Regarded as being of an advanced maternal age with increased risk of producing a fetus with trisomy 21, pregnant women above the age of 35 years old have traditionally been offered genetic counseling. Invasive prenatal diagnosis, such as amniocentesis or chorionic villus sampling (CVS), is also offered but only to those women considered at increased risk of aneuploidy, 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 analyzing cell free DNA (cfDNA) in the maternal serum. As approximately 3%-15% of cfDNA in the maternal blood is of placental or fetal origin (fetal fraction), analysis of cfDNA can help identify fetuses affected with trisomy 21 and several other fetal aneuploidies. This form of testing has a higher sensitivity and specificity for trisomy 21 than other aneuploidy screening tests.
The American College of Obstetrics and Gynecologists (ACOG) recommends 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 in women at increased risk of aneuploidy based on having one or more of the following risk factors:
The ACOG further states that NIPT should be an informed patient choice after pretest counseling 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.
A negative NIPT result does not ensure an unaffected pregnancy. A woman with a positive test result should be referred for genetic counseling and should be offered invasive prenatal diagnosis for confirmation of the test results (ACOG 2012).
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.
Currently, there are limitations to NIPT including the possibility of test failure (2.6%-5.4%). Because NIPT is a screening test, both false positive (0.2%-1%) and false negative results can occur. 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.
The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommends that all women should first be offered a first trimester ultrasound scan regardless of their intention to undergo NIPT. Genetic counseling is strongly recommended prior to this test in order to inform persons being tested about the advantages and limitations of the test as applied to a unique person.
There are two main types of NIPT methods that are commercially available, massive parallel sequencing (MPS) technology and the single-nucleotide polymorphism (SNP) based method. Both NIPT methods screen for fetal genetic disorders that arise from extra or missing chromosomes, such as trisomy 21, trisomy 18, and trisomy 13, along with fetal sex and sex chromosome disorders. NIPT can also screen conditions where a small part of the chromosome is missing, called a microdeletion, such as Di-George, Cri-du-chat, Prader-Willi, or Angelman syndrome.
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 fetus has an extra copy of all of the chromosomes). The trisomy 21 detection rate is 99% and the false positive rate is less than 1%. Turnaround time is about 14 days.
Conclusion: NIPT is a noninvasive genetic screening test that has shown promising results for the detection of trisomy 21, 18 and 13 in clinical trials of women identified by screening as having a high risk pregnancy. When utilizing NIPT, it is important to provide pre-test and post-test counseling regarding the risks and benefits and limitations of the test, as well as to review and interpret the results. 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. In addition, it tests only for common chromosome abnormalities and cannot test for all genetic diseases. NIPT is limited by test failure with a small percentage of no results reported. Negative NIPT results do not ensure an unaffected pregnancy. For women who receive positive results from an NIPT, genetic counseling is recommended along with invasive testing to confirm the diagnosis.
M.D., Faculty of Medicine, Srinakharinwirot University, 1997.