Transcript NIPTRGH2014
Advances in Prenatal Diagnosis
Dr Bryan Beattie Consultant in Fetal Medicine Cardiff and Vale UHB
Advances in Prenatal Diagnosis
• NIPT • CGH • Genome Sequencing • Congenital Heart Disease Smartphone Apps
Brave New World
Brave New World
is a novel written in 1931 by Aldous Huxley and published in 1932. Set in London of AD 2540 (632 A.F. – "After Ford" – in the book), the novel anticipates developments in reproductive technology, sleep-learning, psychological manipulation, and classical conditioning that combine to profoundly change society.
The title is from Miranda's speech in William Shakespeare's
The Tempest
O wonder!
How many goodly creatures are there here!
How beauteous mankind is! O brave new world, That has such people in't.
— William Shakespeare, The Tempest, Act V, Scene I, ll. 203–206
Test Sensitivity False Positive 1:20 Gest.
15-18w 65% TRIPLE 1:30 15-18w 75% QUAD 1:40 11-14w 85% Combined 1:1000 10+w 99% NIPT
National Screening Programmes - UK TRIPLE TRIPLE QUAD Combined TRIPLE QUAD Combined Combined TRIPLE QUAD Combined Combined TRIPLE
Brave New World
YEAR
2009
QUAD
2010
Combined Combined NIPT
2011-13 2014
Plasma Protein Cell Free DNA Maternal Blood Cell Free RNA White Blood Cell Red Cell Syncytiotrophoblast
Cells - Extraction and Separation Fetal Cell Syncytiotrophoblast
Dennis Lo - 1997 Chemical Pathologist Dennis Lo, Chinese University of Hong Kong Discovered in 1997: • roughly 10% of the cell-free DNA floating in a pregnant woman's blood stream stems from her fetus. Published in 2010 “
Science Translational Medicine”
• enough fragments of fetal DNA to reconstruct the fetus's whole genome • should be possible to use this DNA to test the unborn child for genetic diseases without exposing it to the risk of an invasive procedure. • biggest advantage saving all those babies that would be lost Warned • Use it to target specific conditions • Not whole genome or late onset cardiovascular disease, Alzheimers etc
Free Fetal DNA and RNA Cell Free DNA Cell Free RNA
Fetal DNA in Maternal Blood
How It Works • What: – Blood Sample 10+ weeks after counselling • Who: – Advanced maternal age – Positive screening test (Quad, NT) – Ultrasound abnormalities – Previous aneuploidy – ?ANY PREGNANT WOMAN • Accuracy over 99% False Positive 1:1000 • Trisomy 21,18,13,XO, Gender
Anytime from 10 weeks Free Fetal DNA 10wks
USA 2011 Redwood City San Jose San Diego Redwood City
Big Business • Demand for prenatal testing is likely to increase • USA non-invasive market could exceed US$1 billion a year. • Sales volumes by Sequenom “substantially exceeded expectations” • Unaffordable for low-income or uninsured women (or the NHS?) • Costs ranged from £500 for Ariosa to £1700 for Sequenom (same test!)
Legal Battles
14 Oct 2005
Sequenom licenses patent for non-invasive prenatal diagnosis
10 Aug 2010
Sequenom’s lawyers send Verinata warning that Verinata is developing tests that will infringe on Sequenom’s patent and patent application.
30 Aug 2011
Stephen Quake — founder of Verinata — and Hei-Mun Fan issued a patent for ‘Determination of fetal aneuploidies by massively parallel DNA sequencing’.
17 Oct 2011
Sequenom launches the MaterniT21 test.
6 Dec 2011
Sequenom sends Aria Diagnostics a letter warning about patent infringement.
19 Dec 2011
Aria files a complaint against Sequenom.
6 Jan 2012
Natera files a complaint against Sequenom.
24 Jan 2012
Sequenom sues Aria.
22 Feb 2012
Verinata and Stanford University sue Sequenom.
1 Mar 2012
Verinata launches the Verifi prenatal test.
7 May 2012
Ariosa (formerly Aria) launches the Harmony prenatal test.
EUROPE 2012
Praena
Germany Lichenstein Austria Switzerland
Cardiff UK 2012 December 2012 Harmony blood test and scan10 weeks £750 Free CVS if Pos Results 12 weeks
Option STOP
Detection False Pos 99% 0.1%
Cardiff UK 2013 September 2103 Blood test and scan 10 weeks £320 Results 14 working days Detection False Pos 99% 0.1%
RCOG 2014
Non-invasive Prenatal Testing is likely to become a primary screening method in pregnancy
Combined Screening £100 85% for 1:40 FP NIPT in NHS £100 99% for 1:1000 FP
GP MAILSHOT
2014 – Time for Change?
But How Long Will it Take!!
Combined Test - Wales 2014
Welsh Executive National Standards Advisory Group Most Obstetricians
RAPID Study
Lynn Chitty UCLH Publish 2015
Test Detected Amnios / Miscarriage 5000 Gest.
15-18w 65 TRIPLE 55 3300 15-18w 75 QUAD 2500 33 11-14w 85 Combined 25 100 10+w 99 NIPT 1 Wales - 3 years 100,000 births – 100 cases of Down Syndrome . (100% uptake)
Case For Universal NIPT Proven screening test in low risk population
S
imple
A
ccurate
F
lexible
E
conomical
R
eliable simple
blood test, Pos or Neg 99% detection , 1:1000 FP anytime from 10 weeks, twins £100 each test and very few amnios quality control is a laboratory issue
Conventional Karyotyping
G Banding
Array CGH
EACH STUDY Miscarriage Dev. Delay Abnormal Scan 10% Extra RESOLUTION
Standard 5-10kbp High resolution 200 bp
Congenital Heart Disease Commoner than Down Syndrome Detection rate at Anomaly Scan UK poor Detection rate at Anomaly Scan WALES better Detection at Fetal Echo Detection at Pulse Oximetry 1:200 30% 50% 95% 90%
Cardiologist Dr Orhan Uzun and Llanelli sonographers Hand and Foot – 10 minutes
Too Much Too Soon?
Ethics / Counselling
Eugenics and Sex Selection
Brave New World?
P.A.G.E.
Whole genome sequencing
Whats Next?
Smartphone Doppler Unbornheart See, Hear, Record, Monitor, Share
Smartphone Tracker Bellabeat Doppler, Kicks, Diary, weight, Mood
Smartphone Custom Growth Charts
Smartphone Vitals Pulse/BP Body Composition Analysis Glucose