PRENATAL DIAGNOSIS, VOL.

14 527-535 (1994)

INCREMENTAL COST-EFFECTIVENESS OF
INCORPORATING OESTRIOL EVALUATION IN
DOWN SYNDROME SCREENING PROGRAMMES
THEODORE G . GANIATS*, ANDREA L. HALVERSON* AND MARK H. BOGART?
*Division of Family Medicine, Department of Family and Preventive Medicine, UCSD School of Medicine,
La Jolla, California, U.S.A.; f Mid-Pacific Genetics, Inc., Honolulu, Hawaii, U.S. A.
Received July 1993
Revised October 1993
Accepted October 1993

SUMMARY
As screening for Down syndrome becomes increasingly sophisticated, it is important to evaluate the newer
technologies in terms of their cost-effectiveness.One recent addition to Down syndrome screening programmes is
maternal serum unconjugated oestriol (uE,), especially when used in conjunction with maternal serum a-fetoprotein
and human chorionic gonadotropin. Using assumptions used in a California proposal to justify an expanded
screening programme for Down syndrome, we calculated both the average and the incremental cost-effectiveness of
adding uE,. Using the base case assumptions, including an $8 fee for the uE,, the incremental cost-effectivenessof
adding uE, to the proposed California programme is $119 100 per case detected, a value that compares favourably
with other Down syndrome screening programmes. The sensitivity analysis supports this conclusion over a wide
range of assumptions. However, because of the uncertainty with some key data, it is still too early to fully support
the inclusion of uE, in Down syndrome screening programmes.
KEY w o m s D o w n syndrome, screening, cost-effectiveness.

INTRODUCTION in the development of additional screening tests to

Down syndrome (DS) is the result of an extra
number 21 chromosome and is observed in
approximately 1 in every 1000 live-born infants.
DS is characterized by a specific set of facial and
other physical features, mental retardation, con-
genital cardiac defects, congenital gastrointestinal
anomalies, an increased incidence of leukaemia,
defects of the immune system, and an Alzheimer-
like dementia. Currently, over 300 000 individuals
are affected with DS in the U.S.A. (Korenberg
et al., 1992).
DS can be diagnosed prenatally via genetic
amniocentesis, which has routinely been offered to
women 35 years of age or older. However, 75-80
per cent of DS infants are born to women below
age 35. Thus, there has been considerable interest
Addressee for correspondence: Theodore G. Ganiats, MD,
Division of Family Medicine-0807, UCSD School of Medi-
cine, 9500 Gilman Drive, La Jolla, CA 92093-0807, U S A .
CCC 0197-385 1/94/070527-09
0 1994 by John Wiley h Sons, Ltd.
increase the effectiveness of prenatal diagnosis.
Despite the weak association between low mater-
nal serum a-fetoprotein (AFP) concentrations and
DS (Merkatz et al., 1984), AFP evaluation is a
prime component of current screening for DS
because of the value of AFP evaluation in neural
tube defect screening. Currently, the most effective
biochemical screening marker is maternal serum
human chorionic gonadotropin (hCG) (Bogart et
al., 1987). Approximately 50 per cent of pregnan-
cies with DS have a maternal serum hCG concen-
tration greater than twice the median value for
normal pregnancies (Bogart, 1992). The most com-
monly used additional marker is unconjugated
oestriol (uEJ (Canick et al., 1988). Thus, the two
most ‘popular’ types of screening programme are
the ‘Double test’, where the risk of DS is estimated
by a combination of maternal age-related risk and
two maternal blood tests (AFP and hCG), and the
‘Triple test’, where the risk is estimated by a
combination of maternal age and three maternal
528 T. G. GANIATS ET AJl.
blood tests (AFP, hCG and uE,). In essence, the
Double test is the Triple test programme without
the measurement of uE3.
Much of the justification of these programmes is
based on their cost-effectiveness. While the phrase
‘cost-effectiveness’ can have several meanings
(Doubilet et al., 1986), in this context cost-
effectivenesssuggests that the desired medical ben-
efit of a programme (e.g., prenatal detection of
DS) justifies the programme’s financial costs. The
average cost-effectivenessof a programme is calcu-
lated by dividing the total programme costs by the
total health benefits. As a hypothetical example, if
Programme A detects eight cases of cancer at a
cost of $100 000, the average cost-effectiveness of
Programme A is $100000/8=$12500 per case
detected. The average cost-effectiveness of Pro-
gramme A can be improved by either increasing
the benefits (i.e., detection rate) or decreasing the
costs.
However, in determining health policy, average
cost-effectiveness is not as important as incremen-
tal (or marginal) cost-effectiveness. Unlike average
cost-effectiveness, incremental cost-effectiveness
compares two programmes to determine whether
the incremental health benefits of the more expen-
sive test justify the additional expense. For
example, take a second cancer screening pro-
gramme (Programme 8) that costs $210 000
and detects 10 cases (average cost-
effectiveness=$21000 per case detected). While the
average cost-effectiveness of Programme A is bet-
ter than that of Programme B, we may still con-
sider Programme B to be cost-effective. In other
words, we may feel that the cancer is such a severe
disorder that we are willing to pay up to $40 000 to
detect a case, especially if the total programme
detects more cases. Using this criterion, Pro-
gramme B appears to be cost-effective. But the real
question involves how efficiently our last dollars
are spent. In this example, we know that we can
detect the first eight cases for only $100 000 using
Programme A. With Programme B, we must spend
an additional $1 10 000 to detect two more cases.
Thus, the incremental cost-effectiveness of Pro-
gramme B is $110 000/2=$55 000 per case
detected. The incremental cost-effectiveness of
Programme B is more than double its average
cost-effectiveness and is higher than our $40000
cut-off. Because of its high incremental cost-
effectiveness, Programme B should not be con-
sidered cost-effective, even though its average
cost-effectiveness seems acceptable.
Both the Double test and the Triple test are
currently offered to patients throughout the U.S.
through various local and national reference labo-
ratories. The State of California, which currently
offers a maternal serum AFP programme, plans to
introduce a Triple test screening programme in
March 1994. While there is little doubt that a
Double test screening programme is justified
(Seror et al., 1993a), some have questioned
whether the small increase in detection rate
afforded by adding uE, justifies the additional
cost. In this paper we evaluate the incremental
cost-effectiveness of adding uE, to the California
screening programme for DS.
METHODS
Data for the Triple test came from an internal
memo from the Department of Health, State of
California dated 27 August 1990. We considered
only the direct costs of testing, ultrasound, amnio-
centesis, termination, administration and counsel-
ling. When necessary, expert opinion (MHB) was
added. The cost and effectiveness of the Double
test were assumed to be equal to the cost and
effectiveness of the Triple test minus the incremen-
tal cost and the incremental effectiveness of
oestriol screening.
The basic decision tree followed the logic from
the California memo. For both the Double test
and the Triple test, all patients are offered the
screening, and those with a positive screen are
offered amniocentesis. Those with a positive
amniocentesis are then offered a therapeutic abor-
tion. The assumptions are included in Table I. In
the base case, both the Triple test and the Double
test were assumed to include the amniocentesis
that follows a positive screening. While this is
consistent with the California protocol, in other
states the amniocentesis is billed separately. For
this reason, in the sensitivity analysis the cost of
the amniocentesis was varied to facilitate the
generalizability of the results.
The proportions of the population over and
under 35 were based on the State’s assumptions.
The effectivenessof uE, was demonstrated by the
increased sensitivity of the Triple test instead of a
decrease of the positive rate. In addition, the State
assumed that everyone testing positive would
choose an amniocentesis, but of those who have
DS on amniocentesis, only 80 per cent would
choose an abortion. Since some investigators feel
 OESTRIOL EVALUATION IN DOWN SYNDROME SCREENING PROGRAMMES 529
Table I-Assumptions

Base case Sensitivity analysis

Number of births*
To women under 35 596 305
To women 35 and over 64 860
All ages 661 165
Number of DS cases (rate)?
To women under 35 555 (111073)
To women 35 and over 347 (1/187)
All ages 902 (1/733)
DS detection rate of the Triple test
Women under 35 44% 72%
Women 35 and over 85% 92yo
All ages 60% 80%
Dollar costs
Double test $110
Incremental cost of LIE,$ $8 0-$16
Amniocentesis Included 0-$1000
Abortion $479
Positive screening test rate 5.5% 9.8%
Amniocentesis rate (amniocentesis per
positive screening test)$ 1OOYO 50-100Yo
Abortion rate (abortion per positive
amniocentesis)§ 8W/o 50-1Wh
Incremental detection rate of uE1
,1 5% 0-1OOh

*1991-1992 data from California.

?Based on Hook and Chambers’ 1977 estimates of DS incidence by maternal age (Hook and
Chambers, 1976) and California’s maternal age distribution for 1988.
$The increase in the Triple test cost resulting from adding uE,.
§Department of Health, State of California (see Methods).
/\Theincrease in the detection rate of the Triple test resulting from adding uE,. Based on average
value found in the literature.

that the detection rate of the Triple test is as high
as 80 per cent, a second set of analyses were
performed using this sensitivity but keeping the
incremental detection rate of uE, at 5 per cent, the
base case assumption.
To view the cost-effectiveness of both the
Double test and the Triple test from a different
perspective, these tests were compared with the
cost-effectiveness of the old standard, maternal
age. The assumptions used to calculate the costs
and effectiveness of screening by maternal age
alone were also taken from the California memo
mentioned above.
Thc.cost-effectivenessratios were calculated, as
per the California State memo, as the total dollar
cost divided by the number of DS cases detected.
Since the abortion rate is 80 per cent, one can
convert our findings to the number of DS cases
prevented by multiplying by 0.8. Since all mea-
sured future costs and health outcomes occur
within a time period of a few months (screening to
abortion), these outcomes were not discounted
(Ganiats and Schneiderman, 1988). Sensitivity
analyses were performed using the ranges noted in
Table I. All analyses were performed using SML-
TREE Version 2.9 (copyright Jim Hollenberg,
1992) and confirmed using a beta version of
DATA (Version 2-lb7, copyright TreeAge Soft-
ware, Inc., 1993), a decision analysis program for
the Macintosh.
530 T. G . GANIATS ET AL..

3 1.200
Y
4 1,OOo
I
800

3,
rl

E m
*0 4 0 0
8
3E 200

t
Y
I
o
10 9 8 7 6 5 4 3 2 1
Incremental Sensitivity of uE3 (9%)
Fig. 1-Sensitivity analysis showing how the cost-effectiveness of uE, varies as a function of the
incremental detection rate of uE,. (0)uE,=$O; (0)uE3=%4;( W ) uE,=$8; ( x ) uE,=$16

RESULTS uE, when the sensitivity of the Triple test is 80 per

cent. The incremental effectiveness of uE, was
The base case analysis confirms the State’s find- again varied from 0 to 10 per cent, and the other
ings that the Triple test detects 539 cases at a cost variables were kept at the base case values. The
of $78 224 000 for an average cost-effectiveness of comparison of the two sensitivity analyses (Triple
$145 100 per DS case detected. The Double test test sensitivity equals 60 per cent and Triple test
detects 495 cases at a cost of $72918000 for an sensitivity equals 80 per cent) is in Fig. 2. As can be
average cost-effectiveness of $147 400 per DS case seen, the results are quite similar.
detected. The incremental cost of adding uE, is A third set of sensitivity analyses were per-
$8.03 per person, or a total cost of $5-3 million formed by varying either the amniocentesis rate or
dollars per year for the entire programme. Adding the abortion rate. As expected, varying the amnio-
uE, results in the detection of 44 additional cases centesis rate has a marked effect on the incremen-
of DS. Thus, the incremental cost-effectiveness of tal cost-effectiveness of uE3. At the base
adding uE, is $119 100 per case detected. A two- assumption of a 100 per cent amniocentesis rate,
way sensitivity analysis varying the incremental the incremental cost-effectiveness of uE, is
sensitivity of uE, and the incremental cost of uE, $119 100 per case detected; the ratio is $231 300
is plotted in Fig. 1. The incremental cost- per case detected at a 50 per cent amniocentesis
effectiveness of uE, was under $120000 per case rate. The results did not change signiilcantly when
detected when the incremental detection rate of varying the abortion rate. At an abortion rate of
uE, was 10 per cent. However, if the cost of 50 per cent, the incremental cost-effectiveness is
oestriol is $16 and the incremental sensitivity $1 18 974 per case detected; it is $119 213 per case
of uE, is 2 per cent, adding oestriol results in a detected at an abortion rate of 100 per cent.
programme that costs $594 100 to detect one case If the cost of amniocentesis is $1000, excluding
of DS. The incremental cost-effectiveness drops to the cost of the amniocentesis does not affect the
$1 187 700 per case detected when the incremental incremental cost-effectiveness of the oestriol, but it
cost of uE3 is $16 and the incremental sensitivity of does decrease the average cost-effectiveness of the
uE, is 1 per cent. Triple test to $77 600 per DS case detected and
A second sensitivity analysis was performed that of the Double test to $73900 per case
calculating the incremental cost-effectiveness of detected. The cost per patient drops $55 for both

I I I 1
10 9 8 7 6
Incremental Sensitivity of uE3 (95)
Fig. 2-Incremental cost-effectiveness of uE, as a function of the incremental uE, detection rate when
the total programme detection rate ranges from 50 to 60 per cent ( 0 )and from 70 to 80 per cent ( 0 )
programmes ($110.29 to $55.29 for the Double test
and $118.31 to $63.31 for the Triple test). A
threshold analysis reveals that the average cost-
effectiveness of the Double test and the Triple test
are equal when the cost of the amniocentesis is
$385, or a Double test cost of $89.11 per patient
and a Triple test cost $97.14 per patient. Thus,
given the other base assumptions, the Double test
has a higher average cost-effectiveness (is less
cost-effective) until the cost of amniocentesis is
lowered to $385; if the amniocentesis cost is
less than $385, the Triple test is less cost-effective
(Fig. 3).
In evaluating the cost-effectiveness of the
advanced maternal age (maternal age 2 3 5 years)
screening programme, the State assumes that all
64 860 pregnant women over 35 would choose an
amniocentesis and that all 347 cases of DS would
be detected for a total cost of $64 993 OOO. The
average cost-effectiveness (i.e., the incremental
cost-effectiveness compared with doing no screen-
ing) of maternal age screening for DS is thus
$64 993 000/347 = $187 300, or higher than either
the Double test or the Triple test in the base case.
Both the Double test and the Triple test cost more
but detect more cases of DS. Given the base case
assumptions, the incremental cost-effectiveness of
the Double test and the Triple test (compared with
53 1
I I I I I
5 4 3 2 1
maternal age alone) is $53 700 per case detected
and $68 200 per case detected, respectively.
Performing an amniocentesis on all 64 860
females over age 35 years, however, results in an
amniocentesis rate of 9.8 per cent, sigtllficantly
higher than the 5-5 per cent rate for the Double
test and Triple test in the base assumptions.
Increasing the Double test and Triple test amnio-
centesis rate to 9-8per cent increases the sensitivity
of the programmes to about 80 per cent. The
increased number of amniocenteses results in
increased programme costs. These increased costs
were evaluated using the $1000 amniocentesis cost
and the $55 and $63 costs for the Double test and
the Triple test that were calculated above. Using
these assumptions, the average cost-effectivenessof
the Double test becomes $150 200 (675 cases pre-
vented at a cost of $101 417 000), and that of the
Triple test $148 100 (721 cases prevented at a cost
of $106 724 000). The incremental cost-
effectiveness compared with a programme based
solely on maternal age greater than 35 years is
$1 1 1 000 per case detected and $1 11 600 per case
detected for the Double test and the Triple test,
respectively. These data are summarized in Table
11.
Table I11 presents the relative effectivenessof the
three screening programmes (using the base
532 T. G. GANUTS ET AL.

Fig. %Average cost-effectiveness of the Double test ( 0 )and the Triple test (0)programmes using the
base assumptions and varying the cost of amniocentesis

Table II-Cost-effectiveness of three Down syndrome screening programmes

~ ~~ ~

Maternal age
2 3 5 years Double test Triple test
Amniocentesis rate*: 9.8% 5.5% 9.8% 55% 9.8%

Cases detected 347 495 675 539 721

Total programme cost (in millions) $65.0 $72.9 $101.4 $78.2 $106.7
Cost-effectiveness (CE)t
Average CE $187 300 $147 400 $150 200 $145 100 $148 100
Marginal CE to maternal age NA $53 700 $111 000 $68 200 $111 600
Marginal CE to the Double test NA NA NA $119 100 $117000

*The sensitivity of the Double test is 55 and 75 per cent at amniocentesisrates of 5.5 and 9.8 per cent. The sensitivityof the Triple
test is 60 and 80 per cent at amniocentesis rates of 5.5 and 9.8 per cent.
fAverage cost-effectiveness=total costlcases detected; marginal CE to maternal age=(total cost - cost of maternal age
programme)/(cases detected - cases detected by maternal age programme); marginal CE to the Double test=(total cost -cost of
Double test programme)/(cases detected - cases detected by Double test programme).

assumption of a 5.5 per cent amniocentesis rate for DISCUSSION

the Double test and the Triple test) broken down
by maternal age. The Double test and Triple test
offer sigdicant advantages over maternal age in
the overall detection rate and in the detection rate
in those under 35 years old. A programme based
on only maternal age detects more cases of DS in
those over 35.
Using the base case assumptions, the incremen-
tal cost-effectiveness of uE, compared with a
maternal age programme ($68 200 per case
detected) is similar to the incremental cost-
effectiveness of the Double test ($53 700 per case
detected). It is inappropriate for an individual to
 OESTRIOL EVALUATION IN DOWN SYNDROME SCREENING PROGRAMMES 533
Table III-Comparison of three Down syndrome screening programmes
Advanced maternal age Double test Triple test
~ ~~~~~~

Cases detected in those 2 3 5 years 347 27 1 295

Total cases detected in programme* 347 495 539
Detection rate? 39% 55% 60%
Amniocenteses performed$ 64 860 36 364 36 364
Amniocenteses per case detected 187 73 67

*Total cases for the Double test=224 (<35 years)+271 (135 years)=495.
Total cases for the Triple test=244 (<35 years)+295 (235 years)=539.
?Percentage of total cases detected. Based on 555 DS cases in those <35 years old and 347 cases in
those 2 3 5 years old (see Table I).
SBased on a 5.5 per cent amniocentesis rate (see Table I).

declare whether any given programme is ‘cost-
effective’ (Ganiats and Schneiderman, 1988), and
one must look to society to determine cost-
effectiveness. Since the incremental cost-
effectiveness of uE, is less than the incremental
cost-effectiveness of the maternal age programme,
and since the State of California has already
decided that maternal age screening is cost-
effective, the Triple test is also cost-effective in
California given the base assumptions. On the
other hand, the incremental cost-effectiveness of
adding uE, quickly becomes unfavourable as the
incremental cost of uE3 increases or its incremental
effectiveness decreases.
The cost of the amniocentesis does not affect the
incremental cost-effectiveness, and this is not sur-
prising. The number of amniocenteses performed
is a function of the screening test positive rate, and
this rate was held constant for the two pro-
grammes. On the other hand, adding the cost of an
amniocentesis increases the total costs of the pro-
gramme, decreasing its cost-effectiveness. Chang-
ing the cost of the amniocentesis also affects the
average cost-effectiveness of the two programmes.
However, given the similarity of the cost-
effectiveness ratios and given that the incremental
cost-effectiveness remains unchanged, this is
unlikely to be an important factor in determining
health policy.
The base assumptions used in this study are
different from those used in other studies, but these
lfferences have little effect on the results. For
example, in a recent article by Seror et al. (1993b),
the cost of amniocentesis was $700 and the sensi-
tivity of the hCG was 64 per cent. As described
above, the cost of amniocentesis affects only
the average cost-effectiveness of the tests, not the
incremental cost-effectiveness. In addition, the
$700 amniocentesis cost is far above the threshold
value of $385 found in our study. The greater
effectiveness of hCG similarly has little effect on
the results of the incremental cost-effectiveness of
uE,. This is confumed by Fig. 2, which demon-
strates that the incremental cost-effectiveness of
uE3 is essentially unaffected by the overall sensitiv-
ity of the screening programmes.
Similarly, the fact that, contrary to our as-
sumption, not all women will choose a screening
programme has little effect on the programme’s
cost-effectiveness. As fewer women choose the
programme, the programme costs drop roughly
proportional to the decrease in the programme’s
benefits. While the overall benefit of a programme
to society decreases as fewer women participate,
so do the overall costs, and the cost-effectiveness
ratio remains unchanged (except as modified by
economies of scale).
Another factor that may be important is the
spontaneous abortions of normal infants after a
false-positive screening test. While the exact rate of
such abortions is a matter of debate, it is clear that
it vanes as a function of the screening test’s
specificity. In California, a programme based on
maternal age would lead to 64 860 amniocenteses
and detect 347 cases of DS. Thus, about 0-5 per
cent of the positive screening test results are a true
positive (i.e,, the predictive value positive is 0.5 per
cent). In contrast, in the Double test 495 cases of
DS are found after 36 364 amniocenteses (1-4 per
cent predictive value positive); the Triple test finds
539 cases after 36 364 amniocenteses (1.5 per cent
predictive value positive). Thus, the Double test
and the Triple test are associated with a significant
decrease in the total number of amniocenteses and
534 T. G . GANIATS ET AL.
a significant increase in the predictive value
positive. It is reasonable to assume that perform-
ing fewer amniocenteses will result in the fewer
miscarriages of normal fetuses.
An unexpected finding of this study is the
relative cost-effectiveness of the three pro-
grammes (advanced maternal age, Double test,
and Triple test). Society has implicitly stated that
the advanced maternal age programme, at
$187 300 per case detected, is cost-effective. Any
programme that detects a case of DS for less is
more cost-effective and is the preferred pro-
gramme. It is not surprising that both the Double
test and the Triple test have better cost-
effectiveness ratios at the lower amniocentesis
rate (Table 11). However, our figures indicate that
the Double test and Triple test are also more
cost-effective than maternal age, even when the
amniocentesis rate for these programmes is
increased to 9.8 per cent. At this higher amnio-
centesis rate, both the average and the incremen-
tal cost-effectiveness of the newer tests are better
than the current standard, maternal age (Table
11). This implies that the sensitivity of these new
screening programmes should be increased to
allow for the higher amniocentesis rate. This
observation requires further evaluation before
policy decisions are made.
There is one potential concern of the newer tests,
however. Women over 35 are no longer offered
amniocentesis to evaluate the pregnancy for DS. In
the California data (Table 111), this results in 76
cases of DS missed each year by the Double test
and 52 cases missed by the Triple test in women
over 35 years old. In addition, such programmes
will also m i s s a proportion of other chromosome
abnormalities that occur more frequently with
increasing maternal age. The political, social, and
medicolegal ramifications of such a decision are
still unknown.
One way to address this concern is to follow
California’s recent decision and to offer a two-
phase programme where those under 35 are offered
marker screening and those over 35 are offered an
amniocentesis. Surprisingly, such a programme
may not be appealing. Using the data from Table
111, one can calculate that the Double test and the
Triple test ‘save’ 28 496 amniocenteses compared
with the advanced maternal age programme. Even
though these programmes also detect more cases
of DS overall, this saving comes at a cost: the
Double test detects 76 fewer cases of DS and the
Triple test detects 52 fewer cases of DS in those
2 3 5 years. One can evaluate the ‘cost-
effectiveness’ of the maternal age programme at
detecting these additional cases. Such an analysis
shows that compared with the Double test, the
advanced maternal age programme requires 375
amniocenteses per additional case detected
(28 496/76). Compared with the Triple test, the
advanced maternal age programme requires 548
amniocenteses per additional case detected
(28 496/52). Both of these are greater than either
the advanced maternal age (187 amniocenteses per
case detected), the Double test (73 amniocenteses
per case detected), or the Triple test (67 amniocen-
teses per case detected) programmes.
Following the work of Sheldon (Sheldon and
Simpson, 1991) and others, we have chosen not
to carry the cost-effectiveness analysis beyond the
point of the abortion. This is because of the
ethical concerns regarding valuing ‘imperfect
individuals’. Thus, all future dollar savings accu-
mulating after the abortion is performed (e.g., the
health care and disability savings that accrue
when an affected fetus is not aborted) are not
considered.
This study offers several advantages over prior
studies. For example, we compute not only the
incremental cost-effectiveness of adding uE3, but
also the incremental cost-effectiveness of both the
Double test and the Triple test compared with
maternal age, the previous standard. Others have
evaluated only the average cost-effectiveness of
these new programmes. In addition, on occasion
incremental costs and average effectiveness are
used in the cost-effectiveness calculations (Sheldon
and Simpson, 1991). This technique produces
results that are difficult to interpret.
Finally, it should be remembered that this analy-
sis reflects cost-effectiveness estimates for the
detection of DS pregnancies only. The AFP por-
tion of the screening programmes is primarily
beneficial in screening for neural tube defects; the
hCG (and to some extent uE,) portion is useful for
detecting various other abnormalities that affect
placental function. Either the Double test or the
Triple test is capable of detecting a portion of the
pregnancies with fetal hydrops (Saller et al., 1991),
ventral wall defects (Barnes et al., 1992)’ trisomy
18 (Bogart et al., 1989), low birth weight (Hurley
et al., 1992), triploidy (Schmidt et al., 1992), and
various other abnormalities (Beekuhis et al., 1992;
Gonen et al., 1992; Milunsky, 1992). Thus, the
overall usefulness of either the Double test or
the Triple test exceeds the calculations based on
 OESTRIOL EVALUATION IN DOWN SYNDROME SCREENING PROGRAMMES 535

the detection of DS alone. That is, the cost- Ganiats, T.G., Schneiderman, L.J. (1988). Principles of
effectiveness calculations reflect the minimal cost- cost-effectivenessresearch, J. Fam. Pract., 27, 77-84.
effectiveness of such programmes in terms of Gonen, R., et al. (1992). The association between un-
dollars per birth defect detected. explained second-trimester maternal serum hCG
elevation and pregnancy complications, Obstet.
Gynecol., 80, 83-86.
CONCLUSIONS Hook, E.B., Chambers, G.M. (1976). Estimated rates of
Down syndrome in live births by one year maternal
age intervals for mothers aged 2049 in a New York
The addition of uE, to a Down syndrome State study-implications of the risk figures for
screening programme of maternal age-adjusted genetic counseling and cost-benefit analysis of pre-
AFP and hCG appears to be cost-effective given natal diagnosis programs, Birth Defects, 13, 123-141.
our base case assumptions. Caution should be Hurley, T., et al. (1992). Serum human chorionic gona-
exercised when interpreting these results since they dotropin (hCG) as a marker for low birthweight in
are based on retrospective data and several women with unexplained elevations in maternal serum
assumptions, including the valuation of the future alpha-fetoprotein (MSAFP), Am. J. Obstet. Gynecol.,
life of an infant with DS, which are subjects for 166, 355.
debate. Given these constraints, the present analy- Korenberg, J., et al. (1992). Advances in the understand-
sis will assist policy-makers in their decisions ing of chromosome 21 and Down syndrome. In: Down
regarding screening for this important disease. Syndrome: Advances in Medical Care, New York
Wiley-Liss, 3-12.
Merkatz, I., et al. (1984). An association between low
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