Neonatal hemolytic disease in China is mostly seen in mothers and children with ABO blood type incompatibility. Since only 0.3% of the Han population is Rh-negative, neonatal hemolytic disease due to Rh blood group incompatibility is rare. The guidelines for prevention, diagnosis, and treatment of fetal/neonatal hemolysis in Rh-negative fetuses are well established overseas. ABO blood group incompatibility between spouses (O female and non-O spouse) is very common in the population, accounting for about 25% of the population, but it usually results in relatively mild neonatal hemolytic disease, with anemia rarely exceeding moderate levels. The probability of hemolysis in newborns of type A or B mothers is only 5%, and fetal edema is even less common. The reason for the relative mildness of hemolysis in newborns with ABO blood type incompatibility is the relatively weak antigenicity of the A (or B) antigen on the surface of fetal and neonatal erythrocytes, with fewer antigenic sites on the cell surface than in adults. IgG anti-A (or B) antibodies enter the fetus through the placenta and are neutralized by blood group substances and adsorbed by tissue cells, and some of the antibodies are disposed of, resulting in less antigen-antibody binding and less destruction of erythrocytes, which ultimately causes less hemolysis [1]. In the case of mild hemolysis, the bilirubin produced by the fetus can be completely metabolized by the mother, so the majority of fetuses do not show any abnormalities in utero. The potency of maternal IgG anti-A (or B) antibodies is positively correlated with the degree of hemolysis in newborns. Bakkeheim et al [2] evaluated the predictive role of maternal IgG anti-A (or B) potency on the risk of severe hyperbilirubinemia and nuclear jaundice in ABO-naïve newborns. The study investigated 253 newborns delivered from 2004 to 2006 at Ullevål Oslo University Hospital, Norway, who were of type O, of which 61.3% were of type O, 29.6% were of type A, and 9.1% were of type B. Direct anti-human globulin testing (direct level measurement) was performed on type A or B newborns. Of the 98 newborns with type A or B, 49 were positive for DAT. When the maternal IgG anti-A (or B) potency was <1:64, 1:256, and 1:1024, the rates of DAT positivity in neonates were 14%, 55%, and 86%, respectively, and the proportion of neonates receiving phototherapy, blood exchange, and immunoglobulin therapy increased with increasing maternal antibody potency, and invasive therapy increased significantly at antibody titers ≥1:512, but one neonate whose maternal antibody potency was 1 ∶The neonate with an antibody potency of 1:128 also received phototherapy and immunoglobulin therapy. This author concluded that maternal IgG anti-A (or B) potency can help predict the risk of severe hyperbilirubinemia in ABO-naïve neonates, especially in those discharged early. It is important to note that this study tested for blood group antibodies in mothers with postnatal detection of blood group A or B newborns, and did not recommend screening of pregnant women. Whether universal screening for blood group antibodies is required during pregnancy The 2011 Guidelines for Preconception and Pregnancy Care (1st edition) [3], developed by the Obstetrics and Gynecology Section of the Chinese Medical Association, does not explicitly require antibody screening, but only recommends that the first antenatal visit (6-13+6 weeks of gestation) include ABO and Rh blood groups among the mandatory tests; among the preparatory tests, it is recommended that Rh-negative pregnant women should be screened for anti-D antibodies. The American Association of Blood Banks (AABB) is the only blood bank in the United States. The American Association of Blood Banks (AABB) guidelines [4] recommend that all pregnant women should have their ABO and Rh blood types determined as early as possible during each pregnancy, preferably at the time of early gestation. Documentation of the mother's ABO blood group can help determine whether a newborn presenting with signs and symptoms is ABO hemolyzed. The description of ABO blood group incompatibility is also very brief in some of the major foreign obstetrical texts, none of which recommend screening for blood group antibodies in O pregnant women with non-O spouses during pregnancy. The efficacy of Chinese herbal remedies to reduce the potency of blood group antibodies is not yet evidence-based. In PubMed, the terms "ABO", "incompatibility", "treatment", and "prenatal/pregnancy" were used. However, they were all published in Chinese in the Chinese Journal of Integrative Medicine, and none of them were well-designed randomized controlled studies, spanning from 1984 to 2004. No relevant reports in English or other languages were retrieved. There are few studies that support or oppose the question of whether there is over-intervention in the treatment of patients with increased antibody potency with Chinese medicine. In a study conducted by Southern Medical University, among 3947 pregnant women tested, 1599 (40.5%) were O-positive and the spouses were non-O-positive, of which 1255 (78.5%) were prenatal anti-A (or B) antibodies with potency ≥1:64 and 262 (16.4%) were ≥1:256. Even if the standard of Chinese medicine treatment is ≥1:256, 6.6% (262/3947) of all pregnant women tested need Chinese medicine treatment during pregnancy, which is still a high proportion [5]. More importantly, there is no conclusive evidence on the safety of herbal medicine for the fetus. Perinatal management after the occurrence of fetal/neonatal hemolysis Severe intrauterine fetal hemolysis due to ABO blood group incompatibility is rare. If severe hemolysis occurs, progressive anemia may lead to increased fetal cardiac output and decreased blood viscosity, and a significant increase in blood flow rate. Therefore, even in cases of severe hemolysis due to maternal and infant ABO blood group incompatibility, most of them can be detected by routine ultrasonography during pregnancy. According to Williams Obstetrics [6], ABO isoimmunization may cause hemolytic disease but not fetal edema, and therefore ABO isoimmunization is a pediatric condition rather than an obstetric concern. The book also states that prenatal diagnosis of ABO blood group incompatibility is not necessary because it does not cause severe fetal anemia, but careful observation is necessary in the neonatal period because hyperbilirubinemia may require treatment. Even in severe cases of hemolysis, treatment with early neonatal blood exchange does not lead to serious consequences. The task of obstetrics is to detect rare and severe fetal anemia and fetal edema through routine obstetric ultrasonography during pregnancy, and to provide appropriate treatment during pregnancy and terminate the pregnancy when appropriate. In the neonatal period, pathological jaundice should be detected early, and the core problem of its prevention is the detection of neonatal blood group immediately after delivery, early monitoring of bilirubin level and health education of family members for newborns with blood group A (or B), timely and correct treatment of hyperbilirubinemia, and prevention of nuclear jaundice. V. Summary 1. It is recommended that pregnant women with a history of severe neonatal ABO hemolysis should be screened for ABO blood group antibodies during pregnancy, and the occurrence of severe intrauterine hemolysis should be monitored by ultrasound examination of placental thickness, amniotic fluid volume, fetal edema, and fetal middle cerebral artery blood flow rate. If the fetus is found to have severe hemolysis during pregnancy, treatment can be carried out according to the treatment of severe hemolysis in fetuses with Rh blood type incompatibility, such as application of immunoglobulin, maternal blood exchange or intrauterine blood transfusion. 2.For pregnant women with O type without a history of severe neonatal ABO hemolysis, when the spouse is AB type, the pregnant woman can be screened for antibodies during pregnancy, because the newborn and the mother must be blood group incompatible. 3.For pregnant women with O type without a history of severe neonatal ABO hemolysis, if the spouse is A or B type, the decision to perform maternal blood group antibody test and neonatal direct anti-human globulin test can be made after delivery according to the blood group of the newborn, especially if the newborn is discharged early, and for those with high antibody potency, the discharge of the newborn can be postponed and the monitoring of neonatal jaundice in the first few days after birth can be strengthened. Neonates with pathological jaundice should be promptly referred to the neonatal unit for treatment.