I. Diagnosis of non-hemolytic hyperbilirubinemia Measurement of serum bilirubin level is an important indicator for the diagnosis of neonatal hyperbilirubinemia. In the first 4-5 days after birth, most newborns have a peak period of rising serum bilirubin, ranging from 26 μmol/L (1.5 mg/dl) of cord blood bilirubin at birth to 102-205 μmol/L (6-12 mg/dl) 4-5 days after birth. Serum bilirubin levels exceed those of adults even under normal conditions. In adults, bilirubin >34 μmol/L (2 mg/dl) can be seen as yellow staining of the skin and sclera, and in neonates, due to the abundance of capillaries, bilirubin >86-120 μmol/L (5-7 mg/dl) before jaundice appears. Observation and detection of neonatal jaundice should be done daily in nude newborns under appropriate natural light, and jaundice of the skin and sclera can be observed early in most cases. The examiner uses his or her thumb to press on the surface of the skin on harder areas of the body, such as the forehead, chest, or thighs, primarily to whiten the skin to help observe the underlying yellow color. The skin reflex can be used as an alternative method of assessing the degree of clinical jaundice in the infant room using a transcutaneous bilirubin meter. Transcutaneous bilirubinometry correlates well with serum bilirubin levels, and standardized techniques and equipment are available for screening for hyperbilirubinemia. The correlation between transcutaneous bilirubinometry and serum bilirubin is better in Caucasians than in non-Caucasians. Both clinical observations and transcutaneous bilirubinometry confirm that skin jaundice in term infants progresses downward from the face, with jaundice of the sclera and face observed at bilirubin levels of 6-8 mg/dl, jaundice of the shoulders and trunk at 137-171 μmol/L (8-10 mg/dl), and significant jaundice of the lower extremities at 171-205 μmol/L (10-12 mg/dl) levels. Serum bilirubin was estimated at 205-256 μmol/L (12-15 mg/dl) levels when systemic jaundice was seen. Although this is only the crudest assessment, used for daily observation of neonatal jaundice, it often allows timely detection and recognition of progressing hyperbilirubinemia. It facilitates early detection, diagnosis and the administration of intervention and follow-up. Abnormal jaundice observed on the first postnatal day requires prompt evaluation and follow-up. Full-term newborns exhibiting mild jaundice at the 3rd-4th postnatal day or at the time of discharge, which is at the average level of bilirubin, are generally well and can be left unintervened. However, it is necessary to teach parents how to observe neonatal jaundice. In addition to the need for laboratory determination of total and direct bilirubin (conjugated bilirubin), a thorough clinical examination of hyperbilirubinemia should be made, including abdominal palpation, review of the history and laboratory basis of blood group incompatibility between the mother and the newborn, the titer of antibodies and the results of the Coomb test, and the family history of the newborn, siblings or relatives with jaundice during childhood. Second, the diagnosis of neonatal hemolytic disease 1, hemolysis in Rh blood group incompatibility Rh homoimmune hemolysis is one of the causes of severe hyperbilirubinemia and a common cause of kernicterus in full-term infants. Sixteen percent of North American women are Rh-negative, and most are D antigen negative. Rh hemolysis is relatively uncommon in this country. In the delivery of the first Rh-positive newborn due to placental hemorrhage, the mother had an abortion of the Rh-positive fetus when the Rh-negative mother received a small transfusion of Rh-positive fetal cells. When these Rh-positive cells entered the circulation of the Rh-negative mother, the mother’s immune system developed antibodies to the foreign Rh-positive red blood cell antigens. The latter exposure to Rh-positive fetal cells increases the mother’s titer of IgG antibodies against her fetus in any subsequent pregnancy with an Rh-positive fetus, or in the same pregnancy with fetal cells passing through the placenta, and the mother’s anti-Rh-positive IgG antibodies then pass through the placenta to the fetus, destroying the Rh-positive fetal red blood cells. Due to increased maternal antibodies, fetal red blood cells are destroyed and lysed inside and outside the blood vessels once they become antigenic and are recognized by circulating antibodies. The second pregnancy results in further hemolysis and intrauterine hyperbilirubinemia. In severe cases, the intrauterine anemia is so severe that it causes heart failure with high cardiac output and generalized edema, and the edematous fetus can be visualized by ultrasound. The passage of pregnancy in Rh-negative mothers can be monitored by measuring antibody titers to Rh. Hepatosplenomegaly and peripheral edema can be detected by ultrasound monitoring, and the presence of bilirubin in the amniotic fluid can be detected by transabdominal amniocentesis. An increase in bilirubin in the amniotic fluid, especially when combined with ultrasound confirmation of hepatosplenomegaly or edema, suggests a critical prognosis and requires ultrasound-guided transabdominal wall transfusion of red blood cells, and if the fetus is near term the pregnancy should be terminated as soon as possible. 2. Hemolysis of ABO blood group incompatibility ABO hemolysis is more common than Rh hemolysis, but it passes well. In almost all cases, the mother’s blood type is O and the newborn’s blood type is A or B. The mother’s anti-A or anti-B IgG is passively delivered to the infant in late pregnancy or at delivery. With recognition and rejection of the antigen-antibody complex by the spleen, early fetal hemolysis occurs rapidly. This is because the fetus has only nearly 7,500-8,000 A or B antigen attachment sites per 100 red blood cells (compared to 15,000-20,000 in adults). Antibodies do not adhere easily to fetal cells and are not completely destroyed. The low number of antigen-antibody attachment sites on fetal cells can result in a weakly positive or even negative direct Coomb test. Although 25% of pregnant women have an underlying ABO blood group incompatibility, only a minority (10-15%) of newborns have a positive Coomb test. In the absence of a positive antibody result, the diagnosis of neonatal hemolysis cannot be confirmed. Because not all ABO blood group incompatibilities result in neonatal hemolysis, a positive result of direct or indirect Coombs test or antibody release test is necessary to establish the diagnosis. In conclusion, all mothers should be tested for ABO blood group and Rh blood group before delivery and hospitalization, and if the mother is Rh negative, the titer of Rh antibodies should also be determined to determine the passage of labor and emergency management during and after delivery. If the mother’s blood type is O or Rh negative, the newborn should be checked for ABO blood type and Rh blood type; for those with incompatible blood types, antibody screening should be performed. The diagnosis is established. In addition to serum bilirubin, hematocrit, erythrocyte pressure, reticulocyte count, and red blood cell morphology should also be examined when high bilirubin is suspected to be due to neonatal hemolysis. For cases with high suspicion of Rh hemolysis, hematocrit, erythropoietic pressure and bilirubin measurements of cord blood specimens were done immediately after birth. In cases of suspected ABO hemolysis, it is not necessary to do the examination of cord blood because ABO hemolysis rarely causes significant jaundice and anemia at birth. Third, the prediction of hyperbilirubinemia Clinically, the age of the first appearance of jaundice and the subsequent rate of increase in serum bilirubin can be used to speculate on the possible clinical course and the degree of hyperbilirubinemia and whether the remission of bilirubin is delayed later. For example, the maximum rate of bilirubin rise in normal neonates with non-hemolytic hyperbilirubinemia is 85 μmol/L.d (5 mg/dl.d), or 3, 24 μmol/L, h (0.2 mg/dl.h). Jaundice visible to the naked eye on the first day after birth or a bilirubin level ≥171 μmol/L (10 mg/dl) within the first 48 hours after birth, where the rate of increase in bilirubin exceeds the normal range, is likely to have some underlying pathology. Assessment of the rate of bilirubin increase allows estimation of the likely level of bilirubin in the next 12-24 hours. In most cases, if jaundice is observed to be significant in the newborn during the first 24 hours, the serum indirect bilirubin level is determined to be ≥103 μmol/L (6 mg/dl) and the rate of increase of bilirubin exceeds 3.24 μmol/L.h (0.2 mg/dl.h), the measurement should be repeated every 8 hours until the bilirubin level stabilizes or the intervention criteria are met to give treatment. During this time, if the jaundice is not definitely physiological, further laboratory tests and analysis of the underlying etiology can be done clinically based on the initial bilirubin level and its increase. End-tidalCOcorrectedforambientCOETCOc is a good indicator to monitor endogenous CO production. CO is released from hemoglobin produced by senescent erythrocytes and hemoglobin proteins during the conversion of hemoglobin to bilirubin by hemoglobin oxidase, which produces an equivalent number of molecules of CO per gram molecule of metabolized ferrous hemoglobin.In the clinical setting of neonates with severe hyperbilirubinemia, monitoring endogenous CO production can more intuitively predict serum bilirubin production. In addition, hyperbilirubinemia can also occur in the neonatal period due to various causes of obstructive liver disease. Diagnosis requires the measurement of total and direct bilirubin. A direct bilirubin higher than 17.1-26 μmol/L (1.0-1.5 mg/dl), especially in the first days or weeks of life, with a persistent increase in direct bilirubin, should be suspected and requires a differential diagnosis. In principle, all neonatal bilirubin measurements should include both total and direct bilirubin. Rapid microhematology can only measure total bilirubin, which is suitable for follow-up, and direct bilirubin should also be measured if available. IV. Management of hyperbilirubinemia (a) Management of neonatal hemolysis Neonatal hemolysis can be used as a model for the management of severe neonatal hyperbilirubinemia. 1.Before birth, the mother should be screened for blood type before delivery, and the pediatrician should be notified before delivery in cases where the mother is Rh-negative. 2, At birth, cord blood samples should be sent for determination of serum bilirubin, hematocrit, erythrocyte pressure product and reticulocytes as soon as possible. Hemolytic individuals are characterized by the presence of a large number of nucleated red blood cells. The fetus known as myeloid erythropoietic fetus. The presence of these nucleated red blood cells responds to the extremely active bone marrow and increased extramedullary hematopoiesis attempting to make the fetal red blood cells grow at the same rate as the red blood cells destroyed by antibodies. 3, after birth newborns with edema, severe anemia and heart failure require emergency treatment with red blood cell replacement transfusions, diuresis, anti-heart failure and ventilatory support. In a few severe cases, normal at birth but accompanied by progressive anemia and hyperbilirubinemia after birth, the hematocrit can drop >1g/dl.d to severe anemia in untreated cases. Serum bilirubin increases from 86-171 μmol/L (5-10 mg/dl) in cord blood to very high unconjugated bilirubin levels at a rate of >17.1 μmol/L.h (1 mg/dl.h). Correct hematocrit as soon as possible with concentrated red blood cells. If hematocrit is ≤10g/dl at birth, transfusion may be 25-50ml/kg of concentrated red blood cells, estimated to correct hematocrit of 11-13g/dl in newborns, with attention to the rate of transfusion. In addition, if the cord blood bilirubin > 86μmol/L (5mg/dl), or postnatal bilirubin growth rate ≥ 17.1μmol/L.h (1mg/dl.h), exchange the blood with double the amount of whole blood as soon as possible. 4, ABO blood group incompatibility at birth rarely has severe jaundice or anemia. However, in the first few days after birth if the rate of bilirubin increases too rapidly, such as the rate of increase > 17.1μmol/L.h (1mg/dl.h), or there is significant anemia (hematocrit 8,6μmol/L.h (0,5mg/dl.h) for more than 10-12 hours, before the bilirubin reaches 342μmol/L (20mg/dl), the blood should be re-exchanged.