Non-invasive Prenatal Testing
Pregnant women above the age of 35, who are considered to have an increased risk of producing a foetus with trisomy 21 or Down syndrome, have traditionally been offered genetic counselling.
Invasive prenatal diagnosis, such as amniocentesis or chorionic villus sampling (CVS), is also offered, though only to those women considered at increased risk of aneuploidy (a condition in which the number of chromosomes in the nucleus of a cell is not an exact multiple of the monoploid number) in part because of its link to pregnancy loss.
Noninvasive prenatal testing (NIPT) is a recently developed genetic test of the maternal serum that produces a higher detection rate for trisomy 21 and other chromosomal aneuploidies in high-risk pregnancies.
NIPT works by analysing cell-free DNA (cfDNA) in the maternal serum. As approximately three to 15 per cent of cfDNA in the maternal blood is of placental or foetal origin, analysis of cfDNA can help identify foetuses affected with trisomy 21 and several other foetal aneuploidies. This form of testing has a higher sensitivity and specificity for trisomy 21 than other aneuploidy screening tests.
Now the American College of Obstetrics and Gynecologists (ACOG) is recommending that women, regardless of maternal age, be offered prenatal assessment for aneuploidy. NIPT is one option that can be used as a primary screening test based on having one or more of the following risk factors:
l Maternal age of 35 years or older at delivery
l Foetal ultrasound findings indicate an increased risk of aneuploidy
l History of a prior pregnancy with a trisomy
The ACOG further states that NIPT should be an informed patient choice after pretest counselling and should not be part of a routine prenatal laboratory assessment. NIPT should not be offered to low-risk women because it has not been sufficiently evaluated in this group.
However, a negative NIPT result does not ensure an unaffected pregnancy. A woman with a positive test result should be referred for genetic counselling and should be offered invasive prenatal diagnosis for confirmation of the test results.
There are multiple advantages of NIPT over current screening tests, including both higher detection rates and, in the case of high-risk pregnancies, lower false positive rates. First, NIPT is a single blood test compared with some current screening tests that involve multiple blood samples. Second, NIPT can be performed at any gestational age after 9-10 weeks, whereas current screening tests can be performed only in the first and second trimester up to 22 weeks of gestation. Given the greater specificity and lower false-positive rate of NIPT, fewer invasive diagnostic procedures are needed, which may result in a decrease in procedure-related miscarriage.
There are, however, limitations to NIPT including the possibility of test failure. NIPT is not a diagnostic test and confirmatory invasive testing (chorionic villus sampling or amniocentesis) is required in the presence of any abnormal results. Another limitation of NIPT is that it only focuses on the common trisomies and cannot test for all genetic diseases.
Two main types of NIPT methods are commercially available: massive parallel sequencing (MPS) technology and the single-nucleotide polymorphism (SNP) based method. Both screen for foetal genetic disorders that arise from extra or missing chromosomes, such as trisomy 21, trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome), along with foetal sex and sex chromosome disorders.
The MPS method can be used in a twin pregnancy (screen for trisomies only) and egg donor pregnancy. The SNP-based approach can uniquely detect vanishing twins and triploidy (where the foetus has an extra copy of all of the chromosomes). The trisomy 21 detection rate is 99 per cent and the false positive rate is less than 1 per cent. Turnaround time is about 14 days.
In summary, although NIPT appears to be superior to existing screening tests in terms of detecting trisomy 21 in high-risk women, it is validated only in that group. It should be used as a screening test only, and should not be considered as being diagnostic.
DR BONGKOCH NARAPHUT is an OB/GYN and Maternal Foetal Medicine Specialist at Samitivej Sukhumvit Hospital’s Women’s Health Centre. Call (02) 711 8555-6
