Neonatal hemolytic disease is defined as homozygous immune hemolysis caused by maternal and child blood group incompatibility. ABO hemolysis accounts for 85.3% of neonatal hemolysis, Rh hemolysis for 14.6%, and MN hemolysis for 0.1%. about 1/5 of ABO blood group disorders and about 1/20 of RhD blood group disorders develop. 1, ABO hemolytic disease mother does not have the fetal dominant red blood cell A or B blood group antigen (inherited by the father) through the placenta into the mother (at the time of delivery), stimulating the mother to produce the corresponding antibodies, when pregnant again (its fetal ABO blood group is the same as the previous child), incomplete antibodies (1gG) into the fetal blood circulation, combined with the corresponding antigen of red blood cells, the formation of sensitized red blood cells, by the monocyte -The hemolysis is caused by the destruction of the phagocytic system. Due to the existence of A or B blood group substances in nature such as certain plants, parasites, typhoid vaccine, tetanus and diphtheria toxins, O mothers have already received stimulation from A or B blood group substances before their first pregnancy, and the anti-A or anti-B (1gG) potency in the blood is high, so the antibodies can enter the fetal blood circulation during the first pregnancy and cause hemolysis. 2, Rh hemolytic disease Rh blood group system has six antigens, namely D, E, C, d, e, c (d antigen has not been measured only speculation), its antigenic strength in order of D>E>C>c>e, so RhD hemolytic disease is the most common, followed by RhE, Rhe hemolytic disease is rare. The lack of D antigen in red blood cells is called Rh-negative, and having D antigen is called Rh-positive, and the majority of Chinese people are Rh. The mother is Rh-positive (with D antigen), but she can also lack other antigens of Rh system such as E, etc. Rh hemolytic disease can also occur if the fetus has this antigen. Rh hemolytic disease does not usually occur in the first pregnancy due to the absence of Rh blood group substances in nature. At the end of the first pregnancy or placental abruption, Rh-positive fetal blood (>0.5~lml) enters the Rh-negative maternal blood and produces IgM antibodies (primary immune response) after about 8~9 weeks, this antibody cannot pass through the placenta, although a small amount of IgC;antibody can be produced later, but the fetus has been delivered, such as the mother’s pregnancy (fetal Rh blood type is the same as the previous pregnancy), if a small amount of fetal blood during pregnancy ( 0.05-0.1m1) enters the maternal blood circulation, a large amount of IgG antibodies (secondary immune response) is produced within a few days, and this antibody causes fetal erythrocyte hemolysis through the placenta. When an Rh-negative mother has had a previous transfusion of Rh-positive blood or a history of miscarriage or abortion, the first fetus can develop the disease because she was sensitized before pregnancy. In the rare cases where the Rh-negative mother has not been exposed to Rh-positive blood, the onset of the first fetus may be due to the Rh-negative mother being Rh-positive and her mother being sensitized at the time of pregnancy (maternal grandmother theory). [AB0 hemolysis mainly causes jaundice, while Rh hemolysis causes severe anemia and even heart failure in the fetus. Severe anemia, low protein and heart failure can lead to generalized edema (hydrops fetalis). In anemia, extramedullary hematopoiesis is enhanced and hepatosplenomegaly may occur. The bilirubin in the fetal blood is metabolized by the placenta in the mother’s liver, so the jaundice is often not obvious at delivery. After birth, jaundice develops because of the poor bilirubin capacity of the newborn. Excessive serum unconjugated bilirubin can cross the blood-brain barrier and cause yellowing of nerve cells in the basal nucleus and other areas, resulting in bilirubin encephalopathy. [The first fetus is usually born in the second fetus; the first fetus is sensitized before the first pregnancy; the clinical manifestations are severe, and the fetus is even stillborn in severe cases. 1. jaundice Most ABO hemolytic disease jaundice appears in the second to third day after birth, while Rh hemolytic disease generally appears within 24 hours and rapidly worsens. Serum bilirubin is predominantly unconjugated, and if the hemolysis is severe, it can cause biliary stasis and rise in conjugated bilirubin. 2. Anemia The degree varies. Severe Rh hemolysis can be severe anemia or heart failure after birth. In some children, the anemia may persist until 3-6 weeks after birth due to the persistence of antibodies. 3. Hepatosplenomegaly Most children with Rh hemolysis have varying degrees of hepatosplenomegaly, which rarely occurs in ABO hemolysis. [Bilirubin encephalopathy is the most serious complication of neonatal hemolytic disease and is more likely to occur in premature infants. Most of the symptoms appear 4-7 days after birth and are clinically divided into 4 stages. The warning phase is characterized by lethargy, hyporesponsiveness, weak sucking, diminished hugging reflex, hypotonia, occasional screaming and vomiting. It lasts about 12 – 24 hours. 2. Convulsions, corkscrews and fever (mostly occurring simultaneously with convulsions). In mild cases, there is only double eye gaze, while in severe cases, there is increased muscle tone, apnea, clenching of hands, straightening and internal rotation of arms, and even corkscrew. This period lasts about 12-48 hours. 3. Recovery period The number of twitches decreases and the muscle tone gradually recovers. 4. After-effects period Tetralogy of jaundice: ①Hand and foot twitching: involuntary, purposeless and uncoordinated movements often occur. (ii) Oculomotor disorders: impaired upward rotation of the eyeballs, forming sunset eyes. ③ Hearing impairment: deafness and loss of hearing to high frequency sounds. (iv) Dental enamel dysplasia: teeth are green or dark brown. In addition, sequelae such as cerebral palsy, intellectual backwardness, convulsions, head lifting weakness and salivation may also remain. Treatment 1. Phototherapy is a simple and effective method to reduce serum unconjugated bilirubin. (1) Principle: unconjugated bilirubin is converted into water-soluble isomers under the action of light and excreted through bile and urine. Blue light of wavelength 425-475nm and green light of wavelength 510-530nm are more effective, and fluorescent light or sunlight also have certain therapeutic effect. Phototherapy mainly acts on superficial skin tissues, so the remission of skin jaundice does not indicate normal serum unconjugated bilirubin. (2) Equipment: There are mainly phototherapy boxes, phototherapy lamps and phototherapy blankets. Phototherapy box with single-sided light 160W, double-sided light 320W is appropriate, double-sided light is better than single-sided light; the upper and lower lamp distance from the bed is 1000px and 500px, respectively; blue light lamp use 300 hours of its energy reduced by 20%, 900 hours reduced by 35%, 2000 hours reduced by 45%; light, infants with black eye protection, so as not to damage the retina, in addition to the perineum, anus In addition to the perineum and anal area covered with diapers, the rest are exposed, and the duration of exposure should not exceed 3 days. (3) Indications: (i) general children with total serum bilirubin >205umol/L (12mg/d1), ELBW >85/umol/L (5mg/d1), VLBW >103/umol/L (6rng/d1); (ii) children with neonatal hemolytic disease with total postnatal serum bilirubin >85umol (5mg/d1). In addition, some scholars also advocate prophylactic phototherapy for ELBW immediately after birth. 2. Pharmacological treatment ① Albumin: transfusion of plasma 10-20ml/kg or albumin lg/kg each time to increase its association with unconjugated bilirubin and reduce the occurrence of bilirubin encephalopathy. (ii) Correction of metabolic acidosis: apply 5% sodium bicarbonate to raise blood pH to facilitate the association of unconjugated bilirubin with albumin. ③hepatic enzyme inducer: commonly used phenobarbital 5mg/kg daily, divided into 2-3 oral doses for 4-5 days, also can add Niclosamide 100mg/kg daily, divided into 2-3 oral doses for 4-5 days, which can increase the production of UDPGT and the ability of the liver to take up unconjugated bilirubin. (4) Intravenous immunoglobulin: the usage is lg/kg, intravenous drip in 6-8 hours, early application of clinical effect is better, can inhibit phagocytic destruction of sensitized red blood cells. 3. blood exchange therapy (exchangeetransfusion) (1) role: exchange out part of the blood free antibodies and allergic red blood cells, reduce hemolysis; exchange a large amount of bilirubin in the blood to prevent the occurrence of bilirubin encephalopathy; correct anemia, improve oxygen carrying, prevent heart failure. (2) Indications: Most of Rh hemolytic disease and individual severe ABO hemolytic disease have any of the following indications that should be replaced: ① prenatal diagnosis, total bilirubin of cord blood > 68umol/L (4mg/d1) at birth, hemoglobin less than 120g/L, with edema, hepatosplenomegaly and heart failure; ② 12 hours after birth, bilirubin rises > 12umol/L (0.7 mg/d1) within 12 hours after birth; ③ total bilirubin has reached 342umol/L (20mg/dl); ④ regardless of the level of serum bilirubin, there are early manifestations of bilirubin encephalopathy. The indications should be relaxed for small preterm infants, those with combined hypoxia and acidosis, or those with severe hemolysis in the previous pregnancy.