Non-Invasive Prenatal Testing (NIPT) Common Aneuploidy Screening from Maternal Blood
The Harmony prenatal blood test is a relatively new but clinically proven test for screening for chromosomal abnormalities in early pregnancy. The test can be performed at any time after 10 weeks gestation.
Non-invasive prenatal testing (NIPT) analyses cell-free DNA circulating in the pregnant mother’s blood. It is a new option in prenatal screening for Down syndrome (trisomy 21) and other common chromosomal conditions (trisomies 18 and 13) including X and Y chromosome conditions. This test can be requested for any singleton pregnancy, including IVF pregnancies and pregnancies using egg and sperm donors. It can now also be requested for ALL twin pregnancies (without X or Y) conceived naturally or by IVF using the patient’s own egg or a donor egg.
DNA from the fetus circulates in the mother’s blood. Cell-free DNA (cfDNA) results from the natural breakdown of fetal cells (presumed to be mostly placental) and clears from the maternal system within hours of giving birth.
During a pregnancy, cfDNA can be tested to give the most accurate screening approach in estimating the risk of a fetus having a common chromosome condition sometimes called a trisomy. This occurs when there are three copies of a particular chromosome instead of the expected two. The test looks to detect the following trisomies::
- Trisomy 21 (Downs syndrome) is the most common trisomy at the time of birth. This condition is associated with moderate to severe intellectual disabilities and may also lead to digestive disease, congenital heart defects and other malformations.
- Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome)are associated with a high rate of miscarriage. These babies are born with severe brain abnormalities and often have congenital heart defects as well as other birth defects. Most affected individuals die before or soon after birth, and very few survive beyond the first year of life.
- Sex chromosome conditions.The sex chromosomes (X and Y) determine whether we are male or female. X and Y chromosome conditions occur when there is a missing, extra, or incomplete copy of one of the sex chromosomes. The Harmony with X, Y test can assess risk for XXX, XYY, XXYY, XXY (Klinefelter syndrome), and a missing X chromosome in a girl (Turner syndrome). There is significant variability in the severity of these conditions, but most individuals have mild, if any, physical or behavioural features.
The testing is non-invasive. It involves taking a blood sample from the mother. The pregnancy is not put at risk of miscarriage or from other adverse outcomes that are associated with invasive testing procedures such as amniocentesis.
Clinical studies have shown that the Harmony Prenatal Test has exceptional accuracy for assessing fetal trisomy risk.
A ‘high risk’ result is indicative of a high risk for a trisomy. The test identifies in singleton pregnancies more than 99% of fetuses with trisomy 21, 98% of fetuses with trisomy 18, and 80% of fetuses with trisomy 13, and 96% of fetuses with Turner Syndrome. X and Y analysis provides >99% accuracy for fetal sex. Accuracy for detecting other sex chromosome anomalies varies by condition.
After the test, the number of women required to have amniocentesis or a CVS is less than 1%.
It is important to note that if the test results show there is a high risk that the fetus has trisomy 21, 18, 13 or sex chromosome conditions, it does not mean that the fetus definitely has one of these conditions, although it is highly likely. For this reason, in the event of a ‘high risk’ (or positive) result, follow-up testing by an invasive procedure is recommended.
In the same way, if the test results show that there is a ‘low risk’ that the fetus has trisomy 21, 18, 13 or sex chromosome conditions, it is unlikely that the fetus has one of these conditions. However, there is a very small risk that not all trisomy fetuses will be detected. All results should be interpreted by a clinician in the context of clinical and familial data. Patients should continue with their usual scan appointments following testing.
The Harmony Prenatal Test can be performed for women with pregnancies of at least 10 weeks gestational age. The Harmony™ Prenatal Test can now be ordered for all IVF singleton pregnancies, including those with egg donors. Samples from pregnant women with twins naturally conceived, or those conceived using the patient’s own egg or donor eggs, can also be accepted. This test does not assess risk for mosaicism, partial trisomies or translocations.
The results will be available in approximately 5 working days, at which time most women can have their 12-week scan for a detailed examination of the fetal anatomy, including measurement of nuchal translucency, nasal bone and other important factors. In this visit, patients can discuss the DNA and ultrasound results with their obstetricians.
On the basis of the NIPT result and the ultrasound findings, a patient can decide whether or not she wants to have an invasive procedure (for example, CVS or amniocentesis).
There needs to be enough fetal DNA in the maternal blood to be able to provide a result. If there is insufficient fetal DNA in the sample (occurring in 3% of cases), another blood sample from the mother may be required. This will be processed in the laboratory at no extra charge.
Once the mother has taken an independent personal decision that she wants to have the non-invasive prenatal test performed, she will be asked to sign a consent form. An ultrasound scan is performed to check that the fetal heart is beating. Following this, a blood sample is taken from a vein in her arm.
The Harmony Prenatal Test does not provide information on other rare chromosomal abnormalities. If the ultrasound scan shows a high nuchal translucency or other major physical defects such as brain abnormalities, heart abnormalities, the risk for some rare chromosomal defects may be high. In such cases, the mother may choose to have a CVS or an amniocentesis.
The non-invasive prenatal test does not provide information on other physical defects such as spina bifida, or information on fetal growth. It is therefore advisable that the mother has all the usual ultrasound scans during her pregnancy.