- Commonalities and differences between NIPT (new type of prenatal diagnosis) and maternal serum markers
- What is NIPT (New Prenatal Testing)
- What are maternal serum markers
- Differences between NIPT (new type prenatal diagnosis) and maternal serum markers
- Characteristics of Hiro Clinic NIPT’s NIPT (New Prenatal Diagnostic Test) compared to maternal serum markers
- summary
Similarities and differences between NIPT (new prenatal testing) and maternal serum markers
NIPT (New Prenatal Testing) involves taking blood from a pregnant woman and examining the DNA related to the fetus contained in the blood to check whether the fetus in the womb is suspected of having chromosomal disorders, mainly trisomy 21 (Down syndrome) , trisomy 18 (Edwards syndrome) , and trisomy 13 (Patau syndrome) . Depending on the pattern of recent tests, it is also possible to check in detail for all chromosomes, chromosomes that determine gender, and partial deletions and duplications of all autosomes .
On the other hand, maternal serum markers, a characteristic of NIPT, look at certain components contained in the blood taken from a pregnant woman to determine whether trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), or neural tube defects (open neural tube defects) are present in the fetus.
The common denominator is that the risks are small and the results are inconclusive.
What NIPT (non-invasive prenatal testing) and maternal serum markers have in common is that they are both prenatal tests to check whether chromosomal abnormalities or genetic diseases are present in the fetus in the womb of a pregnant woman.Furthermore, they are both “non-invasive tests” that pose little disadvantage or risk to the pregnant woman or fetus, and “non-definitive tests” that cannot be judged as certain based on the results alone.
There are differences in the target diseases and implementation time
The main differences between NIPT (new prenatal testing) and maternal serum markers are as follows:
- Inspection period
- Target disease to be investigated
- Sensitivity (probability of actually having an affected fetus if the test is positive)
- cost
- Advantages and disadvantages
Although NIPT and maternal serum markers have in common that they are non-invasive and non-deterministic tests, it is important to keep in mind the differences mentioned above. As a prenatal test that is considered for early pregnancy, it is important to decide whether to take the test based on the characteristics and differences of the test, or to go through the pregnancy without taking the test from the beginning.
From here, we will explain the characteristics, advantages and disadvantages of NIPT and maternal serum markers, as well as the differences between the two tests.
What is NIPT (New Prenatal Testing)?
NIPT (Non-Invasive Prenatal Genetic Testing) is an abbreviation for “Non-Invasive Prenatal Genetic Testing”. Clinical testing began in the United States in 2011 and was introduced into clinical practice in Japan in 2013.
It is known to be a minimally invasive and highly sensitive test for pregnant women and fetuses , and it is performed at many institutions, with an increasing number of people taking NIPT (new type prenatal testing) every year.
A blood sample is taken after the 6th week of pregnancy
NIPT (New Prenatal Testing) involves taking a blood sample after the sixth week of pregnancy and examining the DNA that is floating in the blood and originates from the fetus. Since about 10% of the DNA in a pregnant woman’s blood that is related to the fetus can be confirmed through the placenta, it is possible to examine the genetic sequence of about 20 million DNA fragments .
The results will be given to the test taker within 2 to 10 days and will be notified as “positive,” “negative,” or in rare cases, “pending judgment.” The cost varies depending on the medical institution, but starts from about 50,000 yen .
Testing for certain chromosomal disorders in fetuses
NIPT (new type prenatal testing) mainly checks whether the fetus has a certain chromosomal disorder.
Trisomy 21
There is an extra chromosome 21, making it three. Possible symptoms include intellectual developmental disabilities and delayed motor development. The probability that a pregnant woman whose fetus has a chromosomal disorder will get a positive result = sensitivity 99.9%, the probability that a pregnant woman whose fetus does not have a chromosomal disorder will get a negative result = specificity 99.90%. The positive predictive value of the result is 93.87% at 10 weeks pregnant at age 40. The negative predictive value is 99.9%.
Trisomy 18
There is an extra copy of the 18th chromosome, making it three copies. There is delayed growth from fetal stage, complications such as heart disease, and retarded intellectual and physical growth. The symptoms are more severe than those of trisomy 21 (Down syndrome) . The test has a sensitivity of 99.9% and a specificity of 99.90%. The positive predictive value is 88.75% at 10 weeks pregnant at age 40, and the negative predictive value is 99%.
Trisomy 13
There are three copies of the 13th chromosome, one extra. There are growth disorders and physical morphological complications, and intellectual and physical growth is delayed. The symptoms are more severe than those of trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome) . The sensitivity of the test is 99.9%, and the specificity is 99.90%. The positive predictive value is 71.04% at 10 weeks pregnant in a 40-year-old woman.
Recently, it has become possible to check for the following additional diseases by undergoing NIPT (non-invasive prenatal testing) .
Sex chromosome aneuploidy
Turner syndrome (monosomy X)
It occurs only in females and is characterized by a complete or partial absence of one of the two X chromosomes normally present. Patients are extremely short in stature and lack secondary sexual characteristics, but do not suffer from intellectual disabilities.
Klinefelter syndrome (47,XXY)
It occurs only in males, and causes poor development of secondary sexual characteristics and a tendency towards feminization. There is no decline in intelligence or significant disability.
Triple X syndrome (trisomy X)
It only affects women and does not cause any physical disabilities.
Jacob syndrome (XYY syndrome)
It occurs only in men and has few physical characteristics other than tall stature.
Whole chromosome aneuploidy testing
All chromosomes are tested, including chromosomes 1-22 and the sex chromosomes.
Autosomal partial deletion/duplication disorders
Tests for partial deletions and duplications of all autosomal regions, which check for abnormalities in all chromosomes or chromosomal structure, are only performed at a limited number of medical institutions, and are not offered at all medical institutions.
It is highly accurate and can be performed early in pregnancy.
The advantage of NIPT (non-invasive prenatal testing) is that it is a minimally invasive test, can be performed early in pregnancy, and is more accurate than other prenatal tests . The fetal diseases that can be confirmed include a wide range of diseases such as chromosomal disorders, sex chromosome abnormalities, and partial deletions and duplications of all autosomal regions .
However, NIPT alone cannot definitively diagnose all chromosomal diseases and abnormalities. If the result is positive, a definitive diagnosis must be made by taking an amniotic fluid sample if desired, and couples are required to decide in advance whether or not to undergo such a definitive diagnosis.
What are maternal serum markers?
Maternal serum markers are the least invasive of the several prenatal tests available, and are not conclusive in diagnosis, having been introduced to Japan from overseas in 1994. By taking a blood sample and examining specific components in detail, the probability of trisomy 21 , trisomy 18 (single pregnancy only), and neural tube defects (brain and spinal cord disorders caused by abnormal formation of the neural tube, such as anencephaly and spina bifida) can be determined.
There are triple marker and quadruple tests.
The “double marker test” that checks two components in the blood (AFP and hCG) first became popular as a maternal serum marker, then the number of components to check increased and the “triple marker test” and “quad test” were developed, with the quadruple test now being the mainstream. The triple marker test can be taken from 14 weeks 0 days of pregnancy, and the quadruple test can be taken from 15 weeks 0 days of pregnancy up until around the first half of the 16th week.
Double Marker Test
Combining the results of AFP (alpha-fetoprotein: a hormone secreted by the fetus) and hCG (human chorionic gonadotropin: produced in the fetal liver)
Triple Marker Test
Combine the results of AFP, hCG, and uE3 (unconjugated estriol: produced by fetal adrenal cortex hormone, liver, and placenta)
Quattro Test
Combining the results of AFP, hCG, uE3, and InhibinA
Each component is said to be produced by the fetus and placenta during pregnancy, and the amount increases or decreases as the pregnancy progresses.Furthermore, the amount can be confirmed to increase or decrease if the fetus has a target disease.
The Quadro Test can be taken from 15 days 0 to 21 weeks 6 days of pregnancy, but if the result is positive, it is recommended to take the test by around 18 weeks of pregnancy, with the amniocentesis being considered in advance. The Quadro Test calculates the incidence of the target disease by including the factors listed below in the values of the four components.
- Age, standard values for Japanese people (measurements vary by race)
- How many weeks pregnant you are (the amount of ingredients changes as your pregnancy progresses)
- Body weight (differences in body weight result in different dilutions of ingredients)
- Family history ( is there a family history of trisomy 21 or neural tube defects)
- Insulin-dependent diabetes mellitus (there have been reports of differences in the amount of ingredients in pregnant women with a history of the condition)
The quattro test uses four components and the factors mentioned above to measure the predicted probability for each pregnant woman. It is known that the older the woman is, the higher the risk of fetal morbidity.
Check the probability of three fetal disorders
The following fetal diseases can be detected with the quadruple test:
- Trisomy 21 (Down Syndrome)
- Trisomy 18 (Edwards syndrome)
- Neural tube defects (open neural tube defects such as anencephaly and spina bifida)
The positive rate for pregnant women aged 35-39 is about 18%, for those aged 40 and over it is about 40%, and for those under 35 it is about 5%. It takes about 1-2 weeks for the results to be returned , and it costs about 20,000-30,000 yen .
If the result is positive, consider undergoing a test that will lead to a definitive diagnosis.
The quattro test gives results with a probability of 1/500.
This means that the probability of one woman with a test result of 1/500 being pregnant with a fetus with the target disease is 1.
Maternal serum markers, like NIPT (new type prenatal testing) , are less invasive to pregnant women and fetuses, and the cost of taking the test is relatively low . It is important to keep in mind that it is an indefinite diagnosis, and if the result is positive, you must consider whether to take a test that will lead to a definitive diagnosis, such as a test to collect and examine amniotic fluid.
Differences between NIPT (new prenatal testing) and maternal serum markers
There are two main similarities between NIPT (new prenatal testing) and maternal serum markers.
- Since the test can be performed simply by taking a blood sample, it has little impact on the pregnant woman or the fetus.
- The results of the test are not conclusive as to the diagnosis.
Differences between the two tests
NIPT (New Prenatal Testing)
- Time: After 10 weeks and 0 days of pregnancy
- Subjects: Trisomy 21 (Down syndrome) , Trisomy 18 (Edwards syndrome) , Trisomy 13 (Patau syndrome) , Sex chromosome, total chromosome, and chromosome deletion disorders (depending on the institution)
- Sensitivity: 99% or more
- Cost: Approximately 55,000-264,000 yen (tax included)
Maternal serum markers
- 時期：妊娠15週0日〜18週頃
- Subjects: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Neural tube defects (open neural tube defects)
- Sensitivity: Trisomy 21 (86.67%), Trisomy 18 (77.27%), Neural tube defects (open neural tube defects) (82.98%)
- Test cost: Approximately 20,000 to 30,000 yen
The main difference is when the test is available.
NIPT is available from the 6th week of pregnancy , while maternal serum markers are available from the 15th week of pregnancy , so NIPT can grasp the condition of the fetus from an earlier stage.
NIPT also has higher accuracy, with a sensitivity (the probability that the test is positive and will remain positive after the baby is born) of 95% for trisomy 21 (Down syndrome) and a specificity (the probability that the test is negative and will remain negative after the baby is born) of 96.5%.
Characteristics of Hiro Clinic NIPT (New Prenatal Testing) compared with maternal serum markers
Hiro Clinic NIPT ‘s NIPT (new prenatal diagnosis) allows you to take optional tests such as whole chromosome and whole autosome partial deletion/duplication disease tests in addition to the usual NIPT. This means that there are more types of fetal diseases that can be confirmed compared to conventional NIPT and maternal serum marker tests.
Another feature is that if certain conditions are met, such as using the amniocentesis support provided by a testing institution affiliated with the clinic, the cost of amniocentesis if the NIPT result is positive can be subsidized up to 200,000 yen (one time only) .
Summary
NIPT (non-invasive prenatal testing) and maternal serum markers are tests that can be taken early in pregnancy and pose little risk to the pregnant woman and fetus. NIPT can check for trisomy 21 (Down syndrome) , trisomy 18 (Edwards syndrome) , trisomy 13 (Patau syndrome), and additional partial deletions and duplications of all chromosomes, sex chromosomes, and all autosomes in the fetus. Maternal serum marker tests check for neural tube defects such as trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and spina bifida.
The two tests discussed here are tests in which the results alone do not provide a definitive diagnosis; in order to make a definitive diagnosis, it is necessary to undergo tests such as collecting amniotic fluid.
Generally, tests to collect and examine amniotic fluid are conducted after the 15th week of pregnancy, with the results being available two to three weeks later. If your NIPT or maternal serum markers are positive and you decide to undergo amniocentesis, keep in mind that it will take some time before you receive a final diagnosis.
Article Editorial Supervisor
Private: Dr. Hiroshi Oka
NIPT Specialist Clinic, Doctor of Medicine
Graduated from Keio University, School of Medicine
