Neonatal hemolytic disease mainly refers to the hemolysis caused by mother-infant blood group incompatibility, where the immune antibody IgG against fetal red blood cells in the mother’s blood enters the fetal circulation through the placenta and an alloimmune reaction occurs leading to the destruction of fetal and neonatal red blood cells. The most basic cause of maternal-infant blood group disorders is that the fetal red blood cells enter the maternal circulation and half of the fetal blood group genes come from the mother and the other half from the father, and the genes from the father happen to be missing from the mother, so the antigens encoded by the parental genes on the fetal red blood cell membrane may stimulate the mother to produce antibodies, which are IgG-like immune antibodies in nature and can pass through the placenta. Once this antibody enters the fetal circulation through the placenta, it may bind to and destroy fetal red blood cells and hemolysis may occur. Among neonates with ABO hemolytic disease, the mother’s type O and the fetus’ type A(B) are the most common, accounting for about 95% of cases. This is because “O” mothers have the highest amount of IgG ABO antibodies. This is because “O” mothers have the highest amount of IgG ABO antibodies, or the IgG ABO antibodies produced by “O” mothers are small in molecular weight and high in potency when stimulated by A or B antigens, and can easily pass through the placenta. In contrast, the body of a mother with type A or B blood group is stimulated by heterotypic antigens and produces mainly IgM ABO antibodies, which have a high molecular weight and cannot pass through the placenta, so type O mothers with type A (B) fetuses are prone to neonatal ABO hemolytic disease. Immunological studies have proven that as little as 0.03 to 0.07 ml of blood enters the mother’s body, it can lead to an immune response from the mother. The more blood that leaks out, the stronger the maternal immune response and the higher the incidence of neonatal hemolytic disease. From the point of view of Rh hemolytic disease, when fetal blood enters the mother’s body such as less than 0.1 ml, the possibility of generating Rh immune response is 3%; if it is 0.25 to 1 ml, it is 25%; if it is greater than or equal to 5 ml, it can be 65%. However, the majority of mothers (75%) leak less than 0.1 ml of blood through the placenta, so mother and child blood type discrepancies do not always develop and hemolytic disease is still a minority. Rh hemolytic disease in newborns rarely occurs in the first trimester, whereas ABO hemolytic disease can develop in the first trimester Rh-negative sera do not contain naturally occurring Rh antibodies, which are only produced by human blood cells as an antigenic stimulus and only after repeated stimulation (unlike ABO blood types). The first fetus is usually delivered in the latent phase of primary immunity. As a result, the first birth does not usually occur. When the primary immune response occurs, the secondary immunity can occur soon after the second pregnancy, even if the amount of transplacental bleeding is small, and the IgG antibodies increase rapidly and bind to the fetal red blood cells through the placenta, resulting in hemolysis. ABO blood group IgG immune antibodies can be caused by ABO blood group incompatibility between the pregnant woman and the fetus, but because of the widespread existence of type A and type B substances in nature, such as parasitic infections, vaccinations, etc. can make pregnant women produce IgG ABO antibodies, that is, IgG immune antibodies can already exist in the pregnant woman’s body before pregnancy, so ABO system neonatal hemolytic disease can develop in the first pregnancy. The possibility and severity of neonatal hemolytic disease in the fetus can be predicted by prenatal immunological examination. Routine prenatal immunohematology tests include: 1. ABO blood grouping of the couple. 2.Rh blood group identification of the couple. Irregular antibody screening for pregnant women (irregular antibodies are mostly immune incomplete antibodies, and mostly IgG antibodies, which can affect the fetus through the placenta, and irregular antibody screening for pregnant women and identification of antibody characteristics can predict neonatal hemolytic disease). 4. Antibody identification for positive screening tests. 5. Determination of the potency of alloimmune antibodies. The first test can be performed in the 12th to 16th week of pregnancy to understand the basic information of the couple and the basic level of antibodies. Then the second test will be done at 28-30 weeks, and the test will be repeated every 2-4 weeks to understand the rate of increase of antibodies. The blood sample used for the test is 5 ml of maternal venous blood, usually non-anticoagulated (normal tube), and no fasting is required. It is also useful to provide 3 to 4 ml of the pregnant woman’s husband’s blood sample to determine the compatibility of the mother and child’s blood type. Factors affecting the severity of ABO neonatal hemolytic disease ① The concentration of IgG-like ABO antibodies in the pregnant woman. The presence of IgG ABO antibodies in the mother’s body that can destroy the fetal red blood cells does not mean that the newborn must suffer from ABO neonatal hemolytic disease, but it is generally believed that only when the potency of the antibody is ≥ 64 may cause neonatal hemolytic disease. When the maternal antibody potency is ≥256, the likelihood of neonatal hemolytic disease becomes higher. However, the relationship between the maternal IgG antibody potency and the severity of ABO neonatal hemolytic disease is not strong, as there are many other influencing factors. ABO antigens can be detected in fetuses at 5-6 weeks of age, but their antigen development is still incomplete until birth and differs significantly in quantity and quality from adult red blood cells. As a result, each newborn’s erythrocytes bind very few IgG-like ABO antibodies (compared to the hundreds of thousands of ABO antigens on each erythrocyte), and there are individual differences. The difference in the number of IgG antibodies bound on erythrocytes is closely related to hemolysis. (iii) IgG subclasses. The amount of IgG1 and IgG3 antibodies is linearly related to the severity of hemolysis, while IgG4 is not. IgG antibodies are actively absorbed into the fetal circulation through IgG receptors on the placental chorionic villus. The rate of absorption of IgG antibodies and the subclasses are related to the number and type of IgG receptors, so the placenta also has an influence on the severity of hemolytic disease in the newborn. ⑤ The amount of blood group substances (not significantly associated with non-secretory types). In some fetuses, body fluids contain soluble A or B substances, which neutralize anti-A or anti-B antibodies, thus protecting fetal red blood cells and acting to prevent the development of ABO neonatal hemolytic disease or to alleviate its clinical manifestations. Factors affecting the severity of Rh neonatal hemolytic disease ① If IgG class Rh antibodies are present in the pregnant woman and the corresponding Rh antigen is present in the fetal red blood cells, the fetus will almost certainly develop Rh neonatal hemolytic disease. The relationship between the concentration of IgG-like Rh antibodies in the mother and the severity of Rh neonatal hemolytic disease is very close, unlike ABO neonatal hemolytic disease, mainly because the Rh antigens in the newborn are already developed and have a strong ability to bind antibodies, so the amount of corresponding antibodies becomes a key factor. According to experience, the prognosis of newborns is better when the potency of IgG-like Rh antibodies in pregnant women is ≤64 in the second trimester, and the fetus may be seriously affected when the potency of antibodies is ≥256. ②Rh neonatal hemolytic disease generally does not occur in the first child, and pregnant women generally do not produce IgG class Rh antibodies as long as there is no obvious immunization process such as blood transfusion and pregnancy. Even in the second trimester, due to bleeding through the placenta, a small amount of fetal red blood cells enter the mother’s body and it usually takes 2 to 6 months for the mother to be immunized and produce antibodies, by which time the pregnancy process is over and no harm is caused to the fetus. ③If Rh antibodies are already present in the pregnant woman’s body and the corresponding Rh antigens are present in the fetal red blood cells at the same time, the immune response between the mother and the baby plays a very critical role at this time. Due to the stimulation of the fetal red blood cells, the concentration of antibodies in the mother’s body increases continuously, and the faster it increases in the second trimester. If left untreated, stillbirths can easily occur. The potency of Rh antibodies in pregnant women and their changes depend on the individual differences of the pregnant women themselves, but also on the compatibility of the ABO blood types between the mother and the baby. If the ABO blood type does not match between mother and baby, it means that the fetal red blood cells will be destroyed by the corresponding ABO antibodies in the mother immediately after entering the mother’s body, and therefore cannot effectively stimulate the increase of Rh antibody potency in the mother’s body. In this case, the newborn tends to have a milder form of Rh hemolytic disease. Prevention and treatment of neonatal hemolytic disease ① Prenatal prevention Once the risk of fetal hemolytic disease is confirmed, the fetus should be followed up during pregnancy in order to estimate the degree of morbidity, determine the most appropriate time for delivery, and draw the physician’s attention to the preparation of the newborn for treatment. Prenatal treatment Pregnant women: Comprehensive treatment: To reduce symptoms and miscarriage, preterm delivery or stillbirth, pregnant women with IgG anti-A (B) potency ≥ 64 should take Yin Chen Tang plus reduction (basic ingredients: Yin Chen, Scutellaria baicalensis, rhubarb, licorice, etc.) for 20 days as a course of treatment. In the middle and late stage of pregnancy, pregnant women should be treated with a combination of western medicine: 50% glucose 40 ml, vitamin C 500 mg intravenously once a day for 10 days, and vitamin E 100 mg orally 3 times a day. 200 mg of immunoglobulin should be injected intravenously 1 week before termination of pregnancy in pregnant women with IgG anti-A (B) potency ≥ 128. Immunoglobulin injection: Its function is to inhibit maternal IgG antibody production, prevent maternal IgG antibodies from entering the fetus, and prevent fetal red blood cells from being destroyed. Plasma replacement: Plasma replacement can reduce antibody levels to 75%, but rebound often occurs. ②Fetal management a) Intrauterine blood transfusion: can correct anemia and prevent intrauterine fetal death, limited to severely affected fetuses with immature lungs. b) Early delivery: the closer the pregnancy is to full term, the more antibodies are produced and the greater the effect on the fetus. Early delivery can be considered when the fetus is close to full term when maternal IgG antibodies are too high. The newborn with hemolytic disease is easily suffocated at birth due to excessive destruction of red blood cells, and should be prepared for resuscitation at the time of delivery to prevent asphyxia. The umbilical cord should be clamped immediately after delivery to avoid excessive inflow of umbilical blood into the fetus. Keep the umbilical cord 5~150px for blood exchange. Retain 3-5ml of cord blood for routine blood, blood group, blood group antibodies and bilirubin determination. Perform careful physical examination to determine the degree of hemolysis. a) Neonatal treatment b) Correction of anemia and heart failure: Immediately after birth, administer oxygen and control heart failure with drugs. c) Treatment of jaundice: The main methods are light therapy, medication, and exchange transfusion, which can reduce serum bilirubin to avoid nuclear jaundice. Intravenous immunoglobulin: It can block Fc receptors and inhibit the hemolysis process, so that bilirubin production can be reduced. Blood exchange therapy: it can remove antibodies, reduce hemolysis, and lower serum bilirubin to prevent the occurrence of nuclear jaundice.