NIPT (or NIPS?)
NIPT NON INVASIVE PRENATAL TESTING Testing of cff DNA (cell free fetal DNA) from maternal blood during pregnancy for trisomy 21, 18 and 13
Trisomy 21, 18, 13 screening Trisomy 21 (Down syndrome) Trisomy 18 (Edwards syndrome) Trisomy 13 (Patau syndrome)
Risk Down syndrome versus Maternal Age Age Frequency (live births) < 35 < 0.3 % 37 0.5 % 40 1 % 50 10 %
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)
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
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
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
NIPT essentials 1. 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 GENDIA 3. TIMING: > week 10 4. TURNAROUND TIME: < 2 weeks 5. RELIABILITY: > 99% for trisomy 21 6. 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
NIPT cff DNA < 1 % of total DNA in maternal circulation is fetal 5-30 % of cell-free DNA in maternal circulation is fetal
NIPT for trisomy 21 NIPT measures the ratio of chromosome 21 sequence versus control chromosome sequence to exclude trisomy 21.
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
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
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 %
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
30 year old mother 1-1000 child with down syndrome Test positive Test negative Down syndrome pregnancy Unaffected pregnancy 99.5 (True positive) 100 (False positive) 0.5 (False negative) 99,800 (True Negative)
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
dewereldmorgen.be Bart 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?
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
ARIOSA vs KUL Trisomies Turnaround time Harmony (Ariosa USA) KUL (Leuven) T21, T18, T13 T21 11 days 21 days External validation +++++++++ --------- Twins Egg donor Women > 100 kg Yes Yes Yes No No 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