Non-invasive prenatal testing by cell-free DNA: the latest in prenatal screening
What is non-invasive prenatal testing by cell-free DNA?
Non-Invasive Prenatal Testing (NIPT) is a screening test to estimate the chance that the unborn baby has Down syndrome or another chromosome condition (trisomy 18, trisomy 13 or an extra or missing sex chromosome). Normally genetic information (DNA) is contained within a cell (see the Additional Resources section online for an introduction to genetics). When a cell dies it releases its contents into the blood stream and the DNA is broken up into tiny pieces. This DNA is called cell-free DNA (cfDNA).
NIPT is also known as cfDNA screening. NIPT/cfDNA screening detects, reads and counts cfDNA in a pregnant woman’s blood stream. Although this cfDNA is not directly from the baby, it is from the placenta and usually represents the genetic profile of the baby.
What are the benefits of NIPT/cfDNA screening?
- Accuracy: NIPT/cfDNA screening is more accurate than conventional screening tests, detecting more than 99% of pregnancies where the baby has Down syndrome (versus 75-90% by other screening methods). See Table 1 in AFTER:The next steps… for more on conventional prenatal screening.
- Timing: The result from NIPT/cfDNA screening is available earlier than other types of prenatal screening. NIPT/cfDNA screening is just one blood test and can be done as early as 9 weeks, with results available about 1-2 weeks after that. Having screening results earlier in pregnancy allows expectant parents more time for decision-making and potentially offers them more options.
What are the limitations of NIPT/cfDNA screening?
- Screening test: While NIPT/cfDNA screening is an excellent test, it cannot tell for sure whether or not your baby has any of the chromosome conditions mentioned above. It is a screening test that provides a risk assessment (high risk or low risk). If the result comes back as high risk for one of the conditions, a diagnostic test such as amniocentesis or chorionic villus sampling (CVS) is recommended before any final decision is acted upon.
- NIPT/cfDNA screening does not screen for all possible conditions: A negative NIPT/cfDNA screening result does not guarantee a healthy baby. A late first trimester ultrasound at 11 to 14 weeks may be offered, where available. An ultrasound at 18-20 weeks gestation is recommended for all pregnancies, regardless of screening results.
- Possibility of re-draw or no results: About 1-8% (1 to 8 in 100) or less of women will need to have their blood drawn a second time because the test fails. About half the time a result will be available after this second try. There are various reasons why a test may fail including technical issues with the sample, or not enough cfDNA from the pregnancy (low fetal fraction). Factors that may result in a low fetal fraction are: too early in the pregnancy, chromosome disorder, maternal obesity.
- Incidental findings: NIPT/cfDNA screening also screens for differences in other chromosomes, like the sex chromosomes. Additionally, because this test is also looking at the mother’s cfDNA, occasionally a genetic difference in the mother may be identified.
Who should have NIPT/cfDNA screening?
NIPT/cfDNA screening is available to all pregnant women. NIPT/cfDNA screening can be used as a second screen (i.e. after receiving a positive First Trimester Screening result or if specific ultrasound differences have been found) or as a first screening test (e.g. before any other screening). Ontario Health Insurance Plan (OHIP) will pay for NIPT/cfDNA screening for women in Ontario who meet certain criteria.
Women who do not meet the criteria (see below) can pay for NIPT/cfDNA screening themselves. Prices vary by company, the average cost being around 500$.
OHIP will fund NIPT/cfDNA screening for women who:
– Have a positive prenatal screening result such as First Trimester Screening or other conventional screening methods described in Table 1
– Are over the age of 40 at the expected date of delivery
– Have had a previous pregnancy or child with a chromosome condition
– Have findings on ultrasound which are associated with an increased risk for Down syndrome, trisomy 18 or trisomy 13
Who offers NIPT/cfDNA screening?
The Ministry of Health and Long Term Care (MOHLTC) has an agreement with two companies to provide NIPT/cfDNA screening in Ontario (Table 2). The technology each company uses to calculate the risk of a chromosome condition is different, but the accuracy of the tests is comparable. If you choose to have NIPT/cfDNA, the company you and your health care provider choose may vary depending on factors listed in Table 2.
Table 2. Non-Invasive Prenatal Testing (NIPT) in Ontario.
Updated April 2017
|HarmonyTM by Ariosa||PanoramaTM by Natera|
|Where is my blood drawn for this test?||DynaCare Next||LifeLabs Genetics|
|How early can I have this test?||10 weeks gestation||9 weeks gestation|
|When would results be available?||10 business days||10 business days|
|Will this test work if this pregnancy:|
|What proportion of the pregnancies where the baby has Down syndrome will be detected? (Detection rate)||>99%||>99%|
|What proportion of the pregnancies where the baby does not have Down syndrome will be falsely called high risk? (False positive rate)||About 1 in 1,000 (0.1%)||About 1 in 1,000 (0.1%)|
What about the other genetic conditions screened for by NIPT/cfDNA screening?
You may have read that the NIPT/cfDNA screening can suggest other genetic conditions, such as microdeletion and microduplication syndromes. These are rare genetic conditions, occurring in about 1 in 5,000 to 1 in 50,000 pregnancies. They are caused by very tiny extra or missing pieces of chromosomes.
Most of these conditions occur by chance, meaning that they tend to not run in families and can occur out of the blue. The risk of these conditions is not associated with the mother’s age, as it is for Down syndrome and trisomy 18 (conditions caused by extra whole chromosomes).
The addition of these rare conditions to NIPT/cfDNA screening increases the false positive rate. This means that more women would receive a positive (high risk) screen result even though the baby does not actually have the condition. This would result in more women having diagnostic tests, with associated risk of miscarriage. Current recommendations do not support the routine inclusion of screening for microdeletion and microduplication syndromes in NIPT/cfDNA screening.