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ORIGINAL RESEARCH |
From the Division of Human Genetics, Department of Pediatrics, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, and the Department of Pediatric Dentistry, University of Connecticut Health Center, Farmington, Connecticut.
Address reprint requests to: Peter A. Benn, PhD, Division of Human Genetics, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-6140, E-mail: benn{at}nso1.uchc.edu
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Abstract |
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Methods: Maternal age-specific sensitivity and false-positive rates for Down syndrome were derived for the triple test (alpha-fetoprotein, hCG, and unconjugated estriol) using gestational age based on ultrasound dating and also time from the last menstrual period (LMP). These rates were entered into a formula to determine the societal financial net benefit of Down syndrome screening. The average per-case net benefits of ultrasound- and LMP-dated pregnancies were then compared. Average net benefits were also calculated separately with ultrasound versus LMP dating for triple tests referred to our laboratory, and the additional costs associated with any post-test ultrasound scans, repeat testing, or recalculations were estimated.
Results: The use of ultrasound dating resulted in higher detection rates for Down syndrome and lower false-positive rates, which translated into an average per-case savings to society of $33.54. For women referred to our program with LMP dating, there was an average reduction of $31.60 in net benefits, plus added costs of $14.39 attributable to extra ultrasound, repeat testing, and recalculation.
Conclusion: When ultrasound dating is available before serum screening, it should be used preferentially to establish Down syndrome risk. Routine first-trimester ultrasound examination can be justified for women with a known LMP if the cost of the ultrasound examination is less than $46.
Second-trimester maternal serum screening to identify pregnancies at high risk for fetal Down syndrome has become routine in prenatal care in the United States. A 1995 survey found that approximately 63% of all pregnant women received Down syndrome screening.1 Most Down syndrome screening programs in the United States base their risk assessment on a combination of maternal age and triple testing, ie, measurement of maternal serum alpha-fetoprotein, hCG, and unconjugated estriol.1,2
Several factors affect the efficiency of Down syndrome screening. In addition to the cutoff chosen to define high-risk pregnancies, sensitivities and false-positive rates are strongly dependent on the maternal ages of the women screened.3 Because analyte values vary with gestational age, the accuracy of pregnancy dating is also important. Routine use of ultrasound evaluation of gestational age should result in more effective screening compared with dating based on the time from the last menstrual period (LMP).4 A retrospective review of screening in our laboratory confirmed that routine use of ultrasound-derived dating provided better Down syndrome screening results.5
The economic benefits of Down syndrome screening to society can be directly evaluated using a formula that incorporates sensitivity, false-positive rate, Down syndrome prevalence, utilization rates for program components, and the costs of testing, diagnosis, and care of affected live-born infants.6 Using current estimates for costs, it has been shown that triple testing provides a positive net benefit to society when applied to pregnant women at most ages.7 These initial studies (carried out on a model population with a 1:630 second-trimester incidence of Down syndrome) showed that the net benefit was higher when the screening was based on ultrasound dating rather than LMP dating. The study did not include an estimate of any additional costs related to follow-up of screen-positive tests in women with LMP-dated pregnancies.
In this study, we analyzed the economic advantages associated with the use of ultrasound dating in Down syndrome screening in the United States and considered whether first-trimester ultrasound should be offered to women with well-established LMP dating.
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Materials and Methods |
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The derivation of the formula for the per-case net benefit (NBi) of maternal serum screening has been described in detail elsewhere6:
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where Pi = the cost of the screening test i; Si = the detection or sensitivity rate of a screening test; I = the incidence of Down syndrome in the second trimester; and Fi = the false-positive rate of a prenatal screening test.
The formula incorporates the fees, intrauterine survival rates, and utilization rates for the various components of screening and follow-up. These are summarized in Table 1
and described in detail elsewhere.7 Fees were based on a national database of fees for medical services8 and are consistent with related studies on the cost-effectiveness of prenatal detection of fetal anomalies.9,10 The maternal age-specific incidence of Down syndrome, sensitivity, and false-positive rate were entered into the formula to calculate the net benefit. The average net benefit per case was determined from the 1995 pregnancy population data for the United States,11 with individual years interpolated from 5-year interval data.
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The means, standard deviations, and correlation coefficients between analytes used in the simulation were as defined by Wald et al.4 A second-trimester risk of 1:270 was used as the cutoff to define a screen-positive result. The second-trimester incidence of Down syndrome was based on the regression formula of Cuckle et al,14 with 23% adjustment for the loss of affected pregnancies and another 3% loss of unaffected pregnancies between the time of screening and full term. The population simulations involved the generation of 100,000 likelihood ratios for normal and affected pregnancies using separate parameters for ultrasound- and LMP-dated pregnancies. The sensitivities and false-positive rates for the two methods of pregnancy dating at each maternal age were compared using the Pearson 
2 test, with P < .05 considered statistically significant.
To evaluate the economics of offering ultrasound to women with LMP dating, we used data published previously from our laboratory.5 The study involved 10,068 women with LMP-based dating and 14,245 women with ultrasound-determined gestational ages. When both ultrasound and LMP data were available, ultrasound dating was preferentially used. Women with large discrepancies between the reported LMP and gestational age estimated by physical examination were likely to have received an ultrasound examination. The LMP group therefore consisted of women whose dating before the test was considered reliable enough for test interpretation. The net benefits for LMP- and ultrasound-based tests were calculated using the separate Down syndrome incidences that corresponded to the mean ages for each group (28.3 and 26.9 years, respectively). The sensitivity rates and false-positive rates used to calculate net benefit were based on revised rates (ie, after any adjustments to risk because of gross inaccuracies in dating).
Per-patient costs of any additional expenses (post-screening ultrasound, repeat testing, and recalculations) incurred in both groups were estimated. The standard protocol for screen-positive tests was to recommend that the gestational age be verified before invasive testing. Women with screen-positive results based on LMP dating frequently received second-trimester ultrasound examinations shortly after screening. In rare instances, women who had received an ultrasound examination before screening received a second ultrasound examination because of inconsistencies between LMP dating, initial ultrasound examination, or physical examination data. We conservatively assumed that the total number of women with a documented recalculation of Down syndrome risk constituted the entire number of women who received ultrasound examination as a result of positive screening tests. A fee of $250 was assumed for each of these ultrasound examinations because they were provided at a time in pregnancy when the standard of care dictated an examination of fetal anatomy in addition to confirmation of gestational age. A repeat of the triple test was recommended when the error in gestational age was more than 10 days and the initial test had been done before 15 weeks’ gestation. Although it was not the policy of the laboratory to charge for repeat tests arising from grossly incorrect gestational age, for the purposes of this study, a fee of $70 was assumed because costs were incurred that were equivalent to those of any other triple-test referral. A nonrecovered cost of $5 was also assumed for recalculation after a major revision in the gestational age estimation. We assumed that fees for the amniocentesis package ($1200) were equivalent whether or not a patient had received a previous ultrasound scan and that ultrasound biometric markers for Down syndrome were not used to modify individual patient risks.10
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Results |
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summarizes the maternal age-specific sensitivities and false-positive rates for the triple test when gestational age was based on ultrasound evaluation and LMP dating. As expected, ultrasound dating generally provided higher sensitivities and lower false-positive rates than LMP dating. At advanced maternal age, the sensitivity appeared to be marginally lower with ultrasound dating, but this difference was small. The differences in sensitivities and false-positive rates for the two methods of dating at each maternal age were statistically significant (2 test, P < .05), with the exception of sensitivity at age 39. Based on the distribution of maternal ages for pregnancies in the United States in 1995, the overall expected performance for ultrasound-based testing corresponded to a 72% sensitivity and 7.1% false-positive rate, whereas for LMP-based referrals, the sensitivity was 67% and the false-positive rate was 8.6%.
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. Without ultrasound dating, testing had a negative net benefit for women up to age 26. In contrast, a positive net benefit was shown for pregnant women at all ages when ultrasound dating was available. The difference in net benefit between the dating methods was not constant across ages; the difference in net benefit was greatest at age 39 ($69.57). At very advanced maternal ages (45 or older), the net benefit appeared to be greater using LMP dating, which can be attributed to the higher detection rates noted with LMP dating for women of advanced age. Using the maternal-age distribution for 1995, the average net benefit for the triple test using ultrasound dating was $185.99 and for LMP dating was $152.44. The average loss in net benefit when ultrasound dating was not used was therefore $33.54. Based on a cohort of women who received triple testing in our laboratory with LMP-based dating,5 the average loss in net benefit due to the absence of ultrasound dating was $31.60. Additional costs associated with LMP dating were also estimated. Of the 10,068 LMP-based referrals, 505 women had documented ultrasound examinations that cost 505 x $250 = $126,250, or an average of $12.54 for each case. Two hundred eighty women required repeat testing because of substantially inaccurate initial estimates of gestational age. Costs for repeat testing were 280 x $70 = $19,600, or $1.95 per case. Recalculation was needed in 192 women, which was associated with a cost of 192 x $5 = $960, or $0.10 per case. In contrast, among the 14,245 referrals with ultrasound dating, only nine women required an additional ultrasound examination, with an expense of 9 x $250 = $2250, or $0.16 per case; and eight required repeat testing, at a cost of 8 x $70 = $560, or $0.04 per case. The net additional costs associated with the LMP-based referrals were therefore $14.39 plus the $31.60 in lost net benefits, for a total of $45.99.
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Discussion |
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We wished to determine whether the improvement in Down syndrome screening economically justified offering prenatal ultrasound examinations to women with well-documented LMP and no specific indications for ultrasound. The analysis of costs was carried out on a cohort of patients whose LMP dating was considered accurate for triple-test interpretation. This analysis suggested that an ultrasound examination would be appropriate for women who subsequently received the triple test if the cost of the ultrasound examination were less than $46.
One approach to providing low-cost ultrasound examinations is to perform a first-trimester crown-rump measurement, which is known to be accurate for gestational age assessment.15–18 Because most women who present for prenatal care in the first trimester are likely to have maternal serum screening for Down syndrome, this approach is reasonable. Delaying ultrasound to immediately before screening would be associated with a higher cost because more comprehensive examinations would be needed.19,20 We recognize that the charges for first-trimester ultrasound are highly variable, and we do not have data to show whether low-cost ultrasound examinations could be provided. The figure of $46 derived in this analysis should not be the sole basis for reimbursement.
Our economic analysis was confined to the issue of the benefits of ultrasound in triple testing. There are many additional advantages to prenatal ultrasound examinations, including avoidance of unnecessary non-stress tests, induction, and inappropriate preterm delivery management; early detection of fetal death; and detection of some anomalies and twins.21,22 Although the financial savings associated with these aspects have not been measured, they augment the benefits achieved in Down syndrome screening.
The effectiveness of a screening program is based on the overall advantage to a population. Therefore, it is appropriate to evaluate financial net benefits from a societal perspective. Overall savings do not necessarily reflect the value to individual payers. For example, in this study we included nonmedical expenses involved in raising an individual with Down syndrome, which may not have great importance to third-party payers but certainly do for families. The total value of a medical service cannot always be limited to the narrow focus of the insurer or even to the direct medical needs of patients. Health policy makers need to recognize the total societal aspects of medical services such as screening, for which the benefits can be far broader than the provision of clinical care.
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Footnotes |
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Received October 5, 1998. Received in revised form December 4, 1998. Accepted December 30, 1998.
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2. Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Royston P, Chard T, et al. Maternal serum screening for Down’s syndrome in early pregnancy. BMJ 1988;297:883–7.
3. Haddow JE, Palomaki GE. Prenatal screening for Down syndrome. In: Simpson JL, Elias S, eds. Essentials of prenatal diagnosis. New York: Churchill Livingstone, 1993:185–220.
4. Wald NJ, Cuckle HS, Densem JW, Kennard A, Smith D. Maternal serum screening for Down’s syndrome: The effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight. Br J Obstet Gynaecol 1992;99:144–9.[Medline]
5. Benn PA, Borgida A, Horne D, Briganti S, Collins R, Rodis JF. Down syndrome and neural tube defect screening: The value of using gestational age by ultrasonography. Am J Obstet Gynecol 1997;176:1056–61.[Medline]
6. Beazoglou T, Heffley D, Kyriopoulos J, Vintzileos A, Benn P. Estimating net benefits of prenatal screening tests for Down syndrome. In: Beazoglou T, Benn P, Cuckle H, Haddow JE, Kyriopoulos J, eds. Down syndrome screening policy and economic evaluation, proceedings of an international conference. Athens: Exantas (in press).
7. Beazoglou T, Heffley D, Kyriopoulos J, Vintzileos A, Benn P. Economic evaluation of prenatal screening for Down syndrome in the USA. Prenat Diagn 1998;18:1241–52.[Medline]
8. Wasserman Y. Physician’s fee reference 1997. 14th ed. West Allis, Wisconsin: Medical Publishers Ltd., 1997.
9. Vintzileos AM, Ananth CV, Fisher AJ, Smulian JC, Day-Salvatore D, Beazoglou T. An evaluation of first-trimester genetic sonography for the prenatal detection of Down syndrome. Obstet Gynecol 1998;91:535–9.[Abstract]
10. Vintzileos AM, Ananth CV, Fisher AJ, Smulian JC, Day-Salvatore D, Beazoglou T, et al. An evaluation of second-trimester genetic sonography for the prenatal detection of Down syndrome. Am J Obstet Gynecol 1998;179:1214–9.[Medline]
11. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Report of final natality statistics, 1995. Mon Vital Stat Rep 1997;45:1–84.
12. Reynolds TM, Penny MD. The mathematical basis of multivariate risk screening: With special reference to screening for Down syndrome associated pregnancy. Ann Clin Biochem 1989;27:452–8.
13. Reynolds TM, Nix AB, Dunstan FD, Dawson AJ. Age-specific detection and false-positive rates: An aid to counseling in Down syndrome risk screening. Obstet Gynecol 1993;81:447–50.[Abstract]
14. Cuckle HS, Wald NJ, Thompson SG. Estimating a woman’s risk of having a pregnancy associated with Down’s syndrome using her age and serum alpha-fetoprotein level. Br J Obstet Gynaecol 1987;94:387–402.[Medline]
15. Robinson HP. Sonar measurement of fetal crown-rump length as means of assessing maturity in first trimester of pregnancy. BMJ 1973;4:28–31.
16. Kurjak A, Cecuk S, Breyer B. Prediction of maturity in the first trimester of pregnancy by ultrasonic measurement of fetal crown-rump length. J Clin Ultrasound 1976;4:83–4.[Medline]
17. Drumm JE. The prediction of delivery date by ultrasonic measurement of fetal crown-rump length. Br J Obstet Gynaecol 1977;84:1–5.
18. Chervenak FA, Brightman RC, Thornton T, Berkowitz GC, David S. Crown-rump length and serum human chorionic gonadotropin as predictors of gestational age. Obstet Gynecol 1986;67:210–3.[Abstract]
19. American Institute of Ultrasound in Medicine. Guidelines for performance of the antepartum obstetrical ultrasound examination. J Ultrasound Med 1991;10:577–8.
20. Hobbins J, American College of Obstetricians and Gynecologists. Ultrasound in pregnancy. ACOG technical bulletin no. 116. Washington, DC: American College of Obstetricians and Gynecologists, 1988.
21. Eik-Nes S, Okland O, Aure JC, Ulstein M. Ultrasound screening in pregnancy: A randomised controlled trial. Lancet 1984;i:1347.
22. Persson PH, Kullander S. Long-term experience of general ultrasound screening in pregnancy. Am J Obstet Gynecol 1983;146: 946–7.
This article has been cited by other articles:
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  J. F. X. EGAN, P. BENN, A. F. BORGIDA, J. F. RODIS, W. A. CAMPBELL, and A. M. VINTZILEOS Efficacy of Screening for Fetal Down Syndrome in the United States From 1974 to 1997 Obstet. Gynecol., December 1, 2000; 96(6): 979 - 985. [Abstract] [Full Text] [PDF]
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