Diagnostic ultrasound ( PDFDrive )

1102 PART IV Obstetric and Fetal Sonography
theorem and likelihood ratios. hey showed that likelihood ratios
could be calculated for each isolated marker, then applied to the
patient’s a priori (presumptive) risk using Bayes theorem. his
resulted in a revised risk of aneuploidy based on the presence
or absence of speciic markers. Table 31.1 shows a comparison
of four studies that computed likelihood ratios for trisomy 21
using isolated markers.
Clusters of markers, even minor ones, confer more risk than
individual markers alone 90,91 (Table 31.2). Winter et al. 89 demonstrated
that the genetic sonogram scoring index and the method
of ultrasound risk assessment using likelihood ratios were
essentially equivalent in the detection rate of trisomy 21. he
advantage of using likelihood ratios is that a patient’s speciic
risk of aneuploidy can be calculated and balanced against the
risk of pregnancy loss associated with an invasive procedure.
Even in the largest studies, the number of fetuses with an isolated
marker is small, leading some to recommend that a revised risk
estimate for aneuploidy is statistically more robust if the overall
likelihood ratio is calculated by the product of the positive and
negative likelihood ratios for each marker. 109,164
Trisomy 21: Revised Risk Ratio Calculations
Revised risk = a priori risk × likelihood ratio (LR)
EXAMPLE 1: METHOD USING ISOLATED LR
A 25-year-old woman with a priori risk of trisomy 21 of
1 : 500 based on quad screen.
Detailed ultrasound shows an isolated echogenic
intracardiac focus (EIF) (LR ≈ 2).
Revised risk = 1 : 500 × 2 = 1 : 250
EXAMPLE 2: METHOD USING “CLUSTER OF
MARKER” LR
A 39-year-old woman with a priori risk of trisomy 21 of
1 : 1000 based combined screen.
Detailed ultrasound shows EIF and urinary tract dilation (LR
≈ 6 from two markers).
Revised risk = 1 : 1000 × 6 = 1 : 166
EXAMPLE 3: METHOD USING POSITIVE AND
NEGATIVE LRS FOR EACH MARKER
Short humerus not used in calculation
A 28-year-old woman with a priori risk of trisomy 21 of
1 : 1000 based combined screen.
Detailed ultrasound shows EIF and short femur. Negative
for nuchal fold, urinary tract dilation, echogenic bowel,
nasal bone, and ventriculomegaly.
Revised Risk: 1 : 1000 × LR for combination of positive/
negative = 4.41 (5.83 × 3.72 × 0.92 × 0.90 × 0.80 × 0.46 ×
0.94) = 1/226
Likelihood ratios in examples 1 and 2 are with permission from
Bromley B, Lieberman E, Shipp TD, Benacerraf BR. The genetic
sonogram: a method of risk assessment for Down syndrome in the
second trimester. J Ultrasound Med. 2002;21(10):1087-1096. 91
Likelihood ratios in example 3 are with permission from Agathokleous
M, Chaveeva P, Poon LC, et al. Meta-analysis of second-trimester
markers for trisomy 21. Ultrasound Obstet Gynecol. 2013;41(3):
247-261. 109
Agathokleous et al. performed a meta-analysis of secondtrimester
markers for Down syndrome using data published ater
1995. Weighted independent estimates of detection rates, FPRs,
and positive and negative likelihood ratios for each marker was
calculated. 109
Genetic sonography is best used in conjunction with a priori
risk estimates based on an accepted screening protocol. 163,165-169
Souter et al. 167 demonstrated that serum biochemical marker
analytes and sonography are independent and therefore can be
used in conjunction with each other to modify the risk of aneuploidy.
Several investigators have shown that patients of advanced
maternal age who had a normal genetic sonogram and reassuring
serum screen are at a lower risk for trisomy 21. 90,91,166,169 he
absence of markers has been shown to reduce the risk of trisomy
21 by (60%-90%). 90,91,109,164 his may be even more dramatic as
many studies were published before the nasal bone was recognized
as an important marker in second-trimester risk assessment.
In a recent meta-analysis, the absence of markers conferred
a 7.7-fold reduction in risk of Down syndrome 109 (Table 31.3).
Most studies on genetic sonography were performed in the
time period prior to the use of irst-trimester risk assessment,
whether by combined screening or integrated screening. he
clinical utility of the genetic sonogram ater irst-trimester risk
assessment for Down syndrome is controversial. Rozenberg
et al. 170 performed a multicenter interventional study in an
unselected population to evaluate the performance of irsttrimester
combined screening followed by second-trimester
ultrasound. First-trimester combined screening identiied 80%
of fetuses with trisomy 21 at a screen-positive rate of 2.7%. Using
a thickened nuchal fold or the presence of a major anomaly on
a second-trimester ultrasound increased the detection rate to
90%, with a screen-positive rate of 4.2%.
Krantz et al. 171 performed a simulation study to assess genetic
sonography as a sequential screen for trisomy 21 ater irsttrimester
risk assessment. First-trimester combined screening
resulted in a detection rate of 88.5% with a 4.2% FPR. A follow-up
with genetic sonography using individual marker likelihood ratios
to modify the irst-trimester risk for screen-negative patients
detected an additional 6.1% of trisomy 21 cases for an additional
1.2% FPR, giving a total detection rate of 94.6% and a total FPR
of 5.4%. If a contingent protocol were adopted in which only
patients with a irst-trimester risk between 1 in 300 and 1 in
2500 were evaluated, the additional detection rate would be 4.8%
with FPR of 0.7%, giving a total detection rate of 93% and a total
FPR of 4.9%. hese authors concluded that second-trimester
genetic sonography, if used properly, can be an efective sequential
screen ater irst-trimester risk assessment.
he clinical utility of genetic sonography ater prior screening
for Down syndrome was studied on 7842 pregnancies, including
59 with Down syndrome, who participated in the FASTER trial. 164
At a set FPR of 5%, adding genetic sonography to the combined
screen or the integrated test increased the detection rate of Down
syndrome from 81% to 90% and 93% to 98% respectively. A
smaller increase in detection rate was noted for the stepwise or
contingent protocols, from 97% to 98% and 95% to 97%, respectively.
Other studies have suggested that genetic sonography ater
combined screening or sequential screening may decrease the