Secondary Logo

Share this article on:

Prenatal Testing in the Genomic Age: Clinical Outcomes, Quality of Life, and Costs

Kaimal, Anjali J. MD, MAS; Norton, Mary E. MD; Kuppermann, Miriam PhD, MPH

doi: 10.1097/AOG.0000000000001029
Contents: Original Research

OBJECTIVE: To use a decision-analytic model to assess a comprehensive set of outcomes of prenatal genetic testing strategies among women of varying ages.

METHODS: We assessed outcomes of six testing strategies incorporating diagnostic testing with chromosomal microarray, multiple marker screening, cell-free DNA screening, and nuchal translucency screening alone, in combination, or in sequence. Clinical outcomes included prenatal detection or birth of a neonate with a significant chromosomal abnormality and diagnostic procedures performed. Other outcomes included maternal quality-adjusted life-years and costs. Sensitivity analyses were conducted to examine the robustness of the findings.

RESULTS: At all ages assessed, screening strategies starting with multiple marker screening offered the highest detection rate when all chromosomal abnormalities were considered. Incorporating cell-free DNA as an optional secondary screen decreased the number of diagnostic procedures, but also decreased the number of abnormalities diagnosed prenatally, resulting in a similar number of procedures per case diagnosed at age 30 years; the option of secondary cell-free DNA screening becomes more favorable at older ages. Multiple marker screening with optional follow-up diagnostic testing was the most effective (highest quality-adjusted life-years) and least expensive strategy at ages 20–38 years. At age 40 years or older, cell-free DNA screening was optimal with an incremental cost-effectiveness ratio of $73,154 per quality-adjusted life-year.

CONCLUSION: When considering all detectable chromosome problems as well as patient preferences and baseline risks, multiple marker screening with the option of diagnostic testing for screen-positive results is the optimal strategy for most women. At age 40 years and older, cell-free DNA as a primary screen becomes optimal and is cost-effective.

LEVEL OF EVIDENCE: II

Multiple marker screening with the option of diagnostic testing for screen-positive results is the optimal strategy for most women desiring prenatal testing.

Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts; and the Departments of Obstetrics, Gynecology & Reproductive Sciences and Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, California.

Corresponding author: Anjali J. Kaimal, MD, MAS, Massachusetts General Hospital, 55 Fruit Street, Founders 422, Boston, MA 02114; e-mail: akaimal@partners.org.

Financial Disclosure Dr. Norton is a Co-Principal Investigator on clinical trial NCT0145167 sponsored by Ariosa Diagnostics. She has received unrestricted research funding to be used at her own discretion from Natera. She is also an unpaid member of the Perinatal Advisory Committee for the California Prenatal Screening Program. Dr. Kuppermann was the University of California, San Francisco site Principal Investigator for clinical trial NCT0145167, sponsored by Arisoa Diagnostics, and her institution has received unrestricted research funding for her research program from Verinata Health and Natera. The other author did not report any potential conflicts of interest.

Participant remuneration for the utility measurement component of this study was funded by an unrestricted research grant to the University of California, San Francisco, from Verinata Health.

Since amniocentesis was introduced into clinical care, prenatal testing has expanded to include a menu of screening and diagnostic testing options. Although compromises among detection rates, false-positive rates, and complications from diagnostic procedures have always been central to prenatal testing decisions, the recent introductions of cell-free DNA screening and chromosomal microarray analysis as a diagnostic tool have increased both the number of options available and the complexity of prenatal testing decision-making.

Cell-free DNA analysis provides highly accurate screening for trisomy 21 and other common aneuploidies, but at the expense of information about other chromosomal conditions.1,2 In contrast, prenatal chromosomal microarray analysis offers high-resolution detection of genetic variations associated with clinically relevant disorders,3,4 but requires invasive diagnostic procedures that have miscarriage risks. In addition, understanding of the clinical implications of some variants detected by chromosomal microarray analysis is incomplete, resulting in a need for decision-making under significant uncertainty—a problematic situation for both patients and health care providers.5 Furthermore, both of these new tests are costly and have the potential to dramatically increase the already substantial resources necessary to identify fetuses affected by relatively rare chromosomal conditions.

Prior evaluations of cell-free DNA analysis as a prenatal screening test have focused on trisomy 21 without considering detection of other chromosomal abnormalities, including copy number variants detectable with diagnostic testing, or contrasting the outcomes with the full range of screening and diagnostic testing options now available.6–10 In addition, none of the previous analyses has included the quality-of-life effect of the processes and outcomes of all screening and diagnostic testing options. Using decision- and cost-utility analysis, we sought to investigate the clinical outcomes, maternal quality-of-life effects, and cost-effectiveness of currently available prenatal testing options for the detection of aneuploidy and pathogenic copy number variants.

Back to Top | Article Outline

MATERIALS AND METHODS

We created a decision-analytic model to compare the clinical outcomes, quality-adjusted life-years (QALYs), and costs associated with six strategies for prenatal testing: 1) multiple marker screening, incorporating first- and second-trimester serum analytes and nuchal translucency measurement, in which women had only the option of diagnostic testing if additional information was desired after screening; 2) multiple marker screening with the option of secondary cell-free DNA analysis or diagnostic testing, in which women could opt for either cell-free DNA screening or diagnostic testing if additional information was desired after the initial screening result; 3) cell-free DNA screening alone, with diagnostic testing if additional information was desired; 4) cell-free DNA screening with concurrent nuchal translucency assessment, with diagnostic testing if additional information was desired; 5) concurrent multiple marker and cell-free DNA screening, with diagnostic testing if additional information was desired; and 6) diagnostic testing without prior screening. The model was constructed and analyses performed using TreeAge Pro 2013.

The model follows a theoretical cohort of women desiring prenatal testing (screening or diagnostic or both) from the time of their initial test through the end of their pregnancy, the birth of their neonate, and the remainder of their own life expectancy. Outcomes assessed included the birth of a chromosomally normal neonate; prenatal detection or birth of a neonate with trisomies 13, 18, or 21, a sex chromosomal aneuploidy (45,X; 47,XXX; 47,XXY; 47,XYY), a pathogenic copy number variant (microdeletion or duplication) or other rare chromosomal abnormality, or a variant of uncertain significance; miscarriage; termination after detection of a chromosomal abnormality; and whether a future birth occurs after either type of pregnancy loss.

Because the theoretical cohort includes only women desiring prenatal testing, the model begins with a screening or diagnostic test. For strategies beginning with multiple marker screening, the test may return positive or negative results. Depending on the strategy, the next step may consist of diagnostic testing, cell-free DNA as a secondary screening test or no additional testing. Diagnostic testing included chromosomal microarray analysis because this optimizes detection of clinically significant chromosomal aberrations. For strategies involving cell-free DNA analysis, the possibility of success or failure of the test was also incorporated; potential outcomes therefore consisted of positive, negative, or no test results. After each test result, options included additional screening tests (if applicable), diagnostic testing, or continuation of pregnancy with no additional testing. After a diagnostic test, procedure-related miscarriage and the possibility of diagnostic error were both included as potential outcomes. Options after the prenatal diagnosis of a chromosomal abnormality or a variant of uncertain significance were pregnancy continuation or termination. For pregnancies affected by trisomies 13, 18, or 21 in which the pregnancy is continued, the possibility of stillbirth was included. For sex chromosomal aneuploidy or a variant of uncertain significance followed by a live birth, potential outcomes included normal or abnormal developmental outcome. The probability of future birth after a pregnancy loss was also included in the model. The schematic of the model is available in Appendix 1 (available online at http://links.lww.com/AOG/A685).

Maternal age of 30 years was chosen for the base-case analysis because this is the average age of a pregnant woman undergoing screening for aneuploidy in large population-based samples in the United States.2,11,12 Additional analyses examined outcomes for women aged 20–40 years incorporating age-specific likelihoods of chromosomal abnormalities, age-specific test characteristics as appropriate, and the age-related likelihood of future birth in the setting of pregnancy loss.

Probabilities were obtained from the literature, primarily from meta-analyses and prospective observational or case–control studies. Selected probabilities are available in Table 1; the full table of model inputs is available in Appendix 2 (available online at http://links.lww.com/AOG/A685). The age-specific midtrimester likelihoods of trisomies 13, 18, and 21 and rare chromosomal abnormalities detected by karyotype were derived from data from the California Department of Public Health Genetic Disease Screening Program13 as well as a comprehensive review of the literature.14–19 The likelihoods of microarray abnormalities and variants of unknown significance were obtained from a prospective study that included 2,054 women undergoing diagnostic testing for advanced maternal age or abnormal screening results.3

Table 1

Table 1

Age-specific test characteristics of multiple marker screening, including both detection and false-positive rates, were obtained from the California Department of Public Health Genetic Disease Screening Program.13 Test characteristics of cell-free DNA screening were obtained from a recent meta-analysis.20 Diagnostic accuracy of karyotype results after amniocentesis or chorionic villous sampling was obtained from large cohort studies.21,22

The likelihood that a woman would choose to pursue diagnostic testing was varied depending on the screening result; however, the option of diagnostic testing was included even if screening results were normal or low risk. Recent literature has indicated that the likelihood of failure to obtain results on cell-free DNA analysis is dependent in part on the underlying karyotype and is higher with an aneuploid fetus.2,23–27 We therefore treated a failed test as a screen-positive result with regard to subsequent testing behavior. The probabilities of undergoing diagnostic testing based on screening test results and of pregnancy termination in the setting of a prenatally detected chromosomal abnormality were obtained from the literature (Table 1).

Costs were obtained from the literature when published costs were available and of high quality. Otherwise, clinical costs were gathered from a wide variety of clinical sources and the mean was utilized. These assumptions were tested in sensitivity analysis. All costs were expressed in 2014 U.S. dollars (Table 1).

To generate QALYs, we used time tradeoff utilities ranging from 0 to 128,29 (Table 2). These utilities were obtained from a diverse group of 281 women presenting for care at the University of California, San Francisco, prenatal care clinic or prenatal diagnosis center, or the San Francisco General Hospital prenatal care clinic. Details of these women and methods used for utility assessment are included in the Appendices 3 and 4 (available online at http://links.lww.com/AOG/A685). Testing utilities were applied for 1 year, because testing experience was hypothesized to affect quality of life for no longer than the duration of the pregnancy and the first few months after the delivery. Utilities for long-term outcomes such as birth of a neonate with a chromosomal abnormality were applied for the remainder of the woman's lifespan.

Table 2

Table 2

All costs and life-years were discounted at a yearly rate of 3%. Sensitivity analyses were performed on all variables. We also performed probabilistic sensitivity analysis (using a Monte Carlo simulation) by simultaneously sampling each model parameter from an appropriate probability distribution to test the model's robustness to simultaneous multivariable changes. Institutional review board approval was obtained for the preference elicitation portion of the study (see Appendix 3, http://links.lww.com/AOG/A685). Institutional review board approval was not required for the decision analysis because other than the utility data, all data used for this analysis were publically available.

Back to Top | Article Outline

RESULTS

Multiple marker screening with only the option of diagnostic testing if additional testing is desired provided the highest screening detection rate for chromosomal abnormalities in all age groups, but resulted in a progressively higher rate of diagnostic procedures in older women and, in turn, of procedure-related losses (Table 3). In contrast, cell-free DNA screening as the initial screening test optimized detection of trisomy 21 but resulted in lower detection of other abnormalities. At age 40 years, using cell-free DNA screening as the initial test yielded the lowest number of diagnostic procedures per case diagnosed; however, detection of all chromosomal abnormalities remained lower than with the other screening strategies. Under the baseline assumption, in which less than half (39.4%) of women receiving screen-positive results would opt for diagnostic testing when either cell-free DNA or diagnostic testing was available, multiple marker screening with these two options for follow-up testing offered improved detection in comparison with cell-free DNA as the first-line screening test. It also decreased the rate of diagnostic procedures in comparison with multiple marker screening with only the option of diagnostic testing. This was particularly true in older women. Combination testing with cell-free DNA plus nuchal translucency or concurrent cell-free DNA and multiple marker screening increased detection over cell-free DNA alone in younger women but required a higher number of procedures per case diagnosed than the optimal strategy of multiple marker screening. At age 40 years, combination testing required a similar number of diagnostic tests per case diagnosed to the optimal strategy of cell-free DNA alone.

Table 3

Table 3

Multiple marker screening with only the option of diagnostic testing for follow-up optimized maternal QALYs for women aged 20–38 years. Multiple marker screening with the option of secondary screening with cell-free DNA analysis or diagnostic testing was the next best choice, followed by diagnostic testing without prior screening for women 30 years and younger. For women aged 38 years and older, cell-free DNA screening as the first-line test maximized QALYs. Combination testing with cell-free DNA plus nuchal translucency or concurrent cell-free DNA and multiple marker screening resulted in lower QALYs than a single test or contingent testing strategies in all age groups (Table 4).

Table 4

Table 4

For women under 38 years of age, multiple marker screening with only the option of diagnostic testing for screen-positive results was both the most effective and the least expensive strategy and was therefore the dominant strategy. At age 38 years, cell-free DNA screening as the first-line test became the optimal strategy but had an incremental cost-effectiveness ratio of $151,424 per QALY compared with multiple marker screening with only the option of diagnostic testing for screen-positive results. At age 40 years, multiple marker screening with the option of either diagnostic testing or cell-free DNA as follow-up became the least costly strategy; relative to that strategy, multiple marker screening with only diagnostic testing yielded an incremental cost-effectiveness ratio of $1,992 per QALY. Cell-free DNA screening as a first-line test also became more cost-effective with an incremental cost-effectiveness ratio of $73,154 per QALY.

One of the inputs that the base-case model was sensitive to was the probability of choosing diagnostic testing when either cell-free DNA screening or diagnostic testing was available as follow-up after screen-positive multiple marker screening results. The baseline assumption was that 77.6% of women who screened positive based on multiple marker screening would pursue diagnostic testing if that was the only follow-up test that was available and that 39.2% of women would choose diagnostic testing when both cell-free DNA and diagnostic testing were available. If instead at least 60.7% of women chose diagnostic testing when both cell-free DNA and diagnostic testing were available, this strategy resulted in equivalent QALYs to multiple marker screening with only diagnostic testing as follow-up. Alternatively, in the case that no one would choose to pursue diagnostic testing after a screen-positive multiple marker screening result, the optimal strategy remained multiple marker screening, but multiple marker screening with cell-free DNA as a follow-up was a reasonable alternative with an incremental cost-effectiveness ratio of $14,618. Under this assumption, compared with multiple marker screening with only diagnostic testing as an option for follow-up, cell-free DNA screening alone had an incremental cost-effectiveness ratio of $372,837. The model was also sensitive to the likelihood of future birth; at age 30 years, if the likelihood of future birth was 42% or less, cell-free DNA was the optimal strategy, but the incremental cost-effectiveness ratio ranged from $213,247 to $2,443,143 per QALY. If the future birth rate exceeded 82.6%, diagnostic testing without prior screening became the optimal strategy.

In probabilistic sensitivity analyses, when compared with cell-free DNA alone, multiple marker screening is dominant (more effective and less costly) 93.7% of the time and dominant or cost-effective at a $100,000 per QALY threshold (a threshold commonly used in current cost-effectiveness analyses30) 94.1% of the time. When compared with multiple marker screening with cell-free DNA or diagnostic testing as follow-up, the model is indifferent 97.4% of the time, meaning that either strategy is reasonable and likely to be cost-effective.

Back to Top | Article Outline

DISCUSSION

We found that screening strategies starting with multiple marker approaches yield the highest detection of significant chromosomal abnormalities, including copy number variants, with the lowest number of procedures performed per case diagnosed, the highest numbers of QALYs, and the lowest costs. Although cell-free DNA as a primary screening test yields a higher detection rate of trisomy 21, this is at the expense of detection of other significant abnormalities. Multiple marker screening with the option of either cell-free DNA analysis or diagnostic testing as follow-up for positive results also offers better detection of these abnormalities than cell-free DNA as first-line screening and decreases the rate of diagnostic procedures, with the caveat that under our baseline assumption, a significant minority of women will choose diagnostic testing after counseling. Even if all women declined diagnostic testing after positive multiple marker screening, the optimal strategy would not change; however, multiple marker screening with cell-free DNA as a follow-up test would become virtually equivalent. Although concurrent testing with cell-free DNA and either nuchal translucency or multiple marker screening is theoretically appealing, this approach always yielded lower QALYs than a single test or contingent strategies and by definition incurs higher costs, making these strategies suboptimal.

For several reasons, the results we obtained were sensitive to maternal age. First, the rate of common aneuploidies increases with maternal age, whereas the incidence of less common chromosomal abnormalities and copy number variants does not.4,14,19 Therefore, younger women are at proportionally higher risk for copy number variants and rare chromosomal abnormalities detectable only with diagnostic testing than for the common aneuploidies for which multiple marker or cell-free DNA screening is available. In addition, the less specific nature of traditional multiple marker screening leads to detection of many of the uncommon chromosomal abnormalities not identified by cell-free DNA.1 Consequently, although multiple marker screening with diagnostic testing as the only option for follow-up yielded the most QALYs for women younger than 35 years of age, cell-free DNA as the first-line test maximized QALYs in women aged 38 years and older. Although this analysis considers outcomes at a population level, the balance between the value of information and risk aversion requires consideration at an individual level, because these may be valued differently. For these reasons, age should be neither a necessary nor a sufficient criterion to constrain testing strategies at a population level.

Our initial goal was to conduct a cost-utility analysis of current testing options. However, for women younger than age 38 years, multiple marker screening with the option of diagnostic testing for screen-positive results was both the most effective and the least expensive strategy and was therefore dominant; there is no cost at which using cell-free DNA as a primary screening test is cost-effective because this test is not as effective when considering the full range of outcomes. At age 38 years, cell-free DNA screening as the first-line test yielded the most QALYs, but with an incremental cost-effectiveness ratio of $151,424. It was only at age 40 years that cell-free DNA screening as a first-line test yielded an incremental cost-effectiveness ratio below $100,000 per QALY.

Prior cost-effectiveness analyses have focused solely on detection of trisomy 21 and have found cell-free DNA to be cost-effective at various cost or risk thresholds.6–10 Our results differ largely because we chose to focus on all clinically significant chromosomal aberrations that can be detected through current screening and diagnostic testing, as it is likely that women who desire prenatal testing for Down syndrome are also concerned about other causes of intellectual disability.

Our study has limitations. Large prospective studies were not always available to provide probability inputs. Our assumptions were tested in sensitivity analyses, which showed that wide variation in these inputs did not change the optimal strategies. Although we attempted to be comprehensive in the strategies that were assessed, we could not incorporate all of the first- and second-trimester variations in multiple marker screening nor the option of diagnostic testing with karyotype alone; we opted to incorporate those multiple marker screening and diagnostic testing options that have the highest detection rates. Our analysis considered only the common aneuploidies included in all cell-free DNA tests; although some platforms include additional aneuploidies and microdeletions, data on detection rates are very limited and these abnormalities contribute little to the overall percentage of detectable genomic aberrations. In addition, although we were comprehensive in our assessment of prenatally detectable chromosomal abnormalities and the processes and outcomes of currently available testing strategies, it is impossible to capture the full complexity of individual patient–provider decision-making as well as societal and financial implications in a model-based approach. However, we believe this analysis provides important information regarding the optimal way to integrate the current testing options.

In summary, we found that the current paradigm of traditional multiple marker screening is the optimal strategy for most women. As women approach 40 years, the larger proportion of chromosomal abnormalities represented by the common aneuploidies changes the optimal strategy to cell-free DNA as a first-line test, which provides excellent detection of the chromosomal problems most common at older maternal ages. For women who desire the most comprehensive information available regarding fetal chromosomal abnormalities, diagnostic testing should be offered regardless of maternal age.

Back to Top | Article Outline

REFERENCES

1. Norton ME, Jelliffe-Pawlowski LL, Currier RJ. Chromosome abnormalities detected by current prenatal screening and noninvasive prenatal testing. Obstet Gynecol 2014;124:979–86.
2. Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, et al.. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015;372:1589–97.
3. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, et al.. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012;367:2175–84.
4. Hillman SC, Mcmullan DJ, Williams D, Maher ER, Kilby MD. Microarray comparative genomic hybridization in prenatal diagnosis: a review. Ultrasound Obstet Gynecol 2012;40:385–91.
5. The use of chromosomal microarray analysis in prenatal diagnosis. Committee Opinion No. 581. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:1374–7.
6. Beulen L, Grutters JP, Faas BH, Feenstra I, van Vugt JM, Bekker MN. The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis. Eur J Obstet Gynecol Reprod Biol 2014;182:53–61.
7. Ayres AC, Whitty JA, Ellwood DA. A cost-effectiveness analysis comparing different strategies to implement noninvasive prenatal testing into a Down syndrome screening program. Aust N Z J Obstet Gynaecol 2014;54:412–7.
8. Okun N, Teitelbaum M, Huang T, Dewa CS, Hoch JS. The price of performance: a cost and performance analysis of the implementation of cell-free fetal DNA testing for Down syndrome in Ontario, Canada. Prenat Diagn 2014;34:350–6.
9. Walker BS, Jackson BR, LaGrave D, Ashwood ER, Schmidt RL. A cost-effectiveness analysis of cell free DNA as a replacement for serum screening for Down syndrome. Prenat Diagn 2015;35:440–6.
10. Neyt M, Hulstaert F, Gyselaers W. Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost-consequences analysis. BMJ Open 2014;4:e005922.
11. Currier R, Wu N, Van Meter K, Goldman S, Lorey F, Flessel M. Integrated and first trimester prenatal screening in California: program implementation and patient choice for follow-up services. Prenat Diagn 2012;32:1077–83.
12. Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, et al.. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014;370:799–808.
13. California prenatal screening program provider handbook. Available at: http://www.cdph.ca.gov/programs/pns/Documents/ProviderHandbook2009WEB.pdf. Retrieved November 12, 2014.
14. Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol 1981;58:282–5.
15. Gravholt CH, Juul S, Naeraa RW, Hansen J. Prenatal and postnatal prevalence of Turner's syndrome: a registry study. BMJ 1996;312:16–21.
16. Snijders RJ, Sebire NJ, Nicolaides KH. Maternal age and gestational age-specific risk for chromosomal defects. Fetal Diagn Ther 1995;10:356–67.
17. Snijders RJ, Sundberg K, Holzgreve W, Henry G, Nicolaides KH. Maternal age- and gestation-specific risk for trisomy 21. Ultrasound Obstet Gynecol 1999;13:167–70.
18. Hillman SC, McMullan DJ, Hall G, Togneri FS, James N, Maher EJ, et al.. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol 2013;41:610–20.
19. Forabosco A, Percesepe A, Santucci S. Incidence of non-age-dependent chromosomal abnormalities: a population-based study on 88965 amniocenteses. Eur J Hum Genet 2009;17:897–903.
20. Gil MM, Akolekar R, Quezada MS, Bregant B, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis. Fetal Diagn Ther 2014;35:156–73.
21. Lippman A, Tomkins DJ, Shime J, Hamerton JL. Canadian multicentre randomized clinical trial of chorion villus sampling and amniocentesis. Final report. Prenat Diagn 1992;12:385–408.
22. Winsor EJ, Tomkins DJ, Kalousek D, Farrell S, Wyatt P, Fan YS, et al.. Cytogenetic aspects of the Canadian early and mid-trimester amniotic fluid trial (CEMAT). Prenat Diagn 1999;19:620–7.
23. Pergament E, Cuckle H, Zimmermann B, Banjevic M, Sigurjonsson S, Ryan A, et al.. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol 2014;124:210–8.
24. Porreco RP, Garite TJ, Maurel K, Marusiak B; Obstetrix Collaborative Research Network, Ehrich M, et al.. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol 2014;211:365.e1–12.
25. Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP, et al.. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 2012;119:890–901.
26. Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, et al.. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012;207:137.e1–8.
27. Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, et al.. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 2011;204:205.e1–11.
28. Torrance GW. Measurement of health state utilities for economic appraisal. J Health Econ 1986;5:1–30.
29. Torrance GW, Thomas WH, Sackett DL. A utility maximization model for evaluation of health care programs. Health Serv Res 1972;7:118–33.
30. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med 2014;371:796–7.
31. Samango-Sprouse C, Banjevic M, Ryan A, Sigurjonsson S, Zimmermann B, Hill M, et al.. SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Prenat Diagn 2013;33:643–9.
32. Chetty S, Garabedian MJ, Norton ME. Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenat Diagn 2013;33:542–6.
33. Nicolaides KH, Chervenak FA, McCullough LB, Avgidou K, Papageorghiou A. Evidence-based obstetric ethics and informed decision-making by pregnant women about invasive diagnosis after first-trimester assessment of risk for trisomy 21. Am J Obstet Gynecol 2005;193:322–6.
34. Crider KS, Olney RS, Cragan JD. Trisomies 13 and 18: population prevalences, characteristics, and prenatal diagnosis, metropolitan Atlanta, 1994–2003. Am J Med Genet A 2008;146A:820–6.
    35. Irving C, Richmond S, Wren C, Longster C, Embleton ND. Changes in fetal prevalence and outcome for trisomies 13 and 18: a population-based study over 23 years. J Matern Fetal Neonatal Med 2011;24:137–41.
    36. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, et al.. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol 2010;88:1008–16.
    37. Natoli JL, Ackerman DL, McDermott S, Edwards JG. Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995–2011). Prenat Diagn 2012;32:142–53.
    38. Forrester MB, Merz RD. Pregnancy outcome and prenatal diagnosis of sex chromosome abnormalities in Hawaii, 1986–1999. Am J Med Genet A 2003;119A:305–10.
    39. Jeon KC, Chen LS, Goodson P. Decision to abort after a prenatal diagnosis of sex chromosome abnormality: a systematic review of the literature. Genet Med 2012;14:27–38.
    40. Invasive prenatal testing for aneuploidy. ACOG Practice Bulletin No. 88. American College of Obstetricians and Gynecologists. Obstet Gynecol 2007;110:1459–67.
      41. Morris JK, Savva GM. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18. Am J Med Genet A 2008;146A:827–32.
        42. Rankin J, Tennant PWG, Bythell M, Pearce MS. Predictors of survival in children born with Down syndrome: a registry-based study. Pediatrics 2012;129:e1373–81.
        43. Cohen-Overbeek TE, Hop WC, den Ouden M, Pijpers L, Jahoda MG, Wladimiroff JW. Spontaneous abortion rate and advanced maternal age: consequences for prenatal diagnosis. Lancet 1990;336:27–9.
        44. Leridon H. Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment. Hum Reprod 2004;19:1548–53.
        45. Roberts SC, Gould H, Kimport K, Weitz TA, Foster DG. Out-of-pocket costs, insurance coverage for abortion in the United States. Womens Health Issues 2014;24:e211–8.
        46. The cost of having a baby in the United States. Available at: http://transform.childbirthconnection.org/wp-content/uploads/2013/01/Cost-of-Having-a-Baby1.pdf. Retrieved November 11, 2014.
          Figure

          Figure

          Supplemental Digital Content

          Back to Top | Article Outline
          © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.