Patients with 2 1- trisomy syndrome have one more chromosome 2 1 than normal people because of the abnormal chromosome number. 80% of the extra chromosomes come from the mother and 20% from the father. As the mother gets older, the risk of illness increases.
It is estimated that there are more than 600,000 2 1 trisomy children in China. According to the current birth rate, there are 1 2 1 trisomy children born every 20 minutes in China, and the number of children with Down syndrome in China will reach about 27,000 every year.
Soviet geneticists Darasenko and Shang Lu Nova summed up the views of some scientists: Some people, such as Steele, think that this is caused by endocrine disorders, especially among some older women; Others believe that the main reason is that drugs, chemicals in food and drinking water lead to chromosome abnormalities in germ cells. They found that the incidence of 2 1 trisomy syndrome in Central America was related to the concentration of fluorine in water.
First, the general situation of congenital stupidity:
Langdon Down, a British doctor, first described the clinical manifestations of congenital stupidity, so he called this disease Down syndrome, that is, Down syndrome. In our country, the word congenital stupidity is often used. 1959, the French cytogeneticist Lcjeune confirmed that the cause of the disease was that the patient had a small G chromosome (later identified as chromosome 2 1). Therefore, the disease is also called 2 1 trisomy syndrome (trisomg 2 1).
2 1 trisomy syndrome is one of the most common chromosomal diseases. Its karyotype is about 92.5% simple trisomy, which comes from the non-segregation of primary chromosomes. 4.8% are robertsonian translocation, mutual translocation and tandem translocation; Half of them come from operators; 2.7% were chimeras, which originated from abnormal chromosome segregation during early cleavage after zygote.
Common karyotypes are:
47, XX, +2 1 simple trisomy, female
47, XY, +2 1 simple trisomy, male
46, xx (xy)/47, xx (xy), +2 1, chimera
46，XX(XY)，-2 1，+t(2 1； 2 1) robertsonian translocation.
It is estimated that there are more than 600,000 children with trisomy 265,438+0 syndrome in China. According to the current birth rate, 1 2 1 trisomy syndrome is born every 20 minutes in China, and about 27,000 children with Down syndrome will be born every year in China.
Second, the incidence of congenital stupidity.
The incidence of neonatal 2 1 trisomy syndrome is about 1.5‰, with the range of11000-1/500. According to the data of Denmark and Sweden, the incidence rate in Copenhagen1960-1971kloc-0/2 in Denmark was1.15 ‰; The incidence rate in Sweden during 1968- 1977 was 1.28‰, and if prenatal diagnosis was added, it was 1.32‰. The incidence of this syndrome is very constant and does not fluctuate with the seasons, but recent studies show a slight upward trend. Scholars in Henan Province reported that the incidence of 2 1 trisomy was as high as 1/400.
The age of the mother is an important factor affecting the incidence rate. According to foreign data, if the average age of mothers at birth is 28.2 years old, then the average age of mothers with congenital stupid children is 34.4 years old. With the increase of age, the risk of having children gradually increases. Clinically, the elderly women of childbearing age refer to women over 35 years old, and the incidence of dementia and deformed children born to them has increased significantly. Because the maternal age is too large, the egg cells will change, and the human body, including the ovaries, will be affected by various harmful substances and various rays. These factors will increase the probability of genetic material mutation, and the carrier of genetic material-chromosome will not separate during cell division. The most common is that chromosome 2 1 does not separate, resulting in three chromosomes 2 1 and one chromosome 2 1 embryo. Almost all singleton embryos and most triplet embryos miscarry in early pregnancy, while only a small number of 2 1 triplet embryos will survive during pregnancy, resulting in congenital idiocy.
Studies have pointed out that the age of pregnant women has the following relationship with the incidence of congenital stupidity:
Age 20, 25, 30, 35, 38, 40, 42, 45.
Risk1140011110001/3501/.
Some data show that the father's age is also related to the onset of this disease. When the father is over 39 years old, the risk of having children increases. Such as air pollution, fluorine content in water, drinking, social and economic conditions, etc. There is no effect on the incidence in the group, and the conclusion has begun to waver. According to the current theory, all the above factors may lead to the embryogenesis of chromosome abnormality. A large number of existing research data show that environmental pollution, exposure to harmful substances, drinking and smoking can cause aging and deformity of sperm and eggs, which is an important inducement of congenital stupidity and congenital malformation. Foreign countries use "Sunday baby" to refer to ugly and mentally retarded children who are pregnant after drinking on holidays. Recently, it has been pointed out that hepatitis virus can affect the chromosomes of fetal cells, and some individuals have congenital idiots. This study shows that viral infection in women before and early pregnancy may also be the cause of congenital stupidity.
Fourth, the clinical manifestations of congenital stupidity
Attached chart of clinical manifestations
The signs of this disease are very diverse, and many organs and tissues are abnormal. However, developmental malformations are usually not serious enough to be life-threatening. The average weight and length of children at birth are generally low, and their muscle tension is low. The most prominent is craniofacial malformation. The skull is small and round, the pillow is flat, the face is round, the nose is flat, the palpebral fissure is thin and inclined outward, the eye distance is too wide, the epicanthus is obvious, the eyelashes are short and sparse, and strabismus often occurs. There are white spots on the iris, often accompanied by lens opacity. The mouth is small and the lips are thick, the tongue is large and often stretched, the ears are small, and the ears are low. Hair is straight and not curly. The back of the neck is short and wide, and the skin is redundant.
Due to chondrodysplasia, the patient's limbs are short. Hands are wide and fat, palms are penetrating, fingers are short, and the fifth finger is often bent inward, short or lacking middle finger. Abdominal distension caused by low muscle tension often leads to rectus abdominis separation or umbilical hernia. About12 patients suffer from congenital heart disease, mainly ventricular septal defect, atrioventricular canal communication, atrial septal defect and patent ductus arteriosus. Gastrointestinal malformations, such as duodenal stenosis, Hirschsprung's disease, rectal prolapse and anal atresia, also occur occasionally. Children's mental development is slow, they can sit up after 1 year old and start walking around 3 years old. They are soft and slow, rarely aggressive, and don't know how to count, but sometimes they have a certain memory and are good at imitating others. Mental retardation is the most prominent and serious manifestation of this syndrome. IQ is usually between 25 and 50. Children with better intelligence can learn to read or do simple manual labor; Poor people have difficulties in language and self-care. With the growth of age, IQ will continue to decline. This is not to say that children are getting more and more stupid, but the intelligence gap is getting bigger and bigger compared with their peers. In fact, through training, they can learn to do more work, and to a certain extent, they can cover up the degree of mental retardation.
There is usually no obvious abnormality in the development of external genitalia, but men may have cryptorchidism. Sperm occurs in testicles, but sperm often decreases and sexual desire decreases, so far no one has given birth. Female patients usually have no menstruation, but a few can get pregnant and give birth. It is reported that 25 female patients gave birth to 27 children. Theoretically, about 1/2 of his children should be patients, but in fact, the ratio of children to non-children is 10: 17.
The average life expectancy of patients is only 16.2 years. 50% of children die before the age of 5. The mortality rate of other age groups is 5-6 times higher than that of the general population. Only 8% patients lived past 40 years old, and 2.6% patients lived past 50 years old. The life span of patients usually depends on the existence of serious congenital heart disease and digestive tract malformation and the degree of reduced anti-infection ability, because these are the main causes of death of patients. In addition, the incidence of leukemia in patients is 15 times that of the general population, which is also one of the causes of death.
If the patient survives for a long time, facial deformity, nasal collapse and epicanthus will gradually become inconspicuous. But the face changed from perfect to shriveled, and her cheeks were red. Many patients will have cataracts and mental disorders before adulthood.
Five, genetic analysis of congenital idiot:
The typical 2 1 trisomy is almost new and has nothing to do with the karyotype of parents. It is the result of not separating during meiosis. Non-segregation can occur in the first meiosis or the second meiosis. In men, meiosis is going on all their lives, and sperm is constantly produced by spermatogonia through spermatogenesis, or "fresh". In women, all eggs have passed the first meiosis at birth, and they are in the resting stage or nuclear reticular stage until ovulation. Therefore, oocytes are affected by internal and external environmental factors for a long time and are constantly aging. All these may lead to the occurrence of non-separation, and may also explain why older mothers are prone to give birth to children with congenital stupidity.
Only a small part of the typical 2 1 trisomy is hereditary, that is, because the mother is a trisomy patient. In addition, it cannot be ruled out that some mothers with normal phenotype are actually chimeras, but the proportion of abnormal cells is very small, such as only existing in certain tissues or ovaries. Trisomy cells in the ovary may lead to the birth of trisomy children. The possible indirect evidence of this situation is that 10% of the children's mothers have abnormal dermatoglyphics. Therefore, although their other phenotypes are normal, they may be potential chimeras, and their children may get extra chromosomes. It can be seen that it is quite difficult to confirm or deny chimera. If the patient is male and infertile, there is no problem of passing it on to the next generation.
Patients with chimeric three body 2 1 have two or more cell lines, which is the result of mitosis after zygote. If the first cleavage does not occur, two cell lines will be produced, 47, +2 1 and 45, -2 1. The latter cells are difficult to survive. Therefore, most mosaics will not separate during mitosis, and all mosaics have normal cell lines. The ratio of the two cell lines is not the same in each tissue, and the percentage of abnormal cells is usually higher in fibroblasts than in blood cells. According to the literature, no trisomy cells were found in patients' blood cells, but 65438 07% fibroblasts were trisomy cells, which indicated that trisomy cells were subjected to different selection pressures in various tissues. Chimera may also be the result that the abnormal zygote of 2 1 trisomy is not separated, that is, one cell line loses a number 2 1 and returns to normal, while the other cell line is still 2 1 trisomy.
There are unbalanced translocation chromosomes in the cells of patients with translocation type 2 1. The latter is usually formed by the centromere fusion (Luo translocation) of a group of D or G chromosomes and the long arm of 2 1 chromosome. 55% of q2 1q translocation is new, and 45% is due to the balanced translocation of one parent. The translocation of 2 1qGq is almost completely new (96%), and only 4% is hereditary. The genetic consequences of various translocations are different. Dq2 1q balanced translocation carriers can form six gametes through meiosis, and after fertilization, they can produce three kinds of fetuses: normal fetuses, trisomy and children of balanced translocation carriers, except those who cannot develop. Therefore, it is of great significance to detect the parents of balanced translocation carriers. In fact, apart from the mother's age, little is known about the etiology of typical 2 1 trisomy, and effective prevention is limited to prenatal diagnosis after pregnancy. In recent years, it has been found that mothers who gave birth to triplets 2 1 have increased serum alpha-fetoprotein during pregnancy, which seems to be a screening and prevention method. For the translocation of 2 1 trisomy, parents can be examined before pregnancy or before marriage and given guidance.
2 1qGq translocation is mostly new. The genetic meanings of 2 1q22q and 2 1q2 1q are not exactly the same. If one parent is the carrier of 2 1q2 1q, it is impossible to give birth to a fetus with normal phenotype, because they can only give birth to a trisomy or a haploid zygote. The genetic consequences of 2 1q2 1q translocation are similar to those of Dq22q, except that the former is mostly transmitted by the father and the latter by the mother.
Sixth, genetic counseling for congenital idiots.
It is of great practical significance to estimate the recurrence risk of 2 1 trisomy. 2 1 The risk of recurrence is different for all types of trisomy. For a typical 2 1 trisomy, having one child does not increase the risk of having another child, at least in theory. Therefore, if both parents' karyotypes have been checked to be normal, there is no reason to persuade them not to give birth, or to excessively aggravate the existing doubts. However, there are indeed reports that some families have more than two patients with typical three symptoms. Some parents (usually mothers) have been proved to be chimeras, although the proportion of trisomy cells is not high; Others have found translocation of other chromosomes. However, most families cannot find a reasonable explanation. Therefore, some assumptions are put forward. For example, germ cells are chimeric and familial, but these assumptions need to be confirmed. Therefore, it is difficult to estimate the recurrence risk of typical 2 1 trisomy, and the risk rate proposed by each author is not the same. Some authors assume that if a mother has given birth to a triplet before the age of 30, the risk of recurrence is 1-2%, but the risk rate after the age of 30 will not increase compared with the same age group. In short, for parents who have given birth to typical trisomy children, what counselors can do is to exclude them as chimeras as much as possible through chromosome examination.
About 1/2 cases were newly added, and another 1/2 cases were caused by balanced translocation of one parent. The possibility of recurrence of the former is very small, and the risk of recurrence caused by balanced translocation can be estimated according to real experience. If the Dq2 1 translocation carrier is a mother, the risk of giving birth to a child with translocation is 10- 15% (some authors think it is 16%), and if it is a father, the risk is 5% or less. The situation of 2 1q22q translocation is basically the same, but the percentage of translocation chromosomes is more than that of D/g translocation, and some data show that the risk rate is below 10%. The offspring of carriers of 1Q2 1Q balanced translocation are all triplets. Carriers are not suitable for childbearing.
Seven. Dynamic prenatal diagnosis of congenital idiocy
Since Steele and Breg successfully used amniotic fluid cell culture for karyotype analysis in 1966, prenatal diagnosis of chromosomal abnormalities has developed rapidly. For Down syndrome, prenatal karyotype analysis is mainly based on chorionic puncture (CVS), amniocentesis or umbilical vein puncture. These methods are all traumatic methods, which are easy to cause fetal abortion and have high detection costs, so they are only used for people over 35 years old and/or with other factors. In recent 20 years, many scholars hope to find a way to replace the traumatic means such as amniocentesis and villus sampling. Golbus of the University of California School of Medicine has paid extensive attention to the technology of separating fetal nucleated red blood cells from pregnant women's blood circulation. The National Institutes of Health believes that this will be the main development direction in the future. After nearly 9 years of research, some achievements have been made, but there are still many problems. At present, many universities in the United States have stopped studying, but a few units are still exploring. In addition, the new development of cytogenetics, fluorescence in situ hybridization (FISH) technology, can detect some tiny chromosome translocation, which is the combination of molecular biology (probe) and cytogenetics (chromosome). FISH can be directly used for rapid prenatal diagnosis of interphase amniotic fluid cells or chorionic villi cells without culture. Methods X, Y, 13, 18, 2 1 chromosome probes were used for in-situ hybridization, and the number of different color spots in the nucleus could be used to detect whether the fetus had chromosomal diseases and whether the fetus was XX or XY. This technology has made great progress in clinical application and is considered as the future development direction. 1996 10 at the annual meeting of American genetics and the third world congress of perinatal medicine held in San Francisco, USA, experts of prenatal diagnosis group believed that amniocentesis and amniotic cell culture were still the basic means of prenatal diagnosis, because their safety and scientificity had been verified for a long time and a large number of cases, and pregnant women under 35 years old could choose two or three indicators (AFP, βhCG and/or E3).
In the mid-1980s, British scholars found that the concentration of serum AFP in pregnant women with Down's syndrome decreased, and then the concentration of free estriol (uE3) decreased and the concentration of chorionic gonadotropin (hCG) increased. Haddow et al. reported in 1992 the effectiveness of screening Down syndrome with multiple indicators (AFP, uE3, hCG). Because the detection method is simple and non-invasive, it is convenient for large-scale screening among ordinary pregnant women, and it can also screen high-risk pregnant women with Down syndrome or NTD. Although the accuracy of current screening methods can only reach 65%-70%, they have been used in Europe and America.
Eight, the significance of prenatal screening of congenital stupidity
2 1 trisomy syndrome is one of the most common causes of fetal congenital defects. Its main characteristics are severe congenital mental retardation, special face, and often accompanied by various congenital malformations. The birth rate is about 1/700- 1/800 of the live births. It is estimated that there are about 600,000 children with Down syndrome in China. According to the current birth rate in China, there are 260,000 patients in ten years, resulting in an upward trend of 65 billion society year by year. Therefore, it is urgent to reduce the birth of such children as much as possible, so that the national policy of prenatal and postnatal care in China can be implemented. In order to improve the quality of population in China, for the happiness of thousands of families in Qian Qian, Qian Qian, and for every couple to have a healthy, beautiful, intelligent and lovely baby, the National Family Planning Commission and the Ministry of Health officially launched the "Birth Defect Intervention Project" in 2000 under the strong appeal of Chinese genetic experts and obstetricians and gynecologists. In addition, due to the lack of effective treatment for Down syndrome, the birth of a child has brought many adverse effects to the family and society. According to an American report (Conley, 1985), 1985, the cost of raising a patient in American society was about140,000 US dollars, and it reached about 200,000 US dollars in the 1990s. Every child born with Down syndrome in China will cause an economic burden of about 250,000 yuan, and the government will pay about 6.75 billion dollars for children's medical care every year. At the same time, it will cause long-term heavy mental burden and economic pressure on children's families, and have a great impact on the population quality, national economic development and social stability in China and Shanghai. It can be seen that Down syndrome has become one of the important factors affecting the development of China's national economy and the quality of the birth population. How to find down's syndrome fetus before delivery and prevent and reduce the birth of down's syndrome fetus is an important task of prenatal eugenics and prenatal diagnosis.
At present, although pregnant women over 35 years old and some other high-risk pregnant women in China need to have a routine examination of amniotic fluid chromosome, it has played a certain role in prenatal detection of Down syndrome fetuses and prevention of such fetuses. However, because amniocentesis is traumatic, it can lead to abortion, and it needs certain technical equipment, which takes a long time and costs a lot, so it is impossible to widely carry out it in all pregnant women. Secondly, even some high-risk pregnant women with indications of amniocentesis refused to have amniotic fluid chromosome examination for fear that amniocentesis might lead to abortion. Therefore, in the past 20 years, the number of births of Down syndrome has remained high.
For many years, under the influence of traditional medical education, pregnant women over 35 years old have been regarded as high-risk groups in China, and prenatal diagnosis of Down's syndrome has been made directly through amniocentesis, cord blood puncture or chorionic sampling. But this method, which has been used for decades, not only brings pain to pregnant women, but also easily leads to abortion. More importantly, the results of large-scale screening in developed countries in recent 5-6 years show that there is no high-risk group in the traditional sense in the high-risk group over 35 years old. 80% of Down syndrome occurs in pregnant women under the age of 35. With the aggravation of urban environmental pollution, such as virus infection, chemical drugs, radioactive radiation, oral contraceptives, aging, etc., Down syndrome may be caused. At present, the age of pregnant women in China is decreasing, and the number of cases of Down syndrome is increasing, which also proves that the disease is different from other monogenic genetic diseases, that is, it is accidental and possible for any population. Therefore, large-scale prenatal screening for ordinary pregnant women has become the goal of geneticists in China. In addition, due to many factors, in the past, only pregnant women over 35 years old with other high-risk factors were examined for amniotic fluid chromosomes, which only accounted for about 5% of the whole pregnant women. Even if all prenatal amniotic fluid chromosomes are examined, only 20% of Down's syndrome fetuses can be prevented from being born, and 80% of Down's syndrome fetuses occur in ordinary pregnant women who are not at high risk but account for 95% of pregnant women. Therefore, how to make prenatal diagnosis of Down's syndrome fetus for ordinary pregnant women is the key to prevent and reduce the birth rate of Down's syndrome fetus. At present, prenatal screening for Down syndrome in maternal blood has been widely carried out in western countries. According to British reports, since the implementation of Down's prenatal screening program, the number of births of children with Down's syndrome has dropped by nearly 50%. How to do a good job in prenatal screening and diagnosis of Down's syndrome, and effectively prevent and reduce the birth of such fetuses, is very necessary for improving the quality of the population born in China and promoting national economic development and social stability.
Nine. Progress in screening for congenital idiotic pregnancy
Down syndrome is the most common chromosomal abnormality disease, accounting for 1% of the pregnant population, and 1 child suffers from Down syndrome in every 700 babies born. Most of them are early spontaneous abortions. Fetuses with Down syndrome are usually stunted and have severe deformities in the head, face, heart and limbs. All children with Down syndrome have mental disorders, and may also be accompanied by digestive tract and musculoskeletal malformations. Because Down syndrome can't be treated at present, only early diagnosis and termination of pregnancy can achieve the goal of prenatal and postnatal care. At present, amniocentesis and chorionic villus biopsy are only performed in high-risk groups, and only 20% of Down syndrome fetuses can be detected. In addition, chorionic biopsy and amniocentesis are both invasive examinations, which can cause complications such as fetal amniotic band syndrome and amputation injury respectively, and the abortion rate is 1% ~ 2%. Therefore, in recent years, many scholars have devoted themselves to the screening of maternal serum markers and the study of early fetal (8 ~ 14 gestational weeks) ultrasound examination. The related research progress is summarized as follows.
Screening of maternal serum markers in (1) early pregnancy
Alpha-fetoprotein (AFP): AFP is the most common globulin in fetal serum, and its structure and function are similar to albumin. It is produced by yolk sac in early pregnancy and fetal liver in late pregnancy. When fetal epithelium is intact, a small amount of AFP is discharged into amniotic fluid from fetal urinary tract. A small amount of AFP can be found in serum of non-pregnant women. The serum AFP of pregnant women gradually increased in the early and middle trimester of pregnancy, and reached a relatively stable period around 28 ~ 32 weeks of pregnancy. When the fetus has open neural tube defect or abdominal wall defect, AFP in amniotic fluid and maternal serum increases significantly.
Due to the different values reported by different laboratories, all laboratories take the multiple of the median of unaffected people (Mom) as the standard of test results. The normal population is1.0mom.
Maternal serum AFP screening was originally used to diagnose open neural tube defects. The maternal serum AFP of most fetuses with open neural tube defects is higher than 2.0MoM. If AFP is slightly increased (2.0 ~ 3.0 mom), it is meaningful to repeat serum determination. If the second AFP is between 1.0 ~ 2.0 mom, it suggests that the fetus may be normal. However, the AFP of pregnant women with Down syndrome is lower than 1.0 MoM. Aitken et al. reported that the result was 0.65MoM, mostly in the range of 0.47-0.86 mom. Generally speaking, AFP needs to be combined with other tests at the same time, which is meaningful for screening Down syndrome.
2. Free estriol (uE3): Estriol is a steroid hormone, which is synthesized by fetal adrenal gland, liver and placenta. It is secreted directly from placenta into maternal circulation in free form. It is rapidly metabolized in the maternal liver in the form of sulfate and estriol gluconate. The serum uE3 level of pregnant women increased with the increase of gestational age. The maternal serum uE3 of Down syndrome fetus is low, which may be related to fetal growth retardation.
3. Human chorionic gonadotropin (HCG): HCG is the most commonly used pregnancy test hormone familiar to obstetricians and gynecologists. It consists of glycoproteins of α and β dimers. The α subunit is found in anterior pituitary hormones. The β subunit is hCG specific. Complete hCG is produced by syncytial trophoblast of placental chorion. It is thought to be produced by transitional cells and syncytial cells in the trophoblast. It increases rapidly in the first 8 weeks of pregnancy to maintain pregnancy. After about 8 weeks, hCG gradually decreased until it reached relative stability around 20 weeks. Maternal serum hCG mainly exists in intact form, and free β-hCG accounts for 1% ~ 8% of total HCG. The serum hCG of pregnant women with Down syndrome increased by about 2. 1 1 MoM. It has been reported that the total hCG, free α-hCG and free β-hCG of Down's syndrome at 8 ~ 14 weeks of pregnancy are 65438 0.23, 0.86 and 65438±0.79 mom, respectively. Jauniaux screened 58862 cases of single pregnancy. In 13 patients with Dovn syndrome, the total β-hCG of1case (84.6%) was >: 2.5 mom. Noble detected the mothers of 76 fetuses with Down's syndrome and 800 normal fetuses at10 ~/4 weeks of pregnancy. It was found that the maternal serum free β-hCG concentration of Down syndrome fetus was significantly higher than that of normal fetus (P
The age of pregnant women can affect the positive rate and estimated detection rate of screening. In normal population, AFP is 1.0 MoM, uE3 is 1.0 MoM, and hCG is1.0mom.. In the normal population, the risk of Down syndrome in pregnant women is11200, which can be reduced from the usual11200 to 1/4800 in the 25-year-old population. The number of people aged 35 dropped from 1/270 to11080; The number of people aged 45 dropped from 1/20 to 1/80.
In Down syndrome, AFP is 0.74 MoM, uE3 is 0.7 1 MoM, and hCG is 2. 1 1MoM. This value shows that the risk of Down syndrome related to the age of pregnant women has increased by four times. The risk in the 25-year-old population increased from the usual incidence11200 to1/300; The number of people aged 35 increased from 1/270 to1/72; The number of people aged 45 increased from 1/20 to 1/5.
Among the 25-year-old population, the positive rate of screening was 3.5% and the detection rate was 46%. Among people aged 35, the positive rate of screening was 13.5%, and the detection rate was 73%. Among the 45-year-old population, the positive rate of screening was 55% and the detection rate was 98%.
4. Pregnancy-associated plasma protein A (PAPP-A): PAPP-A is a macromolecular protein complex produced in placenta.
Zimmermann et al studied11125125-44-year-old pregnant women in/kloc-0 ~13 weeks, and found 2 1 and 18 three weeks. It is suggested that PAPP-A can be used as an independent serum marker. Wald et al. screened 8 ~ 14 weeks pregnant women in 2 1 obstetric centers in 9 countries for AFP, uE3, total hCG, free α-hCG, free β-hCG, PAPP-A and inhibin A7, and 77 fetuses were found to have Down syndrome. It was found that PAPP-A in the sick group was lower at 8 ~ 14 weeks of pregnancy, which was 0.36 MoM at 8 ~ 9 weeks of pregnancy. 0.44MoM pregnant 10 week; 1 1 week's gestational age is 0.33MoM；; The gestational age of 12 ~ 14 is 0.59MoM, which indicates that PAPP-A also tends to increase with the continuation of pregnancy. Wald thinks that PAPP-A and free β-hCG are the best serum markers to distinguish Down syndrome from normal fetus. The maternal serum PAPP-A of 49% fetuses with Down syndrome was lower than the 5th percentile.
8 ~ 14 weeks pregnant women combined with PAPP-A and free β-hCG, the detection rate of Down syndrome was 62%, and the false positive rate was 5%. However, the detection rate of 15 ~ 22 weeks of pregnancy was 59%.
5. Inhibin A: Inhibin is a heterodimeric glycoprotein. β -subunit and a β-A subunit form inhibin A; It forms inhibin b with βB subunit. Blood exists as a free subunit with no biological activity. A large amount of inhibin in maternal serum during pregnancy is thought to come from syncytial trophoblast of placenta. Inhibin B was not detected in maternal serum in early pregnancy. Inhibin A increased, reaching the peak at 10 ~ 12 weeks of pregnancy, then decreased to a plateau in the second trimester, but increased again in the third trimester, reaching the highest level at term.
Inhibin A, like hCG, increases in Down syndrome. Maternal serum inhibin concentration is independent of hCG concentration.
Noble et al. found that inhibin A > 0.05% in maternal serum of 12.8% fetuses with Down syndrome; 95 percent. However, Wald et al. determined that inhibin -A in maternal serum of 77 fetuses with Down syndrome was 1.5438+09.
Mom thinks it is also helpful to diagnose Down syndrome.
(2) Ultrasound examination in early pregnancy
Ultrasound examination plays an important role in screening Down syndrome. Its main function is: (1) All kinds of serum screening are based on gestational age, and AFP, uE3, hCG and inhibin -A all change with the increase of gestational age, so it is necessary to confirm gestational age by ultrasound. (2) Fetuses with Down syndrome are often accompanied by intrauterine growth retardation and malformation, which can be directly detected by ultrasound. (3) Down syndrome has some special manifestations, such as hypotonia, short neck and short limb bones. It is considered that some abnormalities can be found as early as 8 ~ 14 weeks of pregnancy, which are described as follows.
1. Neck translucency (NT): In the second and third trimester of pregnancy, neck hydrocele or neck edema is closely related to chromosome abnormality. Cullen et al. reported 145 cases of cervical edema, 52 cases (36%) had chromosomal abnormalities, among which trisomy syndrome accounted for 43 cases. However, 33 cases (75%) of 44 cases of hydrocystic lymphangioma had chromosomal abnormalities. Therefore, it is necessary to detect whether there is neck edema as a sign of chromosome abnormality in the first trimester. Using 5MHz probe to detect abdomen, first find the sagittal section of fetal head, and measure the length of fetal head and buttock and the maximum transparent thickness between cervical skin and cervical soft tissue, which is nt. Don't mistake amniotic membrane for fetal skin when testing.
Nicolaides et al. measured fetal NT 827 times in pregnant women from 10 to 14 weeks. Among them, 5 1 fetus had NT thickness of 3 ~ 8 mm, among which 18 cases (35%) had chromosomal abnormalities, all of which occurred over 35 years old. Among 776 cases with fetal NT thickness of 0 ~ 2mm, 10 (1%) was chromosomal abnormality, including 4 trisomy cases and 6 chimeras.
By the second trimester, fetal NT can develop into two aspects: (1) hydrocystic lymphangioma, which is often a sign of Turner syndrome, caused by excessive expansion of cervical lymphatic sac. (2) Early symptoms of fetal edema. There are many reasons for fetal edema, of which trisomy is the majority, and the rest are fetal cardiovascular disease, pulmonary malformation, skeletal dysplasia, intrauterine infection or other metabolic and blood organ dysfunction.
At present, the name of cervical edema or cystic lymphangioma is no longer used in clinic, but nt (transparent neck) is used to express the observation results. In normal genome, most of the thickened NT will disappear naturally at the 20th week of pregnancy.
From10 to14 weeks of pregnancy, the translucent thickness of the neck of 80% trisomy fetus increased. Zimmermann et al. performed ultrasound screening on pregnant women aged 25-44 years and 1 15 1 and 13 weeks. Among 23 fetuses with chromosomal abnormalities, 9 cases had NT >: 3mm .Jauniaux et al. found that NT in 66.7% cases exceeded 95 percentile. Martinez et al. on 553