Ethical Issues in

Non-invasive Prenatal Testing

HERMAN KRISTANTO
Maternal Fetal Medicine Division
Department of Obstetrics & Gynecology
Faculty of Medicine – Diponegoro University
Prenatal testing consists of prenatal screening
and prenatal diagnosis, which are aspects
of prenatal care that focus on detecting problems
with the pregnancy as early as possible.
These may be anatomic and physiologic
problems with the health of the zygote, embryo
or fetus, either before gestation even starts (as
in preimplantation genetic diagnosis) or as early
in gestation as practicable.
Screening tests
• Prenatal screening tests can identify whether
the fetus is more or less likely to have certain
birth defects, many of which are genetic
disorders
• These tests include : blood tests, a specific
type of ultrasound and prenatal cell-free DNA
screening
• Usually offered during the first or second
trimester
• Can’t make a definitive diagnosis
Diagnostic tests
• If a screening test indicates a possible problem
consider an invasive prenatal diagnostic test
• A diagnostic test is the only way to be sure of a
diagnosis
• Some diagnostic tests, such as chorionic villus
sampling and amniocentesis, carry a slight risk
of miscarriage
Prenatal testing is one of the ethically most
problematic applications of genetics, at least
as far as it is aimed at conditions which, if
detected in the fetus, are incurable and thus
may lead to selective abortion.
In particular, prenatal diagnosis of genetic
traits typically can only provide information to
assist the prospective parents in their decision
making whether to carry the pregnancy to term
orto terminate it.
Common indications for
diagnostic prenatal testing :
• Abnormal genetic screening results
• Abnormal ultrasound findings
• Known parental carrier status
• Advanced maternal age
• Family history of genetic condition
• Fetal demise/stillbirth
• Parental anxiety
Current Practice of Prenatal Screening
Prenatal screening strategies
Risk-assessment test
• First trimester screening (FTS)
• Integrated prenatal screening (IPS)
• Quad screening (QS)

Ultrasound investigation
Non-invasive Prenatal Testing (NIPT)
• Non-invasive prenatal testing is a new type
of prenatal screening test for genetic and
chromosomal conditions

• It is typically performed by measuring cell-

free fetal DNA in maternal plasma, allowing
the examination of fetal genetic material in a
sample of maternal blood
NIPT promises the detection of a number of
genetic and chromosomal conditions in the
first trimester of pregnancy, obviating the risk
of miscarriage that accompanies invasive
prenatal diagnostic procedures such as
amniocentesis or chorionic villus sampling
Most of the current research and clinical
application focuses on the use of NIPT for the
detection of aneuploidy, in particular trisomies 13,
18 and 21

Clinical research has suggested a wide variety of

other potential uses for NIPT, with varying degrees
of evidence to support the clinical effectiveness of
these uses, meaning that in the future any genetic
condition might be identified by NIPT
5 possible applications of NIPT testing in
prenatal screening strategies :
1. as an additional test to improve overall risk assessment
2. as an intermediate test between risk assessment and
invasive diagnostic testing for high-risk pregnancies
3. As a replacement for current risk-assessment tests
4. as a replacement for current invasive diagnostic tests
5. as a replacement for both risk assessment and
diagnostic tests
As structural abnormalities per se are
not identified through NIPT, its possible
introduction would not affect current
ultrasound screening
• NIPT testing as a substitution for the present
combination of risk assessment and invasive
diagnostic testing seems generally to be
regarded as ultimately the most likely
scenario.
• If NIPT tests can easily, safely, reliably and
cheaply diagnose chromosomal abnormalities
in early pregnancy, this will entail abolishment
of the current two-step testing process.
The introduction of a test with these features
has ethically favourable consequences :
• Absence of iatrogenic miscarriage because of the test
• Earlier reassurance, a longer period for decision-making and
• The possibility of an early abortion, which may be physically
and psychologically less burdening and ethically less
problematic because of presumed lower moral fetal status
Ethical issues in NIPT
• Equity of access
• Informed consent
• NIPT normalization
• Trivilization of early selective abortion
• Changing the scope of prenatal testing
• NIPT for non-medical reason
Equity of Access
The ethical implications of recommending NIPT
when it is available only to patients who can
afford to pay are important for future policy
considerations in public health care systems.
When NIPT is available only to those who can
afford to pay, two types of inequity of access
may occur : inequity of access to the NIPT
technology itself, and, in some instances,
preferential access to related services
Patients who can afford to pay for NIPT can
access a better test and can also have access to
other related services at an earlier gestational age,
which typically means less risk (physical and
psychological) to the mother and less physical
risk to the fetus
Patients who cannot afford to pay for NIPT are
excluded not only from the test but also from
earlier access to other publicly funded services,
such as counselling and pregnancy termination.
Early access to publicly funded services after
private NIPT means that the health care system
implicitly enables different care between patients
on the basis of their economic privilege
Informed consent
Concern has been expressed that offering NIPT
on a wide scale would undermine informed
consent. If current two-step testing is substituted
by a single diagnostic test, it is supposed to be
more difficult to provide all pregnant women with
adequate information and pre-test counselling,
‘despite being conceptually easier’
NIPT Normalization
A further concern that has been raised is that the
introduction of NIPT as a risk-free procedure may
lead to ‘normalization’ of prenatal testing.
Normalization of the offer means that NIPD tests
will be portrayed by clinicians and experienced by
pregnant women as part of routine antenatal care,
because, due to its ease and safety, it seems to be
a rather trivial test to offer and take.
Trivialization of early selective abortion
More generalized use of non-invasive testing
could facilitate selective terminations of
pregnancy in a range of conditions hitherto
not diagnosed prenatally and where the
arguments for and against termination may
not have received sufficiently scrutiny
The lower moral status of the embryo and
the possibly less traumatic psychological
and emotional implications of early abortion
might influence and to some extent justify a
certain broadening of the scope of NIPT
Changing the Scope of Prenatal Testing
NIPT is feared to be applied for more and also
for increasingly minor abnormalities, without
adequate justification.

‘specification creep’
Although not feasible in the near future, a possible
future expansion of the scope of NIPT has been
brought up several times.
If it might indeed become possible to include a kind
of total genome sequencing in NIPT, the scope of
NIPT testing in the context of common prenatal
screening could exceed that of karyotyping.
Then its scope might not only include (mono)genetic
and/or congenital disorders, but also complex and
late-onset disorders.
This could lead to impair the decision-making
process. More intensive counselling would be
needed, which might be too time consuming
and expensive if offered on a wide scale.
Therefore, the requirement of extensive
informed consent for broad NIPT may be
really problematic to comply with
‘Information overload, Generic consent’
Unclear findings might lead to extensive
diagnostic follow-up and even to the
testing of parents to establish inheritance
of unusual results, which may confront
parents with unexpected findings about
themselves as well.
This leads to the question whether such
knowledge would be harmful or beneficial
for the parents and the future child.
Unclear findings regarding the fetus could lead to
confusion and unnecessary anxiety for parents,
which is likely to persist throughout the pregnancy
and into the postnatal period if the pregnancy is
continued. A decision to terminate a wanted
pregnancy on a basis of unclear testing results
may be associated with ‘particular feelings of guilt’
It has been asserted that prenatal screening
for 1000 genetic variations with 99.9%
accuracy for true positives at once may
lead to the consequence that ‘every fetus
will be identified as abnormal’, there by
undermining the aim of this screening.
The issue of the right not to know of the
future child might become a relevant issue in
case of testing for monogenetic late-onset
diseases and for increased susceptibility to
diseases.
Unsolicited knowledge of these traits would
be an invasion of the autonomy of future
children who have prenatally been diagnosed
Disclosure of findings about late-onset
diseases in the neonatal screening context
is considered to be incompatible with the
widely, but not universally, endorsed maxim
that predictive genetic testing should in
principle be avoided in minors to protect
their autonomy and privacy.
The only accepted exception is if medical
interventions are available to alter the
course of the disease.
NIPT For Non-Medical Reasons
NIPT for establishing sex or paternity, which is
currently commercially offered, and subsequent
selective abortion if the fetus is of the ‘wrong’
sex or from the ‘wrong’ biological father are
generally thought to be problematic
Role of The Obstetrician-Gynecologist
In addition to needing to ensure proper
consent, the obstetrician–gynecologist who
orders genetic tests should be aware of when
it is appropriate to test, which particular test
to order, and “what information the test can
provide, the limitations of the test, how to
interpret positive and negative results in light
of the patient’s medical or family history, and
the medical management options available”
ACOG Committees on Ethics and Genetics Recommendation
1. Clinicians should be able to identify patients
within their practices who are candidates for
genetic testing and should maintain
competence in the face of increasing genetic
knowledge
2. Obstetrician–gynecologists should
recognize that geneticists and genetic
counselors are an important part of the
health care team and should consult
with them and refer as needed
3. Discussions with patients about the importance
of genetic information for their kindred, as well
as a recommendation that information be
shared with potentially affected family members
as appropriate, should be a standard part of
genetic counseling
4. Obstetrician–gynecologists should be aware that
genetic information has the potential to lead to
discrimination in the workplace and to affect an
individual’s insurability adversely.
In addition to including this information in
counseling materials, physicians should
recognize that their obligation to professionalism
includes a mandate to prevent discrimination.
Steps that physicians can take to fulfill this
obligation could include, among others, advocacy
for legislation to ban genetic discrimination.
Thank You