12/23/04njm

Q. The 'quad' second trimester screening test is expensive. Is it worth
it?

A. The 'quad' screen is more cost effective and patient friendly. See
details below.

The Alaska Native Medical Center has gone to the quadruple second
trimester antenatal screen or 'quad' test, because it is more cost
effective and more patient friendly.

The overall sensitivity is 85%, (better than the triple second trimester
antenatal screen at 65%), but more importantly from the patient
standpoint, the false positive rate for the \<35 y/o is only 3% (vs. 5%
for the triple second trimester antenatal screen) and 10% (vs. 25%) for
the \>35 y/o women. (Wald et al -- see below)

The false positive rate is significantly lower, so there are fewer:
referrals for travel, comprehensive ultrasounds, Maternal Fetal Medicine
(MFM) consults, and amniocentesis(s. Hence, there is a cost savings.

At our facility, if we perform two less amniocentesis(s) a year (and
that\'s with our MFM performing the ultrasound and amniocentesis), then
we would save money. As one is finding fewer positive tests, you are
also causing much less patient anxiety and fewer procedure-related fetal
losses, as well.

I have discussed this with our administration. They readily saw the
advantages and agreed. I suggest that one inquire about the most cost
effective vendor to see if you can find the 'best deal' both
logistically and financially. You can also try to negotiate with your
lab, perhaps thru your Area Office.

**Here are some good references:**

**-Second trimester maternal serum screening for Down syndrome: Clinical
recommendations**

<http://www.uptodateonline.com/application/topic.asp?file=antenatl/13100&type=A&selectedTitle=2~3>

-Wald NJ; Rodeck C; Hackshaw AK; Walters J; Chitty L; Mackinson AM.
First and second trimester antenatal screening for Down\'s syndrome: the
results of the Serum, Urine and Ultrasound Screening Study (SURUSS).
Health Technol Assess 2003;7(11):1-88.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12709291>

OBJECTIVES: To identify the most effective, safe and cost-effective
method of antenatal screening for Down\'s syndrome using nuchal
translucency (NT), maternal serum and urine markers in the first and
second trimesters of pregnancy, and maternal age in various
combinations. DESIGN: A prospective study of women who booked for their
antenatal care at about 8-14 weeks of gestation, with follow-up to
identify pregnancies with Down\'s syndrome ascertained through second
trimester screening or at birth. SETTING: Twenty-five maternity units
(24 in the UK and one in Austria) offering second trimester Down\'s
syndrome serum screening that agreed to collect observational data in
the first trimester. PARTICIPANTS: The results were based on 47,053
singleton pregnancies, including 101 pregnancies with Down\'s syndrome.
MEASUREMENTS AND TESTS: NT measurements were included if obtained
between 9 and 13 weeks of pregnancy; serum and urine samples were also
taken and stored. Another pair of serum and urine samples was collected
in the second trimester and included if obtained between 14 and 20
weeks. Urine and serum samples from each affected pregnancy and five
matched controls were tested for: (1) Serum: (a) alphafetoprotein (AFP);
(b) total human chorionic gonadotrophin (hCG); (c) unconjugated oestriol
(uE3); (d) pregnancy associated plasma protein A (PAPP-A); (e) free
beta-hCG; (f) dimeric inhibin-A. (2) urine: (a) invasive trophoblast
antigen (ITA); (b) beta-core fragment; (c) total hCG; (d) free beta-hCG.
The matching criteria were gestation (using an ultrasound crown-rump
length or biparietal diameter measurement), duration of storage, and
centre. Screening performance of the individual markers and combinations
of markers together with maternal age was assessed using standard
methods. In addition pairs of first and second trimester serum samples
from 600 controls were tested to secure a larger set in which screening
performance could be determined using distribution parameters based on
dates (time since first day of the last menstrual period). MAIN OUTCOME
MEASURES: The following were determined for different combinations of
markers: (1) efficacy (by assessing screening performance, focusing on
the false-positive rate (FPR) for an 85% detection rate (DR)); (2)
safety (focusing on the number of fetal losses due to amniocentesis (or
chorionic villus sampling) in 100,000 women screened); (3)
cost-effectiveness (focusing on the cost of screening 100,000 women and
the cost per Down\'s syndrome pregnancy diagnosed). RESULTS - EFFICACY
(SCREENING PERFORMANCE): The false-positive rates for an 85% detection
rate for the main screening tests are shown in the following table
\[omitted in this version of the summary\], in decreasing order of
screening performance. With the serum integrated test, 10 weeks is the
preferred time in pregnancy for the PAPP-A measurement. For the
integrated test and the combined test, the timing of the measurement of
the first trimester markers is less critical. RESULTS - SAFETY: The
lower false-positive rate with the integrated test compared with other
tests means that at an 85% detection rate there would be nine diagnostic
procedure-related unaffected fetal losses per 100,000 women screened
compared with 44 using the combined test or 45 with the quadruple test.
RESULTS - COST-EFFECTIVENESS: Screening using the integrated test is
less costly than might be expected because the extra screening costs
tend to be offset by savings in the cost of diagnosis arising from the
low false-positive rate. It was estimated that to achieve an 85%
detection rate the cost to the UK NHS would be GBP 15,300 per Down\'s
syndrome pregnancy detected. The corresponding cost using the second
trimester quadruple test would be GBP 16,800 and using the first
trimester combined test it would be GBP 19,000. CONCLUSIONS -
IMPLICATIONS FOR HEALTHCARE: The results showed that screening
performance in the first trimester of pregnancy was virtually the same
as that in the second trimester, and in either it was much less
effective than integrating screening measurements from both trimesters
into a single test. In applying these results to screening practice
several conclusions can be drawn. The following tests offer the most
effective and safe method of screening: (1) overall - the integrated
test; (2) if an NT measurement is not available - the serum integrated
test; (3) for women who do not attend for antenatal care until the
second trimester of pregnancy - the quadruple test; (4) for women who
choose to have a screening test in the first trimester - the combined
test. At a constant detection rate, the cost-effectiveness of these four
tests is broadly similar, any extra screening costs tending to be offset
by fewer diagnostic costs. The evidence presented in this report does
not support retaining the double test, the triple test, or NT
measurements on their own (with or without maternal age) because each
would lead to many more women having invasive diagnostic tests, without
increasing the proportion of Down\'s syndrome pregnancies detected.

Also try

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14746340>

or

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15198778>