FM AUGUST 2018 ISSUE1 - digital edition

primary care physicians to prevent the
birth of an affected child.
Conventional tests, including screening
and diagnostic techniques, are typically
used to identify foetuses with Down
syndrome. Screening tests, usually
based on serum biochemical tests and
ultrasound scans, are non-invasive
and cheaper. However, they are less
accurate, have low detection rate and
high false positive rate. Diagnostic
tests, which encompass chorionic villus
sampling (CVS)/amniocentesis followed
by karyotyping, are highly accurate
with high detection rate and low false
positive rate. However, these diagnostic
tests are invasive and expensive.
Noninvasive Prenatal
Test (NIPT)
NIPT, which comprises the combined
features of both screening and
diagnostic tests, has emerged, based
on the discovery of the cell-free foetal
DNA (cff-DNA) present in maternal
blood. cff-DNA is released as small
DNA fragments (150–200 bp) into the
maternal blood through the apoptosis
of cytotrophoblastic cells of placenta.
Maternal blood consists of a mixture of
both maternal and foetal cff-DNA, and
foetal DNA accounts for only 5–10% of
it. Foetal DNA, which is usually detected
after 7 weeks of gestation, is not
detectable within hours after the birth.
As a result, NIPT test is considerably
effective from early to late pregnancy.
Moreover, the DNA fragment present
in the maternal blood is indicative of
existing pregnancy only. NIPT, that
involves cff-DNA analysis, a non-invasive
option, is currently available for women
at increased risk of foetal aneuploidy
to evade the risk of spontaneous
abortion associated with the invasive
tests. As per the American College of
Obstetricians and Gynecologists (ACOG)
recommendations, either screening
or invasive prenatal diagnosis can
be offered to women, irrespective of
their maternal age, for the prenatal
assessment for aneuploidy. Moreover,
any woman may choose cff DNA
analysis as a screening strategy for
common aneuploidies irrespective of her
risk status. However, the patient who
opts for this test should understand the
benefits and limitations of the test in the
NIPT is associated
with a considerable
improvement as
compared with the
conventional testing,
and provides a detection
rate of over 99% and a
false positive rate of less
than 0.1%.
context of the availability of alternative
screening and diagnostic options. In
India, NIPT was introduced in 2013.
However, it is still not well recognized in
clinical practice.
NIPT is associated with a considerable
improvement as compared with the
conventional testing, and provides a
detection rate of over 99% and a false
positive rate of less than 0.1%. Moreover,
wherever NIPT has been implemented
in clinical setups, it is associated with
a significant reduction (50–70%) of
invasive procedures.
Although the cost of NIPT is slightly
more than amniocentesis and is
significantly more expensive than
biochemical and ultrasound screening,
using NIPT as a second level test would
reduce the use of invasive procedures
and the risk of test-related miscarriage
by 72% and 66% respectively.
A study by Verma IC et al 2018 assessed
the performance of single nucleotide
polymorphism-based NIPT among 516
pregnant women with intermediateto-high
risk on conventional first
and second trimester screening for
trisomies 21, 18, 13; sex chromosome
abnormalities and triploidy. The results
were confirmed by invasive test or
clinical assessment following the birth.
Amongst 511 samples analysed, results
were obtained from 499. Among these,
480 were at low risk and 19 at high risk.
A sensitivity of 100% was obtained for
detection of trisomies 21, 18, 13 and
sex chromosomal abnormalities, and
specificity ranged from 99.3 to 100% for
the anomalies studied.
The good outcome associated with
NIPT as demonstrated in the study by
Verma IC et al 2018 is in line with the
overall performance of NIPT. Moreover,
the positive predictive values (PPV)
ranged from 80–85.7% as observed in
this study, and is considerably greater
than the conventional tests. A vast
number of women (96.6%), who were
at intermediate-to-high risk based on
conventional screening, were found
to be at low risk on NIPT, and invasive
procedures were avoided in these women
for the confirmation of aneuploidies.
Again the high negative predictive value
is a reassurance to pregnant women
with important benefits. Moreover, the
advantages of SNP based technology
used to analyse cff DNA include the ability
to work without reference chromosome,
the ability to detect a vanishing twin,
triploidy, maternal mosaicism as well as
increased accuracy.
Indian Council of Medical Research
endorses genetic screening to all
pregnant women under the National
Family Welfare Programme. With its
good performance among the Indian
women population, NIPT would be a
useful add-on diagnostic tool to the
prenatal screening programme when
available at a low cost. NIPT can be used
in women with high-risk for aneuploidies
on conventional screening to evade
invasive tests that are not required. To
conclude, the reduction in cost of NIPT
and increased awareness among patients
and physicians would enable the Indian
population to achieve greater benefit
from this emerging technology
AUGUST 2018/ FUTURE MEDICINE / 39