B群溶血性連鎖球菌（Group B Streptococcus, GBS）は、新生児敗血症や髄膜炎の原因となる細菌である。妊娠中にGBSを保菌している母体から新生児に感染することがあり、出生前に母体のスクリーニングを行うことが推奨されている。遺伝子検査（PCR法など）を用いることで、迅速かつ高感度にGBSの検出が可能となり、分娩時の抗菌薬投与の判断に役立つ。
Genetic testing during pregnancy is an important tool to assess the health of the fetus and the presence of genetic abnormalities. While these tests can support appropriate medical management and family decision-making, they also carry risks and ethical challenges. This article details the main types of genetic testing available during pregnancy, the risks and benefits of each test, and the ethical and social aspects.
1. Types of genetic testing during pregnancy
Genetic tests performed during pregnancy can be broadly divided into two categories: non -definitive tests and definitive tests。genetech.co.jp+1cfa.go.jp+1
1.1 Non-conclusive testing
非Non-definitive tests are screening tests to assess the risk of genetic abnormalities in the fetus and do not provide a definitive diagnosis. The main non-definitive tests include:sancha-art.com+2cfa.go.jp+2genetech.co.jp+2
a. Maternal serum marker test
Between the 15th and 20th weeks of pregnancy, the concentration of certain substances in the mother’s blood (such as alpha-fetoprotein, hCG, estriol, and inhibin A) is measured to assess the risk of fetal trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), neural tube defects, etc. genetech.co.jp+3cfa.go.jp+3cem-clinic.com+3
b. Non-invasive prenatal testing (NIPT)
This test analyzes fetal cell-free DNA (cfDNA) present in the mother’s blood after the 10th week of pregnancy to assess the risk of trisomy 21, trisomy 18, and trisomy 13 with high accuracy. NIPT has been attracting attention in recent years because it has higher sensitivity and specificity than conventional non-definitive tests and does not pose the risk of miscarriage。 jstage.jst.go.jp+7genetech.co.jp+7cfa.go.jp+7
1.2 Definitive testing
Definitive tests are tests to directly confirm genetic abnormalities in the fetus. While they have high diagnostic value, they are invasive and therefore carry risks such as miscarriage. The main definitive tests are as follows: cfa.go.jp+1cem-clinic.com+1
Amniocentesis
After the 15th week of pregnancy, a needle is inserted into the uterus through the mother’s abdomen to collect amniotic fluid and test for chromosomal numerical, structural, and genetic abnormalities in the fetus. This test carries a risk of miscarriage of approximately 1/300 to 1/500. jsog.or.jp+3cfa.go.jp+3mhlw.go.jp+3
b. Chorionic villus sampling
Between the 11th and 14th weeks of pregnancy, a needle is inserted into the uterus to collect chorionic villus tissue and test for chromosomal and genetic abnormalities in the fetus. This test carries a risk of miscarriage of about 1 in 100, but the risk of transabdominal chorionic villus sampling has been reported to be equivalent to that of amniocentesis. cfa.go.jp
2. Risks and benefits of each test
Each test has its own risks and benefits, and it is important for pregnant women and their families to understand these before choosing a test.
2.1 Maternal serum marker testing
Benefit:
It is non-invasive and poses no direct risks to the mother or fetus.
It may take some time for the test results to come out.
3. Ethical and social issues of genetic testing
Although genetic testing during pregnancy has medical benefits, it also raises ethical and social issues, including the decision-making regarding testing options, the psychological impact of test results, and societal acceptability.
3.1 Genetic testing options and information provision
Although genetic testing should be a choice made by pregnant women and their families, their decision-making may be influenced by how information is provided and how medical professionals are involved.
a. The Importance of Informed Consent
Medical professionals need to provide appropriate information so that pregnant women can make informed decisions about testing.
If medical professionals do not provide sufficient explanation, the test may be performed without patients understanding its significance and limitations.
b. The role of genetic counseling
Genetic counselors can help ease the psychological burden by explaining testing options and providing support in interpreting and responding to results.
Receiving genetic counseling will help you properly understand the test results and prevent unnecessary anxiety.
(acmg.net)
3.2 Genetic testing during pregnancy and its psychological impact
While the test results provide important information about the health of the fetus, some results can also cause a strong psychological burden for the pregnant woman and her family.
If the test result is negative
Although this provides a “sense of security,” there is a risk of a false sense of security, as not all genetic abnormalities can be ruled out.
It is important to understand the limitations of the tests and pay attention to health management after birth.
b. If the test result is positive
If a chromosomal abnormality or genetic disease is discovered, it can have a significant psychological impact on the pregnant woman and her family.
Even if the result is positive, it is important to reconfirm it with a definitive test (amniocentesis or chorionic villus sampling).
3.3 Social acceptability and ethical issues of genetic testing
The widespread availability of genetic testing during pregnancy may affect societal values and ethics.
a. The question of what is “normal”
The criteria for determining whether a genetic test result is “abnormal” are socially determined and are not determined solely by medical definitions.
A reduction in the births of fetuses with certain diseases or disabilities could have an impact on diversity in society as a whole.
b. Relationship with Eugenics
If advances in genetic testing led to the selection of fetuses with specific diseases, there is a risk that this could lead to the promotion of eugenics.
Disability groups and others have expressed concern that prenatal testing could lead to the denial of the existence of people with certain diseases or disabilities.
(bmj.com)
4. The future of genetic testing and technological advances
Genetic testing technology is evolving every day, and is now able to provide a wider range of information with greater accuracy. How will genetic testing during pregnancy change in the future?
4.1 Utilization of Next-Generation Sequencing (NGS) Technology
Currently, most genetic tests focus on chromosomal abnormalities, but next-generation sequencing (NGS) technology makes it possible to analyze the entire genome of the fetus.
a. Fetal genetic analysis by whole genome sequencing (WGS)
By using WGS, it is possible to gain a more detailed understanding of fetal genetic mutations and the risk of rare diseases.
This will enable risk assessment of abnormalities in gene expression and single-gene diseases (such as mitochondrial disease and cystic fibrosis).
b. Advances in microarray analysis and epigenetics research
Using microarray technology, it is possible to detect minute chromosomal deletions and duplications in fetuses.
By studying epigenetics (the regulation of gene expression), it is possible to analyze the influence of environmental factors on the genes of the fetus.
(genomeweb.com)
4.2 Gene editing technology and the potential for fetal medicine
Advances in gene editing technology (CRISPR-Cas9) have raised the possibility of correcting genetic diseases during fetal development.
a. The possibility of fetal gene therapy
The possibility of correcting genetic abnormalities in a fetus before birth and preventing the onset of disease.
Although still in the clinical research stage, it is being considered for prenatal treatment of certain genetic diseases (such as sickle cell disease and beta thalassemia).
b. Ethical risks of gene editing
Gene editing of fetuses has significant ethical and social implications, and careful discussion is needed about the scope of application of the technology.
There are concerns about the issue of genetically modified “designer babies,” and there are calls for the establishment of international regulations.
Genetic testing during pregnancy is an important tool for assessing the health of the fetus, but its use requires careful consideration. As technology advances, new possibilities as well as ethical challenges arise, and discussion at the level of society as a whole is essential.
b. Rubella virus infection
If the mother is infected with the rubella virus during early pregnancy, there is a risk that the fetus will develop congenital rubella syndrome (CRS). CRS can cause congenital heart disease, cataracts, hearing loss, and mental retardation. The presence or absence of immunity to rubella can be confirmed by measuring the rubella antibody titer of pregnant women, and if the antibody level is low, vaccination before pregnancy is recommended. In recent years, a method has been developed that uses genetic testing technology to detect rubella virus RNA in maternal blood and amniotic fluid and assess the risk of infection for the fetus.
c. Toxoplasma infection and genetic testing
Toxoplasmosis is an infectious disease caused by the parasite Toxoplasma gondii, which is transmitted through cat feces and undercooked meat. Primary infection of the mother during pregnancy can cause congenital toxoplasmosis in the fetus. Symptoms of congenital toxoplasmosis include retinal chorioretinitis, hydrocephalus, intracerebral calcification, and mental retardation. Genetic testing uses PCR to detect Toxoplasma DNA in maternal blood and amniotic fluid, making it possible to assess the risk of infection in the fetus.
d. Human parvovirus B19 infection
Human parvovirus B19 is the virus that causes erythema infectiosum (fifth disease), and infection during pregnancy increases the risk of fetal hydrops and miscarriage. In particular, infection before the 20th week of pregnancy can have serious effects on the fetus. Genetic testing can be used to detect viral DNA in the mother’s blood or amniotic fluid to assess the risk of infection in the fetus. If infection is confirmed, the condition of the fetus is evaluated in detail by ultrasound, and fetal treatment (such as intrauterine blood transfusion) may be performed if necessary.
5.2 Maternal immune status assessment and genetic testing
Genetic testing is also being used as a means of assessing the immune status of the mother. For example, certain human leukocyte antigen (HLA) genotypes may be involved in the maternal immune response and fetal rejection. It has also been suggested that mutations in cytokine genes affect the risk of infection during pregnancy. Analysis of these genetic factors can be useful in preventing and managing infectious diseases.
5.3 Genetic testing and bacterial infections during pregnancy
Not only viral infections, but bacterial infections can also affect fetuses. It is important to utilize genetic testing to detect bacterial infections in the mother and fetus early and provide appropriate treatment.
a. Group B hemolytic streptococcus (GBS) infection
Group B Streptococcus (GBS) is a bacterium that can cause neonatal sepsis and meningitis. Mothers who are carriers of GBS during pregnancy can infect their newborns, so prenatal screening of mothers is recommended. Genetic testing (such as PCR) can rapidly and sensitively detect GBS, which is useful in determining whether or not to administer antibiotics during delivery.
b. Sexually Transmitted Diseases and Genetic Testing
Sexually transmitted diseases such as chlamydia, gonorrhea, syphilis, and HIV have the risk of vertical transmission from mother to fetus. In particular, chlamydia and gonorrhea infections can cause premature birth and neonatal conjunctivitis. By utilizing genetic testing (such as PCR), it is possible to quickly determine the presence or absence of pathogens and provide appropriate treatment.
5.4 Future outlook for infectious disease risk management using genetic testing
Recent technological advances have made it possible to perform comprehensive genetic analysis of infectious diseases using next-generation sequencing (NGS). This allows detailed analysis of changes in the maternal microbiome and predicts the risk of infectious diseases. In addition, new diagnostic methods using CRISPR technology have been developed, which are expected to enable faster and more accurate infectious disease screening.
Furthermore, from the perspective of personalized medicine, efforts are being made to comprehensively evaluate the mother’s genetic background and infectious disease risk and optimize care plans during pregnancy. For example, gene polymorphism analysis can be used to predict the effectiveness of specific antiviral drugs and antibiotics, making it possible to select the optimal treatment for the mother and fetus.
5.5 Practical application of genetic testing during pregnancy to assess the risk of infectious diseases
a. Non-invasive prenatal testing (NIPT) and infectious disease diagnosis
Non-invasive prenatal testing (NIPT) is a technology that analyzes fetal DNA (cfDNA) in maternal blood and is usually used to screen for chromosomal abnormalities such as Down syndrome (trisomy 21). However, in recent years, attempts have been made to apply this technology to infectious disease diagnosis. In particular, research is being conducted to evaluate the presence or absence of fetal infection by detecting viral DNA or RNA in maternal blood. For example, methods have been developed to detect cytomegalovirus (CMV) and toxoplasmosis DNA using NIPT technology, which may complement conventional invasive testing (amniotic fluid testing).
b. Amniotic fluid and chorionic villus sampling and genetic analysis
Amniocentesis and chorionic villus sampling may be performed to assess the risk of infection in the fetus in detail. Amniocentesis is used to detect viral and bacterial DNA in the amniotic fluid using PCR to confirm the presence or absence of infection in the fetus. This is particularly useful when pathogens such as cytomegalovirus (CMV), parvovirus B19, and toxoplasmosis are suspected.
Chorionic villus sampling allows the extraction of DNA from placental chorionic tissue, enabling the analysis of the genetic background and risk of infectious diseases in the fetus. For example, if infection with toxoplasmosis or rubella virus is suspected, PCR analysis using chorionic villus can be used to confirm the fetal infection. Such tests are an important means of improving diagnostic accuracy, especially in the early stages of pregnancy.
c. Genetic analysis of fetal immune response
To assess the risk of fetal infection more accurately, studies are currently being conducted to analyze genes involved in the fetal immune response. For example, it has been suggested that polymorphisms in interferon (IFN)-related genes and Toll-like receptor (TLR) genes affect the susceptibility of the fetus to viral infections.
It has also been investigated whether certain HLA (human leukocyte antigen) genotypes may increase the risk of maternal-fetal transmission, which may allow for individualized prevention of infectious diseases during pregnancy.
5.6 Early detection of maternal-fetal infection using genetic testing
a. Combination of maternal serum biomarkers and genetic testing
Combining genetic testing with maternal serum biomarkers to assess the risk of infectious diseases during pregnancy has been attracting attention. For example, combining genetic analysis with measurements of maternal inflammatory markers (CRP, IL-6, TNF-α) and specific antibodies (IgG, IgM) can enable early diagnosis of infection.
b. Genetic markers of placental function and infectious disease risk
The placenta is an important organ that connects the mother and fetus, and its dysfunction leads to fetal growth restriction and increased risk of infection. Attempts are being made to evaluate the health of the fetus by analyzing gene expression in the placenta. For example, it has been suggested that high expression levels of certain inflammation-related genes (IL-1β, TNF-α, CXCL10) are likely to be associated with placental inflammation and increased risk of fetal infection.
In addition, technology has been developed to analyze placenta-derived exosomes in maternal blood and evaluate the health of the fetus in real time, which is expected to improve the accuracy of early diagnosis and preventive intervention of infectious diseases.
5.7 Genetic vaccines and prevention of infectious diseases during pregnancy
Recent advances in genetic technology have led to the use of genetic vaccines, including mRNA vaccines, to prevent infectious diseases during pregnancy. For example, mRNA vaccines against the novel coronavirus (SARS-CoV-2) have been shown to reduce the risk of infection in pregnant women and provide protection to newborns by transferring maternal antibodies to the fetus.
In the future, it is expected that mRNA vaccines against cytomegalovirus (CMV) and toxoplasmosis will be developed, which may significantly reduce the risk of infection before and during pregnancy, making pregnancy safer.
5.8 Applications of gene editing technology and ethical issues
Gene editing techniques such as CRISPR-Cas9 are also being considered for use in infectious disease risk management. For example, by modifying certain genetic mutations, it may be possible to reduce the susceptibility of the mother and fetus to infectious diseases. However, careful consideration is required for the application of this technology during pregnancy, as it raises ethical and safety issues.
In particular, enhancing resistance to infectious diseases through gene editing of embryos requires ethical discussion, and this is an area in which future guidelines will be required.
5.9 Genetic analysis of the maternal and fetal immune systems
To accurately assess the risk of infectious diseases during pregnancy, it is important to analyze genes involved in the immune systems of the mother and fetus. In particular, the fetus is placed in an immune environment different from that of the mother, and differences in the immune response may affect the risk of developing and becoming severely ill from infectious diseases.
Genes involved in maternal immune responses
The maternal immune system plays a complex role in protecting the fetus from infection while accepting it. In particular, the balance between the innate and adaptive immune systems is important, and the following genes are involved:
Toll-like receptor (TLR) genes : TLRs play an important role in recognizing pathogens and activating immune responses. Polymorphisms in TLR genes during pregnancy have been reported to affect susceptibility to viral and bacterial infections.
Cytokine-related genes (IL-6, IL-10, TNF-α, etc.) : These cytokines control the inflammatory response and suppress the progression of infection. Certain gene mutations may reduce resistance to infection.
HLA genes (human leukocyte antigens) : Differences in HLA genes may alter the maternal immune response and influence the risk of infection for the fetus. It has been suggested that women with certain HLA types may be more susceptible to certain viral infections during pregnancy.
Summary
Genetic testing during pregnancy is used to evaluate fetal chromosomal abnormalities and genetic diseases, as well as to assess the risk of infectious diseases for the mother and fetus. Genetic analysis is used for early diagnosis of viral and bacterial infections, and advances in non-invasive testing and exosome analysis have made safer and more precise evaluations possible. Personalized medicine through analysis of immune genes and optimization of vaccination strategies are also progressing. It is expected that future technological developments will further improve infection control during pregnancy, leading to safer pregnancies and childbirths.
