Australian Doctor Australian Doctor 17th November 2017 | Page 25

Therapy Update
Prenatal testing
REPRODUCTIVE HEALTH
Non-invasive screening has marked a revolution in
detecting chromosomal abnormalities in a fetus.
DR TERRI FORAN
H
UMAN repro-
duction is an
extremely com-
plex
process
and genetic mishaps are not
uncommon.
Prior to fertilisation,
20-24% of all ova have an
abnormal number of chro-
mosomes, or aneuploidy. 1, 2
Another 30% of embryos
become aneuploid after fer-
tilisation. 2 Most of these
early mutations will end in
spontaneous
miscarriage,
but prenatal testing aims to
provide early detection of
aneuploidy should the preg-
nancy continue.
It will often be the GP
who is called upon to advise
on the advantages, limita-
tions and consequences of
such testing.
When did prenatal
testing start?
The British physician Dr
John Langdon Down was

the first to describe Down
syndrome (trisomy 21) in
1866. It is the most common
chromosomal abnormality
in humans. By the 1930s
an association was made
between Down syndrome
and increasing maternal age
(see table 1).
In 1984, a group of
researchers
noted
that
maternal serum alpha-feto-
protein (MSAFP) was signif-
icantly lower in the second
trimester in women carrying
a fetus with trisomy 18 or
trisomy 21, compared with
their peers with a normal
pregnancy. 6
An algorithm was devel-
oped that combined MSAFP
levels with maternal age and
was introduced in many
parts of the world as a use-
ful prenatal screening test
for aneuploidy.
It was subsequently found
that levels of other maternal
serum metabolites (B-HCG,
unconjugated oestriol and
inhibin) were similarly
altered in mothers carry-
ing a child with a chromo-
somal abnormality. The
incorporation of these other
metabolites into maternal
screening in the late-1980s
tion rate of 75% for Down
syndrome, with a false posi-
tive rate of about 5%. 8
First trimester screening
The search continued for a
reliable screening test that
could be applied earlier in
IT IS IMPORTANT TO DISCUSS WHAT
DECISIONS MIGHT BE MADE IF THE
RESULT IS ABNORMAL.
was the basis of what is
now called the ‘triple test’
or ‘quadruple test’. 7,8 Using
a combination of these val-
ues and maternal age, it was
possible to achieve a detec-
pregnancy. Earlier screening
had the advantage of pro-
viding more time to arrange
confirmatory testing and a
safer termination of preg-
nancy if that was what the
www.australiandoctor.com.au
parent/s chose to do. Cho-
rionic villus sampling in
the first trimester had been
available since the 1980s,
but the rate of pregnancy
loss made it an unacceptable
initial test, except in those
with a history of previous
chromosomal abnormality.
By
the
early-1990s,
researchers had identified
several more metabolic
indicators of not only tri-
somy 18, but also trisomy
21, which appeared to be
altered in the first trimes-
ter of pregnancy. The most
promising were free B-HCG
and pregnancy-associated
plasma protein A (PAPP-A).
Although its detection rate
was up to 78% for Down
syndrome, this combined
test was significantly less
effective at detecting other
chromosomal
abnormali-
ties. 9 This limited its useful-
ness as a stand-alone test.
At about the same time,
other
researchers
were
investigating the hypoth-
esis that increased nuchal
thickness on first trimester
ultrasound might be a use-
ful non-invasive indicator of
aneuploidy in the fetus.
In 1998, a large study
established the parameters
that indicated increased risk
(for example, nuchal trans-
lucency 3mm or more at a
gestational age of 10-14
weeks). 10 Such a scan, com-
bined with maternal age,
detected about 78% of tri-
somies 13, 18 and 21.
The real breakthrough
came in 1999 when nuchal
translucency screening and
first-trimester serum screen-
ing were combined in a
single testing algorithm. 11
Combining maternal age,
nuchal translucency, HCG
and PAPP-A gave a detec-
tion rate for trisomy 21
of somewhere between
cont’d next page
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