Non-Invasive Prenatal Testing (NIPT) Dr Glenn

Non-Invasive Prenatal Testing (NIPT)
Dr Glenn Gardener, Director, Mater Centre for Maternal Fetal Medicine
What is NIPT?
Non-invasive prenatal testing (NIPT) refers to testing of the fetal genome (DNA) through a sample of the mother’s
blood, hence it is ‘non-invasive’ and poses no risk to the pregnancy. The major benefit of NIPT is a significant
reduction in the need to perform invasive testing e.g. chorionic villous sampling (CVS) or amniocentesis which carries
a risk of fetal loss of up to 1%.
How does NIPT work?
NIPT is a new technology that detects fragments of cell-free DNA (cfDNA) in the mother’s blood. For the test to be
reliable a threshold of fetal DNA quantity must be detected in the maternal blood sample. The primary source of
fetal cfDNA is thought to be the placenta. NIPT uses next generation DNA sequencing technology or single nucleotide
polymorphism technology (SNP) to provide a risk for trisomy 21 (Down syndrome) and other specific conditions e.g.
trisomies 18 and 13. Some tests include sex chromosome testing which can indicate gender and also provide risk for
some sex chromosome abnormalities e.g. Turner syndrome (XO)
What are the limitations of NIPT?
NIPT does not screen for all fetal abnormalities. NIPT is very specific about the chromosomes it is testing (e.g.
21,18,13, X and Y). A negative NIPT test does not completely rule out the chromosomal abnormalities that it is
testing for. Patients who themselves carry a chromosomal abnormality, who have had a transplant or stem cell
therapy are not suitable for NIPT. IVF pregnancies with donor eggs and multiple pregnancies have specific
restrictions with some NIPT tests. Medicare does not cover any of the costs of NIPT.
How accurate is NIPT?
Reported detection rates (DR) for trisomy 21 using NIPT are >98% and false positive rates (FPR) are <1%. This is a
substantial improvement over current screening tests (e.g. 85-90% DR and 5% FPR for the first trimester combined
screen) making NIPT the most accurate screening test currently available for trisomy 21. With some providers,
detection rates for trisomies 13, 18 and Turner syndrome are less than the detection rates for trisomy 21. Whilst
NIPT is a very good screening test, it is not a diagnostic test and invasive testing (CVS or amniocentesis) is
recommended to confirm a positive NIPT result. NIPT uses a complex interpretive algorithm to calculate a high
likelihood or low likelihood screen result while CVS or amnio is counting chromosomes directly or using FISH for a
diagnostic result
How reliable is NIPT?
All companies offering NIPT have peer reviewed published data available online to support their individual claims of
test performance. All report sensitivity and specificity for trisomy 21 at >98%. The rates of detection of trisomy 18
and 13 and some sex chromosome abnormalities varies between providers with detection rates from 80-99%. Recent
published studies have demonstrated that NIPT can also be used in the low risk population with similar detection and
screen positive results.
Who can have NIPT?
NIPT providers have generally recommended testing for ‘high risk’ women but recent published data supports testing
of low risk women. ‘High risk’ includes advanced maternal age, abnormal ultrasound, personal or family history of
aneuploidy and abnormal 1st trimester or 2nd trimester screen. The test can be done as early as 9 weeks gestation
(Panorama only) but most NIPT providers prefer testing at 10 - 12 weeks.
How can patients access testing?
Patient and doctor information, request forms, consent forms and information regarding blood collection and
interpreting results are available online with each provider. The test is currently only available through private
providers and the blood sample is sent overseas for processing. The turnaround time from blood sampling to result is
2-3 weeks. The ‘no-call’ rate or an indeterminate result occurs in 4-10% of samples and if this occurs a 2nd sample can
be tested usually at no additional charge.
How will NIPT impact on other screening tests e.g. First Trimester Combined Screen?
If NIPT has been already performed in a pregnancy, the risk result for trisomy 21 will be more accurate than any
other currently available screening test. Invasive karyotyping can still helpful in some circumstances because it looks
at all 23 pairs of chromosomes and additional testing may sometimes be indicated e.g. 22q11 and microarray. If the
nuchal translucency measurement is increased (e.g. >3.5mm) or other structural anomalies are seen on scan, a
negative NIPT result will be reassuring for trisomy 21 but other conditions such as atypical chromosomal
abnormalities may not be detected e.g. chromosomal rearrangements. For nuchal translucency measurements
>3.5mm, or first trimester combined test risks of greater than 1 in 50, some patients may prefer invasive testing (e.g.
CVS) over NIPT to obtain an earlier definitive and more comprehensive result. Appropriate counselling is
recommended before undertaking NIPT.
What is happening with NIPT at Mater Mothers Hospital?
Currently patients considering NIPT are seen by their private Obstetrician or by an Obstetrician in antenatal clinic.
The choice of provider is at the discretion of the Obstetrician/MFM Specialist and patient preference. Patients with
positive/high risk results from NIPT testing or who request invasive testing can be referred to the Mater Centre for
Maternal Fetal Medicine for counselling and invasive testing if required.
Test name
(Overseas
Company)
Australian
Provider
Website for detailed
information
Cost
Verifi
(Verinata)
S&N (Sonic)
www.snp.com.au
$595
iGeneScreen
(BGi)
QML
www.qml.com.au
$850
MaterniT21
(Sequenom)
Healthscope
www.healthscopepathology.co
m.au
$700
Harmony
(Ariosa)
Mater MFM
www.ariosa
$495
Panorama^
(Natera)
Virtus
www.qfg.com.au
$720
^ preferred with paternal buccal swab
*This field of prenatal testing is changing rapidly so please check that current information is correct with Provider
1st Aug 2014

Download Report