Diagnostic ultrasound ( PDFDrive )

CHAPTER 31 Chromosomal Abnormalities 1089
10
Trisomy 13
Trisomy 18
Trisomy 21
1.0
Risk (%)
0.1
Turner
Triploidy
0.01
20 25 30 35 40 45
Maternal age (yr)
FIG. 31.1 Maternal Age–Related Risk for Chromosomal Abnormalities.
5000 and 1 in 10,000, respectively. 8 he frequency of aneuploidy
is higher earlier in gestation because of the fetal loss rate associated
with chromosomal abnormalities as gestation progresses. Fetal
death with trisomy 21 between the irst or second trimester and
birth is 30% and 20%, respectively. Fetal death between the irst
trimester and birth with trisomies 18 and 13 is approximately
80%. 6,9
FIRST-TRIMESTER SCREENING
FOR ANEUPLOIDY
First-trimester screening for aneuploidy that incorporates
ultrasound provides a patient-speciic numeric risk estimate of
trisomy 21, 18 and 13. It may also be a clue for other chromosomal
conditions. 10 Most pregnancies are normal, so most women can
be reassured early in gestation that their risk of aneuploidy is
low. Others may ind that the risk estimate is high enough that
to undergo a secondary screening with cell-free DNA or
diagnostic testing (chorionic villous sampling) to obtain a
karyotype or microarray analysis. If the results are abnormal,
the patient has time to obtain additional information and explore
resources that are available before making a decision about
continuing or terminating a pregnancy. he decision to terminate
can be made with privacy and at a time in pregnancy when safe
methods of pregnancy interruption are available. 11
Nuchal Translucency and Trisomy 21
In 1866, Dr. Langdon Down reported a classiication of individuals
with developmental delay who had similar physical characteristics.
He described the skin as “deicient in elasticity, giving the appearance
of being too large of the body.” 12 Fetuses with trisomy 21
as well as other aneuploidies oten have excess luid in the
subcutaneous tissue behind the fetal neck (Fig. 31.2A, Video
31.1). Sonographically, this appears as an echolucent luid
collection between the sot tissue over the cervical spine and an
echogenic line representing the skin edge. his luid space is
called the nuchal translucency (NT) 13 (Fig. 31.2B). he lucency
is thought to represent mesenchymal edema and is oten associated
with distended jugular lymphatics (Fig. 31. 2C). he prevailing
theory suggests an alteration in lymphangiogenesis and delayed
lymphatic development. Other possible causes include cardiac
failure and abnormal extracellular matrix, but these do not explain
the localized and transient nature of the NT. Most likely, the
cause is a complex interaction of factors. 14 NT normally increases
with advancing gestational age, and therefore the measurement
is compared to crown-rump length (CRL, Fig. 31.2D). An NT
greater than 95% for CRL is considered thickened. An NT greater
than 99% does not change signiicantly with CRL and is approximately
3.5 mm 15 (Fig. 31.2E).
In 1992, Nicolaides et al. 13 reported that an NT of 3 mm or
greater in the irst trimester was associated with a 35% risk of
chromosomal abnormality. he association between chromosome
anomalies and a thickened NT was subsequently conirmed in
a large, prospective multicenter trial of 20,804 pregnancies. he
risk of trisomy 21 can be calculated by multiplying the a priori
(presumptive) risk by a likelihood ratio derived from the degree
of deviation in NT from the expected NT. his methodology, in
conjunction with a risk cutof of 1 in 300, resulted in the identiication
of 80% of fetuses with trisomy 21, with a false-positive rate
(FPR) of 5%. 16 Snijders et al. 17 evaluated the use of NT and
maternal age to detect trisomy 21 in a multicenter trial that
included 22 diferent sites and 306 trained sonographers. Using
a threshold of 1 in 300, the sensitivity for the detection of trisomy
21 was 82% for an FPR of 8%. If the FPR was set at 5%, the
sensitivity for the detection of trisomy 21 was 77%.
Serum Biochemical Markers
A variety of serum biochemical markers have diferent concentrations
in pregnancies with trisomy 21 compared with euploid