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however, if an anomaly is detected, then it is likely to be confirmed postnatally
indicating a high positive predictive value (Kevern et al., 2003).
Limitations are imposed on technicians by fetal movement and the fact
that some fetal positions can obscure limb details. The experience of the
technicians may also affect low detection rates with more extensive
examinations by senior staff being reserved for pregnancies with a high risk
for abnormality (Kevern et al., 2003).
Cell-free fetal DNA (cffDNA) testing from the mother’s blood may be
used in prenatal screening for aneuploidy (abnormal number of chromosomes)
and genetically inherited diseases. It is usually offered after 10 weeks’
gestation and especially recommended for high-risk pregnancies. cffDNA
originates from the placental trophoblasts which expel DNA fragments into the
maternal blood. It is estimated that 2-6% of the DNA in the maternal blood is
fetal in origin (Lo et al., 1998). cffDNA is significantly smaller than the
maternal DNA in the bloodstream (approximately 200bp in size), which is the
basis for separating fetal DNA from maternal DNA in the plasma (Li et al.,
2004; Li et al., 2005).
Clinical genetic testing is increasingly becoming a standard practice for
patients with congenital abnormalities including unexplained developmental
delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and
multiple congenital anomalies (MCA) (Miller et al., 2010). Published
guidelines for testing such patients have emphasized (1) testing for
chromosomal abnormalities by G-banded karyotyping and (2) testing for
common single-gene disorders (Moeschler et al., 2006).
G-banded karyotyping allows a cytogeneticist to visualize and analyze
chromosomes for chromosomal rearrangements, including genomic gains and
losses. Molecular karyotyping, also known as a chromosomal microarray
(CMA), performs a similar function, but at a much higher resolution for
genomic imbalances. G-banded karyotyping has been the standard first-tier
test for detection of genetic imbalance for more than 35 years, whereas CMA
is not yet standard in all clinical settings (Miller et al., 2010).
Invasive Diagnostic Tools
Amniocentesis and chorionic villus sampling (CVS) are used to prenatally
rule out chromosomal abnormalities. These tests are usually done if there is a
family history of aneuploidy or if any of the screening tests gives a positive
result. During amniocentesis, a small amount of amniotic fluid, which contains