CELL-FREE

FETAL DNA
TESTING

BULAN | MACADAEG | VISPO

12 - EINSTEIN
GROUP 7

FEBRUARY 20, 2019

IIN
NTTRRO
ODDU
UCCTTIIO
ONN
Prenatal screening for
chromosomal aneuploidies was initiated
in the 1970s, based in maternal age. Non-
invasive prenatal testing (NIPT) is a new
innovative form of genetic screening
allowing for early detection of the most
common fetal aneuploidies in at-risk
pregnant women. It is based on analysis of
cell-free DNA (cfDNA) in maternal blood.
The majority of cfDNA in maternal blood
originates from the mother herself, with
the fetal component (cffDNA)
contributing approximately 10–20% of
the total.
The cell-free DNA is a genetic
material that is released by the
placenta and circulates in a
women’s blood during
pregnancy. CfDNA generally
reflects the genetic makeup of
the developing baby. It is
present in a pregnant woman's
blood in small quantities starting
in the first trimester and increases
throughout pregnancy.
The test can identify
chromosome disorders in a developing
baby, including the presence of extra
chromosomes (trisomies) such as Down
syndrome (trisomy 21), Edwards
syndrome (trisomy 18), and Patau
syndrome (trisomy 13).
To reduce the need for invasive testing
such as chorionic villus sampling or
amniocentesis.
The extra chromosomes affects the
development of the baby and causes
characteristic signs, symptoms, and
complications. This screening or testing can
also provide information about fetal sex and
rhesus (Rh) blood type.
Healthcare providers now have the
option of prescribing non-invasive cell-free
fetal DNA tests that rapidly screen cell-free
fetal and maternal DNA and detect
anomalies. In many cases, these allow
patients to avoid invasive sampling, leading
to improved maternal and child health
outcomes.
Prescribing an NIPT for the prenatal
screening of birth defects offers reliable
initial risk assessment for common
abnormalities. With detection rates
exceeding 99%, cell-free fetal DNA
screening is generally recommended for
mothers over the age of 38 with risks
greater than 1 in 1,000 according to serum
markers.
There are other uses for analysis of
cffDNA already in NHS clinical care,
including determining fetal RhD status in
RhD negative mothers, fetal sex
determination for sex-linked single-gene
disorders, and diagnosis of single-gene
disorders such as cystic fibrosis.
PPUURRPPO
OSSEE
Early detection of extra genetic material
present that can affect the development
of the baby.
1
 CCOONNCCEEPPTT
DDEESSCCRRIIPPTTIIO
ONN
Invasive Testing - Any type of
medical test that requires physicians
to use instrumentation to physically
enter the body.
Non-invasive Testing - It is when no
break in the skin is created and there
is no contact with the mucosa, or skin
break, or internal body cavity beyond
a natural or artificial body orifice.
Down Syndrome (Trisomy 21) - a
genetic disorder caused by the
presence of all or part of a third copy
of chromosome 21.
Edwards Syndrome (Trisomy 18) -
instead of the normal pair, an extra
chromosome 18 results (a triple) in
the developing baby.
Patau Syndrome (Trisomy 13) - a type
of chromosome
disorder characterized by having 3
copies of chromosome 13 in cells of
the body, instead of the usual 2
copies.
Klinefelter syndrome - also known as
47,XXY or XXY, is the set of
symptoms that result from two or
more X chromosomes in males.
M
MEETTH
HOODDO
OLLO
OGGYY
G
GOOA
ALLSS AAN NDD
O
OBBJ
JEECCTTIIVVEESS
To identify if a woman has a
higher chance of having a
fetus with Down syndrome
(trisomy 21), trisomy 18,
trisomy 13 or an abnormality
in the sex chromosomes (X
and Y chromosomes).
To help women who have
certain risk factors make
decisions about invasive
testing that carries a
slight risk of miscarriage,
including amniocentesis
and chorionic villus
sampling (CVS).
To provide important
and accurate
information regarding
the state of a pregnancy
and the possible future
outcomes of that
pregnancy.
2
 During prenatal cell-free DNA screening, a
maternal blood sample is taken and sent to a lab. The
lab analyzes the maternal and fetal DNA in the blood
sample. A higher than expected ratio of chromosome
21 sequences indicates, for example, the likely
presence of trisomy 21 in the fetus. Trisomy 21 is the
most common cause of Down syndrome.
Typically, test results are available within two
weeks.
B
BEEN
NEEFFIITTSS//A
ANNTTIICCIIPPA
ATTEEDD
OOUUTTCCOOMMEE
Maternal serum screening has been used as a
traditional practice to identify women that are at
risk of having a fetus acquiring chromosomal
abnormalities. This process, however, has a
limitation to it. Screening has a reasonable
sensitivity; it identifies 80%-90% of affected
pregnancies but its specificity is very low – only 5%
of those screened as positive actually have a fetus
affected with an aneuploidy. This leaves a woman in
the high risk group with 2 choices:  to have an
invasive prenatal diagnosis or to take a chance. As a
result, there is anxiety among the pregnant women.
Invasive diagnostic procedure could sometimes
induce miscarriage and in worst and unusual cases,
prenatal death. Taking a chance, however, leaves
the baby with a possibility of having abnormalities.
With the advancements in technology, it has
become possible to deliver highly accurate single-
molecule counting and thereby detect small
changes in the number of sequences on the
chromosome of interest in blood. This approach
forms the basis of non-invasive prenatal testing
Laboratory Methods
·   Massively parallel shotgun
sequencing (MPSS) - Method used for
sequencing long DNA strands
·  Single nucleotide polymorphism (SNP)
based approach - is a variation in a
single nucleotide that occurs at a
specific position in the genome, where
each variation is present to some
appreciable degree within a population
(NIPT) for aneuploidy, a maternal blood test to
complement existing methods, which can be
performed in early pregnancy to significantly
refine the risks of abnormalities. Cell-free fetal
DNA testing is used in NIPT, which makes it very
accurate, identifying 99% of affected pregnancies
with a specificity of more than 99%. This adds
another possibility to the two subsequent choices
a woman has – to make a decision based on the
NIPT results. This significantly reduces the need
for unnecessary invasive diagnostic procedures
such as chorionic villus sampling (CVS) or
amniocentesis among pregnant women compared
with traditional screening tests.
The introduction of NIPT has become a major
progression in the world of medicine and has been a
“sea” change in the evolution of prenatal screening.
NIPT is going to fundamentally change the way
pregnancies are dealt with. Anxiety will be
dramatically reduced among the huge majority of
women, babies will have a better health quality, and
the use of money from health care systems will be
minimized.
3
 SSU
UPPPPO
ORRTT
Last January 17, 2018, the Philippine
Society of  Maternal Fetal Medicine
(PSMFM), in cooperation with Natera,
had its first workshop on an
advancement in prenatal screening,
called the Non- Invasive Prenatal Testing
(NIPT).
The Philippine Society of Maternal
Fetal Medicine offers different brands of
Non-Invasive Prenatal Testing such as
Panorama®, a market-leading
noninvasive prenatal screening test
(NIPT) that reveals your baby’s risk for
genetic disorders as early as nine weeks.
Panorama analyzes baby's (placental)
DNA through a simple blood draw from
the mother’s arm; Prévue™, which is the
most validated NIPT test that screens for
the most common chromosomal
abnormalities such as Down syndrome.
The test is done through a simple blood
draw as early as 10 weeks into your
pregnancy; and NICE®, screens for the
most common chromosomal
abnormalities that can affect your
developing baby's future from a simple
blood draw as early as 10 weeks into
your pregnancy. This test is done with
little or no risk to your pregnancy.
CCO
ONNTTA
ACCTT U
Address: Phone:
#56 Malakas Street, 632-9285304
Diliman, Quezon City,
Metro Manila, Philippines
PSMFM VISION STATEMENT
The PSMFM will be the internationally
acknowledged leader, innovator and
authority in the development and security of
maternal, fetal and neonatal health in the
Philippines through competent and ethical
high-risk pregnancy care, research, advocacy
and education.”
PSMFM MISSION STATEMENT
Nurtures maternal, fetal and neonatal
welfare;
Maintains liaison and promotes co-operation
and goodwill within its members and with
other medical and allied medical
organizations;
Provides guidance to governmental and
other bodies pertaining to issues in maternal
and fetal medicine;
Advocates and maintains competent, ethical
and resource-appropriate practice of
maternal and fetal medicine in the
Philippines;
Maintains excellence in training and
promotes continuing medical education in
maternal and fetal medicine;
Advances and supports research in maternal
and fetal medicine.
USS
Email:
admin@info.psmfm.ph
4
REFERENCES
Mayo Staff Clinic. (2018). Prenatal cell- free DNA screening.
Retrieved from https://www.mayoclinic.org/tests-
procedures/noninvasive-prenatal-testing/about/pac-20384574

UCSF Health. (2018). Cell-free DNA screening. Retrieved from

https://www.ucsfhealth.org/education/cell-free_dna_screening/

Macedonia et al. (2016). Cell-free DNA. Retrieved from

http://jlgh.org/JLGH/media/Journal-LGH-Media-
Library/Past%20Issues/Volume%2011%20-%20Issue%202/Cell-Free-
DNA.pdf

AACC. (2019). Cell-Free Fetal DNA Testing for Fetal C

hromosomal Abnormalities. Retrieved from
https://labtestsonline.org/tests/cell-free-fetal-dna

Pract et al. (2009). Cell-free fetal DNA and non-invasive prenatal

diagnosis. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673181/

Rafi et al. (2017). Non-invasive prenatal testing: use of cell-free fetal

DNA in Down syndrome screening. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565870/