What is fetal chromosomal abnormality screening? The definition given in the Technical Standards for Prenatal Screening and Diagnosis of Common Fetal Chromosomal Abnormalities and Open Neural Tube Defects promulgated by the Ministry of Health in 2011 is to identify certain pregnant women at high risk of having fetuses with congenital defects and genetic disorders from a population of pregnant women for further definitive diagnosis through simple, economical and less invasive testing methods. Screening for fetal chromosomal abnormalities is done mainly through maternal serum markers and ultrasound screening of the fetal body surface and vital organs to identify high-risk pregnant women for subsequent diagnostic testing. These screenings can detect fetuses with trisomy 21, trisomy 18, trisomy 13 and neural tube defects. How many types of chromosomal abnormality screening are there? Early pregnancy screening: performed at 10 to 13+6?weeks, mainly the duplex screening method with the combination of two serum markers, PAPP-A and β-hCG, and fetal nuchal translucency (NT) thickness measurement. Among them, maternal PAPP-A concentration will be decreased (mean 0.43 MoM) and β-hCG concentration will be increased (mean 1.98 MoM) in children with Down’s syndrome. Middle-trimester screening: It is performed at 15 to 20+6?weeks, mainly by triple screening with the combination of three serum markers, AFP, β-hCG and μE3, and quadruple screening with the combination of four serum markers, AFP, β-hCG, μE3 and Inhibin-A. The maternal AFP and μE3 concentrations of children with Down syndrome will decrease (mean levels of 0.74 MoM and 0.75 MoM, respectively), and β-hCG and Inhibin-A concentrations will increase (mean levels of 2.06 MoM and 1.77 MoM, respectively); midtrimester screening is the most widely used is screening method in China, and is also the screening method given in the Ministry of Health standards. Integrated screening: i.e. early pregnancy screening + mid-pregnancy screening, which finally results in a risk value, according to which the risk value is used to determine whether prenatal diagnosis is performed, mainly including: serological integrated screening and comprehensive integrated screening (serological integrated screening + NT). Sequential screening: there are two ways of sequential screening: first, segmental sequential screening: that is, early pregnancy screening is performed first, and the risk value of early pregnancy is derived, and prenatal diagnosis is recommended for those at high risk, and those at low risk receive mid-pregnancy screening until mid-pregnancy, and finally comprehensive risk analysis is performed according to the results of early and mid-pregnancy screening; second, discretionary sequential screening: that is, after early pregnancy screening, the screening population is divided into three categories, and those with risk values greater than 1/60 are subject to The second is sequential screening: that is, after screening in early pregnancy, the screening population will be divided into three categories, and those with risk values greater than 1/60 will undergo prenatal diagnosis; those with risk values less than 1/1000 do not need to undergo mid-pregnancy screening but only routine physical examination, while those in between will be screened in mid-pregnancy to determine whether to undergo prenatal diagnosis. The difference between sequential screening and integrated screening is that the former has a risk assessment after early pregnancy screening and decides whether to undergo mid-pregnancy screening according to the risk level, while the latter has no risk assessment in the middle, and goes directly to mid-pregnancy screening and assesses the risk level according to the results of both screenings. Screening population and how to choose the screening program When the age of pregnant women exceeds thirty-five years, the chances of babies with chromosomal abnormalities being born are greatly increased. Therefore, the Technical Standards for Prenatal Screening and Diagnosis of Common Fetal Chromosomal Abnormalities and Open Neural Tube Defects issued by the Ministry of Health stipulates that midtrimester maternal serological prenatal screening is applicable to midtrimester pregnant women under the age of 35 for screening. However, there is now a growing body of opinion that although the chance of birth of chromosomally abnormal infants is higher in pregnant women over 35 years of age, the proportion of chromosomally abnormal infants born to mothers over 35 years of age is not high among all chromosomally abnormal infants, and therefore all pregnant women should participate in screening before 20 weeks of pregnancy, regardless of their age. Before choosing which screening program to take, patients should be fully informed about the false-positive and detection rates, advantages, disadvantages, and limitations of the various screening methods, as well as the risks and benefits of the diagnostic program. The choice of screening procedure depends on a number of factors, including: gestational age at the time of the first prenatal visit, singleton and twin or multiple births, family history, previous maternal history, availability of NT measurement, sensitivity and limitations of screening tests, risk of invasive diagnostic tests, willingness to undergo early pregnancy screening, and willingness to terminate the pregnancy early. Whenever possible, screening programs with high detection rates and low false-positive rates (e.g., integrated screening or sequential screening) should be selected, especially if diagnostic tests are not available. Advantages and disadvantages of screening tests compared to diagnostic tests The advantage of screening tests is that they can identify people at high risk for Down syndrome, trisomy 21 and trisomy 18. Screening positive people have a higher rate of positive diagnostic tests than those who do not participate in screening tests, and screening can reduce the number of invasive diagnostic tests and the resulting adverse outcomes such as miscarriage. The most important disadvantage of screening tests is that the detection rate is not 100%. Pregnant women and their doctors should understand that screening tests provide a risk level rather than a diagnostic result and cannot detect all chromosomal abnormalities. Moreover, the presence of false positives can add to the psychological burden of a pregnant woman with a false positive screening test. In contrast, diagnostic tests can detect all chromosome trisomies, and can reliably detect sex chromosome aneuploidy, and large chromosome insertions and deletions. However, because it is an invasive test, it may be harmful to the mother and fetus. Non-invasive prenatal screening is an emerging technology that screens for chromosomal abnormalities by high-throughput sequencing of free DNA in the plasma of pregnant women. Free DNA in maternal plasma is a mixed set of DNA, of which 3-13% is of fetal origin after 10 weeks of gestation. Non-invasive prenatal screening can only screen for trisomy and sex chromosome abnormalities, and is indicated for pregnant women aged 35 years and older, pregnant women at high risk for ultrasound screening, pregnant women with a history of pregnancy and delivery of babies with chromosomal abnormalities, pregnant women with a family history of chromosomal abnormalities, and pregnant women at high risk for serum screening. Compared with traditional screening techniques, non-invasive prenatal screening has higher sensitivity and specificity, with sensitivities of 99.3%, 97.4%, 91.6% and 91% for trisomy 21, trisomy 18, trisomy 13 and sex chromosome polyploidy, respectively, and false positive rates of only 0.2%, 0.2%, 0.1% and 0.4%. Several countries have included it in their screening guidelines, but it is important to note that noninvasive prenatal screening is still a screening method and cannot replace diagnostic testing.