NIPT - Welkom op AZ Herentals | AZ Herentals Huisartsensymposium 2014 NIPT NON – INVASIVE PRENATAL...
Transcript of NIPT - Welkom op AZ Herentals | AZ Herentals Huisartsensymposium 2014 NIPT NON – INVASIVE PRENATAL...
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NIPT (or NIPS?)
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NIPT
NON – INVASIVE PRENATAL TESTING
Testing of cff DNA (cell free fetal DNA)
from maternal blood during pregnancy
for trisomy 21, 18 and 13
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Trisomy 21, 18, 13 screening
Trisomy 21 (Down syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome)
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Risk Down syndrome versus Maternal Age
Age Frequency (live births)
< 35 < 0.3 %
37 0.5 %
40 1 %
50 10 %
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History Down syndrome screening
• 1980 : Amniocentesis (advanced maternal age)
• 1990 : Triple screening (T21, T18 and T13)
• 2000 : First trimester screening (T21, T18 and T13)
• 2012 : First trimester screening + NIPT (T21, T18
and T13)
• 201? : NIPT (extensive genetic screening)
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Serum Down syndrome screening
• Triple screening ( > 1990)
– Maternal age
– Serum : AFP, HCG, free oestriol
• Combi test ( > 2000)
– Maternal age
– Nuchal translucency (NT)
– Serum : free B-HCG, PAPP-A
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Classical Down syndrome screening First trimester serum screening (combi test)
Combi test: Risk calculated from:
1. Maternal age: the higher the age, the higher the risk of T21, T18, T13
2. Nuchal translucency (NT): the higher the NT,
the higher the risk of T21, T18, T13
3. Serum parameters PAPP-A and free B HCG
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NIPT history
• 1997: Lo et al.:cff DNA in maternal circulation
• 2006: Sexing fetus for:
1. X-linked genetic disorders
2. Sexing in China
300.000 girls / yr killed
• 2011: Detection trisomy 21/18/13
• 2013: Daily > 2000 NIPT tests worldwide
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NIPT essentials1. TEST : trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome),
trisomy 13 (Patau syndrome).Also sex of the fetus is determined.
2. SAMPLE: Specific test kits provided by GENDIA3. TIMING: > week 104. TURNAROUND TIME: < 2 weeks5. RELIABILITY: > 99% for trisomy 216. INDICATIONS: Although NIPT can be performed in every pregnancy, it is
especially indicated: • If the triple test or first trimester screening indicates an increased risk• Advanced maternal age • Anxiety for invasive procedures
7. CONTRAINDICATIONS: NIPT is not the test of choice when there is : • Fetal anomalies on ultrasound • Severely elevated NT (nuchal translucency) with normal PAPP-A and
free B HCG• A triplet pregnancy, vanished twin
8. PRICE: 450,- Euro
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NIPT cff DNA
• < 1 % of total DNA in maternal circulation is fetal
• 5-30 % of cell-free DNA in maternal circulation is fetal
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NIPT for trisomy 21
NIPT measures the ratio of
chromosome 21 sequence versus
control chromosome sequence to
exclude trisomy 21.
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NIPT Indications
NIPT is currently the test of choice when there is:
• Increased maternal age
• Increased risk on Combination or triple test
• Down syndrome in previous pregnancy
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NIPT Contra indications
NIPT is NOT the test of choice when there is:
• Fetal anomalies on ultrasound
• Severely elevated NT (nuchal translucency) with normal PAPP-A and HCG
• A triplet pregnancy
• Vanishing twin
• Known genetic anomalies that cannot be diagnosed by NIPT
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NIPT advantages versus combi test with AC / CVS
• High sensitivity (few false-negatives)
• High specificity (few false-positives)
• Non-invasive: no fetal risk• CVS: Risk of miscarriage: 1-2 %• AC: Risk of miscarriage: 0.5 %
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NIPT versus classical screening in a country with 10 million inhabitants
Classical NIPT
Number screenings 100.000 100.000
Expected T21 200 (1/500) 200 (1/500)
Detection rate 73 % < 99 %
T21 146 199
False-negatives 54 (27 %) < 1 (0.3 %)
False-positives 4990 (4.8 %) < 100 (0.03 %)
Iatrogenic Miscarriage 50 1
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30 year old mother 1-1000 child with down syndrome
Down syndrome pregnancy Unaffected pregnancy
Test positive99.5 (True positive) 100 (False positive)
Test negative0.5 (False negative) 99,800 (True Negative)
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NIPT : the future
1. Comparative genomic hybridization– All chromosomes– Small deletions - duplications
2. Detection common monogenic mutations - cystic fibrosis- Spinale musculaire atrofie
3. Whole exome / genome sequencing
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dewereldmorgen.beBart Moens gezinswetenschapper
• Zullen ouders zich in de toekomst alsmaar meer moreel en/of sociaal verplicht voelen om te kiezen voor prenatale diagnostiek?
• Zullen ouders in de toekomst nog vrij kunnen en mogen kiezen om een problematische zwangerschap uit te dragen?
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Mark Leach is an attorney with a Master's in
Bioethics, focusing on health law and public.• not the holy grail
of prenatal testing• it is a screening
test, of placental DNA, effective in high-risk populations
• fewer invasive diagnostic procedures
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Harmony(Ariosa – USA)
KUL(Leuven)
Trisomies T21, T18, T13 T21
Turnaround time 11 days 21 days
External validation +++++++++ ---------Twins Yes No
Egg donor Yes NoWomen > 100 kg Yes No
Total patients analysed > 300.000 < 1000
Fetal fraction Yes ??????
Publications with clinical studies 6 0
Earlist sample Week 10 Week 11
Logistics Sample taken by AML ??????
Price 450 Euro 460 Euro
ARIOSA vs KUL