C h a p t e r 6
Genetic and Congenital Disorders
125
implantation in the uterine wall. It increases rapidly
in the first 8 weeks of gestation, declines steadily until
20 weeks, and then plateaus. The single maternal serum
marker that yields the highest detection rate for Down
syndrome is an elevated level of hCG.
Unconjugated estriol is produced by the placenta
from precursors provided by the fetal adrenal glands
and liver. It increases steadily throughout pregnancy to
a higher level than that normally produced by the liver.
Unconjugated estriol levels are decreased in Down syn-
drome and trisomy 18.
Other maternal serum markers include pregnancy-
associated plasma protein A (PAPP-A) and inhibin A.
62
PAPP-A, which is secreted by the placenta, has been
shown to play an important role in promoting cell dif-
ferentiation and proliferation in various body systems.
In complicated pregnancies, the PAPP-A concentration
increases with gestational age until term. Decreased
PAPP-A levels in the first trimester (between 10 to 13
weeks) have been shown to be associated with Down
syndrome. When used along with maternal age, free
β
-hCG, and ultrasound measurement of nuchal trans-
lucency, serum PAPP-A levels can reportedly detect
85% to 95% of affected pregnancies with a false-
positive rate of approximately 5%.
62
Inhibin A, which
is secreted by the corpus luteum and fetoplacental
unit, is also a maternal serum marker for fetal Down
syndrome.
63
Non-Invasive Prenatal Testing (NIPT)
Circulating cell free DNA (cf-DNA) fragments are
short fragments of DNA found in the blood. During
pregnancy, there are cf-DNA fragments from both the
mother and fetus in maternal circulation. It is pos-
sible to analyze cf-DNA from the maternal blood to
detect common fetal trisomies such as Down syndrome
as early as 10 weeks. Non-invasive prenatal testing
using cf-DNA offers tremendous potential as a screen-
ing tool due to its increased accuracy over maternal
serum markers and the nuchal translucency tests.
64
The
recent and rapid adoption of non-invasive prenatal
screening in high-risk pregnancies in the United States
suggests that NIPT may change the standard of care for
genetic screening (ACOG 2013).
11
Ultrasonography
transducer
Fetoscope
Cordocentesis
Transcervical
chorionic villus sampling
Catheter
Vagina
Cervix Rectum
Umbilical cord
Chorion frondosum
Amniotic cavity
Transabdominal
amniocentesis
Syringe for collecting
chorionic villus sample
FIGURE 6-15.
Methods of prenatal screening.
