Diagnostic ultrasound ( PDFDrive )

CHAPTER 31 Chromosomal Abnormalities 1091
he detection rate of trisomy 21 was 87%, 85%, and 82% at 11,
12, and 13 weeks’ gestation, respectively, at a 5% FPR. For a
detection rate of 85%, NT alone (without biochemical data) had
an unacceptably high FPR of 20%. If the FPR was set at the more
acceptable level of 5%, the sensitivity for detection of trisomy
21 fell to 68%. 25
Screening for aneuploidy in twin gestations is less robust
than in singleton gestations and is hampered by nuances of
placentation. Determination of amnionicity and chorionicity is
crucial. Sebire et al. 26 studied a series of 448 twin pregnancies
and identiied 88% of trisomy 21 fetuses (FPR 7%) using an
NT less than 95%. he prevalence of a thickened NT is higher
in euploid monochorionic twins than in euploid dichorionic
twins, which may relate to placental structure or fetal anomalies.
Discordance of NT measurements in monochorionic twins may
predict twin-to-twin transfusion syndrome. 27,28 Additionally, the
contribution of biochemical markers increases the complexity
of risk assessment in twin gestations because the concentration
of markers relates to the pregnancy (as opposed to the
individual fetus). Spencer and Nicolaides 29 identiied 75% of
trisomy 21 fetuses (FPR of 7%) using biochemical markers and
NT measurement. Wald and Rish 30 reported that at a set FPR
of 5%, the estimated detection rate of trisomy 21 was 84% in
monochorionic twins and 70% in dichorionic twins. his compares
to an 85% estimated detection rate in singletons. Recently, it has
been reported that the risk of trisomy 21 in twins may not be as
high as previously thought, especially in monozygotic twins; these
data add to the complexity of risk assessment. In a large population
study based in Europe examining the prevalence of Down
syndrome among monozygotic and dizygotic twins, the adjusted
risk ratio (RR) of Down syndrome was 0.58 (95% CI, 0.53-0.62)
for twins compared with singletons. his was most pronounced
in monozygotic twins where the adjusted RR was 0.34 (95% CI,
0.25-0.44). In dizygotic twins the adjusted RR was 1.34 (95% CI,
1.23-1.46). 31
A major question is whether an NT measurement exists above
which there is no beneit to additional biochemical screening.
Results of the FASTER trial were evaluated with speciic attention
to this question. An NT of 4 mm or greater was identiied in 32
patients (0.09 %). In this group the lowest combined risk assessment
for trisomy 21 in euploid fetuses was 1 in 8 and for aneuploid
fetuses was 7 in 8. here were 128 patients with NT of 3 mm or
greater. he lowest risk of trisomy 21 among euploid fetuses
using combined screening was 1 in 1479, and the lowest risk
among those with aneuploidy was 1 in 2. Only 10 patients (8%)
had the risk lowered below 1 in 200, all of whom had normal
outcome. hese authors concluded that there is minimal beneit
in waiting for combined screening results in fetuses with NT of
3 mm or larger and no beneit for those with NT of 4 mm or
larger. 32
Integrated and Sequential Screening
Wald et al. 33 introduced the concept of integrated screening, in
which irst- and second-trimester evaluation is used to provide
a single risk estimate for trisomy 21.
he FASTER trial compared screening strategies across the
irst and second trimesters. here were 33,546 patients with
complete irst- and second-trimester data available, including
87 fetuses with trisomy 21. he fully integrated screen that
included irst-trimester NT measurement along with PAPP-A
and a second-trimester quad screen resulted in the detection
of 95% of fetuses with trisomy 21 at a 5% FPR or 87% if the
FPR was set at 1%. 25 A disadvantage of integrated screening
is that the patient does not have any screening results in the
irst trimester, and fetuses at high risk of trisomy 21 are not
identiied until the midtrimester. 34 Compounding this, as many
as 20% of patients may not comply with the second-trimester
screen. 24,35
Two alternative approaches have been proposed in response
to the criticism of late notiication of patients at “high risk” of
aneuploidy. Each of these sequential protocols discloses irsttrimester
results to patients above a speciic “high-risk” threshold.
35,36 Women above the threshold and therefore considered
at highest risk can be referred for genetic counseling and diagnostic
testing early in gestation. In the step-wise protocol, those
not identiied in the high-risk group undergo second-trimester
biochemical screen. In the contingent protocol, only those women
at intermediate risk (≥1 : 50 and <1 : 1500) go on to the secondtrimester
biochemical screening while those at low risk (<1 : 1500)
are not ofered additional screening. In each protocol the results
of irst- and second-trimester screening are integrated and
reported as a single number because if they are independently
interpreted, the FPR is unacceptably high. 1,37 hose with a risk
of 1 in 270 or higher were ofered genetic counseling and
diagnostic testing.
Cuckle et al. 35 retrospectively calculated the midtrimester
risks of trisomy 21 from the FASTER trial data. In this study,
patients were categorized as “high risk” (>1 : 30), “borderline
risk” (1 : 30-1 : 1500), and “low risk” (<1 : 1500) based on the
results of the irst-trimester evaluation. Only patients in the
borderline category underwent recalculation of risk based on
second-trimester biochemical screening. he initial detection
of trisomy 21 (>1 : 30) ater irst-trimester screening was 60%
with an FPR of 1.2%. Of the remaining population, 23% were
at borderline risk and calculated as having additional screening.
Contingent screening identiied 91% of fetuses with trisomy
21, with a 4.5% FPR. Stepwise screening, in which all women
other than those at highest risk had calculated irst- and secondtrimester
testing, had a detection rate of 92% with an FPR of
5.1%. Integrated screening, in which all women had both irstsemester
and second-trimester testing, had a detection rate of
88% with an FPR of 4.9%. his study showed that contingent
screening, in which only 23% of the population went on to
the second-trimester biochemical serum screen, had a similar
detection rate of trisomy 21 as the protocols in which most if
not all patients had recalculation of risk with second-trimester
biochemistry.
Standardization of Nuchal Translucency
Measurement Technique
For NT screening to be accurate, standardization of technique,
training, and ongoing monitoring are crucial. his education,
validation, and ongoing quality assurance has been