Introduction:
The introduction of cell-free deoxyribonucleoside (DNA) based non-invasive prenatal testing (NIPT) in the United States in 2011 accelerated the practice of the medical organization. The healthcare providers have adopted the new technology by issuing their opinion. Patients at later gestational ages (less than 22 weeks) have limited aneuploidy testing options. Cell-free DNA based-NIPT is a non-invasive procedure performed in patients at a gestational age of less than 23 weeks. NIPT is the accurate prenatal screening for pregnant women. NIPT reduced fetal loss by 94 percent by identifying trisomy cases in pregnancy. The most common aneuploidy found at birth is down syndrome. Down syndrome is caused by trisomy of chromosome no- 21. NIPT screening is done for Down syndrome in many countries.
What Is Fetal Aneuploidy?
Human cells consist of genetic information, which is present in deoxyribonucleoside (DNA). The set of DNA Is called the genome. It consists of a map that provides information about the whole genome, which is important for embryonic development. The human genome provides a road map of the cell development of an unborn baby (fetus) into an adult. The fetus is made up of a set of chromosomes inherited from their parents. The presence of an abnormal chromosome in the fetus is called fetal aneuploidy. Aneuploidy refers to one or more extra chromosomes or the absence of one or more chromosomes.
What Is Non-invasive Prenatal Testing?
DNA consists of a group of 23 sets of chromosomes (genetic material). This DNA is present in the nucleus of the cell In the human body. When a cell undergoes apoptosis (programmed cell death), all the intracellular content (DNA) is released into the blood. The fragment of DNA is found in the blood known as cell-free DNA (cfDNA). These intracellular content are either broken down or excreted through the body. The amount of cell-free DNA secreted depends upon different organs or tissue of the body. Some conditions, such as cancer, blood transfusion, and pregnancy, contribute to total cell-free DNA present in the body.
The technique of a non-invasive test is called the cfDNA test. The technique of non-invasive aneuploidy test is known by other names such as ‘‘non-invasive prenatal screening’’ (NIPS) or ‘‘non-invasive prenatal testing’’ (NIPT). It is done for fetal aneuploidy detection. The risk of Down syndrome is associated with the second or third trimester of pregnancy. Down syndrome is a condition in which aneuploidy of chromosome number 21 occurs, causing abnormal fetus development. The majority of aneuploidy fetuses abort (termination of the fetus). The incidence and severity of Down syndrome are higher in pregnancy, focusing on the need for prenatal (before the baby's birth) screening. The ultrasound is used for screening in the first-trimester screen (FTS). The newest technique, using cfDNA, is currently the best screening for trisomy 21. Most clinicians report a 99 percent sensitivity or detection rate. NIPT is also used to detect other aneuploidies, such as Edwards syndrome (trisomy 18), Patau syndrome (trisomy 13), and sex chromosome aneuploidies.
How Is Non-invasive Prenatal Testing Done?
NIPT is done by collecting blood samples from pregnant women. It is a non-invasive test and can be done in women at a gestational period of less than 23 weeks.
NIPT is done with the help of cfDNA, which is performed with a blood sample taken at or after three months of pregnancy. The test report usually takes seven to ten days to come. It provides information on the trisomy of chromosome 21 and the presence of any abnormalities in a chromosome. NIPT measures the concentration of cfDNA.
The clinicians select women for NIPT. The criteria for selecting patients for NIPT are
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Pregnant women at later stages (23 weeks).
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Abnormal ultrasound indicates an abnormality in the fetus.
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Abnormal finding during examination.
This NIPT analyzes the mother's cfDNA in whole genome sequencing. This test detects trisomy of chromosomes 13, 18, and 21. If the concentration of cfDNA from that chromosome is higher than expected for a pregnant patient normally, then a fetal trisomy can be predicted. In the first trimester, the screening utilizes two serum proteins, human gonadotropin (HCG) and pregnancy plasma protein, as a serum protein marker. These tests provide preliminary information about trisomy in the first trimester only. NIPT only identifies 85 percent of fetal cases in the first trimester and gives 5 percent of false positive reports, which is its main drawback. The evidence of ultrasound should be considered before NIPT. NIPT has a high accuracy rate in the screening of fetal trisomies.
What Are the Advantages of Non-invasive Prenatal Testing?
The following are the advantages of NIPT:
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NIPT is a non-invasive method that can easily be done in pregnant women.
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NIPT provides preliminary information on chromosomal abnormality.
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This invasive testing yields a perfect diagnosis instead of an assumption.
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Cell-free DNA testing is used to detect fetal Rh (rhesus factor is present in the blood grouping system in humans) status in Rh-negative mothers.
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Cell-free DNA testing is useful for the early determination of the gender of a baby in pregnancies, which resolves the risk for sex chromosomal-linked disease by proper medical intervention in the fetus.
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A positive ultrasound or blood test facilitates NIPT to avoid false reports of abnormalities.
What Are the Disadvantages of Cell-free DNA Testing?
The following are the disadvantages of NIPT:
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Sometimes, non-invasive prenatal testing gives false reports irrespective of the presence of normal chromosomes.
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Cell-free DNA testing does not always give a result. It gives false results in one or two percent of cases.
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This screening test is more expensive than other screening tests.
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Several studies do not recommend using cfDNA in twin gestation (period of pregnancy).
Conclusion:
The healthcare providers are responsible for educating patients and counseling them for the test. Patients should know about the advantages, disadvantages, and costs of the various available screening tests for aneuploidy as they do not have to go for a test twice for detecting aneuploidy. Doctors should guide them toward a test that best suits their needs. Several studies concluded that NIPT is the best non-invasive technique for detecting aneuploidy in pregnancy. However, patients should not opt for a cfDNA test without any ultrasound or blood examination.
