Congenital malformations - Edocr

32 PART I GENERAL CONSIDERATIONS
screen is incorporated with the information provided
by the second trimester screen to calculate
one overall risk for Down syndrome. The
integrated screen is reported to have a 96% detection
rate for Down syndrome with a 5% false
positive rate. 8 If a patient, however, has a significantly
increased risk based on the first trimester
combined screen or observance of an increased
nuchal translucency, she should be offered the
option of chorionic villus sampling, instead of
waiting for an amniocentesis in the second
trimester. Studies have now shown that even
with normal chromosome analysis, if a fetus has
an increased nuchal translucency measurement
of 3.5 mm in the first trimester, there is a significant
increased risk for other congenital anomalies,
such as cardiovascular defects, other single
gene disorders such as Noonan syndrome,
Smith-Lemli-Opitz syndrome, spinal muscular
atrophy, and poor pregnancy outcome. 9 The
risk increases exponentially with measurements
above 3.5 mm. The majority of anomalies associated
with an increased nuchal translucency
can be detected by a fetal echocardiogram and
detailed fetal ultrasound at 18–22 weeks gestation.
If these screens are normal and a chromosome
abnormality has been excluded, the risk
for adverse outcome or developmental delay is
not significantly increased. 9 However, a newborn
infant with a history of an increased nuchal
translucency in pregnancy should have a careful
assessment for other possible single gene
disorders.
Methods of Prenatal Diagnosis
Amniocentesis and chorionic villus sampling
(CVS) are two methods of prenatal diagnosis
that are being routinely offered to couples. Both
methods can be used to detect chromosome abnormalities
and single gene disorders with equal
sensitivity and accuracy of results (>99%). Chromosome
analysis (Figs. 3-8 and 3-9) is generally
performed on cultured amniocytes or villi with
a 1.5–2 week turnaround time for results. In
the majority of laboratories, fluorescence in
situ hybridization (FISH) studies are performed
on direct cells for a quick analysis of common
aneuploidy disorders: trisomy 21, trisomy 18,
trisomy 13, and sex chromosome conditions. The
FISH results are typically available in 2–3 days.
Amniocentesis has been available since the
1970s for the detection of chromosome abnormalities.
Traditionally, ultrasound-guided amniocentesis
(Fig. 3-10) is performed after 15 weeks
gestation and the risk of fetal loss is 0.5–1.0%.
Various centers may quote a risk specific to their
center’s experience, but the national reported
loss rate as recommended by the Centers for Disease
Control and Prevention is 0.5%. In addition
to the standard chromosome analysis or testing
for single gene disorders, a-fetoprotein can be
measured in the amniotic fluid between 15 and
22 weeks gestation to assess risk for ONTDs.
This cannot be measured in CVS tissue.
Early amniocentesis is performed between
13 and 15 weeks gestation but associated with
a higher risk of fetal loss and leakage of amniotic
fluid. A significant increased risk for talipes
equinovarus (club foot) has also been observed
with early amniocentesis, especially if leakage
of amniotic fluid is present. Given these findings,
the American College of Obstetricians and
Gynecologists does not recommend early amniocentesis
as a method of prenatal diagnosis.
Chorionic villus sampling (Fig. 3-11) has been
readily available since the mid 1980s as a method
of detecting chromosome abnormalities and single
gene disorders in the fetus. The majority of
cases are performed transcervically with the use
of ultrasound guidance and a catheter between
10 and 12 weeks gestation. If the placental villi
cannot be obtained transcervically, a transabdominal
CVS can be performed using a needle.
The WHO-sponsored registry 10 monitoring the
safety of CVS reported a fetal loss rate similar
to that observed in early amniocentesis. Controversy
remains regarding the risk of CVSassociated
fetal anomalies such as limb reduction
defects. In the 1990s, several centers reported
a clustering of limb reduction defects in infants