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

Program Disclosure Nothing to disclose. Presenter Disclosure

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

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.

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

SOGC – CCMG guideline on screening for Aneuploidy J Obstet Gynaecol Can 2011;33 (7):746-750 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)

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)

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

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

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)

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

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

Ideal Timeline for SIPS and IPS SIPS part 1 any time before 13+6 SIPS part 2 at 15+2 10 days for results Only 64% have blood drawn this early- we could do better For pos SIPS offer NIPT 10 days for results For pos NIPT offer amnio 4-14 days for results

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

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

SNPS method PANORAMA Explain SNPs

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

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

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

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.

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%

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.

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

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

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:

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 14-20 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

Medical Genetics experts are only a phone call away! Medical Genetics Dept. at C&W T: 604-875-2157 Prenatal Biochemistry Screening Lab at C&W T: 604-875-2331

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

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

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 2001 - Volume 76 - Issue 4 - p 390–393

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.

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

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?

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

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

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

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

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

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

Video Demonstration https://www.dropbox.com/sh/917au874e4npmbh /AAAwoeZlwrzOdHBfL0rhfbkaa?dl=0#lh:null- Pegasus%20EN%20vFINAL%20CHOIX%20WEB.mp 4

Teaching Aid

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