Blood group is one of the main characteristics of human blood, and there are about 30 known blood group systems, the ABO blood group we are familiar with is one of the most important blood group systems, and the Rh blood group system is also one of them. Human blood types are divided into four categories, A, B, O and AB, and on the red blood cells of these four blood types, there are corresponding A, B and AB agglutinogens. Regardless of the blood type, most people have an Rh antigen on their red blood cells, called Rh-positive; a small number of people have no Rh antigen on their red blood cells, called Rh-negative. For example, if someone’s blood type is A, and he has another Rh antigen on his red blood cells, he is an A Rh-positive blood type; conversely, he has no Rh antigen expression on his red blood cells, he is an A Rh-negative blood type. So Rh blood type is also a separate antigen system. Rh is the first two letters of the foreign name of the rhesus macaque (Rhesus Macacus). It was named after scientists such as Randsteiner who, while doing animal experiments in 1940, discovered the presence of Rh blood group antigenic material on red blood cells in rhesus monkeys and most humans. The discovery of Rh blood group is very important for guiding blood transfusion more scientifically and further improving the experimental diagnosis of hemolytic disease in newborns and maintaining the health of mothers and infants. There are six types of Rh antigens on human red blood cell membranes: C, c, D, d, E, and e. Among them, D antigen is the strongest antigen. The Rh blood group system is characterized by the absence of natural antibodies in human serum that react with Rh antigens. Therefore, the first time an Rh-negative recipient receives Rh-positive blood, no coagulation reaction occurs. However, as the Rh-positive blood is given to the recipient, the Rh-positive blood will cause the recipient to develop Rh antibodies, which will cause the Rh-positive red blood cells to agglutinate when the Rh-positive blood is given later. In clinical work in gynecology and pediatrics, it is seen that Rh-negative women who have conceived Rh-positive fetuses can also cause the mother to produce Rh antibodies after the red blood cells of the Rh-positive fetus enter the mother’s body for some reason (e.g., a small amount of placental villi are shed and enter the mother’s circulation). Therefore, during the second pregnancy, maternal Rh antibodies (mainly Igh) can enter the fetus through the placenta, causing hemolytic anemia in Rh-positive fetuses and even death in severe cases. Rh-positive blood types account for about 99.7% of Han Chinese and most ethnic groups in China, and about 90% of individual ethnic groups. In some foreign countries, Rh-positive blood types account for about 85% of people, and Rh-negative blood types account for about 15% of Caucasians in Europe and the United States. The Rh blood group system is second only to the ABO blood group system in clinical importance, and approximately 70% of Rh-negative individuals will develop anti-D antibodies after blood transfusion or pregnancy exposure to the D antigen. The method of identifying the Rh blood group is simple: a small amount of blood is taken and reacted with a special blood grouping reagent, and the result is determined to be positive if there is agglutination, or negative if there is no agglutination. The Rh blood grouping system is clinically important because approximately 70% of Rh-negative individuals who are exposed to D antigen through blood transfusion or pregnancy will develop anti-D antibodies. This antibody can cause destruction of imported Rh-positive red blood cells, and during pregnancy, anti-D can affect Rh-positive fetuses and cause neonatal hemolytic disease. Nowadays, some large general hospitals are routinely identifying Rh blood types for transfusion patients and pregnant women, which is important for reducing the occurrence of hemolytic transfusion reactions and improving eugenics. There are five main types of Rh blood group antibodies, with anti-D being the most important and common, followed by anti-c. Therefore, hemolytic disease of newborns with the Rh system can also occur in Rh-positive mothers, which is the result of immune reactions from mothers and infants with incompatible C, c, E and e antigens. The incidence is relatively low and it is not necessary to test for all antibody types, but the possibility of the presence of additional antibodies needs to be ruled out when performing immunohematological prenatal testing. Antibody potency is a measure of the level of antibodies in the serum and is used to determine the likelihood of hemolytic disease. If the antibody potency in the serum of a pregnant woman is higher than 1:64, drug therapy is required, and if it is >1:128, plasma exchange or removal therapy is required in the transfusion department of a hospital that is equipped for this purpose. Special reagents are needed to identify Rh blood type, but it is very convenient for the test subject. To find out her blood type, all she needs to do is to collect a little ear blood from the hospital and she will know whether she is Rh negative or positive. It is necessary for a couple to have Rh blood group identification before a woman gets pregnant. Do not be negligent and do early examination, early prevention and early treatment. Of course, blood donation is also an important way to know whether your blood type is Rh negative. Rh blood group identification should be done routinely before pregnancy. Some people in rural areas or lack of knowledge in this area, if the woman has a history of repeated miscarriages, a history of fetal death in the womb, or a newborn with unexplained severe jaundice, or even nuclear jaundice, should think that there may be maternal and infant Rh blood group incompatibility, before preparing for the next child, must go to the hospital to do Rh blood group identification. Knowing that the couple’s Rh blood type is incompatible does not necessarily mean that fetal or neonatal hemolysis occurs. About 50% to 70% of Rh-negative individuals can be immunized by Rh-positive red blood cells through blood transfusion or pregnancy and produce anti-D antibodies. Therefore, couples with Rh-negative blood types who want to know if their fetus will develop hemolysis should undergo regular prenatal antibody potency screening at regular hospital obstetrics clinics; usually a high potency means a high number of antibodies. Some people do not know much about the significance of blood group check during pregnancy checkups, and even think that blood group can be checked or not. In fact, from the medical point of view, the blood type check during pregnancy has at least the following three meanings: ① Prepare for blood transfusion: in some pathological cases, such as premature birth, miscarriage, ectopic pregnancy in early pregnancy; placenta praevia, early placental abruption, severe anemia in pregnancy in the middle and late stages of pregnancy; lack of uterine contraction during delivery, abnormal placental abruption causing hemorrhage, etc., all of which may endanger the maternal life due to excessive blood loss. The maternal blood loss may be life-threatening. In particular, there is a shortage of RH-negative blood supply, and timely blood type identification can help prepare blood supply. ② Facilitate timely detection of neonatal hemolysis: This is a hemolytic disease caused by immunization with blood group antigens due to maternal-infant blood group incompatibility. More than 90% of neonatal ABO hemolysis occurs in mothers with type O blood and fetuses with type A and B. This may be related to the high potency of immune antibodies produced by the mother after being stimulated by type A or B antigenic substances. This immune antibody can enter the fetus through the placenta and cause hemolysis in the newborn, and Rh blood type causes hemolytic disease in newborns with Rh-negative mothers and Rh-positive fathers. Early blood group testing can monitor pregnant women who are O or Rh negative during pregnancy and take appropriate measures to prevent and treat hemolytic disease. ③ Provide reference basis for parentage identification: Of course, blood group test can only be used as an auxiliary basis for parentage identification, and the most accurate one still depends on DNA test. When the father is Rh-positive blood type and the mother is Rh-negative, and the fetus is Rh-positive, especially when family planning is needed, abortion should not be done easily, and if there is already a history of abortion or blood transfusion, predictive tests for neonatal hemolytic disease should be performed during pregnancy. Since there will be a few blood exchanges between mother and baby through the placenta, if the child is of positive blood type, when the baby’s blood refluxes to the mother, antibodies will be produced in the mother, and these antibodies may then be passed back to the fetus through the placenta, at which time the fetus will have a hemolytic reaction in the mother, and miscarriage may occur in early pregnancy, and preterm delivery may occur in mid to late pregnancy. The fetus may die in utero due to severe anemia. The hemolytic reaction to Rh blood group incompatibility occurs mostly after the second pregnancy, accounting for about 99% of cases. The hemolytic reaction is less severe in the first pregnancy. When another pregnancy occurs, if the fetus is still Rh-positive, the existing antibodies and newly generated antibodies in the mother’s body will destroy the fetal red blood cells one after another. For these reasons, Rh-negative women need regular immunohematological prenatal testing of their blood before and after pregnancy to estimate the risk of neonatal hemolytic disease in the future when the child is born. Once this risk is established (i.e., irregular antibodies that can cause neonatal hemolytic disease are found), monthly tests should be done in the first trimester and weekly tests in the second trimester, along with related obstetric tests, including blood typing, antibody screening and antibody potency determination. If no problem is found at 32 weeks of gestation, no further antibody testing is necessary. Fetal Rh antigen is mature at 32 days, and fetal blood can enter the mother to sensitize her during miscarriage due to placental damage. The amount of blood that enters the mother’s body during a spontaneous abortion is usually at least 0.02 ml, and this small amount of blood is sufficient to sensitize 6% of mothers. If the fetus is Rh-positive in another pregnancy, there is a risk of hemolytic disease. The maternal sensitization rate increases to 25% with abortion. In women with a prior history of stillbirth, the stillbirth rate is more than twice as high in consecutive pregnancies when the potency of the anti-human globulin test is greater than 1:64. In miscarriages before 12 weeks of gestation, fetal red blood cells can be detected in the blood of only 9.4% of pregnant women, while in miscarriages after 12 weeks, fetal red blood cells can be detected in 40.3% of pregnant women, so the later the miscarriage, the greater the likelihood of maternal sensitization. The principle is that passive immunity can inhibit the active immune response to the same antigen. Injection of concentrated Rh immunoglobulin G into the Rh-negative primigravida can prevent the pregnant woman from being sensitized by the fetal Rh antigen. The method is to give 100-300 μg of Rh-IgG intramuscularly to the mother within 72 hours after delivery, which destroys Rh-positive fetal red blood cells that may be present in the blood and reduces the occurrence of Rh immunization by about 80-85%. This prophylactic treatment is only effective for first-time Rh-immunized primiparous mothers who have not been transfused with Rh-positive blood. After the Rh globulin injection, no antibodies will be produced in the blood, and when she gets pregnant again, the next baby will not be affected by Rh antibodies, which means she can still give birth to a healthy and normal child. A foreign scholar once injected 300μg of anti-Rh(D)-IgG into 1357 Rh-negative women at 28 or 34 weeks of gestation, and then injected it again within 72 hours after the delivery of Rh-positive babies, and no one was sensitized, so the preventive effect was positive. However, there are 30% of Rh-negative women who do not produce antibodies from multiple blood transfusions and pregnancies, and the reason for this needs further study. This immunoglobulin is only available in a very few hospitals in China and is expensive. And it can only be used for Rh-negative women whose blood has not produced antibodies within 72 hours after delivery and miscarriage. The first step is to ensure a healthy baby for the negative mother-to-be, which requires attention to the following three aspects: First, pre-conception preparation: if it is the first pregnancy, there is generally no need to be nervous, starting from the fifth month of pregnancy for regular blood immunology prenatal checkups; Rh-negative women generally need to go to a designated hospital for ABO and Rh blood group identification before pregnancy, and if the mother-to-be has previously delivered a newborn with hemolytic disease, the body’s If a mother-to-be who has given birth to a newborn with hemolytic disease is still at a high value of IgG antibody, it is not suitable to get pregnant immediately, otherwise, the fetus in the middle and late stages of pregnancy may occur serious intrauterine anemia, causing fetal edema and stillbirth, for this situation, it is necessary to take drugs with antibody immunosuppressive effect beforehand, and if necessary, plasma exchange or plasma removal treatment to make the antibody potency in the body drop to a low value before conception, the prognosis is better. Secondly, pregnancy monitoring: ① Periodic immunohematological prenatal examination of pregnant women: once the presence of antibodies is confirmed, oral jaundice inoculation or infusion therapy should be given immediately, and if the antibody potency is >128, plasma exchange is required at the same time. ② Intrauterine transfusion of fetus. Very few fetuses with Rh system incompatibility have premature hemolysis, and intrauterine transfusion should be performed early in order to correct the severe anemia and save the fetus. Third, post-delivery treatment: ①If the fetus is in good condition during pregnancy, it can be treated according to the general neonatal routine, but should be closely observed for the possibility of progressive jaundice. ②Newborns with Rh system incompatibility are often already compromised in the fetal period and can be delivered by cesarean section appropriately early. If there is aggravation of progressive jaundice, blood exchange should be used along with light and drug treatment. Prenatal diagnosis: ① Maternal blood antibody determination: Rh-negative pregnant women should be tested for their husband’s Rh blood type, and if they do not match, they should undergo regular antibody testing. The first measurement is usually performed at 16 weeks of gestation, and the test is performed once every two months in early pregnancy, once a month in mid pregnancy, and once every half month in late pregnancy. When the antibody potency is 1:128, plasma exchange should be considered for the pregnant woman to remove the antibody from the maternal blood. ②Amniotic fluid examination: normal amniotic fluid is transparent and colorless, while fetal fluid with severe hemolysis is yellow, so amniotic fluid examination has a reference value for the decision of further treatment methods. ③B ultrasound examination: it is important to know whether the fetus has edema, if the edema is serious, it indicates that the fetus is seriously anemic and needs intrauterine blood transfusion or early delivery. Postnatal diagnosis: If the couple’s Rh blood type is incompatible and the maternal blood type antibody potency is high during pregnancy, all newborns should be screened for hemolysis by taking venous blood after birth, and a positive result (anti-human globulin test or release test) can confirm the diagnosis of Rh hemolysis. It is generally believed that Rh-negative women with anti-D potency less than 1:8 should not intervene for the time being, while ≥1:16 will have an impact on the fetus, and ultrasound should be done to see how the fetus is growing, and whether there is ascites and edema. If antibodies are rising rapidly, umbilical vein puncture is needed to check fetal blood type, hemoglobin, red blood cell count, bilirubin level and anti-human globulin test. If the fetus is severely anemic, intrauterine blood transfusion is possible. These conditions are only available in tertiary hospitals, such as the PLA Baiqiu’en International Peace Hospital, which has more mature treatment experience. In Rh-negative women, it is best to have a pregnancy with zero anti-D potency, usually not more than 1:8. Hemolysis caused by Rh maternal and child blood group incompatibility usually occurs in the middle or late pregnancy, but there are also cases of potency growth in early pregnancy, which should be observed dynamically. Therapeutic measures may include: ① plasmapheresis: exchange the material produced by the mother that destroys the fetal red blood cells (blood group antibodies); ② intrauterine blood transfusion: correct fetal anemia; ③ maternal injection of gammaglobulin to inhibit the production of blood group antibodies in the body, and at the same time can prevent antibodies in the mother from entering the fetus. ④Early delivery: If the amniotic fluid is obviously yellowish, early delivery is necessary to prevent the fetus from worsening and developing into fetal edema or stillbirth. The purpose of plasma exchange is to remove the pathological components present in the patient’s or pregnant woman’s plasma and exchange them with normal fresh plasma. Plasma exchange for Rh-negative mothers before or during pregnancy can reduce the intrauterine condition of the affected child, achieve the therapeutic purpose of blocking hemolysis in the affected child, avoiding nuclear jaundice in the affected child, correcting anemia in the affected child, improving the prognosis and saving the life of the affected child. This method can effectively reduce the level of immune antibodies in the pregnant woman and reduce the damage to the fetus, but whether the survival of the fetus can be ensured depends on a number of factors: (1) the amount of “transplacental hemorrhage”, which is more likely to occur especially in the second trimester. (2) The degree of maternal transfer of antibodies to the fetus, i.e. the barrier effect of the placenta. ③Type of blood group antibodies: generally, IgG1 and IgG3 subtypes cause neonatal hemolytic disease, while IgG2 and IgG4 have mild symptoms or do not mediate red blood cell hemolysis. ④ Other factors cause neonatal hemolytic disease, such as those caused by platelet and granulocyte immunity, inherited erythrocyte membrane abnormalities, viral infections, premature maturation, and glucuronosyltransferase deficiency. In addition, the degree of hemolysis is related to the strength of fetal red blood cell antigens and the amount of maternal blood group substances. The number of times to do plasma exchange (removal) is determined by the high potency of antibodies in pregnant women. If the medication can control the potency of antibodies below 64, it is not necessary to do plasma exchange (removal) treatment. In the middle trimester, plasma exchange (removal) therapy can be done in order to stop and reduce the increase in the number of antibodies in order to protect the fetus from being involved until delivery. It is usually collected once a week, during which the pregnant woman’s blood biochemistry, electrolytes and fetal ultrasound need to be monitored for routine obstetric fetal monitoring, and amniotic fluid testing can be done when available. The cost of plasma removal is not high, only one or two hundred dollars per visit, compared to the higher cost of plasma exchange, which is mainly the cost of a one-time blood collection line and fresh plasma, about 2,500 dollars per visit.