Key words
NIPT - prenatal diagnosis - counselling - trisomy 13 - abortion
Schlüsselwörter
NIPT - Pränataldiagnostik - Beratung - Trisomie 13 - Spätabbruch
Introduction
Non-invasive prenatal testing (NIPT) of cell-free fetal DNA has been entering and
transforming prenatal care rapidly during the last three years, which led to a number
of position statements in relation to practical standards for NIPT services from professional
organisations [1], [2], [3], [4]. At the moment, NIPT is recommended for high-risk pregnancies only, but recent studies
tend to confirm good results also in low-risk populations, at least for trisomy 21
[5]. NIPT-related research in large part focuses on the testing methods, their accuracy,
validity and implementation in general. However, studies and case reports with the
aim to discover potential pitfalls for NIPT services regarding individual decision
making and counselling in daily practice are still underrepresented. The existing
studies are often hard to compare due to highly variable implementation processes
and differing national regulative frameworks for prenatal testing [6].
While, for example, the UK or the Netherlands proactively have established national
boards and research programs [7], [8] in order to shape and monitor the implementation of the emerging technology, no
such action has been taken in the majority of countries – among them Germany, where
the first provider entered the market in 2012. This is particularly noteworthy, since
NIPT has been defined as a genetic examination in accordance with the German Genetic
Diagnostics Act (GenDG), which means among other things that a special training in
genetic counselling issues is required from the offering gynecologists. The qualitative
and quantitative specifications of this training are still a matter of inter- and
intraprofessional debate and in the meantime NIPT is being offered also by non-specialists.
It is reasonable to assume that many gynecologists yet are not sufficiently prepared
for offering NIPT to pregnant women. Apart from other NIPT-related aspects like the
validity of the test, this is a serious problem for the implementation process in
almost all countries. Studies from several countries are indicating that there are
substantial educational gaps with regard to the limitations of NIPT also among maternal-fetal
medicine (MFM) specialists [9], and these gaps are likely to be even more significant
among non MFMs. The following case may show this assumption in an unsettling clarity.
Case
B., a 36-year-old healthy woman (with an 11-year-old child) got pregnant in a new
partnership. Her gynecologist – she knew him as being generally reluctant to do prenatal
diagnosis beyond basic ultrasound (as a part of standard maternal care) – at her second
visit during pregnancy (8th week of gestation) advised her not to do any further testing.
Everything would go well with the baby and the maternal age would not be that important
until she would be 37 years old. B., however, who had already heard about the new
blood test from friends and through the media, together with her 52-year old partner
decided to undergo NIPT. In Germany, NIPT is not generally covered by statutory health
insurances yet (expected soon to be covered), so they would have to pay for it by
themselves. She received no further counselling related to NIPT from her gynecologist,
but he agreed to take the blood sample in the 11th week of pregnancy and to send it
to an US provider, although he did not support this idea from his professional point
of view and had no experience with the test procedure, too. When she came for her
third visit in the 11th week, he had forgotten to arrange everything for the test,
so that she had to wait another week and then came back. When the blood sample was
taken, she was in the 12th week of pregnancy. A long time of waiting followed: after
two weeks, when results should have been available at the latest, B. asked for results,
but was told by the doctorʼs receptionist that they had received nothing so far and
that she had to wait longer. During the following days and weeks B. repeated her inquiries,
but still got no information about any results. In the 18th week of gestation, the
physician finally called her to let her know that the blood sample obviously had been
lost in the US (according to his account). He advised her to check the bank account
in order to see if any costs for the test had been debited (which had not).
She then, together with her partner and again without any further counselling, opted
for a special ultrasound scan for fetal anomalies in her 20th week of gestation and
thus arranged an appointment with a prenatal diagnostics specialist by herself. At
her next regular visit in the 19th week, her gynecologist suspected a cardiac anomaly
of the fetus during ultrasound scan. With regard to the consequences of this finding
he told B., who wanted to have a home birth, that she should not worry – birth just
would have to take place in a hospital now. At that time he recommended to see a specialist
for prenatal ultrasound in order to further evaluate his findings.
The special ultrasound scan revealed multiple and severe malformations of the fetus
in e.g. the heart, brain and face. Immediately, a chorionic villus sampling and an
amniocentesis had been performed and both confirmed the result of a trisomy 13 in
the fetus. Now B. was in her 20th week – a medical induction of labour was her only
option at this point if she wanted to terminate pregnancy. The sudden shock of the
result without any warning signs before, together with the following late termination
of pregnancy inevitably caused a trauma.
Discussion
Several insufficiencies in the medical and counselling process are obvious in this
case. For a deeper understanding we focus on two levels: individual failure as well
as the structural, regulative setting. On the individual level this case illustrates
impressively how influential personal attitudes and knowledge of clinicians in prenatal
testing are. Apart from NIPT, physicians must be aware of their individual skills
and honestly scrutinize their attitudes towards prenatal testing in order to enable
autonomous reproductive choices. There is a broad agreement – not only in the opinions
and statements mentioned above – that NIPT in practice needs a profound pre- and post-test
counselling [10], [11]. B.ʼs gynecologist from the beginning did not hide his personal aversion towards
advanced prenatal testing. Furthermore, he had not the additional, legally required
training for offering NIPT and no practical experience with the test at all. In this
constellation, adequate pre-test counselling is hardly possible and the resulting
shared decision making (SDM) can only be deficient. While a physicianʼs personal aversion
to NIPT of course is a general problem for the decision making process, the lacking
knowledge leads to a concrete deficit: information sharing, one of SDM main pillars,
cannot be conducted. It would have been the physicianʼs liability in this case to
recognize his lack in knowledge as a potential risk, not only for the SDM. He then
should have recommended that B. should see a colleague with more specific expertise.
As B. told us, one main reason for her to do the blood test was being able to terminate
at an early gestational age in case of a serious disorder in the fetus. With his skeptical
attitude towards prenatal testing, the lacking knowledge about NIPT and the resulting
inactivity in his interaction with B. and the provider, the physician therefore ultimately
restricted B.ʼs reproductive autonomy.
Since this case was not persecuted legally, we are finally not able to clarify what
happened to the blood sample. The situation for German physicians regarding liability
aspects has been improved since NIPTʼs market launch in 2012: Lifecodexx (“PraenaTest”)
and Ariosa (“Harmony”) laboratories analyse blood samples in Germany CE-certified,
Natera (“Panorama”) still in the United States, the German provider declares to take
liability risks. However, the solution of liability questions of course does not guarantee
an absence of process- and communication related risks, especially for unexperienced
providers. Besides, B.ʼs case had been discovered accidentally during our search for
pregnant women as interview partners for our research. This leads us to assume a larger
estimated number of unreported cases of a failed NIPT usage, hopefully not many with
similar consequences as reported here.
So, regarding this case of medical malpractice only as a physicianʼs individual failure,
and therefore as an unfortunate exceptional event, would be shortsighted. Deficits
in the regulative framework promote such potential misconduct and must be taken into
consideration as well. The problem here is that regulations not only need to be improved
and adjusted with regard to the new NIPT technologies. At least in Germany they have
already shown to be insufficient for the regulation of established procedures of prenatal
(genetic) diagnosis at all. Many well-known ethical difficulties and practical problems
now simply are transferred to the new technology. It is no secret that there is often
a gap between legal framework requirements such as from the GenDG and actual consultations.
This gap could be reduced, for example, by sharpening the counselling requirements
for gynecologists in prenatal testing together with an improvement of the existing
advanced trainings. Basic requirements should become more standardized in order to
ensure sufficient skills levels. At this point, the professional organisations bear
responsibility for their membersʼ qualification status in order to be less volatile
than today.
Structural safeguards in prenatal care with regard to necessary professional skills
are indispensable, if cases as described above shall be prevented henceforth. Thus,
it is not enough to limit the provision of NIPT to MFM specialists. The question here
is not only who now should be allowed to provide NIPT [12]. In one study several clinicians and also MFM specialists (13 %) declared to offer
NIPT as a diagnostic test [9]. Another study showed 6 % of women terminating pregnancy without karyotype confirmation
after getting pathological findings from NIPT [5].
Therefore it has to be ensured effectively that the providing clinician has a sufficient
training in prenatal care counselling which allows her to reflect upon and professionally
dissociate herself from own personal attitudes towards prenatal testing. Again, professional
organisations have to make sure that physicians are well informed and, thus, are able
to inform women thoroughly in turn.
More NIPT specific questions include: Is there a sufficient failure management on
the commercial providersʼ side? The significant difference between shipping a blood
sample thousands of miles for doing a genetic testing and an on-site blood test result
must be internalized by all agents involved. There should be standardized procedures
in the prenatal care pathway for occurring process-related problems in order to minimize
time loss – little delay might not be an obvious risk for providers and physicians
but in total can become essential for the pregnant woman as the reported case shows.
Furthermore, it can be argued that NIPT at least in the short run should not replace
the first-trimester screening (FTS), although it has significantly lower false-positive
rates and a significantly higher positive predictive value [13], [14]. As long as NIPT is not implemented together with an adequate quality management,
a parallel testing procedure even can be seen as a clinical utility. In B.ʼs case
NIPT alone, if performed accurately, most likely would have shown a trisomy 13. A
FTS would have shown signs of variation as well. Since NIPT for trisomy is superior
to the combined test, the role of high-quality first-trimester ultrasound scan should
be emphasized [15]. Still too expensive for most pregnant women, NIPT with its limited diagnostic scope
should be seen as an additional screening test rather than an alternative to high-quality
ultrasound-scan, which is able to detect a much wider range of potential anomalies.
This is an important difference that should be communicated more clearly – to pregnant
women as well as within the professional community. With a combination of both non-invasive
testing procedures, process-related vulnerabilities of each procedure could be moderated
more effectively. Returning to B.ʼs case, a well performed FTS ultrasound scan could
have compensated the time loss caused by the failed NIPT usage.
Many questions of how to include NIPT responsibly into every day practice have not
been answered adequately yet in many countries and become more urgent in light of
the forthcoming coverage by health insurances and increasing numbers of tests. Clinicians
report insecurities with regard to the adequate provision of NIPT services and ask
for specific legal regulations [10], as also expert interviews from our project confirm (unpublished data). If cases
like the reported example shall be avoided in the future, it is inevitable to install
effective safeguards for the shared decision making process in prenatal testing against
individual and structural inadequacies related to the increasing use and significance
of NIPT.
Acknowledgements
We are much obliged to B. We had heard from the case during the recruiting of pregnant
women for an interview study and contacted her several weeks after this event. B.
read the manuscript and gave us written informed consent for publication. Our research
project “Indication or Information? The physicianʼs role in the context of non-invasive
prenatal diagnosis” is funded by the Federal Ministry of Education and Research (BMBF,
funding number 01GP1201).
