What is fetal chromosomal abnormality screening? In 2011, the Ministry of Health issued the “Technical Standards for Prenatal Screening and Diagnosis of Common Fetal Chromosomal Abnormalities and Open Neural Tube Defects”, which defines screening as a simple, economical and less invasive test to identify certain pregnant women at high risk for congenital defects and genetic disorders from a population of pregnant women for further definitive diagnosis. 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 trisomy 21, trisomy 18, trisomy 13 and neural tube defects. What are the types of chromosomal abnormalities screening? First Trimester Screening: It is performed between 10 and 13+6 weeks and is mainly a duplex screening method combining two serum markers, PAPP-A and β-hCG, and fetal nuchal translucency (NT) thickness measurement. The maternal PAPP-A concentration is reduced (mean 0.43 MoM) and the β-hCG concentration is increased (mean 1.98 MoM) in children with Down’s syndrome. Second Trimester Screening: The screening is performed between 15 and 20+6 weeks, and is mainly a triple screening with the combination of three serum markers, AFP, β-hCG and μE3, and a quadruple screening with the combination of four serum markers, AFP, β-hCG, μE3 and Inhibin-A. The maternal AFP and μE3 concentrations in children with Down syndrome are reduced (mean levels 0.74 MoM and 0.75 MoM, respectively), and the β-hCG and Inhibin-A concentrations are increased (mean levels 2.06 MoM and 1.77 MoM, respectively); midtrimester screening is the most widely used screening method in China, and is also the screening method given in the Ministry of Health standards. Integrated Screening: Early pregnancy screening + mid-pregnancy screening, resulting in a risk value according to which prenatal diagnosis will be performed, mainly including: serological integrated screening and comprehensive integrated screening (serological integrated screening + NT). Sequential Screening: There are two types of sequential screening: first, Stepwise Sequential Screening, i.e., early pregnancy screening, early pregnancy risk value, prenatal diagnosis is recommended for high-risk patients, low-risk patients receive mid-pregnancy screening until mid-pregnancy, and finally, comprehensive risk analysis is performed based on the results of early and mid-pregnancy screening. The second is Contingent Sequential Screening (CSSS), where the population is divided into three categories after early pregnancy screening, with those with risk values greater than 1/60 being screened for prenatal diagnosis; those with risk values less than 1/1000 not requiring midtrimester screening but only routine physical examination, and those in between being screened for midtrimester screening. Prenatal diagnosis will be determined after midtrimester screening. The difference between sequential screening and integrated screening is that the former has a risk assessment after early pregnancy screening and the decision to undergo midtrimester screening is based on the risk level, while the latter has no risk assessment in between and proceeds directly to midtrimester screening and the risk level is assessed based on the results of both screenings. The detection rates of various screening methods According to the literature, the detection rates of various screening methods are shown in the following table: Screening population and how to select screening items The chance of birth of chromosomal abnormal babies increases greatly when the age of pregnant women exceeds thirty-five years, therefore, the Technical Standards for Prenatal Screening and Diagnosis of Common Fetal Chromosomal Abnormalities and Open Neural Tube Defects promulgated by the Ministry of Health stipulates that midtrimester maternal serological prenatal screening It is applicable to mid-pregnancy pregnant women under 35 years of age for screening. However, it is now increasingly accepted that although the chance of birth of a chromosomally abnormal infant 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 enough for all pregnant women to be screened before the 20th week of pregnancy, regardless of 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: week of gestation at the time of the first prenatal visit, singleton and twin or multiple births, family history, previous maternal history, availability of NT measurements, sensitivity and limitations of screening tests, risks of invasive diagnostic tests, willingness to undergo early pregnancy screening, and willingness to terminate the pregnancy early. Whenever possible, choose screening tests with a high detection rate and a low false-positive rate (e.g., integrated screening or sequential screening), 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. The screening test has a higher rate of positive diagnostic tests than those who do not participate in the screening test, and screening reduces the number of invasive diagnostic tests, resulting in fewer miscarriages and other adverse outcomes. The most important disadvantage of screening tests is that the detection rate is not 100%. Pregnant women and physicians 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 increase the psychological burden of pregnant women with false positive screening tests. 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. Noninvasive Prenatal Screening (NPS) is an emerging technology that screens for chromosomal abnormalities by high-throughput sequencing of free DNA in maternal plasma. Free DNA in maternal plasma is a mixed set of DNA, of which 3-13% is fetal in 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 chromosomally abnormal babies, pregnant women with a family history of chromosomal abnormalities, and pregnant women at high risk for serological 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 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.