Prenatal diagnosis mainly detects whether the fetus is suffering from congenital/genetic diseases from four aspects: 1. Observe the fetus’ external structure and organ development: Apply ultrasound, X-ray, magnetic resonance imaging (MRI), fetoscopy and other examinations to observe whether the fetus has congenital malformations such as cleft lip and palate, limb malformation, congenital heart disease, congenital pyloric stenosis, locked anus, etc. Currently the most widely used in prenatal diagnosis is B-type ultrasonography. Ultrasound examination is non-invasive to both the pregnant woman and the fetus and has no obvious adverse effects, so the status of prenatal ultrasound examination in prenatal imaging diagnosis is the most valuable and irreplaceable by any kind of technology at present. Fetal chromosome karyotype analysis: Using amniotic fluid, chorionic villus cells or fetal blood cell culture, chromosome karyotype analysis can be used to diagnose fetal chromosome number and structure abnormalities, such as trisomy 21, trisomy 18, trisomy 13, chromosome translocation and sex chromosome abnormalities. Most patients with chromosomal abnormalities are associated with various congenital defects such as growth retardation, mental retardation, malformations, and sexual developmental disorders. The FISH technology developed in recent years has enabled further development of fetal chromosome analysis techniques. 3. Analysis of biochemistry: The analysis of proteins, enzymes and metabolites using amniotic fluid, amniotic fluid cells, chorionic villus cells or fetal blood can detect and find certain congenital metabolic diseases, hemoglobin molecular diseases, etc. When doing prenatal diagnosis, it is important to have a full understanding of the biochemical nature of the disease. Only metabolic diseases with a fully defined biochemical nature can be diagnosed prenatally in the fetus, otherwise they cannot be performed. In the past, specimens for diagnosing metabolic defective diseases mainly used cultured or uncultured amniotic fluid cells and amniotic fluid supernatant, so only metabolic defective diseases that get manifested in amniotic fluid or amniotic fluid cells can be diagnosed prenatally, which limits the scope of diagnosis to a certain extent. In recent years, the rise and development of genetic diagnosis has led to a more direct and effective means of diagnosis for congenital metabolic diseases. 4. Genetic testing and analysis: Prenatal genetic diagnosis is the analysis of disease-related genes using modern molecular biology techniques such as PCR, DNA sequence analysis, RFLP, MLPA and DHPLC before the birth of the fetus to determine whether the fetus has a certain single-gene genetic disease. At present, the prenatal diagnosis techniques for genetic diseases such as hemophilia A, hemophilia B, pseudohypertrophic progressive muscular dystrophy DMD, spinal muscular dystrophy, classic phenylketonuria, and thalassemia are very mature and have a high accuracy rate. For example, in DMD, children often develop around the age of 10 and die from complications by the age of 20, and in the past, family carriers could only be told that they could only have girls, not boys. Currently, prenatal genetic diagnosis can detect children with DMD, greatly reducing the burden on families and society. Prenatal diagnosis of several common congenital defects: 1, prenatal diagnosis of neural tube defects: neural tube defects (NTD) refers to a group of central nervous system malformations caused by impaired closure of the neural tube during fetal life or re-perforation due to other reasons after closure, including anencephaly, open spina bifida and brain expansion. The incidence of NTD in China is 0.66-10.53‰, with an average of 2.74‰, which is the first in the birth defect parity in China and has been listed as a key research topic by the state. (1) maternal blood AFP determination as a preliminary screening, such as maternal blood AFP > 2 standard deviations of the level of normal pregnant women in the same period, that is, re-examination, if still significantly elevated, for amniotic fluid AFP determination. (2) Amniocentesis will be performed at 16-24 weeks of pregnancy to determine the AFP content in amniotic fluid, and if it exceeds the normal value by more than 3-5 standard deviations, the diagnosis of NTD will be established. About 90% of NTDs can be diagnosed by AFP measurement. (3) Determination of amniotic fluid acetylcholinesterase (AChE). AchE is produced in neural tissue and can penetrate into amniotic fluid during NTD, resulting in a significant increase of AchE activity in amniotic fluid. This enzyme content is more stable, not affected by pregnancy and fetal blood contamination, and makes up for the lack of amniotic fluid AFP assay. (4) Ultrasound examination, performed in the middle of pregnancy. The ultrasound image of anencephalic infants is characterized by the following features: ① lack of cranial halo; ② the head of the fetus is replaced by a “nodule”; ③ the orbit and nasal bone are visible on the “nodule”; ④ the meninges are visible behind the “nodule”; ⑤ the spinal cord is often combined with a sac. (5) X-ray abdominal radiograph (5) X-ray abdominal plain film and amniotic cavity iodography can also be used. (5) X-ray abdominal plain film and amniotic cavity iodine oil imaging can also be used. The prenatal diagnosis of chromosomal diseases: Down syndrome (congenital stupidity, trisomy 21) is the most common chromosomal abnormalities, the incidence of 1/700 to 1/800 in the population. children with Down syndrome, in addition to mental retardation, will be accompanied by other abnormalities, such as: congenital heart disease, digestive duct malformation, many patients will also develop cataracts before adulthood, mental abnormalities. According to statistics, the average survival age of patients with Down syndrome is only 20 to 30 years old. Due to the prevalence of Down syndrome and the severity of the disease itself, it has always been of concern to medical practitioners from various countries. In the late 1980s, scientists found that pregnant women with Down syndrome had decreased serum alpha-fetoprotein (AFP), decreased free estriol (uE3), and increased chorionic gonadotropin (hCG) concentrations, so the combined measurement of maternal serum AFP, uE3, and hCG could predict the risk of congenital dysmorphism. Screening results can be categorized as low risk or high risk. Low risk means that the risk of Down syndrome in the fetus is relatively low, but it is not possible to exclude the disease completely. In the vast majority of cases, a fetus with a low-risk screening test is normal. However, there have been cases where the fetus was diagnosed with Down’s syndrome after the birth of a low-risk pregnancy. High risk means that the fetus is at relatively high risk of developing Down’s syndrome, but not necessarily the disease. In clinical practice, many pregnant women with high risk of DS have been confirmed to be normal fetuses by amniotic fluid karyotyping. Therefore, it is important to further examine pregnant women with high risk of DS rather than informing them to recommend induction of labor. Because the prenatal screening method is easy to perform, non-invasive, and convenient for mass screening in the population of pregnant women, and can screen for both congenital dysmorphic and fetal neural tube defects in high-risk pregnant women, prenatal serum screening of mothers with congenital dysmorphic syndrome has been affirmed and widely adopted in many countries. The prenatal diagnosis of Down’s syndrome is mainly made by fetal karyotype analysis technique. The diagnosis can be made by early direct filming of chorionic villi, amniotic fluid cell culture, maternal blood and fetal blood cells for karyotype analysis. In conditional units, DNA recombination, DNA gene amplification (PCR), gene analysis and other new technologies are available for diagnosis. 3, prenatal diagnosis of metabolic genetic diseases: Metabolic genetic diseases are caused by mutations in genes on chromosomes, resulting in the absence or abnormality of enzymes, the catalytic process of a certain enzyme controlled by the original gene cannot be carried out normally, and the metabolic process is disrupted and destroyed, resulting in the lack of some substances and a large accumulation of others, thus affecting the metabolism and development of the fetus. More than 1000 kinds of diseases have been found, most autosomal recessive inheritance, a few X-linked recessive inheritance and autosomal dominant inheritance. Diagnostic methods: 1, maternal blood or urine to check specific metabolites, such as the determination of methylmalonic acid in urine; 2, amniotic fluid analysis, the determination of abnormal metabolites released from the fetus in the amniotic fluid, such as adrenogenital syndrome can be checked for 17 ketosteroid content; 3, ultrasound guidance or fetal microscopy to take fetal blood, chromaffin cells, amniotic fluid cell culture, etc., to determine enzymes or other biochemical components for diagnosis. Similarly new techniques such as DNA recombination and DNA amplification enzyme-linked polymerization reaction (PCR) can be used. Prenatal diagnosis is a great progress of modern medicine, and with the increasing improvement of fetal specimen taking technology, molecular diagnostic technology and imaging technology, prenatal diagnosis will have a broader space for development.