With the development of society, more and more women are undergoing prenatal screening during pregnancy. Even free prenatal screening is becoming popular. However, many people do not know what prenatal screening is actually screening for. Some people are blindsided by the results of prenatal screening for high risk. Is a high risk prenatal screening really that scary? The main reason why people feel scared when they see a high-risk prenatal screening report is because they don’t know enough about prenatal screening technology. As long as we understand what it really means, it’s not so scary.
Prenatal screening is based on the concentration of HCG, AFP and free estriol in the serum of the pregnant woman, combined with her age, weight and week of pregnancy to screen for trisomy 21, trisomy 18, neural tube defects and other diseases. Therefore, pregnant women should pay attention to filling in their personal information accurately, for example, they should fill in their actual age, some of them fill in their ID card age, which will cause the result to be wrong. Some pregnant women fill in the date of birth and the last menstrual period for the lunar calendar, which will also affect the results of the examination. We need to fill in the date of the solar calendar, the results need to be calculated by the computer, the computer does not recognize the lunar date. If the last menstrual period is not remembered, or if the menstrual cycle is irregular, a measurement of the fetal biparietal diameter is required to verify the corresponding gestational week. Otherwise, incorrectly filling in the gestational week will also affect the accuracy of the prenatal screening report.
Screening for diseases include: (not that these are the only abnormalities in nature, but prenatal screening can only screen for these diseases)
Trisomy 21, also known as Down’s syndrome (Downs), has a natural incidence of 1/700 and increases with maternal age, mainly due to increased HCG levels and decreased AFP and free estriol levels in maternal serum.
Trisomy 18, also known as Edwards syndrome, has a natural incidence of 1/5000 and is mainly characterized by a decrease in HCG, AFP and free estriol levels in the serum of pregnant women. The syndrome is lethal and the fetus can be delivered, but often survives less than one month after birth.
Neural tube defects include conditions such as anencephaly and spina bifida.
Prenatal screening is a screening test, not a definitive diagnosis. In cases such as trisomy 21, because Downs children are the most common of the chromosomal disorders. It is expected to detect 60-70% of Downs children, in other words it means that 30-40% of Downs children will be missed in pregnant women who undergo prenatal screening. The initial goal in designing the screening was to have a 5% expected true fetus with trisomy 21 among the high-risk pregnancies screened. (That is, 5 out of 100 high-risk pregnant women are actually at risk.) This is the reason prenatal screening was designed in the first place. Although prenatal screening is becoming more and more common, we are actually doing a terrible job of it at the moment. The percentage of high-risk pregnant women who actually have a problem with prenatal screening is about 2 to 3%.
One important reason why we are doing so badly is that many hospitals can now perform prenatal screening. Some hospitals have very small sample sizes, so these hospitals with small sample sizes cannot perform good quality control and cannot correct the test values. Because of the small sample size, it is not possible to perform valid statistics. Our hospital is one of the first prenatal screening centers in Quanzhou and is responsible for prenatal diagnosis of all pregnant women in Quanzhou. The sample size is quite large. So the results are relatively reliable.
Prenatal screening itself has a 30% risk of missing a child with trisomy 21. If the prenatal screening positive rate is high because we are not doing our job properly, it is possible that more pregnant women will be exposed to the risks associated with prenatal diagnosis. If the risk posed by a low prenatal screening rate is still not to be underestimated, there may be a few more births of children with trisomy 21, and the birth of these children often brings a heavy blow to the family. It is possible to destroy Chinese families that are just entering the well-to-do. A very authoritative scholar once said that if a pregnant woman did prenatal screening for low risk and ended up having a child with trisomy 21, even if the person signed an informed consent form willing to assume the risk of a 30% missed diagnosis, if they take our hospital to court, a significant number of hospitals will still lose because the 30% missed diagnosis is possible if your hospital does its duty to test carefully, and if you cannot get Valid accreditation, effective laboratory quality control records in the case, you will be held legally responsible. Perhaps because of this, academics now require further testing in cases where the risk of prenatal screening is greater than 1:1000 to reduce the risk of missed diagnoses, and so the term critical risk for prenatal screening has now emerged.
Some patients have asked me, if I have a prenatal delivery screening for high risk of Down’s, how about I do it again? Of course there is nothing wrong with doing it if you want to. Do you know how the 1:1,000 risk threshold for prenatal screening comes about? If you had a 1:100 prenatal screening, you will not have a 1:100 prenatal screening, and if you do, it is a coincidence. When you have a second prenatal screening it could be 1:500 or it could be 1:50, and if it is 1:500 and you have a third screening it could be in the traditional high risk category of 1:200. There is no point in repeatedly screening with an inaccurate screening test. So now the critical risk for prenatal screening has been expanded to 1:1000 because of the above experience that when a patient has a prenatal screening risk of 1:500 which used to be called low risk, then a second and third time there is a chance that they will be in the high risk category of 1:200 or 1:100. So it is only the academic community that has artificially expanded the range of recommended further tests in prenatal screening to 1:1000. Although the risk of missing Down’s children is smaller and the detection rate is higher, I wonder how many more people are having amniocentesis? The test will not be accurate with an imprecise test any more.
Whether prenatal screening is high risk, prenatal screening is critical risk, or prenatal screening is low risk, it represents risk after all. This screening method is theoretically feasible, but in practice, in today’s increasingly complex doctor-patient conflict, whether you are a doctor or a patient, you see the risk, even if it is a very small risk. The last thing patients want to hear is “it’s okay”, and the last thing doctors want to say is “it’s okay”.
The prenatal diagnosis positive rate in the so-called high-risk group of patients with prenatal screening is about 2 percent. This is a statistic of the percentage of all high-risk patients who have a real problem, not limited to how many have a real problem at a 1:50 risk, or how many have a real problem at 1:150.
Screening for a high risk of neural tube defects (OSB) can be done with further ultrasound testing only, and it is better to go to the spine at 16 to 18 weeks of pregnancy.
Screening for trisomy 21 or trisomy 18 is a fetal chromosomal abnormality, and this requires further testing with amniocentesis or cord blood sampling or non-invasive DNA. Only these three methods can directly detect fetal chromosomes. The main differences between the three are as follows.
Amniocentesis: The test is performed between 18 and 24 weeks of pregnancy and the miscarriage rate is about 5 per 1,000. In terms of accuracy, theoretically it should be 100% if chimerism is not included, unless the cells in the amniotic fluid are contaminated with other cells. A certain number of karyotypes, usually at least 20, are examined for karyotyping. Chimerism is a condition in which the fetus has a portion of normal chromosomes and a portion of abnormal chromosomes. The percentage of normal cells with abnormal nuclei is not always the same, or the percentage of normal cells is high or the percentage of abnormal cells is high, and the percentage of 21-trisomy chimerism is about 2%. If 20 karyotypes can be analyzed, it should be possible to exclude most cases of chimerism. However, sometimes the fetal cells contained in the amniotic fluid are small, or the cells are not growing well and there are many dead cells, so it is possible that 20 karyotypes cannot be analyzed and chimerism cannot be excluded 100% of the time.
Cord blood puncture: After 24 weeks of gestation, when the fetal cells in the amniotic fluid start to decrease, it is possible that the results of amniocentesis will not be obtained if amniocentesis is performed again. Therefore, after 24 weeks of gestation, we take the fetal cord blood to test for fetal chromosomes. The risk of miscarriage with cord blood puncture is about 1%. The operation is more complicated than amniocentesis. Therefore, we generally try to avoid performing cord blood puncture when choosing the method of prenatal diagnosis. We try to reduce the risk of prenatal diagnosis for pregnant women by having the patient undergo prenatal diagnosis before 24 weeks. Cord blood chromosome testing also has its advantages and is more accurate than the cells in amniotic fluid. It has a high cell content, fast growth rate, quick results, and high purity, and is less likely to be contaminated by other maternal cells.
Non-invasive DNA testing: After 12 weeks of pregnancy, 5-10 ml of maternal blood is taken from the mother’s vein, and the free fetal DNA is used to exclude the possibility of fetal trisomy 21, trisomy 18 and trisomy 13 abnormalities. There is no risk of miscarriage, and the results are available quickly (10-14 days). Current academic reports report figures of 99.97% accuracy. Because this testing technology cannot be done in hospitals at this time and requires testing at a genetic company, the government only requires 99% accuracy to be written in terms of publicity. The main difference between this technology and karyotyping performed after traditional amniocentesis or cord blood puncture is not in the accuracy rate. Rather, the difference lies in the scope of the test. As the following table shows.
These are the main chromosomal abnormalities that we humans face in newborns, followed by the incidence indicated. As for other chromosomal karyotypes other than those mentioned above, we generally do not need to consider them because abnormalities in other chromosome numbers are generally not born to the child i.e. abortion occurs during pregnancy. All of these chromosomal abnormalities can be detected by traditional amniocentesis and karyotyping after cord blood sampling. The non-invasive DNA testing technique only detects trisomy 21, trisomy 18 and trisomy 13. The reason for testing for these three chromosomal abnormalities is that fetuses with these three chromosomes can be born, but fetuses with trisomy 18 and trisomy 13 often do not survive more than one month after birth. For sex chromosomal abnormalities such as 45, XO, 47, XYY, 47, XXY, etc. non-invasive DNA testing technology will also test for these abnormalities, but for technical reasons there is no guarantee of accuracy and the current accuracy of testing for targeted chromosomal abnormalities is very low. In other words, the main difference between non-invasive DNA testing and traditional amniocentesis and cord blood sampling is that non-invasive DNA testing does not guarantee the detection of fetuses with sex chromosomal abnormalities.
There are also some chromosomal abnormalities such as structural abnormalities of fetal chromosomes, such as Robertson’s ectopic and balanced ectopic, which can be detected by traditional karyotyping but cannot be detected by noninvasive DNA technology. However, the detection of such abnormalities is not very significant. The incidence of these abnormalities is low and is not related to fetal intelligence, but is mainly manifested by an increased risk of miscarriage when the fetus has the next generation in adulthood.
So how do we choose a prenatal diagnosis technique?
There are currently some academic opinions. Fetuses with chromosomal abnormalities often show some signs on ultrasound, such as multiple calcified spots in the ventricles, enhanced echogenicity in the lower abdomen of the fetus, single umbilical artery, thickening of the zona pellucida behind the fetal neck, and hydrocystic lymphoma. These are called soft indicators of ultrasound detection. The so-called soft indicators are those that have an increased chance of occurrence in the case of fetal chromosomal abnormalities, but can also occur in normal fetuses. Therefore we cannot be sure if the fetus has chromosomal abnormalities and the fetus is at increased risk of having chromosomal disorders, so we may recommend further indicators for fetal chromosome testing. When there are these soft indicators present we can choose to perform traditional karyotyping by amniocentesis or cord blood puncture depending on the case, as this is a more comprehensive test. However, I believe that the strong ventricular spot, the enhanced fetal lower abdominal echo, and the bilateral choroid plexus cysts in the fetus before 22 weeks of gestation are of limited significance and I do not recommend paying too much attention to them and can be ignored.
In cases of purely prenatal screening for high risk of trisomy 21 or trisomy 18 without combined ultrasound abnormalities, pregnant women may consider the non-invasive DNA testing technique. This is because this technology allows 97% of pregnant women with high risk prenatal screening to avoid the risks associated with amniocentesis. The significance of putting this number into the overall population is understandable.
This is despite the fact that the technique has a 1 in 1,000 risk of missing a diagnosis. The main concern is the case of chimerism in DOWNs syndrome. Chimerism refers to a condition in which the fetus has partly normal and partly abnormal chromosomes. If the percentage of abnormal cells is low, chimerism may be missed, but not necessarily undetectable.
Any current prenatal testing technology is a double-edged sword, with a small risk of missed diagnoses and a small risk of miscarriage that cannot be ignored when placed in the context of the overall population. However, as individuals, we should be tolerant of the flaws in different prenatal diagnostic technologies when choosing them, depending on our individual needs, and there is no need to get too worked up about them.
If people can look at prenatal screening at a certain level, many things will be seen, and prenatal screening is a program that will be phased out soon. It is only with the current strength of the hospital can only carry out prenatal screening technology. Non-invasive venous blood prenatal testing hospitals currently do not have the relevant strength to carry out. Some of the medical institutions that have the ability to perform non-invasive prenatal blood testing belong to genetic companies that are similar in commercial terms. Many genetic companies are much larger than hospitals and are not to be underestimated. UW Genetics, for example, is the largest genetic company in the world and has undertaken the Chinese part of the Human Genome Project. Sooner or later, non-invasive prenatal screening with venous blood will be promoted. The reason for the delay in mass promotion is simple: the hospital is behind prenatal screening, and the government is behind the hospital. But what about non-invasive prenatal blood testing? It is the genetic companies that operate on an individual basis. With such huge profits, it is only when the government, the hospital and the genetic company coordinate that it can be done on a large scale. I think that NIV prenatal testing is a very good technology and will sooner or later gain popularity.
If both non-invasive venous blood and amniocentesis are unacceptable, please have a normal late delivery. But the fetus has about 2% chance of morbidity. At present, pregnant women with high risk of prenatal screening are recommended for further testing according to the “Management of Prenatal Diagnosis” issued by our government in ’03. So every medical professional will recommend you for further testing, but the final choice is yours.