What is NIPT?

Screening test-A sample of maternal blood-

tested - to determine if the developing baby

has certain chromosomal conditions.

During pregnancy, some of the DNA from

the baby (fetal DNA) crosses in to the

mother’s bloodstream .These DNA’s carry

genetic information.

This fetal DNA is analyzed during NIPT to

check for certain chromosomes.

cffDNA

Short DNA fragments present in the maternal

circulation

Maternal and fetal components (usually 90% /

10%)

Produced by the placenta and shed into maternal

plasma

Short half-life: fetal fraction cleared hours after birth

Fetal fraction increases with placental mass

Decreases with ↑ maternal weight

History

In 1997 the presence of cell-free fetal DNA

(cffDNA) in the maternal circulation was

reported.

Since 2000- Fetal RhD typing- cffDNA

tested to determine fetal Bl.Grp status

from maternal blood to help and direct

management of Rh isoimmunization.

2008- robust evidence-detection of

cffDNA- Down syndrome

Initial clinical application:

- sex-linked disorders

- Rhesus disease

- monogenic conditions

.

Trisomy 21

• Overabundance of cfDNA fragments

originating from fetal chromosome 21

• Small difference can be detected

through massive parallel sequencing

(MPS)

.

.

Sequencing techniques:

MPS (‘shotgun sequencing’)-

DNA molecules contained in maternal

plasma sample are sequenced at random.

+ potentially be applied for detecting

chromosomal or genetic aberrations

anywhere in the genome

- genomic regions that are not

directly relevant to NIPT are also analyzed

as the sequencing is random.

Selective sequencing(targeted):-

Genomic regions containing the chromosomes at risk of the aneuploidy are selectively targeted for sequencing

+ the sequencing power can be concentrated on genomic regions of interest

- may not pick up other genome aberrations.

What does NIPT test for?

Most NIPT tests will test for common

conditions including

Down syndrome (Trisomy 21),

Edward syndrome (Trisomy 18),

Patau syndrome (Trisomy 13)

and certain sex chromosome problems

Who might want to have NIPT?

Useful for women in the following situation/s:

An ultrasound indicates a problem with the baby’s growth

and/or development

A screening test during the pregnancy has indicated that

the baby is at increased risk of having a chromosome

condition

A previous pregnancy has been affected by a

chromosome condition

Older mothers (aged 35 years or more at the date of

delivery) who are at a higher risk of having a baby with a

chromosome condition

How Accurate is NIPT?

Highly accurate for the chromosome

conditions that it tests for however the

accuracy is not 100%.

There are also differences in the

accuracy, depending on the

chromosome condition. Eg-, Down

syndrome may be more accurate.

>99% of pregnancies affected by trisomy 21,

trisomy 18 and trisomy 13, and

92% of pregnancies with monosomy X

(Turner syndrome).

If other sex chromosome conditions (extra or

missing copies of the X and/or Y

chromosome) are identified they are

reported as incidental findings.

The sex of the baby can be determined with

>99% accuracy .

Error?

Occasionally following testing, no results are

given.

This may be due to there being too little fetal

DNA(<4%) in the mother’s blood or difficulty

identifying fetal DNA in the mother’s blood.

May ask for second sample.

Most companies refund most part of money

if pt chooses not to go ahead.

Sources of error

Early gest age (harmony-10,VCGS-9)

Obesity(low levels-dilution effect?)

Multiple pregnancy(monozygotic-more

accurate)

Placental mosacism(isolated placental

mosacism)

Maternal conditions-malignancy.

RESULTS

Summary

A screening test -early pregnancy to detect Down

syndrome and other chromosome conditions

Test is safe –no risk to mother or baby

Currently only offered through specialist Centre's

at a cost to the patient – no Medicare rebate

NIPT, like all prenatal tests, is optional

Accuracy of NIPT tests is high though not 100%

A definite diagnosis of a chromosome condition in

the baby can only be made following an invasive

prenatal diagnosis test like CVS or amniocentesis.

Two Major providers

Harmony test (ARIOSA DIAGNOSTICS)

$575+30 (collection kit)

Epworth Freemasons Suite 6, 320 Victoria Pde

Melbourne East, Victoria 3002Phone 9417 6788 Fax 9416 1084

Tooronga Village Suite G12-13, 762 Toorak Road

Glen Iris, Victoria 3146

Phone 9822 1411 Fax 9822 1433

Frances Perry House Suite 13, Level 2, 20 Flemington Road

Parkville, Victoria 3052

Phone 9348 2299 Fax 9348 2599

Panorama test ( VCGS) (NATERA diagnostics)

$721(699+22collection & handling fee)

Royal Children’s Hospital (VCGS)

The Royal Women’s Hospital (Suite 6)

Selected St Vincent’s Pathology Collection Centres

(see website: vcgs.org.au)