and chorionic villous sampling) in a racially/ethnically diverse group of pregnant women of all ages in the San Francisco Bay Area by using estimates of willingness to pay for these procedures. METHODS: We surveyed 447 women of varying ages, ethnicity, and socioeconomic levels to assess their desire to undergo and willingness to pay for invasive prenatal testing for chromosomal disorders. Each woman was asked what she would be willing to pay for invasive diagnostic testing up to the full cost of the procedure. We also asked several demographic and attitudinal questions. RESULTS: Overall, 49% of the women indicated an interest in undergoing invasive prenatal diagnostic testing. Women aged 35 years and older were more likely to desire testing as compared with women aged less than 35 years (72% versus 36%, P <.001). Of the women aged less than 35 years who desired testing, 31% indicated that they would be willing to pay the full price of $1,300, whereas 73% were willing to pay a portion of the cost. Maternal age of 35 years or greater (odds ratio [OR] 3.3; 95% confidence interval [CI] 2.0, 5.6) and willingness to have an elective abortion (OR 2.8; 95% CI 1.6, 4.9) were significant predictors of desire to undergo prenatal diagnostic testing after controlling for income, race/ethnicity, and education. Maternal age of 35 years or greater (OR 3.5; 95% CI 1.59, 7.88) and having an income greater than $35,000 (OR 2.3; 95% CI 1.02, 5.26) were significant predictors of willingness to pay the full price of testing. CONCLUSION: A substantial proportion of women of all ages indicate a desire to undergo and a willingness to pay for prenatal diagnostic testing. Variations in willingness to pay are correlated with both socioeconomic and attitudinal differences in addition to age. Guidelines regarding use of prenatal genetic diagnosis should be expanded to offer testing to all women, not just those deemed at increased risk. LEVEL OF EVIDENCE: II-2

Cost utility of prenatal diagnosis and the risk-based threshold.

BACKGROUND: Prenatal testing guidelines recommend offering amniocentesis or chorionic villus sampling to women aged 35 years or older, or who have been found by screening to be at a similarly high risk of giving birth to an infant with Down's syndrome or another chromosomal abnormality. This threshold was chosen, in part, because 35 was the approximate age at which amniocentesis was cost beneficial when testing guidelines were developed in the USA in the 1970s. We aimed to assess the economic validity of thresholds based on age or risk for offering invasive prenatal diagnosis. METHODS: We did a cost-utility analysis of chorionic villus sampling and amniocentesis versus no invasive testing using data from randomised trials, case registries, and a utility assessment of 534 diverse pregnant women aged 16-47 years. FINDINGS: In the USA, compared with no diagnostic testing, amniocentesis costs less than US15000 dollars per quality-adjusted life year gained for women of all ages and risk levels. The results do not depend on maternal age or risk of Down's syndrome-affected birth. The cost-utility ratio for any individual woman depends on her preferences for reassurance about the chromosomal status of her fetus, and, to a lesser extent, for miscarriage. INTERPRETATION: Prenatal diagnostic testing can be cost effective at any age or risk level. Current guidelines should be changed to offer testing to all pregnant women, not just those whose risk of carrying an affected fetus exceeds a specified threshold.