1. Vancouver Division of Family Practice and Perinatal Services BC Prenatal Genetic Screening Program Present: Prenatal Genetic Screening Langley Division of Family Practice Mar 1, 2016

2. Program Disclosure
Nothing to disclose.
Presenter Disclosure

3. AGENDA Prenatal Genetic Screening Tests Counselling Patients & video
Workflow and Practice Tips
Wrap Up & Evaluations
Here is our plan for the evening. Speak about the additions that were brought up.
Anything not mentioned here? Anything to emphasize?
Resource Binder

4. Learning Objectives
At the end of this workshop, the participants will:
Know what tests to offer for screening for Down syndrome and the importance of timing.
Be familiar with the technology of non-invasive prenatal testing (NIPT) using cell free fetal DNA in maternal blood.
Know what screening options are available in the public system and what is available as self-pay
Know how to use the patient decision aid and follow up counseling.

5. Screening for Aneuploidy Important for all ages
~40% of fetuses
with trisomy 21
occur in women <35 years

6. SOGC – CCMG guideline on screening for Aneuploidy
J Obstet Gynaecol Can 2011;33 (7):
1. All pregnant women in Canada, regardless of age, should be offered through an informed counseling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies in addition to a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples . (I-A)

7. What Are The Tests? SIPS IPS TEST METHOD WHEN WHAT QUAD FTS NIPT
1st Blood test
2nd Blood Test
9w to 13+6w
15w to 20+6w
PAPPA
AFP, HCG, UE3, and Inhibin A
IPS
1st Blood Test and
Nuchal Translucency US
AFP ,HCG, UE3, and Inhibin A
QUAD
Blood test
FTS
Blood test and US: NT, nasal bones, Ductus Venosis flow, and fetal heart rate
11w-14w
PAPPA, AFP, HCG
NIPT
10w plus
Cell free fetal DNA
Nipt detection rate for t21 is 99%. Maternal blood sample. 10 days turn aroun. 2-4% give no result due to technical reasons. women choose NIPT as a first line test. Refer to Lifelabs in lower mainland
Panoarama by life labs.
Harmony test used by Womens Hospital,
BCWH genetics will arrange testing for women eligeable for amniocentesis (still have to pay)

8. Who gets what? SIPS (two blood tests):
Singleton pregnancies of women < 35 yrs. who present up to 13 weeks +6 days.
IPS (NT + two blood tests): if woman seen up to 13 weeks + 6 days and:
> 35 years
Previous history of Trisomy
IVF/ICSI
HIV positive women
All pregnancies of multiples

9. Who gets what? Quad: CVS or Amnio
Singleton or twin pregnancies that present > 13 weeks 6 days
CVS or Amnio
Women age 40 or more with singletons or age 35 with multiples have option of CVS or amniocentesis without prior screening
Women with a positive SIPS, IPS, NIPT

10. Prenatal Genetic Screening Private Pay Options
First Trimester Screen (FTS) alternative to IPS or SIPS
11-14 weeks
Ultrasound and one blood sample: T, nasal bone, fetal heart rate, Ductus Venosis flow, PAPPA-A/fbHCG
Advantage? result same day as US; fewer false positives
Available at PCRM
Non Invasive Prenatal Test (NIPT) prior to amniocentesis
10+ weeks
Fetal DNA in maternal blood
Highly accurate screen to detect T21 and T18
Advantage?: result 10 days after blood draw. Fewest false pos.
Does not screen for open neural tube defect
Nipt detection rate for t21 is 99%. Maternal blood sample. 10 days turn aroun. 2-4% give no result due to technical reasons. women choose NIPT as a first line test. Refer to Lifelabs in lower mainland
Panoarama by life labs.
Harmony test used by Womens Hospital,
BCWH genetics will arrange testing for women eligeable for amniocentesis (still have to pay)

11. Prenatal Genetic Screening Timing Chose test by woman’s GA and her characteristics
Acronyms are defined on the Summary/checklist
Women >35 qualify for IPS-- better because reduces false positives
Women >30 in Northern Health, East Kootnay, Kootenay, Boundary eligeable for IPS at younger age
Also: twins, prev T21,18,13,and IVF, ICSI eligible for IPS
NOTE: IPS available for women: > 30 in Northern Health, Kootenays, Boundary; twins; previous trisomy; IVF and ICSI

12. Prenatal Genetic Screening Timing
PSBC Resource cards summarize all tests for whom and when:
Tests available & best times
Tests for woman characteristics and time she presents for care

13. Ideal Timeline for SIPS and IPS
SIPS part 1 any time before 13+6
SIPS part 2 at days for results
Only 64% have blood drawn this early- we could do better
For pos SIPS offer NIPT days for results
For pos NIPT offer amnio days for results

14. Non Invasive Prenatal Testing
~ 10% of DNA in maternal plasma is FETAL

15. Counting methodologies counted vs. expected HARMONY
= Maternal DNA from chr. 21
= Fetal DNA from chr. 21
Unaffected pregnancy
Pregnancy with Trisomy 21
~ 10% of cfDNA in maternal blood is fetal (placental)
The difference in the amount of DNA in an unaffected pregnancy vs an affected pregnancy is small: 21/20 = 1.05

16. SNPS method PANORAMA
Explain SNPs

17. Comparison of Available Tests:
Ariosa
Harmony
Natera
Panorama
Degree of validation
13 clinical studies
>22,000 pregnancies with known outcomes
3 clinical studies
1,306 pregnancies with known outcomes.
Measures fetal fraction
YES
Failure rate on 1st draw 3%
6-7%
Twins NO
Where
C&W laboratory;
JPOC Surrey
Olive; Grace; PCRM; Gamma Dynamics
Life Labs 17

18. Non Invasive Prenatal Testing (NIPT)
What role should NIPT play in prenatal screening?

19. Position Statements: NIPT
SOGC Position Screening 2013
Endorses NIPT in lieu of invasive testing for increased risk of trisomy
Pre and post-test counselling re:
false pos., false neg., and limitations
Does not “replace” the accuracy and precision of invasive testing

20. NEW: Public Funding in BC for NIPT
NIPT has been approved by the BC Ministry of Health effective immediately for women who meet one of the following criteria:
Has received a Positive Screen result from IPS, SIPS, or Quad; OR
Has had a previous trisomy 13, 18, 21 pregnancy; OR
Has a risk of Down syndrome greater than 1 in 300 based on results of serum screening and ultrasound marker of aneuploidy
Funding is available for NIPT analysis of Trisomy 21, 13, 18 and sex aneuploidy.

21. NIPT in lieu of invasive testing in high risk patients: “2nd tier test”
Pre-screen counseling
FP, MW, OB, GC
SIPS / IPS / Quad
Increased risk for aneuploidy (**)
Genetic counselling
Invasive testing* Amniocentesis
CVS
**Increased risk
for trisomy
Pos. screen
Family hx
US markers
NIPT
+ve
NOTE: *Invasive testing still required for pos. NIPT
*NIPT not offered for soft markers alone
unless serum testing done
*Fetal loss rate 0.5-1%

22. Where to access FUNDED NIPT
Dynacare Harmony NIPT chosen to be the FUNDED NIPT provider for BC
Hospital out-patient labs will be collecting for Harmony
New PGSP / Dynacare NIPT Lab Req
will be provided to you by the PBL each time you receive a patient’s positive screen result; OR
For the other funded indications, refer patient to Med Gen. or fax information and form faxed back.
Patient-specific authorization codes to be used for monitoring funding eligibility.

23. Important: NIPT can be false positive
REASONS:
Confined placental mosaicism: trisomy 18, trisomy 13 or 45,X line confined to the placenta
Maternal mosaicism: low grade T21 mosaicism, low grade 45,X mosaicism
Fetal demise in a twin pregnancy
Maternal malignant cell line: multiple chrom abn.
Sample error

24. Soft Markers on Ultrasound
Several markers identified on 2nd trimester ultrasound are associated with increased risk of Down syndrome.

25. Which soft markers impact Down Syndrome risk?
Significantly increased risk:
Nuchal thickness ≥ 6mm
Echogenic bowel (equal or greater than bone)
Absent nasal bone (2nd T)
Aberrant right subclavian artery
Echogenic intracardiac focus (EICF)
Pyelectasis 5mm-10mm
Abnormal femur/foot ratio (≤0.9)
*RISK CALCULATOR UNDER DEVELOPMENT
Small impact on Down Syndrome risk:

26. Take home messages Provide informed consent - offer tests
Remember some women choose no screening
Be aware of your own biases and choices
See women early to be able to do SIPS or IPS
Order second SIPS early: close to 15+2
Quad screen at weeks is an inferior test
Offer private pay options
NIPT does not test for open neural tube defect
Positive NIPT is not diagnostic. Confirmatory test needed

27. Medical Genetics experts are only a phone call away!
Medical Genetics Dept. at C&W T: Prenatal Biochemistry Screening Lab at C&W T:

28. Vancouver Division of Family Practice and UBC Division of Continuing Professional Development Present: Prenatal Genetic Screening: Counseling Tips and Techniques

29. Things to Keep in Mind
Local resources - What prenatal screening options are available in your area?
Informed choice - Before ordering the test, discuss benefits, risks and limitations (screening vs. diagnosis)
Autonomy - The patient should choose the option that is best for her (her family)
Shared decision making

30. Essential Elements of Communication in Medical Encounters
Open the discussion
Gather Information/Understand the patient's perspective
Share Information
Share Decision-making
Agree on Plan
Provide Closure
Ref: Essential Elements of communication in Medical Encounters: The Kalamazoo Consensus Statement Academic Medicine April Volume 76 - Issue 4 - p 390–393

31. 1. Open the Discussion
Allow the patient to complete his or her opening statement
Elicit the patient's full set of concerns
Summarize what the visit entails- encourage Q
Establish/maintain a personal connection
“Is it ok to have this visit focus on genetic screening - are there any other pressing concerns?”
What is the context re timeline? Decision needs to be made by ____
If a second appointment is needed and possible, let woman there is an opportunity for future discussion.
Check if everyone who is part of the decision is here or can be included.

32. 2. Gather Information Ask what the woman/partner understand
“Do you know what Down Syndrome is? …NTD?”
Use open-ended and closed-ended questions
Actively listen and encourage
Nonverbal (eye contact)
Verbal (words of encouragement)
Summarize and clarify
Acknowledge her feelings, values, and ideas

33. 2. Understand Woman’s Perspective
Explore her context (family, culture, age)
Explore beliefs and expectations about health and illness, knowing/not knowing
Why might one get tested? Why would you want to know?
What does she and her family think about this?
How are decisions made in her family?
Be aware of your own biases and values : cultural, ethical, emotional on this topic.
Reflect on this for a minute. Do you have a strong preference for what you would do in her shoes?
and… How does your family make decisions?

34. 3. Share Information Use language the woman can understand
Think about grade 6 reading level or ESL
Check for understanding
Pause and ask what they understand
Reflect back what you are hearing from them
Encourage questions

35. 3. Share Information: Content
All pregnant women have some risk of trisomy/NTD
Specific risks of trisomy/NTD based on age
Screening vs. diagnosis
Pro’s and con’s of screening: reassurance, worry, true and false pos/neg
Results given as a risk: what this means
Types of tests to choose, advantages/disadvantages of each.
Her options based on:
Age, resources available, gest. age, ability/choice to pay private
Timing and next steps such as diagnostic testing

36. 4. Share Decision Making
Encourage the patient to participate in decisions to the extent he or she desires, and provide time frame
Describe options:
No testing
Screening with no further testing
Screening with further testing
Describe scenarios or elicit from her
Ask which scenario/choice makes sense for her
Check if she has enough information; if anyone else needs to be involved in decision

37. 5. Agree on Plan Summarize and affirm the plan of action Next steps
next visit
further information offered/ needed?
further discussion offered/needed?
results
plan for unexpected outcomes

38. 6. Provide Closure Ask whether the woman has other issues or concerns
Discuss follow-up

39. Information for Families and Patient Decision Aid
PSBC Pamphlet:
Its Your Choice
Genetic Screening Prenatal Decision Aid
 A decision to make
Information to help
Not doing the test
Doing the test
Discussion with your care- provider
What matters most to you?
*this is in your course binder

40. Video Demonstration
/AAAwoeZlwrzOdHBfL0rhfbkaa?dl=0#lh:null- Pegasus%20EN%20vFINAL%20CHOIX%20WEB.mp 4

41. Teaching Aid

42. Questions/Comments?