The Facts about Natera`s Non-Invasive Prenatal Test

The Facts about
Natera’s
Non-Invasive
Prenatal Test (NIPT)
THE ONLY NIPT THAT CAN IDENTIFY TRIPLOIDY
PANORAMA TM
IS THE MOST ACCURATE, COMPREHENSIVE NON-INVASIVE
PRENATAL SCREENING TEST WHICH CAN HELP YOU PROVIDE YOUR PATIENTS WITH THE REASSURANCE THEY NEED DURING THEIR PREGNANCY.
TURNAROUND - MOST RESULTS REPORTED IN LESS THAN 10 DAYS
WHY NIPT? Helps avoid unnecessary chorionic villus sampling and amniocentesis.
For every 20 women who show High Risk for
Down syndrome with biochemical screening, only
one (5%) will be carrying a fetus with Down
syndrome,1 and many who are not carrying a
positive fetus will have invasive procedures.
PANORAMA
With Panorama’s high sensitivity and low
False Positives, >99% of women who
screen positive for Down syndrome will be
carrying a fetus with Down syndrome.2
The next generation in NIPT
Panorama is the only NIPT that uses the advanced science afforded by SNPs (single nucleotide polymorphisms) to differentiate
the maternal from the fetal cell-free DNA (cfDNA) to determine the genotype of the fetus.2
Brought to you by
in partnership with
NATERA’S NATUS TECHNOLOGY ( NE XT- G E NE R ATI O N ANE UPLO I DY TE ST U S ING SNP S ).
Personalised
Result
Panorama uses a proprietary, patented
algorithm, called Natera’s NATUS, to
take into account the actual DNA of
the mother, and uses that to deduce
the fetal genotype. The result is a
report that provides a personalised risk
score. Through the use of this science,
Panorama is accurate at fetal fractions
as low as 4%3, and can be used earlier
in the pregnancy than other NIPTs.
The NATUS algorithm incorporates
over 3,000 SNPs per chromosome
evaluated, allowing Panorama to
select SNPs that are not impacted
by ethnicity.
THE VALUE OF PANORAMA OVER OTHER NIPTS
Panorama delivers more accuracy than other NIPTs. There are several versions of NIPT available for you to offer your patients.
However, Panorama’s accuracy remains excellent even at fetal fraction (ff) as low as 4%. The accuracy of all other NIPTs that
use quantitative counting methods, falls markedly when fetal fraction drops below 8%. This is true even for T21, typically the
easiest trisomy to identify.3,5
LOW FETAL FRACTION DECREASE SENSITIVITY RATES FOR COUNTING NIPT TECHNOLOGIES
%Fetal
Fraction
of
cell-free
DNA
Counting
Down
syndrome
Sensitivity
Rate5
Panorama
Down
syndrome
Sensitivity
Rate2
≥8%
>99%
>99%
4-8%
75%
>99%
–– In the non-Panorama data set (average gestational age 15 weeks), 10-15% of women had fetal fraction between 4-8%.
–– Panorama research determined that 25% of women at gestational ages between 9-14 weeks had fetal fraction between 4-8%.3
–– In addition, Panorama is able to report both high sensitivity and specificity for all chromosomes evaluated, even X and Y.6,7,8
COMPARISON WITH OTHER NIPTS WHICH ARE BASED ON COUNTING TECHNOLOGIES
Panorama Test
Other NIPTs
Uses more robust data – the actual DNA from the mother – to “subtract
out” the mother’s cfDNA from the fetus and does not require use of a
reference chromosome
Do not separate out the maternal from the fetal cfDNA – they simply
count cell-free DNA strands and compare to a reference chromosome
>99% combined accuracy for T21, T18, and T13, male and female, and
triploidy at levels as low as 4% fetal fraction in published clinical trials
Up to 25% false negatives at fetal fraction of 4-8%
Always reports fetal fraction
Most do not report fetal fraction
Always reports risk score for monosomy X - an aneuploidy that is more
common at mid trimester than T13, T18 and T21 combined
Some only call monosomy X when found, and do not confirm the
absence of monosomy X
Provides every patient with a Personalised Risk Score
May include grey areas like “aneuploidy suspected”
Identifies triploidy, a major cause of miscarriage
Unable to detect triploidy
22q11.2 deletion syndrome screening which occurs in approximately
2,000 births can be requested
Most do not offer 22q11.2 deletion syndrome screening
MICRODELETION SYNDROMES MICRODELETION
SYNDROMES
Panorama™ ow sscreens creens ffor or tthe he m
most ost ccommon ommon aand nd ssevere evere m
microdeletion icrodeletion ssyndromes, yndromes, iin n aaddition ddition tto o iits ts bbasic asic sscreen creen ffor or TT21, 21, Panorama™ nnow Incidence Incidence oout ut oof f 1100,000 00,000 BBirths irths Panorama
now offers a screen for the most common and severe microdeletion syndromes, in addition to its basic screen for
T18, 13, ttriploidy, riploidy, aand nd sex ex cchromosome hromosome aabnormalities. bnormalities. T18, 13, TTT18,
T21,
T13, tripoidysand
sex chromosome abnormalities.
Why SSScreen
creen ffor or MMicrodeletion
icrodeletion SSyndromes? yndromes? Why
forM
Syndromes?
Why creen icrodeletion 22q11.2 I
s C
ommon 22q11.2 I
s C
ommon • •Are
commonAand
be severe
COMMON ND SScan
EVERE • COMMON AND EVERE •Carry equal risk across all maternal ages
140 140 OFTEN UNDIAGNOSED NDIAGNOSED OFTEN U
• ••Often
undiagnosed
120 120 • •Respond
to early
childhoodRintervention
100 HAVE EEQUAL QUAL MATERNAL ATERNAL ISK AACROSS CROSS AALL LL 100 • HAVE M
RISK 80 MATERNAL GES 80 MATERNAL AAGES Scientifically
Validated
60 60 Microdeletion
validation has
been completed
by Natera™ with
EARLY CCHILDHOOD HILDHOOD NTERVENTION MATTERS ATTERS •• EARLY IINTERVENTION M
40 40 469 samples, including 110 confirmed positives. Accuracy of
20 20 performance has been validated at fetal fractions as low as 3.8%.
0 0 Limitations of the Test
Scientifically VValidated alidated Scientifically Panorama
entire
targeted
Patients
who screen
positive
should be
Natera™ with ith 44region.
69 ssamples, amples, ncluding 10 cconfirmed onfirmed Natera™ w
69 iincluding 1110 offered a follow-up invasive procedure to confirm diagnosis.
positives. AAccuracy ccuracy oof f pperformance erformance hhas as bbeen een vvalidated alidated positives. How
tofractions order Panorama’s
Microdeletion Screening
at ffetal etal s llow ow aas s 33.8%. .8%. at fractions aas MicrodelePons aare
are re M
More ore Common
ommon tthan
than han MicrodelePons CCommon Microdeletions
More
Down yndrome iin
in n YYounger
Younger ounger W
Women omen Down SSsyndrome
Women
Down yndrome /250 11/250 You may order the Panorama pre-natal screen alone or the
extended panel with one of these two options:
•22q11.2 Deletion syndrome (also known as DiGeorge
Down SSyndrome yndrome ((T21) T21) Down syndrome)
alone
Limitations he TTest est Limitations oof f tthe /500 11/500 •
22q11.2
/2000 11/2000 syndromes. PPerformance erformance sspecifications pecifications rreflect eflect ppresence resence syndromes. Panorama™ M
Microdeletions icrodeletions Panorama™ Please Note: Microdeletion screening cannot be ordered
or aabsence bsence oof f tthe he entire ttargeted argeted rregion. egion. PPatients atients w
who ho or separately
from theentire Panorama prenatal
screen.
20 20 22 22 24 24 26 26 28 28 30 30 32 32 screen ppositive ositive sshould hould bbe e ooffered ffered aa ffollow-­‐up ollow-­‐up iinvasive nvasive screen 34 34 Maternal AAge ge Maternal procedure tto o cconfirm onfirm ddiagnosis. iagnosis. procedure How tto o O
Order rder PPanorama’s anorama’s M
Microdeletion icrodeletion SScreening creening O
Outside utside he U
USA SA Location How tthe Syndrome deletion, Prader-Willi, Angelman, Cri-du-chat and
Panorama ddoes oes not sscreen creen ffor or aall ll m
microdeletion icrodeletion Panorama 1p36 deletionnot syndromes
/1000 11/1000 does not screen for all microdeletion syndromes.
Microdeletion alidation hhas as een presence
ompleted by y Performance
specifications
reflect
or b
absence
of the
Microdeletion vvalidation bbeen ccompleted Incidence Sensitivity 1 1
Size of Region Specificity Lifespan Mental Effects You m
may ay oorder rder tthe he ““Panorama Panorama TTest” est” aalone lone oor r w
with ith oone ne oof f tthese hese wo ooptions: ptions: # of SttNPs You wo •
22q11.2 •
Deletion/ DiGeorge ••
••
Other features 22q11.2 (also known as DiGeorge syndrome) 2 D eletion syndrome 5, 6
22q11.2 yndrome (also k(nown as syndrome) Reduced 1 in 2,000 Deletion 95.7% (s
45/47)
>99% 419/422) DiGeorge 22q11.2 Mild to moderate Yes Palate and feeding issues, 7
7
(85.5-­‐99.5%) (97.9-­‐99.9%) (2.9 MB) intellectual disorder & immune problems, low “Panorama EExtended xtended PPanel” anel” w
which hich iincludes: ncludes: 222q11.2 2q11.2 dSeletion, eletion, rader-­‐Willi, AAngelman, ngelman, ri-­‐du-­‐chat, calcium, seizures “Panorama PPrader-­‐Willi, CCri-­‐du-­‐chat, 672 d
NPs schizophrenia 1p36 ddeletion eletion ssyndromes yndromes 1p36 3
Prader-­‐
Willi Heart Defects 1 in 10,000 93.8% (15/16) >99% (453/453) 15q11-­‐q13 Paternal 6
7
(69.8-­‐99.8) o
(5.9 M
B) Fetal ssex ex rreporting eporting s aan n option ption (99.2-­‐100%) where here aallowed llowed y llocal ocal aws Fetal iis w
bby llaws 1,152 SNPs Reduced Mild
Mild tto
o ssevere
evere intellectual d
isorder & intellectual
disorder
behavioral pproblems
roblems behavioural
No Hypotonia in babies, insatiable appetite No “Happy” affect, ataxia, microcephaly, no speech, seizures Please N
Note: ote: M
Microdeletion icrodeletion sscreening creening ccannot annot bbe e oordered rdered sseparately eparately ffrom rom PPanorama. anorama. Please 3
Angelman information n 12,000 o r 95.5% (21/22) >99% 866-­‐6478, 15q11-­‐q13 aternal Normal Severe intellectual For m
more ore 1 iinformation to o oorder rder anorama kits, its, (c447/447)
call all 8855-­‐
55-­‐
sM
end an email to [email protected]. 6
7 8
For or t(77.2-­‐99.9%) PPanorama k(99.2-­‐100%) oor r sM
end 66-­‐6478, (5.9 B) an email to [email protected]. disorder 1,152 SNPs Cri-­‐du-­‐
chat 4
1 in 20,000 February 22014 014 February 5p15.2 (20 MB) 1,152 SNPs Infancy to adult Moderate tto
Moderate o ssevere
evere intellectual ddisorder
isorder intellectual
& behavioral pproblems
roblems behavioural
No Cat-­‐like cry, growth problems, wide set eyes 1p36 (10 MB) 1,152 SNPs Normal in most Severe intellectual
Severe intellectual disorder
disorder && behavioural
behavioral problems
problems Yes Limited/no language, hearing loss, abnormal ears, seizures, 2:1 M:F >99% (24/24) 7
(85.8-­‐100%) >99% (444/445) 7
(98.8-­‐99.9%) >99% (1/1) 7
(2.5-­‐100%) >99% (468/468) 7
(99.2-­‐100%) PANO-­‐M
MD-­‐INSRT-­‐
D-­‐INSRT-­‐RREV1(2/14)INTL EV1(2/14)INTL PANO-­‐
1p36 Deletion 3
1 in 5,000 incidence: approximately 1 in 1,000 Total 1
Performance specifications reflect presence or absence of the complete targeted region 2
th
Nussbaum et al 2007. Thompson and Thompson Genetics in Medicine (7 edn). Oxford Saunders: Philadelphia 3
http://www.genetests.org. 4
http://ncbi.nlm.nih.gov/entrez/disponim.cgi?id=123450 5
Calculated based on the test performance including pregnancy samples 6
Calculated based on the test performance including artificial plasma samples 7
95% confidence interval These tests were developed by Natera, Inc., a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). These tests have not been cleared by the Food and Drug Administration (FDA). REASSURANCE The Panorama test provides:
Comprehensive clinical coverage.
• Identifying chromosomal abnormalities T21, T18, T13, Monosomy X and Triploidy
•Comprehensive microdeletion screening including 22q11.2 deletion syndrome
(also known as DiGeorge syndrome)
Superior accuracy over other NIPTs available and serum screening.
• Consistently high accuracy across all chromosomes evaluated
•Highest levels of sensitivity and lowest levels of false positives of all NIPTs, even
at low fetal fractions
• Accurate results as early as 9 weeks gestation
Excellent customer support.
•Supplemental information sheets can be provided with positive reports that the provider can refer to when discussing
the findings with the patient
• Turnaround - most results reported in less than 10 days
A safe, convenient method that can help you avoid invasive fetal testing.
• Uses a simple blood sample from the mother
–– h
•
Explain the test to your patient and complete/sign the
request /consent form give to the patient to bring to a
Melbourne IVF Clinic
•
Patient to telephone a Melbourne IVF Clinic to book a
blood collection
•
Results will be sent directly to you the requesting
doctor
•
If there is a positive result Melbourne IVF will telephone
you to ensure you have seen the result and explained
the requirement and further testing for the patient.
Melbourne IVF
Melbourne IVF is part of Australia’s leading group of fertility
specialists, Virtus Health. We offer a wide range of
in-house diagnostic laboratory services, including
cytogenetics and DNA testing. We also work with patients
at risk from a variety of inherited conditions, such as birth
defects and genetic disorders e.g. cystic fibrosis. Our
doctors and counsellors can help you with advice and
information about these risks, and support any decisions
you make.
References
1. Average for Down syndrome detection rates for multiple laboratories.
2. Zimmermann, B et al. Noninvasive prenatal aneuploidy testing of chromosome 13,18,21, X
and Y, using targeted sequencing of polymorphic loci. Prenat. Diagn, 2012;doi: 10.1002/
pd.3993.
3. Natera internal data.
4. Noninvasive prenatal testing for fetal aneuploidy. Committee Opinion No. 545. American
College of Obstetricians and Gynecologist. Obstet Gynecol 2012;120:P1532-4.
5. Palomaki GE et al.DNA sequencing of maternal plasma to detect Down syndrome: an
international clinical validation study. Genet Med. 2011 Nov; 13(11):913-20.
mivf.com.au
1800 111 483 for more information
Melbourne IVF Collection Centres
East Melbourne
Mon-Thu 8am - 4pm
No appointment required
(03) 9473 4444
Box Hill By Appointment only
(03) 9006 5500
Mt Waverley By Appointment only
(03) 8805 7888
Werribee By Appointment only
(03) 8742 9300
Natera, a company you can trust,
has a history of being first.
–– The first to offer you 24-chromsome evaluation on
a single cell during preimplantation genetic
diagnosis.
–– The first to offer SNP-array technology on
products of conception.
–– The first, and still the only, to offer accurate SNP
based non-invasive paternity testing during
pregnancy.
6. Levy, B et al. Massively multiplexed targeted amplification and sequencing of SNPs as a method
for identifying fetal chromosome disorders from cell-free DNA in maternal plasma .Poster at
ACMG 2013.
7. Nicolaides, KH, et al. Validation of targeted sequencing of single-nucleotide polymorphisms for
non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X and Y. Prenat
Diagn, 2013; June 33(6):575-9.
8. Samango-Sprouse, C et al. SNP-based non-invasive prenatal testing detects sex chromosome
aneuploidies with high accuracy. Prenat Diagn, 2013: July 33(7):643-9.
“*” In countries where gender reporting is not allowed or must not be offered before a certain
gestational age, Panorama follows the laws of that country.
For more information about the Panorama™
screen visit panorama.com
These tests were developed by Natera Inc., a
laboratory certified under the Clinical Laboratory
Improvements Amendments (CLIA). These tests have
not been cleared or approved by the U.S. Food and
Drug Administration (FDA).
© 2013 Natera. All rights reserved.
HP-COM-0065.3 | 21MAY2014
To request the Panorama screen for
your patients: