Los días 8 y 9 de junio de 2017 organizamos en la Fundación Ramón Areces con el Ciberer y la Fundación Jiménez Díaz un simposio internacional sobre 'Diagnóstico prenatal no invasivo y diagnóstico genético reproductivo'. Coordinado por la doctora Ana Bustamante, del servicio de Genética del Hospital Universitario Fundación Jiménez Díaz, tuvo como objetivo mostrar los últimos avances en el campo de la genética reproductiva a nivel preimplantacional, prenatal, e, incluso, preconcepcional.

1. Sarah Mason
2nd February 2016
Counselling for aneuploidy in the era of cell
free DNA testing
Celine Lewis
Senior Social Scientist

2. My background
• Social scientist – genetics and fetal medicine
• Work focuses on how patients and families relate to
and make decisions around personal genetic
information, and the subsequent emotional and
behavioural impact
• 2012-2017 empirical research in NIPT looking at
patient and health professional views, experiences
and information needs: ‘RAPID’ project
• 2015 – RAPID report to the UK National Screening
Committee making recommendations as to how NIPT
should be implemented in UK NHS

3. Talk objectives
1. General objectives and principles of prenatal counselling
2. Identify counselling challenges of prenatal screening
3. Assess the impact of NIPT and identify some of the
challenges that have arisen as a result of this new technology

4. Talk objectives
1. General objectives and principles of prenatal counselling
2. Identify counselling challenges of prenatal screening
3. Assess the impact of NIPT and identify some of the
challenges that have arisen as a result of this new technology

5. Prenatal testing for aneuploidy – historical overview
NIPT using cell free
fetal DNA
Fetal anomaly screening
Amniocentesis
CVS
50 years of prenatal testing and diagnosis

6. Overall objective of prenatal counselling
1. To provide prenatal diagnostic testing services that enable
families to make informed choices, consistent with their
individual needs and values
2. To support them in dealing with the outcome of such testing
Offering prenatal diagnostic tests: European
guidelines for clinical practice. EJHG; Skirton et
al. 2015.

7. General principles of prenatal counselling
1. Patient education and discussion of options
2. Gathering information and providing risk assessment
3. Psychosocial assessment and support
4. Remaining non-directive
The role of the genetic counsellor: a systematic
review of research evidence. EJHG; Skirton et al.
2015.

8. Talk objectives
1. General objectives and principles of prenatal counselling
2. Identify counselling challenges of prenatal screening
3. Assess the impact of NIPT and identify some of the
challenges that have arisen as a result of this new technology

9. Counselling challenges: informed decision-making
1. Women do not realise
screening is optional
2. Women unclear as to the
purpose and potential
implications of screening

10. Counselling challenges – screening is optional
Study design: Quantitative survey study to assess women’s
knowledge about DSS
Included question concerning optional nature of DSS
Sample: Pregnant women who consented (n=226) and
declined (n=79) DSS
Results: A third of participants thought DSS was obligatory

11. Counselling challenges – purpose and implications
Study design: Quantitative survey study conducted in France
including questions around motivations and understanding of
screening
Sample: 391 women in maternity ward
Results: 11% not aware a purpose of ultrasound screening was
to look for indications for DS
51% not aware it could lead to decision-making about
termination

12. Counselling challenges: presenting risk

13. Counselling challenges: presenting risk
• Study design: Observation survey study conducted in Sweden
• Questionnaire looked at risk recall and risk perception
• Sample: 796 pregnant women
• Methods: High risk (>1.250) women given told they were ‘high risk’ and
given a risk score e.g. 1 in 30.
• Low risk told ‘low risk’
• Questionnaire completed at 24 weeks gestation
• Results: 36% of HR women could not recall exact/approx score
• Of 31 women who thought they were high risk, over half were low risk

14. Counselling Challenges: Presenting risk
• Study design: RCT including pregnant women with low DSS risk
• Methods: Sent letter either citing DS risk as ‘1 in 1000’ or ‘your chance of
having a baby with DS is low’
• Sent questionnaire 1 week later to assess understanding of results
• Results: 97% in the numerical probability and 91% in the verbal
probability group correctly understood there was a small risk of having a
child with DSS
• Communicating residual risk in terms of 2.6 in 1000 was found to
increase awareness of residual risk

15. Talk objectives
1. General objectives and principles of prenatal counselling
2. Identify counselling challenges of prenatal screening
3. Assess the impact of NIPT and identify some of the
challenges that have arisen as a result of this new technology

16. Biological properties of NIPT
• Originates from placenta
• Represents whole fetal genome
• Detectable from 4 weeks gestation
• % increases with gestation
• Recommended from 10 weeks gestation
• Cleared from circulation within 30 minutes
• NIPT is an advanced screening test
• Small risk of false positive (<0.1%)
• Requires confirmation through invasive testing
Cell free DNA

17. NIPT for aneuploidy

18. USA Europe China

19. Study Country Population
Qualitative
Lewis et al 2013 UK Pregnant women
Yi et al 2013 Hong Kong Women having NIPT
Kellogg et al 2014 USA Mothers of children with DS
Vanstone et al. 2015 Canada Pregnant women
Quantitative
Kooij et al 2009 Netherlands Pregnant women and med students
Sayres et al 2011 USA HPs
Tischler et al 2011 USA Pregnant women
Yotsumoto et al 2012 Japan Pregnant women and HPs
Hill et al 2012 UK Pregnant women, support group & HPs
Kelly and Farrimond
2012
UK General Public
Musci et al 2013 USA HPs
Silcock et al 2013 UK Pregnant women and HPs
Allyse et al 2014 /
Sayres et al 2014
USA General Public
Lewis et al 2014 UK
Pregnant women, support group & parent chat
group
Sahlin et al. 2016 Sweden Pregnant women
Van Schendel et al. 2016 Netherlands Pregnant women
Ahmed et al. 2017 Pakistan Obstetricians
Stakeholder views

20. Aim: Investigate consequences of introducing NIPT in public sector
Methods: Prospective cohort study across 8 sites
All women offered DSS in line with current practice
Women DSS risk >1000 offered NIPT free of charge
Women with DSS risk >1.150 offered option of IPD or NIPT
Women given 30 mins pre-test counselling with research midwife and
written information
Outcomes: uptake, reduction in IPD, DS detection, pregnancy
outcomes
Sample: Offered to 3175 women; 934 HR & 2241 MR

21. NIPT: Women’s views and experiences
Subset invited to take part in qualitative interviews
Aim: To explore views and experiences of being offered NIPT

22. NIPT Benefits
Opportunity to have a test that is:
safe
accurate
easy to conduct
“The first huge benefit is the lack of invasive
requirement, which means that you’re taking the test, it
takes out a whole level of concern. You become purely
concerned about the result, not the process, which is
very significant when you’re in that situation.”

23. Reduces the need for invasive testing
NIPT Benefits

24. NIPT Benefits
Results in cases of aneuploidy being identified
that might have been missed
42 DS pregnancies in HR group
9 DS pregnancies in MR group
“Although it’s incredibly difficult what we’re going
through and obviously the parts after the NIPT were
very, very difficult it’s enabled us to make an informed
choice about what happens for the result of our lives.”

25. Motivations for NIPT
Desire for reassurance (MR)
“Peace of mind” about health of fetus
“Relax” and enjoy rest of pregnancy
Facilitates decision making (HR)
Clarifies need for invasive testing and ToP
Information to plan and prepare for birth
“If we hadn’t done it we would have not known [that the baby has DS],
so we’re glad we've done it so we can prepare for ourselves and it’s not
a shock at the end. And it gives us time to accept and then prepare
ourselves.”

26. Barriers to NIPT
Preference for invasive testing (18%):
Not wanting to wait 7-10 days for test results (likely to decrease)
NIPT is not diagnostic
Indication for aneuploidy very high so invasive testing most
appropriate

27. Barriers to NIPT
Preference for no further testing (14%)
Sufficiently reassured by DSS results
Not wanting to return to clinic
Would not act on NIPT results

28. Concerns around NIPT
Ethical concerns
Increasing termination rates
Reducing number of people born with DS
Knock-on effect of reducing research and support for people
with DS
‘Slippery slope’ arguments
“How do you decide that one thing
warrants screening and another disability
doesn’t?”

29. Concerns around NIPT
Routinisation of testing
Women have many blood tests in pregnancy
May not consider possible implications of test result
“I’d kind of wonder, if people would just walk in like they
probably do [with] the Downs screening test now and just
think ‘yeah, I’ll just do that, it’ll be easy’. And then you
might not actually get the result you’re hoping for. I think
it would be the main issue for me would be, how you
counsel people to make a decision like that. So they’re
walking in to it with their eyes open.”

30. Concerns around NIPT
Increasing anxiety
Period of being ‘in limbo’ whilst waiting for NIPT result
Fear of ‘over screening’
“There’s always the risk of a false positive or creating
additional anxiety . So sometimes you can just feel, if you
look hard enough you'll probably find something. So it’s
more just the risk of over screening, if you know what I
mean.”

31. Concerns around NIPT
Misunderstandings about reliability
The meaning of a positive NIPT result
 5 false positive NIPT result (PPV of 91%)
Possibility of an ‘inconclusive’ NIPT result
 31 (1.2%) inconclusive NIPT results

32. Concerns around NIPT
1. Routinisation of testing
2. Increased Anxiety
3. Misunderstanding about reliability

33. Informed Choice Study 2015

34. Informed Choice Study 2015
Aim
Measure whether women are making an informed choice about NIPT
Design
Women being offered NIPT as part of implementation study at 6 hospital sites
Survey at 2 time-points
T1: immediately after accepting/declining NIPT
T2: one month following test results
Outcome measures: Informed choice at T1
Anxiety at T1 and T2
Results
592 surveys
NIPT
Invasive
Declined further testing

35. Multidimensional Measure of Informed
Choice
A decision made with sufficient knowledge, in line
with the persons attitudes to testing, deliberated
on and behaviourally implemented

36. Good knowledge
-ve
Attitude
Deliberated
+ve
Attitude
Informed choice
Multidimensional Measure of Informed Choice
Accepted
NIPT
Declined
NIPT

37. Questionnaire
Knowledge scale
Knowledge
scale

38. Knowledge scale
Multidimensional Measure of Informed
Choice

39. Questionnaire
Attitude Scale
Knowledge
scale
Attitude
scale

40. Multidimensional Measure of Informed
Choice
Attitude scale

41. Questionnaire
Deliberation scale
Knowledge
scale
Attitude
scale
Deliberation
scale

42. Multidimensional Measure of Informed
Choice
Deliberation scale

43. Questionnaire
Uptake
Knowledge
scale
Attitude
scale
Deliberation
scale
Uptake

44. Multidimensional Measure of Informed
Choice
Uptake

45. 95% Good knowledge
<1% -ve
Attitude
92% Deliberated
88% +ve
Attitude
89% Informed choice
Informed choice
Accepted
NIPT
Declined
NIPT
10% Neutral
Attitude
Excluded
Main reason for
uninformed
choice

46. Informed Choice
Hi levels of informed choice can be achieved if there is
dedicated time and resources for pre-test counselling
Greatest number of uninformed choices due to lack of
deliberation
 Not enough time to deliberate about NIPT
 Already deliberated about DSS
Highlights importance of patients assessing their own attitudes
and motivations

47. NIPT Challenges
1. Routinisation of testing
2. Increased Anxiety
3. Misunderstanding about reliability

48. Increased anxiety
6 Item State Anxiety Scale

49. Increased anxiety
KEY FINDINGS
Time 1:
30% (n=179) had an elevated anxiety score
Unsurprisingly, HR women significantly more anxious than MR
women (55% v 20%)
Women who had IPD more anxious than NIPT women (74% v
51%)
Time 2:
Decrease in anxiety (30% down to 14%)
30 women with a –ve NIPT result still had elevated anxiety

50. Increased anxiety
1. We may be increasing anxiety for MR women
(however don’t have baseline anxiety)
2. Small number of women had elevated anxiety even after -
ve NIPT result
concerns around false negative risk
don’t have full confidence in test
conflicting messages between DSS and NIPT
elevated baseline anxiety
3. Further research to explore why anxiety persists for a subset
of women would be useful to determine how post-test
counselling could support these women.

51. NIPT Challenges
1. Routinisation of testing
2. Increased Anxiety
3. Misunderstanding and reliability

52. Misunderstandings about reliability
What does a positive NIPT result mean?
The baby definitely has the condition
It is highly likely the baby has the condition
Don’t know
11% incorrectly answered
What does a negative NIPT result mean?
The baby definitely does not have the condition
It is highly likely that the baby does not have the condition
Don’t know
8% incorrectly answered this question
Highlights misunderstandings around NIPT being an advanced
screening test and not a diagnostic test

53. Misunderstandings and reliability
Will you always get a test result?
Yes it is certain you will receive a test result
No, in a small number of cases the laboratory is unable to give a result and the
test can be repeated
Don’t know
33% incorrectly answered question
Important to ensure women clearly counselled about potential
for an inconclusive result

54. International comparison of prenatal preferences
Aim: compare preferences for different types of prenatal test
Sample: XXX pregnant women (and health professionals)
from: Canada, Denmark, Iceland, Israel, Italy, the Netherlands,
Portugal, Singapore, and UK
Method: Participants asked to choose between different test
attributes: accuracy, time of test, risk of miscarriage, type of
information

55. International comparison of prenatal preferences

56. International comparison of prenatal preferences
Women asked to choose directly between NIPT, invasive
testing or no test

57. Addressing NIPT challenges
Requires careful counselling!!!

58. 1. NIPT is an advanced screening test, and a positive result
requires confirmation by invasive testing.
2. Specifically what the test is screening for (including “extras” if
tested for—e.g. fetal sex, subchromosomal anomalies, sex
chromosome aneuploidies).
3. The possibility of a false positive and false negative NIPT result
4. A description of the major trisomies, using information
regarding DS that is balanced and including the fact that Edwards
and Pataus are usually but not always lethal.
Careful counselling: key points

59. 5. How long the results will take to come back and how the result
will be fed back.
6. The test may fail or give an inconclusive result—and what the
options are then.
7. That it is the parents’ choice whether or not to have NIPT, and if
positive it will be their choice what to do next—invasive test or not.
8. If offering this as an alternative to invasive testing, the fact that
a substantial number of potentially pathogenic chromosomal
rearrangements will not be detected by NIPT.
Careful counselling: key points

60. Health professionals must be well educated, maintain
professional development and work within a
multidisciplinary team when required in order to offer
comprehensive advice to parents.
A key factor for the successful introduction of NIPT will be
maintaining approaches to counselling and strategies for
information provision that will safeguard informed decision
making
Important to be mindful of the variety of motivations and
preferences women have regarding prenatal testing
Concluding remarks

61. Acknowledgments
NETRGL
Lyn Chitty
Fiona McKay
Sarah Mason
Sandra Moore
Natalie Chandler
Helena Ahlfors
Funding
RAPID NIHR PGfAR
GOSH CC Charity
GOSH BRC
This work described here was partially funded by the National Institute for Health Research (NIHR) under its Programme
Grants for Applied Research Programme (RP-PG-0707-10107 – “RAPID”) and the GOSH BRC. The views expressed are
those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.
Research Team
Samantha Edwards
Melissa Hill
Suzanne Drury
Jane Hayward
The People
Health professionals
Women who participated