Hemolytic Disease of the Fetus and Newborn (HDFN)

Background

• Hemolytic disease of the fetus and newborn is a severe form of anemia caused by the production of maternal antibodies against fetal red blood cells.
• RhD, ABO, and less commonly other blood group antigen incompatibility between the fetus/infant and the mother can lead to the production of maternal antibodies (alloimmunization) when there is fetomaternal hemorrhage.
• After birth, hemolysis in newborns may continue for several months due to the persistent action of maternal immunoglobulin G (IgG) antibodies.

Evaluation

• All pregnant women should have blood antigen typing for ABO and RhD groups and maternal antibody screening that detects IgG at the first prenatal visit.
• First-time alloimmunized pregnancies should be monitored with maternal RhD antibody titers every 4 weeks until 24 weeks, then every 2 weeks if the titers are < 1:8. Once the titers reach 1:8-1:32 (> 15 units/mL), the infant is at an increased risk for HDFN and fetal hydrops. For non-D alloantibodies (except Kell), a critical titer of 1:16-1:32 is typically used.
• Pregnancies in women that were previously Rh alloimmunized in which the current fetus is RhD positive also increase the risk for hemolytic anemia in the infant.
• In alloimmunized pregnancies, if there is a possibility that the fetus is positive for the immunizing antigen, then testing of the father or fetus is indicated.
• In the newborn with suspected hemolysis:
  • Obtain complete blood count, blood smear, red blood cell indices, lactic dehydrogenase, bilirubin, and carboxyhemoglobin.
  • Hemolysis may be suspected if there is a decreased red cell count, hemoglobin, and hematocrit; elevated bilirubin; widening of the red cell distribution; reticulocytosis; or a peripheral blood smear with increased nucleated red blood cells, spherocytosis, and polychromasia.

Management

• Prophylaxis for pregnant Rh-negative women:
  • If negative maternal Rh antibody screening result (indicating no prior anti-D alloimmunization), repeat screen at 28 weeks to assess for alloimmunization.
  • If second screen is negative, give 300 mcg Rh immune globulin intramuscularly with a repeat dose within 72 hours after delivery.
  • Refer women with history of alloimmunization to a perinatal center experienced in managing severely alloimmunized pregnancies.
• Management of fetus in alloimmunized pregnancy:
  • Monitor using fetal middle cerebral artery (MCA) Doppler ultrasound every 1-2 weeks starting at 16-24 weeks gestation or when a critical antibody titer is reached. If the fetal MCA Doppler ultrasound value is > 1.5 times the median for gestational age, then suspect moderate-to-severe anemia from hemolysis and perform a cordocentesis for fetal hematocrit.
  • Perform intrauterine transfusion (IUT) in cases of moderate-to-severe anemia or a hematocrit < 30% (if cordocentesis is performed) in a fetus of a gestational age considered unacceptable for delivery.
  • If moderate-to-severe anemia is present at 35 weeks gestation, assess for fetal lung maturity and amniotic bilirubin level to guide the decision as to when and if labor should be induced.
  • Consider delayed umbilical cord clamping to reduce anemia and the need for transfusions.
• Neonates with severe hemolytic anemia may require red blood cell transfusion with the decision to transfuse based on specific hemoglobin thresholds or signs and symptoms of anemia such as poor feeding, tachycardia, tachypnea, and increased oxygen requirements.
  • The most common regimen for neonatal red blood cell transfusion is 10-20 mL/kg of ABO/Rh type-specific and antigen-negative (for maternal antibodies) red blood cells which have been irradiated due to immaturity of the immune system.
  • Consider supplementation with folic acid and iron in infants without high ferritin levels.
  • Antenatal IV immunoglobulin for reduction of maternal antibody and recombinant erythropoietin for neonatal anemia are not routinely recommended.
  • Treat hyperbilirubinemia, which may result from hemolysis. First line therapy is typically ultraviolet phototherapy, however, IV fluids, IV immunoglobulin (IVIG), and blood exchange transfusions may be necessary depending on severity.