Non invasive prenatal test

婦健 Femina Healthcare 4D Ultrasound, Prenatal Diagnosis & Treatment Centre 8 704-707 ( A2 ) Suite 704-707, Grand Centre, 8, Humphrey Avenue, Tsim Sha Tsui (TST MTR A2 Exit) 23682333

Non-invasive Prenatal Screening or Testing (NIPS or NIPT) Booking telephone: 23682333

We are panel list clinic for the American Consulate, Australian Consulate & Teachers Union.

We strive to ensure you have a healthy baby.

We care, we provide various range of accurate NIPT to suit your need.

Like cars, telephone, flowers and cakes; everyone may need different type of NIPT.

We  are the only few clinics in Hong Kong offering wide range of Cap certified NIPTs.

Verifi, Faest, Harmony, Panorama all has College of American Pathology (CAP) certified Laboratories.

We are the only few clinics in Hong Kong offer wide range of high quality oversea NIPTs with CAP certifications

All NIFTY & safeT21  in HK are performed in laboratories that DO NOT have CAP certification.

All blood tests performed in our clinic are certified by Medical Lab Technicians (including safeT21 & NIFTY). Government regulation required blood test to be certified by qualified MLT.

Brand NEW: NIPT for 46 chromosomes & 30-44 gene mutations.

Most complete and comprehensive NIPT ($14,000-25,000).

Chromosome, 30-44 gene disorders + 300 AR gene defects ($19,000 or more)

Now NIFTY only offers NIFTY PRO, new price $4400/4900

NEW:  VISTARA can screen for new gene mutation (1 in every 600 babies has it).

VISTARA is the only NIPT in the market that can screen for gene mutation.

2019 Clinic Price (original price):

safeT21 from $4900 ($6000); NIFTY PRO $4400/4900 ($6500)

NEW: Verifi $4500/4900/5500 (performed in USA $8000)

Harmony $3500/4000 (performed in USA price $5500)

Panorama from $4000/4500; Extended $5500 (price $6000/$8000)

Faest $3000/3500 (Korean largest Bio-Technology company $5000)

NEW: Vistara 30 single gene mutations $13,000 (price $20,000)

Single gene disorder plus 300 autosomal recessive genes ($17,000)

(affecting cardiac, skeletal and neurology)

Do I need NIPT? If you afford it or high risk of chromosome abnormality.

How to choose the best NIPT for me?

1. If you want most comprehensive

safeT21 Advance or Verifi-Extend (from$5500).

Screened 23 pairs of chromosomes.

T21 has >99% in detecting Trisomy 13, 18 & 21.

More false positive and amniocentesis for tests that are not validated.

Problem maybe at placenta, called confined placenta mosaicism (5-10/1000).

Detection of this may increase your chance of amniocentesis.

Advance panel safeT21 may detect extra 1/1000 abnormal chromosome.

The test can double your risk of amniocentesis due to uncommon trisomies.

2. If you have high risk Down syndrome.

Choose Harmony, Faest or Panorama Basic (from $3000).

Detection rate for Down Syndrome is >99% (same as NIFTY & T21).

Panorama has the highest detection rate compared among all NIPTs.

Accurate, more specific, better pricing.

Panorama is being offered at Hong Kong University private clinic.

3. If you concerned about microdeletion and DiGeorge syndrome (22q11)

Panorama ($4500/$5500), detect more than 90% microdeletions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825123/

ALL other panels (T21, NIFTY, Harmony) only can detect 60-80% of microdeletions.

https://www.karger.com/Article/Pdf/484317

4. If you have nuchal translucency > 3.5mm or structural anomalies

It is advisable to have invasive procedure (amniocentesis) for microarray (a-CGH).

If you refuse, can choose safeT21 Advanced panel, but may miss many conditions.

PACKAGE:

Those with safeT21 Advanced done at our clinic $500 rebate for the Anomaly Scan (package)

Fetuses with fetal anomalies & thick nuchal translucency (>3.5mm), should considered amniocentesis/CVS (not NIPT).

NIPT is originally developed for the screening of Down syndrome.

1. Test performs at or after 9-10 weeks pregnant.

2. Most common trisomies (13, 18 & 21) can be screened

Down Syndrome, Edward & Patau syndromes (1-2 babies per 1000)

HARMONY has largest published data support.

3. Most sex chromosome abnormalities (1-2 babies per 1000)

Turner syndrome, Jacob, Klinefelter syndromes.

4. Molar pregnancy or Triploidy (1 in 1000)

ONLY be detected by Panorama test.

5. Microdeletion chromosomal abnormalities (defect < 5Mb)

PANORAMA is most accurate in detecting >90% microdeletions.

https://onlinelibrary.wiley.com/doi/full/10.1111/cge.13098

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825123/

All other brands (NIFTY and safeT21 only detect 60-80%).

Because they only detect defect > 3Mb), Panorama can detect defect < 3Mb.

DiGeorge syndrome (22q11.2, prevalence 1 in 1000-2000);

1p36 deletion (Prevalence 1 in 5000);

Cri-du-chat syndrome (Prevalence 1 in 20000);

Angelman syndrome (Prevalence 1 in 12000)

Prader Willi syndrome (Prevalence 1 in 10000).

The above are the most common microdeletion syndromes (1 in 1000)

6. Other extra chromosome analysis (less than 1 in 1000)

NIFTY-PRO test offers 85 microdeletion and duplication.

Advanced Panel: Checked all 3 billions base pairs, 23 pairs of chromosomes.

Disadvantage: Most conditions are not validated, thus may not be very accurate.

More amniocentesis because of wrong diagnosis, mostly confined placenta mosaicism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1050657/pdf/jmedgene00261-0001.pdf

False positive:2-3 abnormal results only detect 1 abnormal case.

7. Vistara NIPT Single Gene Mutation Screening (1-2 per 1000 babies)

https://www.feminahealthcentre.com/vistara-natera

De Novo gene mutations occur in 1 in every 600 babies.

During pregnancy, the unborn child releases DNA into mother's blood.

NIPT measures the amount of DNA from chromosomes 21, 18 and 13 in the blood.

An abnormally increased amount of chromosome 21 DNA is suggestive of Down syndrome.

Large-scale clinical studies have shown:

1. NIPT can detect >99% of Down syndrome fetuses.

The test has a false-positive rate of 0.1%.

2. NIPT can detect 95-99% of Trisomy 18 (Edward syndrome) fetuses.

3. NIPT can detect 90-95% of Trisomy 13 (Patau syndrome).

All abnormal result need invasive prenatal procedure to confirm (amniocentesis).

Other chromosome abnormality can be detected:

A. Sex chromosome aneuploidies)

B. Other syndromes (e.g. microdeletions related syndromes)

C. New mutations VISTARA (De Novo)

 

Advantages and disadvantage of each panel:

1. safeT21 Advanced Panel

Advantages:

a. Accurate in detecting Down Syndrome, Edward & Patau syndromes

b. Validated for Trisomy 13, 18, 21 and sex chromosomes.

c. Fastest (Turn around time, 3-7 days

d. Screen more chromosomes than other panels.

e. Fetal gender accuracy 99.6%

Disadvantages:

a. Less accurate than Panorama in detecting microdeletions (70% versus 90%).

b. Likely to have more false positive (more amniocentesis).

c. False reassuring (not suitable for those with structural anomalies or thick NT).

2. NIFTY PRO

Advantages:

a. Accurate in detecting Down Syndrome, Edward & Patau syndromes

b. Screen more chromosomes & microdeletions

Disadvantages:

a. Not validated for all tests covered, accuracy not known.

b. Less accurate than Panorama in detecting microdeletions (<70% versus 90%).

c. Least accurate in detecting fetal gender or sex (98%, other panels > 99%).

d. Likely to have more false positive (more amniocentesis)

e. False reassuring (not suitable for those with structural anomalies or thick NT).

3. PANORAMA

Advantages:

a. Validated for all chromosomes and microdeletions covered

b. Highest detection for microdeletions

c. Can differentiate fraternity twin, sex for each twins, DNA fraction for each twin.

d. Likely to be more accurate for twin.

e. Less likely to need amniocentesis after test (false positive)

f. Only test that can screen for triploidy.

g. Most accurate in fetal gender or sex determination (99.9-100%).

h. Screened after 9 weeks (other panel after 10 weeks).

Disadvantages:

a. Small trials included.

b. Panel only included 15 items

4. HARMONY

Advantages:

a. Validated for all chromosomes and microdeletion covered

b. Have the largest published data in the medical literature

c. Less likely to need amniocentesis after test (false positive)

f. Good value for money (pricing)

Disadvantages:

a. Panel only included 6 items

5. FAEST (Korean, biggest bio technology company, World no. 6)

Advantages:

a. Accurate in detecting Down Syndrome, Edward & Patau syndromes

b. Cheap but result not validated.

c. Accurate in detecting fetal sex (> 99.8%)

d. Fast, 5-7 days for result

Disadvantages:

a. Not validated in trial (only company data provided).

 

Company information:

safeT21, Xcelom, Berry Genomics, China.

NIFTY PRO, BGI, China.

Harmony, Roche, United States of America.

Panorama, Natera, California, United States of America.

Faest, Macrogen, South Korea (Korea largest Bio-Technology company, world number 6).


Key messages and Q&A document for women

What are the key messages for women from this Royal College of Obstetrician & Gynecologists (RCOG) Scientific Impact Paper?

Non-invasive Prenatal Testing (NIPT) uses an ordinary maternal blood sample and carries no risk to the mother or her baby.

NIPT uses fetal DNA from the placenta and is much more accurate than previous screening tests. It does not have the risks of the current invasive tests, which carry a small but significant risk of miscarriage and will be needed much less often.

It is already being used for some conditions, however, it is becoming a primary screening method for chromosomal abnormalities, such as Down syndrome, in pregnancy.

The high degree of accuracy, however, means that pregnant women may be informed of findings of uncertain significance, such as placental mosaicism, when there is a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the baby, which can result in a healthy pregnancy, however, in some pregnancies it can lead to complications.

Excellent communication between women and health professionals is therefore essential to understanding the implications of the test results and families need pre-test information and support for informed decision making.

Q&A

1. What is the difference between invasive and non-invasive prenatal testing?

Invasive prenatal testing such as amniocentesis involves needles being inserted into the uterus to detect chromosomal abnormalities. This method carries a small but significant risk of miscarriage.

Non-invasive prenatal testing is a new technique that uses DNA from the baby present in a pregnant woman's blood from early pregnancy and is a much more accurate form of screening for a number of fetal disorders, such as Down syndrome. It is obtained via an ordinary blood test from the mother.

2. What is non-invasive prenatal testing currently used for?

Obstetricians currently use non-invasive prenatal testing to guide women whose baby is at risk of haemolytic disease of the fetus and newborn (HDFN), a condition where antibodies develop in a pregnant woman’s blood and subsequently destroy the blood cells of the baby she is carrying.

It is also used for fetal sex determination in pregnancies at high sex-linked genetic risk, such as Duchenne muscular dystrophy, an inherited condition which affects the muscles, causing muscle weakness.

In some parts of the world and in the UK in the private sector, NIPT is now available to detect Down syndrome and other chromosomal abnormalities.

3. What type of conditions will non-invasive prenatal testing screen for?

Non-invasive prenatal testing is able to detect the baby’s blood group, sex-linked diseases, and chromosomal abnormalities. There is the potential for other genetic conditions to be determined in this way.

4. How accurate is non-invasive prenatal testing?

Non-invasive prenatal testing is highly accurate. However, possible sources of error include the test being undertaken too early (before 10 weeks), or due to maternal obesity.

Furthermore, the test result does not predict the severity of the abnormality and further testing may be necessary.

5. Are there any risks to the mother and baby if non-invasive prenatal testing is conducted?

Non-invasive prenatal testing carries no risk to mother or baby. The sample required is an ordinary blood test taken from the mother.

6. At what stage of the pregnancy would non-invasive prenatal testing be conducted?

Non-invasive prenatal testing should be conducted after 10 weeks of pregnancy. If the test is carried out before 10 weeks there may be insufficient fetal DNA circulating in the mother’s blood to carry out the test.

7. How is NIPT different from the combined/triple/quadruple test?

Although both tests involve a sample of maternal blood, NIPT analyses the cell-free DNA in the mother’s blood, whereas the combined and quadruple test analyses the mother’s hormone levels. With more than 99% accuracy, NIPT is more accurate than the first trimester combined test or second trimester quadruple test for estimating the chance or the risk that the baby has Down syndrome.

NIPT is more accurate than the combined or quadruple test for estimating the risk of Down syndrome’

8. What results can we get from NIPT for Down syndrome?

There are three possible results from NIPT for Down syndrome:

Positive: Predicted to be affected by Down syndrome. An invasive test should be offered to confirm the result.

Negative: Highly unlikely to be affected by Down syndrome.

Inconclusive: Inconclusive results happen in up to 1-2% of cases. This is usually because the proportion of fetal DNA present in the sample is not high enough to give an accurate result. NIPT may be repeated with the hope that the cffDNA levels will have increased due to the increased gestation.

NIPT detects around 98-99% of all babies with Down, Edwards and Patau syndromes.

9. Why are the results not 100% accurate?

Both positive and negative results may be inaccurate due to the following reasons:

False positives

These occur in around 0.3% of cases (or 1 in 300). Possible causes of false positive results include:

When used early in pregnancy, cell-free DNA from a ‘vanishing twin’ may be present, as the placenta continues to shed fetal DNA after embryonic demise. A scan is needed to look for multiple pregnancies or an empty sac prior to the test.

The cell-free fetal DNA comes from the placenta, and we know that sometimes there are ‘cell lines’ that grow in the placenta but not the baby. This is called ‘confined placental mosaicism’ causing a false positive result, which reflects an abnormal cell line that is only present in the placenta but not present in the baby.

Very occasionally, because we are testing all the cell-free DNA in the mother’s blood (this includes the mother’s and the baby’s DNA), we may detect a problem that is present in the mother but not the baby.

False negatives

NIPT detects more than 98-99 out of 100 of all babies with Down, Edwards and Patau syndromes. Possible causes of false negative results include:

The proportion of fetal DNA present in the blood is too low. This may be due to early gestation or to the mother’s BMI being high. A scan is needed to confirm gestation prior to the test.

The cell-free fetal DNA comes from the placenta, and we know that sometimes there are ‘cell lines’ that grow in the placenta but not the baby. This can cause a false negative result if an abnormal cell line is only present in the baby but not in the placenta.

Technical issues.

NIPT detects more than 98-99 out of 100 babies with Down syndrome’

10. What support is available?

Following the non-invasive test, if the result shows an abnormality, the woman would be offered further testing to re-confirm the diagnosis. A team of obstetricians and midwives would provide the necessary counselling and advice for families.

11. Where can I find more information about non-invasive prenatal testing?

The RAPID research programme has a guide to non-invasive prenatal testing:

http://www.rapid.nhs.uk/guides-to-nipd-nipt/introduction/

Public Health England has further information on non-invasive prenatal testing for Down Syndrome:

http://fetalanomaly.screening.nhs.uk/programmestatements

Femina Healthcare Website (will update)

NIPT website (will update)

12. Where can I find out more about current screening?

Currently all pregnant women in the UK are offered a test for fetal anomalies, including Down Syndrome, as part of The NHS Fetal Anomaly Screening Programme (NHS FASP).

More information on the current fetal anomaly screening programme can be found on the NHS FASP website: http://fetalanomaly.screening.nhs.uk/testsabout.