bubble_chart Overview

Hemolytic disease of the newborn is an alloimmune blood group disorder caused by blood type incompatibility between the mother and fetus, which can occur in the early stages of fetal or neonatal development. When the dominant antigen inherited by the fetus from the father happens to be absent in the mother, this antigen can enter the maternal circulation during {|###|}pregnancy or childbirth, stimulating the mother to produce immune antibodies. When these antibodies cross the placenta into the fetal bloodstream, they can cause agglutination and destruction of red blood cells, leading to immune-mediated hemolysis in the fetus or newborn. This condition does not affect the mother, but the affected infant may die from severe anemia or {|###|}heart failure, or from kernicterus caused by excessive bilirubin penetrating brain cells. Even if the infant survives, their nerve cells, intellectual development, and motor functions may be impaired.

Maternal-fetal blood group incompatibility primarily involves ABO and Rh types, with other systems like MN rarely causing the disease. ABO incompatibility is more common but usually milder and often overlooked. Rh incompatibility is rare in China but more severe, frequently resulting in intrauterine fetal death or neonatal kernicterus.

bubble_chart Etiology

In the ABO blood group system, pregnant women are mostly type O, while the father and fetus are type A, B, or AB. The A and B antigens of the fetus serve as sensitizing agents. The Rh blood group system includes six antigens: C, c, D, d, E, and e, with the D antigen being the most immunogenic. It has the highest hemolytic potential, so anti-D serum is used clinically for testing. When maternal or neonatal red blood cells agglutinate with known anti-D serum, the result is Rh-positive; otherwise, it is Rh-negative. Rh-negative pregnant women may occasionally be sensitized by other antigens, producing antibodies such as anti-E or anti-C, leading to maternal-fetal blood group incompatibility.

Normally, fetal red blood cells cannot cross the placenta. Only during pregnancy or childbirth, if the placenta is damaged, can fetal red blood cells from the chorionic vessels enter the maternal circulation. The amount of cells entering and the number of sensitizations influence the level of antibody production and the severity of hemolysis in the fetus or newborn.

Blood group antibodies are immunoglobulins, including IgG and IgM. IgG has a small molecular weight (7S-γ globulin) and is an incomplete antibody (colloidal medium antibody or blocking antibody), capable of crossing the placenta. In contrast, IgM has a large molecular weight (19S-γ globulin) and is a complete antibody (saline agglutinating antibody), unable to cross the placenta. Among Rh and ABO blood group antibodies, only IgG can cross the placenta and exert its effects.

bubble_chart Clinical Manifestations

(1) Due to increased red blood cell destruction, the reticuloendothelial system, liver, and kidney cells may exhibit hemosiderin deposition.

(2) The bone marrow and extramedullary hematopoietic tissues show compensatory hyperplasia, with hepatosplenomegaly. Microscopic examination reveals scattered extramedullary hematopoietic foci in tissues such as the liver, spleen, lungs, pancreas, and kidneys.

(3) Anemia leads to cardiac enlargement, hypoproteinemia, generalized pallor, edema, and scattered extramedullary hematopoietic foci in tissues such as the pleura, abdomen, and pericardium.

(4) Hyperbilirubinemia can cause systemic jaundice and kernicterus. Kernicterus predominantly occurs in the basal ganglia, hippocampus uncus, globus pallidus, subthalamic nucleus, caudate nucleus, and dentate nucleus. Neuronal degeneration is observed, with yellow-stained cytoplasm and nuclear disappearance.

Mild cases often present no specific symptoms, whereas severe hemolysis may lead to fetal hydrops, late abortion, premature labor, or even stillbirth. After delivery, the main manifestations include anemia, edema, hepatosplenomegaly, jaundice, and kernicterus. The severity of symptoms depends on the antibody levels, neonatal maturity, and compensatory hematopoietic capacity.

bubble_chart Diagnosis

It mainly relies on specific antibody tests in the laboratory. For those with a history of late abortion, unexplained dead fetus, blood transfusion, or severe neonatal jaundice, the possibility of maternal-fetal blood group incompatibility should be ruled out.

Pregnant women should routinely have their blood type checked before delivery. If the mother is type O and the father is type A, B, or AB, specific antibody tests should be performed. A negative result indicates sensitization. For Rh blood group incompatibility, an antibody titer >1:32 suggests severe disease, while for ABO blood group incompatibility, a titer >1:512 indicates a serious condition.

If conditions permit, amniotic fluid testing can be performed. Using a spectrophotometer, amniotic fluid bilirubin absorbance is analyzed. At 450 mµ, an absorbance difference (△OD450) >0.06 is a dangerous value; 0.03–0.06 is a warning value; and <0.03 is a safe value. After 36 weeks of pregnancy, an amniotic fluid bilirubin content of 0.03–0.06 mg% is considered normal, while >0.2 mg% suggests fetal hemolytic damage.

bubble_chart Treatment Measures

(1) Prenatal Management

1. Comprehensive Therapy

   To enhance fetal resistance and bilirubin metabolism capacity, a 10-day comprehensive treatment is administered at 24, 30, and 33 weeks of pregnancy. The method is as follows: daily intravenous injection of 40mg of 50% glucose plus 100mg of vitamin C; oxygen inhalation, 2-3 times daily, 15-20 minutes each session; and 30mg of vitamin E, 3 times daily. If necessary, the treatment duration and number of courses can be extended. Approximately 2 weeks before delivery, oral phenobarbital 10-30mg, 2-3 times daily, can enhance the activity of glucuronyl transferase in fetal liver cells, improve bilirubin metabolism, and reduce the risk of kernicterus.

2. Chinese Medicinals

   Virgate Wormwood Decoction (Virgate Wormwood 9g, prepared Rhubarb Rhizome 4.5g, Skullcap Root 9g, Liquorice Root 6g) is decocted and taken daily until childbirth.

3. Induction of Labor

   After 36 weeks of pregnancy, induction of labor may be considered under the following circumstances: (1) Antibody titer: Rh incompatibility antibody titer >1:32, ABO incompatibility antibody titer >1:512; (2) History of stillbirth, especially due to hemolytic disease; (3) Changes in fetal movement or heart rate indicating that continuing the pregnancy is unsafe for the fetus; (4) Deep yellow amniotic fluid or elevated bilirubin levels.

(2) Intrapartum Management

Aim for natural childbirth and avoid the use of sedatives or anesthetics to reduce the risk of neonatal asphyxia. Prepare for neonatal resuscitation. Immediately clamp the umbilical cord after delivery to minimize antibody transfer to the newborn, and leave about 10cm of the cord for potential medication or exchange transfusion. After birth, immediately inject 10ml of 25% glucose, 100mg of vitamin C, 125mg of nikethamide, and/or 25mg of hydrocortisone into the umbilical vein. Retain placental-side umbilical blood for testing blood type, bilirubin, specific antibodies, red blood cells, hemoglobin, and nucleated red blood cells.

(3) Neonatal Management

Pay attention to three critical periods:

1. Days 1-2 after birth: For mild cases, monitor the onset, progression, and severity of jaundice. If severe anemia is present at birth (umbilical blood hemoglobin <12g%), consider blood transfusion;
2. Days 2-7: Focus on preventing kernicterus due to hyperbilirubinemia. Closely monitor the rate and degree of increase in serum indirect bilirubin to ensure it does not exceed the critical concentration for kernicterus (18-20mg%);
3. Within 2 months postpartum: Monitor for anemia due to impaired red blood cell regeneration and transfuse if necessary.

   Three methods to prevent kernicterus: (1) Medications to accelerate normal bilirubin metabolism and excretion; (2) Phototherapy to alter bilirubin excretion pathways; (3) Exchange transfusion to mechanically remove bilirubin, sensitized red blood cells, and antibodies.

   1. Drug Therapy

   (1) Hormones

4. Plasma
5. Glucose Comprehensive Therapy: Adrenal corticosteroids activate liver enzyme systems, promote bilirubin conjugation with glucuronic acid, and suppress antigen-antibody reactions to reduce hemolysis. Albumin binds free bilirubin, preventing its passage through the blood-brain barrier. Thus, prednisone 2.5mg orally 3 times daily, or hydrocortisone 10-20mg IV, and 25% albumin 20ml or plasma 25-30ml IV may be used.
   (2) Phenobarbital: 5mg/kg orally 3 times daily for 5-7 days.
   (3) Chinese Medicinals: Sanhuang Decoction—Virgate Wormwood 9g
6. Prepared Rhubarb Rhizome 1.5g
7. Skullcap Root 4.5g
8. Phellodendron Bark 4.5g
9. Gardenia 3g
10. Decoct and take to detoxify and promote bile flow.

    2. Phototherapy

    Phototherapy can oxidize and decompose indirect bilirubin into water-soluble products, dipyrrole and biliverdin, which are excreted through bile and urine. The optimal wavelength for light therapy is 425–475 nm of blue light. If blue light is unavailable, white light from fluorescent tubes can also be used, though the effect is slightly inferior. If serum bilirubin levels do not decrease or even increase after 24 hours of phototherapy, exchange transfusion should be considered.

    3. Exchange Transfusion Therapy

    For cases where prenatal diagnosis is clear and the newborn exhibits obvious

11. signs, and bilirubin levels continue to rise approaching 18mg% despite treatment, exchange transfusion should be considered.