Diagnostic ultrasound ( PDFDrive )

CHAPTER 31 Chromosomal Abnormalities 1097
was performed on 425 euploid fetuses, and an abnormality was
identiied in 50 fetuses (12%). Of fetuses with a suspicious or
abnormal scan, 86% had an adverse outcome. A normal secondtrimester
ultrasound was reported on 375 (88%) of fetuses, and
96% of those were alive and well. Of fetuses with a thickened
NT in the irst trimester, normal karyotype, and normal secondtrimester
scan, 4% had an adverse outcome, which included
intrauterine demise, structural defects, and genetic syndromes.
he most frequently missed anomalies on ultrasound were cardiac
defects, underscoring the need for detailed fetal echocardiography
in fetuses with a thick NT.
Senat et al. 77 prospectively evaluated long-term outcome in
children with a normal karyotype and a NT at or greater than
99%. he study population consisted of 179 fetuses that underwent
midtrimester sonography as well as fetal echocardiography.
here were 17 fetal losses, including 10 malformations, 5
intrauterine demises, 1 miscarriage, and 1 termination. At 2
years of age, 89% (of 162 liveborns evaluated) of children had
no malformations and normal developmental testing. Eleven
percent of children had a structural abnormality noted ater
birth. Two children (1.2%) had neurologic delay. In one child,
the delay was isolated, and in the other it was associated with
an unidentiied syndrome. hese authors concluded that when
the karyotype is normal and the sonogram is normal with resolution
of the NT, the outcome is not adversely afected at 2
years of age. his was supported by Miltot et al. in a prospective
study of chromosomally normal fetuses with NT of at least
99% and normal ultrasound indings who were evaluated by an
Ages and Stages Questionnaire and found no increased risk of
developmental delay at 2 years of age when compared with a
control group. 78 Sotiriadis et al. in a review of the literature
concluded that there does not appear to be a higher risk of
developmental delay than the general population in chromosomally
normal fetuses with an increased NT, normal anatomy,
and no identiiable genetic syndromes. 79
he inding of a thickened NT should prompt a comprehensive
conversation concerning genetic associations by an experienced
provider. Advances in diagnostic testing include chromosomal
microarray analysis (CMA), which can detect chromosomal
abnormalities that are too small to be detected by standard
karyotype. he beneit of CMA in fetuses with a thickened NT
is controversial. Schou et al. did not detect any chromosomal
aberrations of clinical importance in 100 fetuses with an NT of
99th percentile or greater. 80 Similarly, Huang et al. did not ind
additional pathogenic CNVs in fetuses with an NT between 3
and 4 mm without other detectable abnormalities. 81 Leung et al.
reported that 8.3% of fetuses with an NT greater than 3.5 mm
and a normal karyotype had a pathologic submicroscopic
chromosomal abnormality. In those fetuses with additional
sonographic indings, pathogenic CNVs were identiied in 20%
compared with 5.3% in those without additional sonographic
indings. 82 In a prospective series of patients with an NT of at
least 3.5 mm and normal quantitative luorescence–polymerase
chain reaction for aneuploidy, CMA identiied pathogenic CNVs
in 12.8% of fetuses and variants of uncertain signiicance in 3.2
%. 83 In a recent meta-analysis, Grande et al. reported that genomic
microarray provides incremental yield in 5% of fetuses with an
increased NT and normal karyotype. he pooled prevalence of
variants of uncertain signiicance was 1%. 84 A thickened NT has
been associated with myriad genetic disorders, the most common
being Noonan syndrome. 9,15,85
SECOND-TRIMESTER SCREENING
FOR TRISOMY 21
Although irst-trimester risk assessment allows a patient the
beneit of time in using the information to make decisions
regarding pregnancy, not all women present for prenatal care
early enough in gestation to take advantage of this beneit.
Ultrasound is an integral part of risk assessment for aneuploidy
in the second trimester. 86-94 Approximately 25% of fetuses with
trisomy 21 have a major congenital anomaly, such as cardiac
defect or duodenal atresia 90,91 (Fig. 31.7). he cornerstone to
identifying fetuses with trisomy 21 has been the recognition of
sonographic “markers,” which are variations in anatomy that
are usually associated with normal outcome but carry a statistically
increased risk of aneuploidy. Some of these markers are wellknown
physical entities such as the thickened nuchal fold and
the small nasal bone. 12 Others are indings speciic to prenatal
sonography, such as an echogenic intracardiac focus, urinary
tract dilation, slightly short femoral and humeral length, and
echogenic bowel. he identiication of a marker should prompt
a comprehensive fetal sonographic examination to look for other
markers and structural abnormalities. he presence or absence
of a marker and the associated clinical signiicance must be
interpreted in the setting of the patient’s a priori risk for aneuploidy
(Figs. 31.8-31.10 and Tables 31.1-31.3).
Nuchal Fold
Early studies showed that the presence of a thickened nuchal fold
identiied 40% of fetuses with trisomy 21 with FPR of 0.1%. 95-98
his measurement is obtained using an axial view through the
TABLE 31.1 Likelihood Ratios (LRs) of
Isolated Markers for Trisomy 21
Marker LR 90 LR 91 LR 94 LR 109a
Nuchal fold 11.0 — 17 3.79
Short humerus 5.1 5.8 7.5 .78
Short femur 1.5 1.2 2.7 .61
Echogenic bowel 6.7 — 6.1 1.65
Echogenic intracardiac focus 1.8 1.4 2.8 .95
Urinary tract dilation 1.5 1.5 1.9 1.08
Ventriculomegaly — — — 3.81
Absent or hypoplastic nasal — — — 6.58
bone
Aberrant right subclavian — — — 3.94
artery
Structural anomaly — 3.3 — —
a Derived by multiplying positive LR for the given marker by the
negative LR for each of the other markers excluding short humerus
but including absent or hypoplastic nasal bone, mild ventriculomegaly,
and aberrant right subclavian artery.