September 12th is China's Day for Preventing Birth Defects, and the theme of this year's event is "Preventing Birth Defects, Guarding the Health of the Starting Point of Life". What are the common birth defects? What are the methods to prevent birth defects? What role can genetic testing play in it? Recently, reporters conducted an interview on this matter. Every family hopes to have a healthy baby, but some families suffer from the pain caused by birth defects. What exactly is a birth defect? Birth defects refer to abnormalities in the body structure, function, or metabolism that occur in infants before birth, and are the main causes of early miscarriage, stillbirth, infant death, and congenital disabilities Zhao Lijian, CEO of BGI Genomics, introduced that there are currently at least 8000-10000 known birth defects, including congenital heart disease, neural tube defects, Down syndrome, Duchenne muscular dystrophy, polydactyly, cleft lip, phenylketonuria, thalassemia, and deafness. China is a populous country and also a country with a high incidence of birth defects. According to the "Report on the Prevention and Control of Birth Defects in China (2012)", it is estimated that the total incidence of birth defects in China is about 5.6%. According to the calculation of 9.02 million births in China in 2023, if the ability to prevent and control birth defects is not improved, behind 5.6% are more than 500000 families carrying heavy burdens. The vast majority of birth defects lack effective treatment methods, and some major birth defects often accompany children throughout their lives, requiring lifelong treatment. This not only seriously affects the quality of life of patients, but also brings heavy economic burden and mental pressure to families and society Zhao Lijian introduced that even if a small number of birth defects can be treated with medicine, the cost of treatment is often sky high. Taking spinal muscular atrophy (SMA) as an example, it is an autosomal recessive genetic disease. Children with SMA often present with muscle weakness and atrophy in the early stages, which can progress to swallowing weakness, difficulty breathing, and high disability and mortality rates. The overall incidence rate of SMA is about 1/10000-1/6000, but the population carrying rate is as high as about 1/50. In 2019, the first drug capable of treating SMA, sodium methoxam injection, was officially launched in China, but the price per injection was as high as 700000 yuan; In 2021, after eight rounds of medical insurance negotiations, sodium methoxam was finally included in medical insurance at a price of 33000 yuan per injection, greatly reducing the economic burden on families. However, such children still need lifelong medication. Therefore, moving the prevention and control of birth defects forward, exploring the establishment of new models for birth defect prevention and control, and vigorously promoting appropriate advanced technologies are important guarantees for reducing the occurrence of birth defects and improving the quality of the birth population, "he said. The key to reducing birth defects is prevention. China has always attached great importance to the prevention and control of birth defects. In recent years, China has included the prevention and control of birth defects in the "Healthy China 2030" plan outline, and issued documents such as the "National Comprehensive Prevention and Control Plan for Birth Defects" and the "Plan for Enhancing Birth Defect Prevention and Control Capacity (2023-2027)"; The National Health Commission, together with relevant departments, actively promotes the comprehensive prevention and control of birth defects, especially the equalization of birth defect prevention and control services, and establishes a three-level prevention and control system for birth defects covering the entire chain - first level prevention, which means controlling the pre marital and pre pregnancy checkpoints, through health education, pre marital medical examinations, pre pregnancy eugenics examinations, folic acid supplementation services, etc., to minimize the occurrence of birth defects; Secondary prevention refers to controlling the pregnancy stage, providing comprehensive prenatal and postnatal health services, strengthening prenatal screening, diagnosis, and informed intervention, and further reducing serious birth defects that cause death or disability; Third level prevention refers to ensuring the quality of postpartum care, conducting specialized examinations for congenital and genetic diseases that seriously endanger the health of newborns, and striving to achieve early detection, intervention, and recovery of birth defects. In fact, 70% of birth defects cannot be clearly detected by the naked eye at the time of a child's birth and require professional medical equipment for diagnosis Zhao Lijian introduced that for genetic hearing loss, some children's hearing loss does not immediately manifest after birth, and progressive hearing loss may occur later, even after exposure to certain specific drugs. If a newborn is tested early after birth and intervention measures are taken in a timely manner, there is a chance to avoid irreversible damage to the child's hearing in the later stages. Genetic testing helps to accurately prevent and control birth defects. There are many diseases with complex causes, and prevention and treatment often begin at the beginning of life. Data shows that currently 24 provinces in China are implementing free premarital check ups, and the national premarital check rate has increased to 76.5%; 23 provinces have implemented free prenatal check ups, with a national pre pregnancy check rate of 96.5%; The national prenatal screening rate has increased to 91.3%; The screening rate for genetic metabolic diseases and hearing impairment in newborns nationwide is over 90%... Prenatal screening is an important line of defense for preventing and reducing birth defects. In recent years, prenatal screening for birth defects has gradually expanded to genetic screening on the basis of biochemical screening and ultrasound screening. Among them, genetic testing represented by non-invasive prenatal genetic testing plays an important role. Zhao Lijian introduced that some genetic diseases often manifest in mid pregnancy, late pregnancy, and even after birth, and routine examination methods alone are far from enough, which may lead to missing the most effective intervention period. For such diseases, genetic testing can identify whether parents carry genetic mutations that cause genetic diseases or whether the fetus has genetic or chromosomal abnormalities before or in the early stages of pregnancy, which can detect potential risks of birth defects early and provide scientific information for expectant parents to make informed decisions or prepare corresponding treatment plans. What is non-invasive prenatal genetic testing? Non invasive prenatal genetic testing refers to the application of high-throughput sequencing technology to detect fetal free DNA fragments in maternal peripheral blood during pregnancy, in order to assess the risk of common chromosomal aneuploid diseases in fetuses, such as Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), Patao syndrome (Trisomy 13), etc Zhao Lijian introduced that this screening technology only requires one tube of pregnant mother's blood to be drawn for testing, which can effectively avoid the risks brought by amniocentesis and has higher safety. In recent years, both domestic and international clinical guidelines and expert consensus have suggested that non-invasive prenatal genetic testing should be used as a first-line method for screening chromosomal aneuploidy in pregnant women of different ages. Currently, both traditional serological screening and non-invasive prenatal genetic testing are used as prenatal screening methods and cannot be used as diagnostic criteria. If the screening results indicate high risk or other abnormal conditions, pregnant women should further undergo prenatal diagnosis to determine whether the fetus has chromosomal abnormalities. Huada Gene's non-invasive prenatal genetic testing technology has a sensitivity of over 99% for detecting trisomy 21, which causes Down syndrome. Compared with the detection rate of about 70% in traditional serological screening, genetic testing has great advantages, "Zhao Lijian said. On the other hand, the positive predictive value of non-invasive prenatal genetic testing is significantly higher than that of traditional serological screening, which greatly reduces the occurrence of false positives and further reduces the unnecessary number of amniocentesis, helping to reduce the risk of adverse pregnancy outcomes in pregnant women and alleviate the pressure on clinical prenatal diagnostic resources. In July 2019, the Hebei Provincial Government, in collaboration with BGI Genomics, launched the province's first non-invasive prenatal genetic screening project for pregnant women nationwide. From 2022 to 2024, the Hebei Provincial Party Committee and Government have included this project in the province's 20 livelihood projects for three consecutive years. As of now, the local area has provided non-invasive prenatal genetic testing services to over 2 million pregnant women, with a coverage rate of over 98.5% in the province. In the latest local research, it is difficult to find children under the age of 3 with Down syndrome, which intuitively reflects the significant achievements made by Hebei in the prevention and control of Down syndrome Zhao Lijian stated that this achievement cannot be separated from the advantages of genetic technology innovation and transformation, as well as the screening model for large populations. Before 2019, the price of non-invasive prenatal genetic testing in Hebei Province was around 2400 yuan per case. However, after the implementation of the government's livelihood project, this project will only cost 345 yuan per case by 2024, and it will be collected by the government and free for the public. A health economics evaluation shows that the overall cost-effectiveness ratio of the project is as high as 1:16.21, which means that with a government investment of 1 yuan, social expenditure can be saved by 16.21 yuan. The health economics benefits of the project are significant. Large population, low-cost, and efficient genetic screening is the key to assisting in precise prevention and control and reducing birth defects Zhao Lijian introduced that currently, BGI Genomics has also carried out large-scale livelihood screening in Heilongjiang Province, as well as in many places such as Shenzhen, Fuyang, Changsha, and Wuhan, and the cost-effectiveness ratio of the projects is quite considerable. With the development of technology, can genetic testing technology detect multiple types of birth defects at once? With the rapid development of high-throughput sequencing technology, genetic testing technology has become possible to detect multiple types of birth defects at once. However, living organisms are too complex, and there are still many challenges waiting for us to overcome Zhao Lijian stated that due to the wide variety and complex mechanisms of gene related diseases, many rare and genetic diseases still face diagnostic difficulties, especially in the special prenatal stage where the window period for testing is often only a few months, and the observable phenotypes are very limited, which increases the difficulty and risk of prenatal testing and diagnosis. When conducting relevant genetic testing, the first step is to obtain the informed consent of the test subject. This ensures that the examinee can fully understand which health hazards and genetic risks a testing technology can help explore and solve, while also recognizing that each technology has certain limitations and is not a universal solution that can completely avoid all risks. Zhao Lijian said that we cannot give up embracing new technologies because it will cause many families to miss the opportunity for early prevention and timely intervention. To this end, it is necessary to popularize knowledge related to genetic technology to the public and enhance their awareness and understanding of genetic testing. Zhao Lijian introduced that around the three-level prevention and control system for birth defects, BGI Genomics is continuously improving its "five front" (covering pre marital, pre pregnancy, prenatal, neonatal, and child growth stages) maternal and child health management product system based on high-throughput sequencing. For example, in the pre pregnancy stage, BGI's single gene carrier screening program can simultaneously screen for hundreds or even thousands of pathogenic single gene recessive genetic diseases, including thalassemia and spinal cord atrophy, for couples with family planning, in order to assess the risk of individuals carrying pathogenic gene mutations. Seemingly healthy parents may also have children with genetic diseases, which are usually monogenic genetic diseases Zhao Lijian introduced that single gene genetic disease refers to the genetic disease caused by the variation of a single pathogenic gene. The incidence rate of single gene genetic disease in the population is not high, but the carrier rate is high. Taking autosomal recessive genetic diseases as an example, carrying the disease causing gene is not scary. What is scary is that if both partners happen to carry the same disease causing gene, without intervention, the children born to such couples have a 25% chance of developing related genetic diseases. Therefore, couples preparing for pregnancy should undergo screening for carriers of monogenic genetic diseases in advance. If there is a risk of related reproductive diseases, genetic counseling combined with necessary prenatal diagnosis or assisted reproductive technology intervention can be used to significantly reduce the incidence of related birth defects from the source. Data shows that China's birth defect prevention and control network is constantly improving. As of now, there are over 3000 pre marital examination institutions and pre pregnancy examination institutions nationwide, as well as prenatal screening machines