NIPTRGH2014

Report
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
65%
False Positive
Gest.
1:20
15-18w
1:30
15-18w
1:40
11-14w
TRIPLE
75%
QUAD
85%
Combined
1:1000
99%
NIPT
10+w
National Screening Programmes - UK
TRIPLE
TRIPLE
TRIPLE
QUAD
Combined
QUAD
Combined
Combined
TRIPLE
QUAD
Combined
Combined
TRIPLE
QUAD
Combined
Combined
Brave New
World
YEAR
NIPT
2009
2010
2011-13
2014
Maternal Blood
Cell Free
DNA
Plasma
Protein
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
UK 2012
December 2012
Harmony blood test
and scan10 weeks
£750
Cardiff
Free CVS if Pos
Results 12 weeks
Option STOP
Detection
False Pos
99%
0.1%
UK 2013
September 2103
Blood test and scan
10 weeks
£320
Cardiff
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
65
Amnios / Miscarriage
5000
TRIPLE
Gest.
15-18w
55
75
3300
15-18w
QUAD
33
2500
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
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
Cardiologist Dr Orhan Uzun
and Llanelli sonographers
1:200
30%
50%
95%
90%
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

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