I. What is non-invasive DNA prenatal testing
In the past, in order to detect chromosomal abnormalities in fetuses early, three means, such as amniocentesis, fetal chorionic villus cell taking and fetal umbilical vein blood, were often used to collect cells from pregnant women for prenatal testing and screening. However, these methods are invasive and associated with a miscarriage rate of about 1%. Pregnant women and their families are very worried and fearful about this. So is there a way to avoid trauma and achieve safe and accurate detection of fetal chromosomal abnormalities?
In 1997, a professor discovered that maternal blood contains free fetal DNA, almost all of which comes from the trophoblast of the placenta. Small amounts are present in maternal blood at 4 weeks of gestation, and levels rise and persist at 8 weeks, at 3-13% (and higher). This becomes the basis for non-invasive DNA testing/. The presence of free fetal DNA in maternal peripheral blood, which is low at about 4 weeks of gestation, increases significantly at 8 weeks of gestation, is present steadily with increasing weeks of gestation at levels of about 3-13%, is thought to be primarily of placental origin, and is cleared from maternal blood within hours after delivery. The presence of fetal free DNA in maternal blood provides the theoretical basis for noninvasive DNA testing.
The DNA prenatal testing technology only requires taking maternal venous blood, sequencing the free DNA fragments (including fetal free DNA) in maternal peripheral plasma using next-generation DNA sequencing technology, and performing bioinformatics analysis of the sequencing results, from which fetal genetic information can be obtained to detect whether the fetus has trisomy 21 (Down’s syndrome), trisomy 18 (Edward’s Trisomy 21 (Down’s syndrome), Trisomy 18 (Edward’s syndrome) and Trisomy 13 (Patau’s syndrome) are three major chromosomal disorders.
The technology was tested in a clinical trial in 2011, which was designed and performed according to international standards. Using a non-invasive DNA prenatal testing platform, 2236 random samples from outpatient clinics were subjected to deep sequencing of free DNA in maternal peripheral blood and combined with bioinformatics analysis methods to quantify the information of fetal segments contained in free DNA and make a determination of their genetic status. The results of this clinical trial show that the accuracy of non-invasive DNA prenatal testing technology for the three major chromosomal aneuploidy disorders (Down’s syndrome, Edward’s syndrome, and Patau’s syndrome) in fetuses above 12 weeks of gestation is close to 100%, and the false-positive rate is 0.05%.
II. Advantages of non-invasive DNA
1.Only 5ml of blood is taken, which greatly reduces the invasiveness of the test and maximizes the relief of the huge pressure caused by the current prenatal test to the pregnant women’s psychology and relieves their anxiety and fear.
2. The accuracy rate of non-invasive DNA prenatal testing is more than 99%, and the false positive rate (that is, the chance of no problem becoming a problem) is very low, 0.05-0.1%, which can be said to be very, very reliable.
3, non-invasive DNA prenatal testing false negative rate (that is, the rate of missed diagnosis) is also very low, about 0.0-13.04%, so this technology has further improved the level of prevention and treatment of birth defects in China’s newborns.
4, the previous serological screening is mainly screening for trisomy 21, trisomy 18, while non-invasive DNA prenatal testing on this basis, adding the screening of trisomy 13 and sex chromosome abnormalities and other diseases.
5.Non-invasive DNA prenatal testing can be performed in early and middle pregnancy as well as late pregnancy, regardless of age and gestational week.
6, IVF pregnant women can also do.
The positioning of non-invasive DNA prenatal testing technology
Authoritative experts almost unanimously agree that fetal free DNA testing technology based on second-generation sequencing should be clearly located in the field of prenatal screening for trisomy 21, trisomy 18, trisomy 13, and some sex chromosome abnormalities, which can be called “near-diagnostic screening”.
On November 20, 2012, the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Maternal-Fetal Medicine (SMFM) jointly issued a committee guideline: Non-invasive DNA prenatal testing can be recommended as primary screening for people at high risk for aneuploidy according to the following indications.
1. Maternal age over 35 years
2. Ultrasound results indicating high risk for aneuploidy
3, having given birth to a child with trisomy
4, early pregnancy, middle pregnancy or triple screening or quadruple screening showing positive aneuploidy results
5. Balanced Robertsonian translocation of the parents and a fetus at high risk for trisomy 13 or trisomy 21
This statement indicates that there is an industry consensus in the U.S. obstetrics and gynecology community that clearly supports the use of non-invasive DNA prenatal testing for primary screening in high-risk, high-risk populations. This clear signal also signals a major step forward in the field of non-invasive DNA prenatal testing at the international level.
IV. Populations to which non-invasive DNA is adapted
By 2012, the method can accurately detect the three major chromosomal disorders of Down’s syndrome (T21), Edward syndrome (T18), and Papanicolaou syndrome (T13). The non-invasive nature of non-invasive DNA prenatal testing can avoid the risk of miscarriage and infection due to invasive diagnosis. The maturity of DNA sequencing technology ensures the accuracy of the technology. Pregnant women can be tested at 12 weeks or more, and the test results can be available in 10 working days.
To date, there is no effective treatment for chromosomal disorders, so the best way to reduce the risk of having a child with a chromosomal disorder is through early prenatal genetic counseling and prenatal testing, diagnosis, and problem solving.
Internationally, this technology is already available in the United States, and the cost of this test is partially covered by commercial insurance in some areas (states), making it popular with pregnant women, especially those of advanced age. However, due to the relatively conservative nature of obstetric technology and religious beliefs in Europe, the technology has been slow to develop compared to the United States. Data from foreign clinical trials show that the detection rate of non-invasive DNA prenatal testing technology for the three major chromosomal disorders of the fetus (Down’s syndrome (T21), Edward’s syndrome (T18), and Patau’s syndrome (T13)) is above 90%.
In mainland China, only a few companies with real qualification and strong technical strength have the ability to develop and implement this technology. Through cooperation, this technology has been spreading like a spring in mainland China since 2010, benefiting the majority of pregnant women.
Every couple is at risk of having a child with a chromosomal disorder. The incidence of chromosomal disorders is random and occasional, with no prior warning, no family history and no clear history of toxic exposure, and the incidence increases with maternal age. There is no effective treatment for chromosomal disorders.
1, pregnant women of advanced age (age ≥ 35 years) who do not want to opt for invasive prenatal diagnosis.
2, Pregnant women whose serology is high risk in early or mid-pregnancy, or whose single index value is altered and who do not want to do invasive prenatal diagnosis
3.Pregnant women with increased fetal NT value or other anatomical structure abnormalities on ultrasound during pregnancy who do not want to choose invasive prenatal diagnosis
4, pregnant women who are not suitable for invasive prenatal diagnosis, such as virus carriers, placenta previa, placenta hypoplasia, too little amniotic fluid, RH blood group negative, history of miscarriage, preterm abortion or precious children
5. Pregnant women whose amniocentesis cell culture has failed and are unwilling to receive it again or cannot undergo invasive prenatal diagnosis again.