Human Reproduction Update, Vol.12, No.5 pp. 513–518, 2006 doi:10.

1093/humupd/dml021
Advance Access publication May 3, 2006

An update on antenatal screening for Down’s syndrome and

specific implications for assisted reproduction pregnancies

Boaz Weisz1,3 and Charles H.Rodeck2

1
Department of Obstetrics and Gynaecology, Sheba Medical Center, Tel-Hashomer, Israel and 2Department of Obstetrics and
Gynaecology, University College London, London, UK
3
To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Sheba Medical Center, Tel-Hashomer
52321, Israel. E-mail: boazmd@zahav.net.il

Downloaded from humupd.oxfordjournals.org by guest on January 18, 2011

Since the introduction of antenatal serum screening for Down’s syndrome (DS) more than two decades ago, several
screening approaches have been utilized in routine clinical practice. The current DS screening strategies involve mid-
trimester serum biochemistry tests, first trimester tests combining sonographic markers and serum biochemistry and
integration of first and second trimester markers. In this review, we evaluate the performance of DS screening strat-
egies according to the Serum, Urine and Ultrasound Screening Study (SURUSS), the First and Second Trimester
Evaluation of Risks (FASTER) Trial and the Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN)
Study. We also evaluate the performance of first trimester screening in studies and meta-analyses by other groups.
Specific issues related to assisted reproduction technology (ART) pregnancies are also addressed in this review.

Key words: Down’s syndrome/integrated screening/nuchal translucency/screening

Introduction at sufficient high risk of a specific disorder, preliminary to a diag-

Since the introduction of antenatal serum screening for Down’s
syndrome (DS) more than two decades ago (Cuckle et al., 1984),
several screening approaches have been utilized in routine clinical
practice. The original method for screening women of advanced
maternal age involved invasive testing that was offered to 5% of
the population and identified fewer than 30% of fetuses with DS.
Subsequently, newer tests incorporating ultrasound and/or maternal
serum biochemistry have been introduced to improve the detection
rate (DR—proportion of affected pregnancies with positive
results) and reduce the number of unnecessary invasive proce-
dures. The current DS screening strategies involve the more tradi-
tional second trimester serum biochemistry tests, first trimester
tests that combine sonographic markers and serum biochemistry
and integration of first and second trimester markers.
In this review, we will discuss the concept of DS screening, eval-
uate the performance of DS screening strategies and present spe-
cific issues with relevance to assisted reproduction pregnancies.
Concept of screening
Screening is a systemic application of a test or enquiry to identify
subjects at sufficient risk of a specific disorder so that they can
benefit from further investigation or direct preventive action
(Wald, 1994). There is no universally accepted definition of med-
ical screening, but there is a general agreement that it should con-
tain three elements: (i) It should identify those individuals who are
nostic test and, if required, preventive action. (ii) It should be
offered systematically to people with no signs or symptoms of the
disease for which screening is being conducted. (iii) It should be
beneficial to the individuals being screened. Routine screening in
modern reproductive medicine was initiated as serum screening
for open neural tube defects (NTD) (Wald et al., 1977). This, fol-
lowed by preventive measures (folic acid uptake), has dramati-
cally reduced the prevalence of NTD in England and Wales (Wald
and Leck, 2000). While screening for NTD has remained rela-
tively unaltered during the last three decades, screening for DS has
evolved substantially and is still a matter of debate in national
clinical policies.
The three elements of screening apply also to DS where screen-
ing is offered systematically to every pregnant woman and selec-
tion is for high-risk pregnancies, which are then offered an
invasive diagnostic test, that is, chorionic villus sampling (CVS)
or amniocentesis. Beneficence relates to the ability to choose
whether to discontinue an affected pregnancy and the ability to
prepare for a delivery of a DS baby for those who choose to con-
tinue the pregnancy.
Assessing the abundant screening tests available today is done
by evaluating the DR of each test, the false-positive rate (FPR—
proportion of unaffected pregnancies with positive results) and the
odds of being affected, given a positive result (OAPR—the ratio
of the number of affected to unaffected individuals with positive
results, i.e. affected positive : unaffected positive). The OAPR is
equivalent to the positive predictive value (PPV), but it conveys a

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B.Weisz and C.H.Rodeck
clearer impression of the performance of the test when the PPV is
high. A better test has a higher DR and OAPR and lower FPR.
Comparisons between tests cannot be done by evaluating a sin-
gle factor such as the DR or the FPR. For every test, increasing the
DR will increase, unavoidably, the FPR. Therefore, to compare
DR between tests, the FPR should be controlled for. A common
presentation used for comparison of the DR between several tests
is the DR5, which is the DR for 5% FPR. Alternatively, in cases
where low FPR is important due to an inherent risk in the diagnos-
tic test (i.e. possible pregnancy loss), the FPR is compared for a
constant DR. For example, FPR85 and FPR90 represent the FPRs
for 85 and 90% DR, respectively. Comparison of DS screening
between tests performed in the late first or early second trimesters
should take into account the bias of spontaneous miscarriage of
DS pregnancies and the bias of markers predicting miscarriage or
loss in chromosomally normal pregnancies.
Many studies have evaluated the performance of each screening
modality. The literature is abundant with papers describing the
performance of each screening test. However, there is a paucity of
information that clearly compares first and second trimester tests
and that can be used for guidance for physicians and patients to
choose the most appropriate test. The two major multi-centre stud-
ies that have compared several first and second trimester screening
modalities are the Serum, Urine and Ultrasound Screening Study
(SURUSS) (Wald et al., 2003b, 2004) and the First and Second
Trimester Evaluation of Risks (FASTER) Trial (Malone et al.,
2005a). The SURUSS, which aimed to determine the most effect-
ive, safe and cost-effective method of antenatal screening for DS,
involved 25 maternity units, and results were based on 47 053 sin-
gleton pregnancies, including 101 DS patients. The FASTER Trial
was conducted in 15 centres throughout USA, recruiting 42 367
women, and results were based on 38 033 eligible singleton preg-
nancies with 117 DS patients. The comparison of the various
screening tests in this review is based on the SURUSS and
FASTER Trial, as well as on other studies and meta-analyses
reporting the performance of first trimester screening (Wapner
et al., 2003; Nicolaides et al., 2005).
Second trimester screening tests
Screening for DS by maternal age started three decades ago when
amniocentesis was offered only to older women. Finding an asso-
ciation of low serum α-fetoprotein (AFP) and fetal chromosomal
abnormalities, including DS (Merkatz et al., 1984), led to a single-
marker screening test using AFP along with maternal age (Cuckle
et al., 1984, 1987). Subsequently, the association between ele-
vated serum hCG and DS led to the double test (AFP and hCG).
The third marker for DS was unconjugated estriol (uE3), which
was found to be lower in affected pregnancies (Canick et al.,
1988). This led to the triple test, which is still very commonly used
(Wald et al., 1988). The most recent addition to the second trimes-
ter serum markers has been Inhibin-A, which is found at higher
levels in affected pregnancies (van Lith et al., 1992; Wald et al.,
1999a). The quadruple test, the combination of AFP, hCG, uE3
and Inhibin, is currently the most popular second trimester screen-
ing test in the USA (D’Alton and Cleary-Goldman, 2005). The
DR5 and the FPR85 for each of the second trimester tests are pre-
sented in Table I.
514
Table I. DR5, FPR85 and OAPR for each second trimester screening test
(combined with maternal age)
Test DR5 (%) FPR85 (%) OAPR
Double test 71 13 1 : 68
Triple test—SURUSS 77 9 1 : 49
Triple test—FASTER 69 14 NA
Quadruple test—SURUSS 83 6 1 : 32
Quadruple test—FASTER 81 7 1 : 37
DR5, detection rate for 5% FPR; FASTER, First and Second Trimester Evalu-
ation of Risks Trial; FPR85, false-positive rate for 85% DR; NA, not applic-
able; OAPR, the ratio of the number of affected to unaffected individuals with
positive results; SURUSS, Serum, Urine and Ultrasound Screening Study.
Interpretation of the results of the second trimester screening
tests by the SURUSS shows that the quadruple test is superior to
the triple test by increasing the DR5 by only 1.07-fold. However, a
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more important observation is that for a similar DR, the need of
invasive tests is reduced by 35%. Assuming that each woman with
a positive screening test chooses to have an amniocentesis, women
tested by the quadruple test have a 35% lower risk of requiring
amniocentesis relative to the triple test. Many centres quote 1%
excess risk of pregnancy loss after amniocentesis (Tabor et al.,
1986). However, recent (non-randomized) studies showed a rela-
tively smaller risk that varies between 0.6% (Seeds, 2004) and
0.2% (Nassar et al., 2004). With these more recent figures, chan-
ging the policy of DS screening from the triple test to the quadru-
ple test would result in 6–18 less fetal losses per 100 000
pregnancies. The FASTER Trial shows a much greater difference
in DR and FPR between the triple and quadruple tests.
First trimester screening
First trimester screening for DS is a relatively novel practice. The
major breakthrough of early screening was the identification
(Szabo and Gellen, 1990; Nicolaides et al., 1992) and implementa-
tion (Pandya et al., 1995) of nuchal thickness (NT) measurement
at 11–14 weeks’ gestation. The performance of NT screening var-
ies between studies. In the SURUSS, the DR5 of the NT (and
maternal age) at 12 weeks was 69% and the FPR85 was 20%
(Wald et al., 2003b). Similar results were published in other two
multi-centre studies. In the Serum Biochemistry and Fetal Nuchal
Translucency Screening Study (BUN Study), the DR5 was 69% and
the FPR85 was about 15% (Wapner et al., 2003). In the FASTER
Trial, the DR5 was 68% and FPR85 was 23% (at 12 weeks). The
conclusion of these studies was that although NT has comparable
DR to second trimester tests, it is accompanied by a relatively high
FPR. However, other studies presented better results, and a review
of 19 prospective studies (including about 200 000 patients)
suggested a higher DR of 77% for 4% FPR (Nicolaides, 2004). A
recent single-centre prospective study that included 30 564 preg-
nancies presented a DR5 of 82% with a FPR85 of 8% (Avgidou
et al., 2005). The differences between the studies are not entirely
understood but might in part reflect more meticulous NT measure-
ments in single-centre studies compared to national and multi-
centre studies.
During the early 1990s, several studies reported the association
between DS and low levels of pregnancy-associated plasma

protein A (PAPP-A) (Wald et al., 1992) and high levels of hCG
(Spencer et al., 1992) and the use of these for screening in the first
trimester (Forest et al., 1997). The combinations of NT measure-
ment (11+0 to 13+6 weeks) with these two serum biochemical
markers in the first trimester compose the combined test (Wald
and Hackshaw, 1997). The incorporation of these two serum
markers to the NT measurement caused a significant and import-
ant decrease in the FPR of first trimester screening. By combining
these two serum markers with the NT, the FPR85 declined by 3.3-
and 4.6-fold in the SURUSS and FASTER Trial, respectively
(Wald et al., 2003b; Malone et al., 2005a). This important reduc-
tion leads to the conclusion that there is no justification for retain-
ing the NT alone in antenatal screening in singleton pregnancies
(Wald et al., 2004). The DR5 of the combined test in the SURUSS,
BUN and FASTER Trial are presented in Table II.
Analysis of six major studies that included 91 666 singleton
pregnancies with 316 DS cases shows a DR5 of 85% (Krantz et al.,
2000; Spencer et al., 2000, 2003; Bindra et al., 2002; Schuchter
et al., 2002; Wald et al., 2003b; Wapner et al., 2003). Therefore, it
is reasonable to conclude that the combined test offers an efficient
test with a high DR and a relatively low FPR. The advantage of
the combined test is the availability of the results in the late first
trimester, enabling karyotyping by CVS and early surgical termi-
nation of pregnancy, when indicated.
Several sonographic markers in the first trimester might
increase the sensitivity and specificity of early screening tests.
Fetuses with DS have an increased resistance (higher PIV—pulsa-
tility index for veins and negative a-wave) in the ductus venosus
(DV) during early pregnancy. It is estimated that the addition of
DV Doppler studies would increase the DR5 of the NT measure-
ment by 11% and of the combined test by 4% (yielding a DR5 of
up to 92% by combined test and DV) (Borrell et al., 2005). How-
ever, such a test requires specific skills and is time consuming;
therefore, it is not considered as a screening test for the general
population. Another promising marker of DS is the absence of
nasal bone (NB) on the first trimester scan (Cicero et al., 2001). It
was estimated that combining this marker with NT measurement
and serum markers (NB+NT+PAPP-A+β-hCG) might increase
the DR5 up to 97% (Cicero et al., 2003). However, other studies
challenged the reproducibility of this test (Senat et al., 2003). The
FASTER study found poor correlation between the absence of NB
and DS and concluded that first trimester NB evaluation was not a
useful test for population screening for trisomy 21 and that it
added little to first trimester NT screening (Malone et al., 2004).
The difficulty in performing first trimester NB sonography
Table II. Screening performance of the combined test by the SURUSS,
BUN studies and FASTER Trial
Study DS/eligible patients DR5 (%) FPR85 (%)
SURUSS 101/47 053 83 6 personal communication), and the rate of not attending for the
BUN 61/8 514 79 9 second blood analysis is about 5%. This rate is even lower in hos-
FASTER 92/36 120 85* 5*
BUN, Serum Biochemistry and Fetal Nuchal Translucency Screening Study;
DS, Down’s syndrome; DR5, detection rate for 5% FPR; FASTER, First and
Second Trimester Evaluation of Risks Trial; FPR85, false-positive rate for 85%
DR; SURUSS, Serum, Urine and Ultrasound Screening Study.
*At 12 weeks.
Antenatal screening for Down’s syndrome
consistently, in the general population setting, will significantly
limit the usefulness of this screening technique. It is possible that
due to specific teaching and guidance of NB scanning in the first
trimester, this technique will be reserved for high-risk cases.
First and second trimester screening
The integration of first and second trimester screening markers in
order to report one risk factor was initiated in the late 1990s (Wald
et al., 1999a). The assumption was to use each marker at its opti-
mal time point, that is, when the difference between the DS cases
and controls is largest. The integrated test combines first trimester
NT measurement and serum PAPP-A levels with second trimester
AFP, β-hCG, E3 and Inhibin (quadruple test). In the initial report
(Wald et al., 1999a), the estimated DR5 of the integrated test was
94%. This is similar to the DR5 results of the SURUSS and
FASTER Trial of 93 and 95%, respectively (Wald et al., 2003a;
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Malone et al., 2005a). The major advantage of this test is the low
OAPR (1 : 6 in SURUSS), which implies that with the integrated
test fewer women will need to undergo invasive testing with its
inherent risk of miscarriage, and equally importantly, fewer
women are made anxious about their pregnancy (Marteau et al.,
1993). The integrated test has been challenged ethically since the
integration of first and second trimester markers in a single test
could pose the problem of withholding first trimester results and
thus denying the possible advantages of an earlier pregnancy ter-
mination (Canini et al., 2002). A recent study has shown that com-
pared to pregnant women, health-care professionals place a higher
value on earlier tests. This concern may result in screening pol-
icies that favour timing in the selection of a test and neglect tests,
associated with lower miscarriage rates and higher DRs, con-
ducted later in pregnancy (Bishop et al., 2004). Indeed, a study of
pregnant women who underwent the integrated test (after having a
second trimester test in their previous pregnancy) concluded that
women receiving prenatal care are prepared to wait until the
second trimester for more accurate DS risk estimates on which to
base their decision-making (Palomaki et al., 2005). This issue was
addressed by the FASTER Trial, which suggested another policy
of ‘stepwise sequential screening’: women with positive first tri-
mester combined test are offered CVS, while those with low-risk
results continue to have the quadruple test at 15 weeks’ gestation,
and a new risk estimate is provided by combining the first and
second trimester variables. This approach yields a DR of 95% for
5% FPR (while the integrated test yields the same DR for 4%
FPR). This represents a small trade-off in the FPR for earlier inter-
ventions in high-risk pregnancies. Another issue that was raised is
that in national screening programmes, some women will fail to
attend for the second blood analysis. The integrated test has not
yet been implicated in routine large-scale screening programmes.
However, an initial report of screening by the integrated test in a
teaching hospital in central London is promising (C.H.Rodeck,
pitals that have a routine antenatal visit at 16 weeks of gestation.
In cases when the NT is not measured, either due to technical
difficulties or due to lack of expert sonographers, it is possible to
perform the serum integrated test (PAPP-A in the first trimester
and quadruple test in the second trimester), which also yields a rel-
atively high DR (Knight et al., 2005).
515
B.Weisz and C.H.Rodeck
An important aspect of the integrated test is that it links with the
gold-standard diagnostic test (i.e. amniocentesis). With rapid diag-
nostic testing available nowadays (i.e. PCR or fluorescence in-situ
hybridization [FISH]), final diagnosis is made by 16 weeks rather
than 19 or 20 weeks and well before fetal movements are felt by
the pregnant woman.
Current screening programs
In the UK, the National Screening Committee evaluated the DS
screening service in 1998 and found deficiencies such as inequity in
provision of services, variation in type and quality of service, an
absence of performance standards and a lack of capacity to support
a nationwide programme (National Down’s Syndrome Screening
Programme for England, 2004). In order to address these issues, in
October 2003 the National Institute for Clinical Excellence (NICE)
recommended that screening programs should have DR5 of at least
60% by 2004–05 and that by April 2007 a DR of greater than 75%
with a FPR of less than 3% should be achieved (National Collabo-
rating Centre for Women’s and Children’s Health—Commissioned
by the National Institute for Clinical Excellence [NICE, 2005]). At
present, the available tests that meet the criteria for 2007 are the
combined test, the Integrated or the serum integrated test (if nuchal
translucency measurement is unavailable) and the quadruple test for
women who attend for screening after the first trimester.
Current policies in the USA vary, and there are no national
guidelines. A survey conducted in 2001 reported that the most
common method of screening was the triple test (Egan et al.,
2002) and more recently the quadruple test (D’Alton and Cleary-
Goldman, 2005). It is reasonable that the results of the SURUSS,
BUN and FASTER studies may change the trend in favour of first
trimester or an integration of first and second trimester screening.
Indeed, in 2004, the American College of Obstetrics and Obstetri-
cians (ACOG Committee Opinion #296, 2004) issued a Commit-
tee Opinion stating that first trimester screening may be
considered provided that there is (i) appropriate training and mon-
itoring programs, (ii) sufficient counselling to women regarding
the differences between the tests and (iii) access to an appropriate
diagnostic test (i.e. CVS) when screening test results are positive.
Specific issues for assisted reproduction technology (ART)
pregnancies
Pregnancies conceived by ART carry a higher psychological and fin-
ancial burden compared to spontaneous pregnancies (Oddens et al.,
1999). The uptake of amniocentesis in ART pregnancies is believed
to be lower compared to controls, mainly due to the inherent risks of
amniocentesis in these ‘more precious’ pregnancies (Geipel et al.,
2004). Therefore, this population gains specifically from the low
OAPR of the integrated test, which reduces their risk of being high
risk for trisomy 21 and having an invasive test. Other issues, which
apply to ART pregnancies, are (i) a relatively older population of
pregnant women, (ii) differences in serum markers compared to spon-
taneous pregnancies and (iii) a higher rate of multi-fetal pregnancies.
Maternal age in ART pregnancies
The proportion of women aged 35 years or more in some IVF clinics
is approximately 50% (Gissler et al., 2004). Inherently, an older
516
population of women would gain from a higher DR, but this is fol-
lowed by a higher FPR and OAPR, whatever screening pro-
gramme is used (Wald et al., 1999a). Comparing all screening
methods for women older than 35 years, the probability of a posit-
ive result (giving the indication for amniocentesis) is specifically
lower when using the integrated test (Wald et al., 1999a). Indeed,
in the FASTER Trial, the screening performance of the integrated
test for women aged 35 years or more was a DR of 91% for FPR
of 2%. This should be compared to a DR of 92% and FPR of 13%
for the quadruple test and a DR of 95% and FPR of 22% for the
combined test (Malone et al., 2005a). In that view, the evidence
suggests that women with advanced maternal age benefit most by
integrated test screening.
Serum marker levels
Initial studies reported a significant difference in the level of
second trimester biochemical markers between IVF patients and
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spontaneous pregnancies (Wald et al., 1999b). Evaluating 151 IVF
pregnancies in which AFP, uE3, free hCG and total hCG were
measured, median uE3 levels were 6% lower, median free hCG 9%
higher and median total hCG 14% higher (all statistically signific-
ant) in IVF pregnancies compared with controls. These results
might explain the higher FPR in IVF pregnancies, which is about
twice as high as that in controls (Barkai et al., 1996). High hCG
levels may be explained partly by a greater number of corpora lutea
(Frishman et al., 1997), by multiple implantation sites or by pro-
gesterone supplementation, which increases placental hCG produc-
tion. Alternatively, it may represent placentation failure that could
result in changes in the trophoblast function and thus hCG produc-
tion (Raty et al., 2003). The low uE3 levels remain unexplained. It
was suggested that in DS screening in IVF pregnancies, hCG and
uE3 values should be adjusted to avoid the high screen positive
rate. A recent multi-centre study analysing 1515 singleton pregnan-
cies by assisted reproduction techniques (ART) found a similar
trend of 12% lower uE3, 7% higher hCG and 6% lower AFP, but
these differences were not significant. In this study, the FPR did
not differ from age-matched controls (Muller et al., 2003). This
might suggest that the significance found by Wald et al. (Wald
et al., 1999b) was a type I error. Other comparative studies show
that serum levels of all three second trimester markers in ART
pregnancies do not differ from controls (Rice et al., 2005).
The effect of ART on first trimester screening is also controver-
sial. Some studies show an increase in hCG levels (Niemimaa et al.,
2001) and a decrease in PAPP-A levels, which increase the FPR (in
ART pregnancies) by an additional 1.2% (Liao et al., 2001). How-
ever, other study found no significant difference in serum levels of
hCG, PAPP-A or FPR between ART and spontaneous pregnancies
(Wojdemann et al., 2001). Interestingly, some recent studies found
increased NT in ART pregnancies (MoM, multiples of median)
(Maymon and Shulman, 2004; Hui et al., 2005).
The effect of ART on Integrated (first and second trimester)
screening was assessed in a group that underwent a serial disclosure
DS screening programme (Maymon and Shulman, 2004). The rate
of first trimester screening FPR was comparable to controls. The
rate of second trimester FPR was two-fold higher in the ART group.
It was concluded that ART singleton patients should be screened
either by the combined or by the integrated tests (Maymon and
Shulman, 2004). To conclude, it is postulated that DS screening in

ART pregnancies is associated with a higher FPR. To decrease the
magnitude of such uncertain experience, it is advised to use better
screening modalities, such as the combined or integrated tests.
Multiple pregnancies
The current concept is that first trimester NT measurement is
superior to second trimester serum screening for multiple pregnan-
cies (Maymon et al., 2005). All monochorionic pregnancies are
monozygotic. On the other hand, most but not all dichorionic
pregnancies are dizygotic. For a dizygous twin pregnancy, the risk
of DS for each fetus is independent of the risk for the other. This
implies that for dichorionic twin pregnancies, the pregnancy-
specific risk is calculated by summing the individual risk esti-
mates for each fetus (Meyers et al., 1997). On the other hand, in
monochorionic pregnancies, the risk is based on an average of
likelihood ratios derived from NT measurements of both twins.
Therefore, diagnosis of chorionicity should be the first step in
ultrasound evaluation of twins during the first trimester, and it has
major implications on the noninvasive screening for aneuploidy in
twins. First trimester scanning and measurement of NT enable the
identification of a fetus-specific risk for Down’s syndrome in
dichorionic pregnancies. In twin pregnancies, the sensitivity of
fetal nuchal translucency thickness in screening for trisomy 21 is
similar to that in singleton pregnancies, but the specificity in mon-
ochorionic pregnancies is lower because translucency is also
increased in chromosomally normal monochorionic twin pregnan-
cies (Sebire et al., 1996). In another small study, a DR of 100%
was achieved with screen positive results of 4.3% (Maymon et al.,
2001). The use of the first trimester combined test (Spencer and
Nicolaides, 2003) can lower the FPR of NT measurement. It is
estimated that by using ‘pseudo-risk’ and not specific risk figures,
the integrated test can reach a DR5 of 78 and 93% for dichorionic
and monochorionic twin pregnancies, respectively (Wald et al.,
2003a).
Conclusion
Three major national studies (SURUSS, BUN and FASTER Trial)
as well as many local studies (evaluated by Nicolaides, 2004)
demonstrate that the first trimester combined test is equivalent or
superior to second trimester serum screening (Simpson, 2005).
The best test (with highest DR and lowest FPR) is the integrated
test, which is also the safest (leading to lower rate of invasive pro-
cedures) and most cost-effective (Wald et al., 2004). We believe
that current practice of screening should employ either the inte-
grated test or the combined test for those women who want an
early result and who are prepared to accept the higher risk of hav-
ing an unnecessary invasive procedure. Stepwise sequential or
contingent screening might be beneficial since not all women need
to return for second trimester markers’ evaluation (Malone et al.,
2005b), but these tests require implementation and cost-effectiveness
studies before they can be recommended. The quadruple test
should be reserved for women who only reach prenatal care in the
second trimester. There is still limited data on the performance of
these tests in ART pregnancies. Screening in twin pregnancies can
be done only when chorionicity is certain. Twin pregnancies
should be screened by NT measurement, combined or integrated
tests, and it is not clear which test is superior.
Antenatal screening for Down’s syndrome
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Submitted on January 27, 2006; resubmitted on March 21, 2006; accepted on
March 31, 2006