Down syndrome is one of the most serious birth defects, also known as “trisomy 21” or congenital dysmorphia, caused by the non-segregation of chromosome 21 in the mother’s egg. The theme of the 2017 International Down Syndrome Charities is: “My Voice, My Community”. -gives courageous voices and attention to people with Down syndrome throughout the community, and influences government policy and action.”
A child with Down’s syndrome is born approximately every 20 minutes in China, so standardized prenatal screening for expectant mothers is extremely important to prevent the birth of children with Down’s syndrome, but the detection rate is only 60 to 70 percent. As the age of two children becomes more and more popular in China, the screening for Down’s syndrome during pregnancy should be given more attention. On this occasion, we would like to talk to you about Down syndrome in the eyes of obstetricians and gynecologists.
A. “Down baby”, the problem is not only “intelligence”
There are many people who believe that Down’s syndrome is only a delay in intellectual development, but in fact this is only one aspect. More than half of the patients have congenital heart disease, duodenal atresia, umbilical bulge, cystic lymphadenoma and other physical defects, and as they grow older, they are unable to take care of themselves, and there is no cure. The average life expectancy of a person with Down’s syndrome is only 16.2 years. Once the child is born, it will bring a heavy mental and economic burden to the family and society.
Who is more likely to have a “Down baby”?
1.Advanced pregnancy
According to the genetic typing of Down syndrome, there are standard, chimeric and translocation types.
The majority of children with Down’s syndrome have chromosome 21 dissections at the time of maternal egg formation. Ovarian decline is positively correlated with age, and as the ovaries of older women age, germ cells or fertilized eggs are prone to chromosomal segregation or chromosomal aberrations during cell division. So whether you have a first child or a second child, don’t be too late!
2.Insufficient folic acid supplementation
Folic acid deficiency in pregnant women is an important cause of neural tube defects in fetuses, and folic acid deficiency or metabolic disorders can cause DNA
Folic acid supplementation in early pregnancy increases the concentration of folic acid in plasma to maintain the stability of chromosomes, which can reduce the incidence of Down’s syndrome.
3. Pre-pregnancy fever
It is believed that fever caused by pathogenic microbial infections can cause harm to the mother, and the drugs used to treat the infection may also have adverse effects on certain chromosomes during the specific period of embryo formation, leading to the occurrence of fetal birth defects.
4.Multiple abortions
A study found that multiple abortions (3 or more) are a risk factor for Down syndrome. Although abortion surgery only injures the functional layer of the endometrium, repeated scraping can easily damage the basal layer of the endometrium and affect cell growth, division and later fertilization of the egg. Multiple abortions leading to Down’s syndrome are also associated with decreased ovarian function and egg cell quality due to multiple pregnancies. Both negative pressure aspiration and medication abortion can damage a woman’s own defense barrier and the endometrium, creating potential damage to the reproductive system and its function.
5.Environmental factors
Activities such as home renovation or the purchase of a new car or makeup can expose the mother to chemicals such as benzene, and some studies have confirmed that the rate of chromosomal aberrations is significantly higher in benzene exposed individuals than in non-exposed individuals. Long-term exposure to high concentrations of benzene can cause cellular mutations and more constant chromosomal aberrations in human peripheral lymphocytes, resulting in the occurrence of birth defects. Toxic chemicals contained in cosmetics and hair-dyeing products, a large number of toxic substances can enter the blood circulation through the hair scalp and enter the uterus through the placental barrier during the mother’s hair-dyeing process, thus endangering the fetus and leading to the risk of abnormal neurological development.
How to screen for Down’s syndrome during pregnancy?
The methods and means commonly used for Down’s syndrome screening include fetal ultrasound screening, serum biochemical screening, amniotic fluid chromosome examination by amniocentesis and peripheral blood karyotype analysis, all of which have their own advantages and disadvantages, and the timing of the examination is different. The following is an introduction to the screening tests that need to be performed at different gestational weeks.
(a) Early pregnancy
1. Fetal posterior nuchal translucency thickness
NT is the maximum thickness of the translucent soft tissue between the skin layer and the fascia layer on the back of the fetal neck, which is an echogenic layer in the subcutaneous tissue of the back of the fetal neck. The screening time is from 10 to 13 weeks of gestation, and if NT ≥ 3
mm, the risk of Down’s syndrome pregnancy or heart malformation is increased and needs to be noticed. The detection rate of Down’s syndrome in early pregnancy by screening NT alone is 64% to 70%.
2.Serum biochemical screening
It refers to the Down screening duplex in early pregnancy: it includes serological testing of free β-chorionic gonadotropin (β-hCG) and pregnancy-associated protein-A (PAPP-A).
β-hCG is a glycoprotein produced by the secretion of fetal placental syncytial trophoblast cells. Under normal conditions, free β-hCG in the blood is present from the 2nd week after maternal conception.
The free β-subunit in the blood normally starts to rise from the 2nd week after conception, peaks at the 10th week after conception, and then decreases rapidly until the 16th week after delivery. In contrast, the free β-subunit in the blood of pregnant women with Down’s syndrome is not decreasing until the 16th week of pregnancy, although they are in the middle of pregnancy.
subunits do not decline and remain at high levels. The placenta of a child with Down’s syndrome synthesizes a higher level of pregnancy-associated plasma protein-A (PAPP-A
) is less than that synthesized by the placenta of normal fetuses, resulting in lower PAPP-A values in maternal blood in early gestation. This test is recommended between 9 and 13 weeks of gestation. The detection rate of Down’s syndrome in early pregnancy by serological screening alone is 78%.
NT + early pregnancy Down screening duplex: The detection rate of Down’s syndrome is 82% to 87%. If NT≥3mm, no further serum biochemical screening will be performed and invasive diagnostic tests will be done directly.
(II) Mid-pregnancy
1. Fetal posterior cervical skin fold thickness
Abbreviated as NF, it refers to the thickness between the lateral edge of the occipital skull and the lateral edge of the skin. NF thickness ≥6 mm at 16 to 18 weeks of gestation is often used as the basis for the diagnosis of Down syndrome.
2.Serum marker screening
The serological screening quadruplex for pregnant women includes: alpha-fetoprotein (AFP), human chorionic gonadotropin (β-HCG), free estriol (uE3) and Inhibin-A.
All these substances are synthesized by placental tissues and fetal involvement, and their changing levels can reflect to some extent the placental and fetal conditions. Maternal serum AFP levels are significantly lower in pregnancies with Down’s syndrome than in normal pregnancies, and AFP is considered one of the effective markers for screening for Down’s syndrome in mid-pregnancy. Maternal serum uE3 levels are 25% lower in Down’s syndrome than in normal pregnancies. uE3 is a valid marker for screening for Down’s syndrome in mid-gestation. Inhibin-A is significantly elevated at about 10 weeks of gestation.
The level of uE3 is significantly elevated at about 10 weeks of gestation and gradually decreases thereafter, remaining at a stable level after 15 to 25 weeks of gestation. Inhibin-A values in maternal serum during Down’s syndrome pregnancies show a tendency to remain elevated and not decrease. The best time for serologic screening in mid-pregnancy is recommended between 16 and 18 weeks of gestation. The detection rate of serum quadruple screening can reach 80%, with a false positive rate of 5%.
3.Amniotic fluid cell chromosome test
Amniotic fluid chromosome test is the “gold standard” for confirming the diagnosis of fetal screening for Down syndrome in high-risk pregnant women. The most commonly used technique is amniocentesis, in which a fine needle puncture is performed under ultrasound guidance to extract amniotic fluid from the abdomen of the pregnant woman, and then chromosomal analysis is performed. It is suitable for pregnant women in the middle 16 to 20 weeks of pregnancy.
weeks of pregnancy.
Since advanced age is the only identified risk factor for an increased risk of birth of a Down’s child, the means of screening for Down’s children is closely related to the age of the pregnant woman. Prenatal diagnosis, including chorionic villus biopsy in early pregnancy and amniocentesis in midtrimester, is usually recommended for older women without blood biochemistry screening. Amniocentesis has a 100% detection rate of trisomy 21 and is a confirmatory tool, not a screening test.
4.Non-invasive DNA testing technology
Non-invasive DNA testing technology collects 5mL of peripheral blood from pregnant women, extracts free DNA, and uses new generation high-throughput sequencing technology combined with bioinformatics analysis to accurately determine the risk rate of fetal chromosome aneuploidy, i.e. trisomy 21, trisomy 18 and trisomy 13, which can largely reduce the false-positive rate of test results. The limitations of this technique are that it cannot detect fetal chromosomes such as chimeric and heterozygous, and that maternal chromosomal abnormalities and maternal involvement in allogeneic blood transfusion, transplantation and immunotherapy within 2 years can also affect the test results. The timing of the non-invasive DNA test is 12 to 26 weeks of pregnancy.
For pregnant women aged >35 years old, it is safer to do amniocentesis directly. I have a friend who was 38 years old and had a non-invasive DNA test because she was afraid of the risks of infection and miscarriage that may result from amniocentesis. However, the baby was born with Down’s syndrome, which is a bloody lesson.
If you have a low risk of Down’s syndrome screening, surely you will not have a “Down baby”?
Many families have high hopes for Down’s syndrome screening and think that as long as the results of Down’s syndrome screening are low risk, the possibility of a “Down baby” can be ruled out, but in fact, passing Down’s syndrome screening only means that the probability of a Down’s child is lower than the average, even if the risk factor is 1/10,000, there is still a possibility of 1 in 10,000. Every year, a large number of children with Down’s syndrome are born in China, and some of them are born to pregnant women who have no abnormalities in their Down’s syndrome screening. Therefore, even if the results of the Down’s syndrome screening are not problematic, you should be aware of the possibility of Down’s syndrome if abnormal ultrasound results such as increased amniotic fluid and fetal growth retardation are found during subsequent maternity examinations. After all, Down’s syndrome screening is only a “screening” test, which can only reduce the birth rate of Down’s syndrome babies, not make them disappear completely.
Can I have more than one screening?
Many pregnant women don’t want to go for follow-up non-invasive DNA or amniocentesis because of the high risk of Down’s syndrome, and want to change hospitals and do it several times. This is definitely not true! Down screening is calculated by testing the hormones in the mother’s blood and using a formula after combining the gestational week and weight, so the result can be easily affected. If you are a week early or a week late, or if you have taken medication that affects hormones during pregnancy, the results can be seriously affected. Even if the same pregnant woman goes to different hospitals on the same day for Down screening, the results may not be the same. Different hospitals have different calculation methods and indicators, so it is not very meaningful to do more.